Conference Coverage

Don’t wait to give patients with first-episode psychosis long-acting injectable formulations of second-generation antipsychotics, according to Henry A. Nasrallah, MD.

Many clinicians wait to use long-acting injectables (LAIs) until the patient has experienced multiple relapses, but using them after the first discharge may help prevent future relapse, Dr. Nasrallah, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education.

LAIs and clozapine are “vastly underutilized” after the first discharge, he noted. “I really encourage everybody to use them without hesitation as early as possible.”

In patients with first-episode psychosis, “the most important thing, in my opinion, is to start establishing a therapeutic alliance with the patient from day one,” Dr. Nasrallah said. “It’s always important in psychiatry, but it’s particularly important for first-episode psychosis.”

These patients respond to low doses of antipsychotics and should not be given first-generation antipsychotics because of a risk for acute extrapyramidal symptoms, tardive dyskinesia, and neurotoxicity.

“I usually select an antipsychotic that is extended release and also available as a long-acting injectable formulation,” Dr. Nasrallah said, noting that it helps when he gives a patient a long-acting injectable right after discharge. During hospitalization, Dr. Nasrallah said, he educates the patient and their family about psychosis, treatment, how psychosis affects the brain, and adherence to treatment.

“The primary goal, of course, is to achieve remission and very importantly, to prevent a second episode,” he said. “This is the golden opportunity for us psychiatrists to prevent the patient from relapsing again and again. That is the reason for disability and for brain damage, because every psychotic episode destroys brain tissue. That is why I am very eager to not only achieve a remission in the first episode but also to position the patient to be protected after discharge by giving them long-acting injectable.”

After a clinician performs a full workup to rule out substance use or a general medical condition inducing first-episode psychosis, Dr. Nasrallah recommends paliperidone extended-release (ER), given to patients in the morning because of its tolerability and the availability of an LAI version of the drug. “I start with 3 mg a day; that’s the lowest dose,” he said. “If the patient is very sick and agitated, I might go to 6 mg a day, which is actually a very good dose for first-episode patients, and it’s still quite well tolerated.”

Oral or injectable lorazepam taken as needed may be given to a patient with first-episode psychosis with agitation. For patients who manifest akathisia, twice or thrice daily propranolol at dose of 10-20 mg can be used off label, he said. Dr. Nasrallah also recommended twice-daily omega 3 at a dose of 1,000 mg or N-acetylcysteine at a dose of 600 mg per day as supplements.

“They’re not approved by the [Food and Drug Administration] for first-episode psychosis, but there are numerous publications in the literature by academic psychiatrists showing that they are quite beneficial, and they reduce the two destructive processes during psychosis, which are neuroinflammation and oxidative stress, or free radicals,” he said. “Those two supplements can help in the acute phase of the illness.”

Another option for clinicians is to begin a patient with first-episode psychosis on oral aripiprazole at a dose of 5 mg per day for 2 days, increasing the dose to 7.5 mg per day for 2 days, then increasing to 10 mg per day. “It is not extended-release, so you have to start with low doses to protect the patient from side effects,” Dr. Nasrallah explained. “Some patients may need 15 or 20 [mg], but most first-episode patients may do well on 10 [mg] without risking side effects.”
 

Planning for discharge

Patients who tolerate aripiprazole can start the long-acting aripiprazole lauroxil at discharge, and clinicians have two options to choose from. One formulation “requires 2 weeks of oral supplementation, which you can do in the hospital if you start the patient on oral aripiprazole, and then you can give that injection prior to discharge.” Another option involves giving the patient “any antipsychotic you like and then switch[ing] the patient to aripiprazole lauroxil. The full dose can be given without oral supplementation on the day of discharge.”

Dr. Nasrallah emphasized the use of LAIs in patients discharged for first-episode psychosis. In a study published in JAMA Psychiatry, researchers found use of LAI risperidone in patients with first-episode psychosis significantly reduced the risk of psychotic exacerbation and relapse compared with patients who were given oral risperidone (JAMA Psychiatry. 2015;72:822-9).

“This kind of well-done study shows you that you can do a great job protecting your patient from the very beginning by giving long-acting injectables,” Dr. Nasrallah explained. “That’s why you have to develop rapport with the patient. That’s why you have to convince the patient to take the injectable, and that’s why you have to educate the patient about the hazards of psychosis to the brain, and the fact that it’s very hard to remember to take the pills, because the illness itself can interfere with that due to cognitive impairment [and] negative symptoms.” Another reason for nonadherence is that the patients might not believe they are sick, he added.

After 2 or 3 weeks, if a patient with first-episode psychosis has a minimal response or does not response at all to an LAI, clozapine is an “aggressive” option that may help nonresponders. For patients with schizophrenia, “about 65%-70% would respond to a dopamine antagonist and the remaining 30% are going to need clozapine sooner or later,” Dr. Nasrallah said. “For clozapine after one or two failures [on LAIs] with an adequate dose and adequate duration, don’t wait. Give the patient clozapine, give them an opportunity to regain their life. I’ve seen some very gratifying results with clozapine in those who respond to it.

“The outcome of schizophrenia may be far less malignant than the perception out there if we actually ensure adherence very early and manage the first-episode aggressively, like cardiologists manage the first heart attack,” he said. “[Cardiologists] do everything in their power to protect the patient from a second heart attack, and I regard psychosis as a ‘brain attack.’ ”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reported that he has received research grants from Acadia; served as a consultant for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim; and is on the speakers bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.

Don’t wait to give patients with first-episode psychosis long-acting injectable formulations of second-generation antipsychotics, according to Henry A. Nasrallah, MD.

Many clinicians wait to use long-acting injectables (LAIs) until the patient has experienced multiple relapses, but using them after the first discharge may help prevent future relapse, Dr. Nasrallah, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education.

LAIs and clozapine are “vastly underutilized” after the first discharge, he noted. “I really encourage everybody to use them without hesitation as early as possible.”

In patients with first-episode psychosis, “the most important thing, in my opinion, is to start establishing a therapeutic alliance with the patient from day one,” Dr. Nasrallah said. “It’s always important in psychiatry, but it’s particularly important for first-episode psychosis.”

These patients respond to low doses of antipsychotics and should not be given first-generation antipsychotics because of a risk for acute extrapyramidal symptoms, tardive dyskinesia, and neurotoxicity.

“I usually select an antipsychotic that is extended release and also available as a long-acting injectable formulation,” Dr. Nasrallah said, noting that it helps when he gives a patient a long-acting injectable right after discharge. During hospitalization, Dr. Nasrallah said, he educates the patient and their family about psychosis, treatment, how psychosis affects the brain, and adherence to treatment.

“The primary goal, of course, is to achieve remission and very importantly, to prevent a second episode,” he said. “This is the golden opportunity for us psychiatrists to prevent the patient from relapsing again and again. That is the reason for disability and for brain damage, because every psychotic episode destroys brain tissue. That is why I am very eager to not only achieve a remission in the first episode but also to position the patient to be protected after discharge by giving them long-acting injectable.”

After a clinician performs a full workup to rule out substance use or a general medical condition inducing first-episode psychosis, Dr. Nasrallah recommends paliperidone extended-release (ER), given to patients in the morning because of its tolerability and the availability of an LAI version of the drug. “I start with 3 mg a day; that’s the lowest dose,” he said. “If the patient is very sick and agitated, I might go to 6 mg a day, which is actually a very good dose for first-episode patients, and it’s still quite well tolerated.”

Oral or injectable lorazepam taken as needed may be given to a patient with first-episode psychosis with agitation. For patients who manifest akathisia, twice or thrice daily propranolol at dose of 10-20 mg can be used off label, he said. Dr. Nasrallah also recommended twice-daily omega 3 at a dose of 1,000 mg or N-acetylcysteine at a dose of 600 mg per day as supplements.

“They’re not approved by the [Food and Drug Administration] for first-episode psychosis, but there are numerous publications in the literature by academic psychiatrists showing that they are quite beneficial, and they reduce the two destructive processes during psychosis, which are neuroinflammation and oxidative stress, or free radicals,” he said. “Those two supplements can help in the acute phase of the illness.”

Another option for clinicians is to begin a patient with first-episode psychosis on oral aripiprazole at a dose of 5 mg per day for 2 days, increasing the dose to 7.5 mg per day for 2 days, then increasing to 10 mg per day. “It is not extended-release, so you have to start with low doses to protect the patient from side effects,” Dr. Nasrallah explained. “Some patients may need 15 or 20 [mg], but most first-episode patients may do well on 10 [mg] without risking side effects.”
 

Planning for discharge

Patients who tolerate aripiprazole can start the long-acting aripiprazole lauroxil at discharge, and clinicians have two options to choose from. One formulation “requires 2 weeks of oral supplementation, which you can do in the hospital if you start the patient on oral aripiprazole, and then you can give that injection prior to discharge.” Another option involves giving the patient “any antipsychotic you like and then switch[ing] the patient to aripiprazole lauroxil. The full dose can be given without oral supplementation on the day of discharge.”

Dr. Nasrallah emphasized the use of LAIs in patients discharged for first-episode psychosis. In a study published in JAMA Psychiatry, researchers found use of LAI risperidone in patients with first-episode psychosis significantly reduced the risk of psychotic exacerbation and relapse compared with patients who were given oral risperidone (JAMA Psychiatry. 2015;72:822-9).

“This kind of well-done study shows you that you can do a great job protecting your patient from the very beginning by giving long-acting injectables,” Dr. Nasrallah explained. “That’s why you have to develop rapport with the patient. That’s why you have to convince the patient to take the injectable, and that’s why you have to educate the patient about the hazards of psychosis to the brain, and the fact that it’s very hard to remember to take the pills, because the illness itself can interfere with that due to cognitive impairment [and] negative symptoms.” Another reason for nonadherence is that the patients might not believe they are sick, he added.

After 2 or 3 weeks, if a patient with first-episode psychosis has a minimal response or does not response at all to an LAI, clozapine is an “aggressive” option that may help nonresponders. For patients with schizophrenia, “about 65%-70% would respond to a dopamine antagonist and the remaining 30% are going to need clozapine sooner or later,” Dr. Nasrallah said. “For clozapine after one or two failures [on LAIs] with an adequate dose and adequate duration, don’t wait. Give the patient clozapine, give them an opportunity to regain their life. I’ve seen some very gratifying results with clozapine in those who respond to it.

“The outcome of schizophrenia may be far less malignant than the perception out there if we actually ensure adherence very early and manage the first-episode aggressively, like cardiologists manage the first heart attack,” he said. “[Cardiologists] do everything in their power to protect the patient from a second heart attack, and I regard psychosis as a ‘brain attack.’ ”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reported that he has received research grants from Acadia; served as a consultant for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim; and is on the speakers bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.

Don’t wait to give patients with first-episode psychosis long-acting injectable formulations of second-generation antipsychotics, according to Henry A. Nasrallah, MD.

Many clinicians wait to use long-acting injectables (LAIs) until the patient has experienced multiple relapses, but using them after the first discharge may help prevent future relapse, Dr. Nasrallah, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education.

LAIs and clozapine are “vastly underutilized” after the first discharge, he noted. “I really encourage everybody to use them without hesitation as early as possible.”

In patients with first-episode psychosis, “the most important thing, in my opinion, is to start establishing a therapeutic alliance with the patient from day one,” Dr. Nasrallah said. “It’s always important in psychiatry, but it’s particularly important for first-episode psychosis.”

These patients respond to low doses of antipsychotics and should not be given first-generation antipsychotics because of a risk for acute extrapyramidal symptoms, tardive dyskinesia, and neurotoxicity.

“I usually select an antipsychotic that is extended release and also available as a long-acting injectable formulation,” Dr. Nasrallah said, noting that it helps when he gives a patient a long-acting injectable right after discharge. During hospitalization, Dr. Nasrallah said, he educates the patient and their family about psychosis, treatment, how psychosis affects the brain, and adherence to treatment.

“The primary goal, of course, is to achieve remission and very importantly, to prevent a second episode,” he said. “This is the golden opportunity for us psychiatrists to prevent the patient from relapsing again and again. That is the reason for disability and for brain damage, because every psychotic episode destroys brain tissue. That is why I am very eager to not only achieve a remission in the first episode but also to position the patient to be protected after discharge by giving them long-acting injectable.”

After a clinician performs a full workup to rule out substance use or a general medical condition inducing first-episode psychosis, Dr. Nasrallah recommends paliperidone extended-release (ER), given to patients in the morning because of its tolerability and the availability of an LAI version of the drug. “I start with 3 mg a day; that’s the lowest dose,” he said. “If the patient is very sick and agitated, I might go to 6 mg a day, which is actually a very good dose for first-episode patients, and it’s still quite well tolerated.”

Oral or injectable lorazepam taken as needed may be given to a patient with first-episode psychosis with agitation. For patients who manifest akathisia, twice or thrice daily propranolol at dose of 10-20 mg can be used off label, he said. Dr. Nasrallah also recommended twice-daily omega 3 at a dose of 1,000 mg or N-acetylcysteine at a dose of 600 mg per day as supplements.

“They’re not approved by the [Food and Drug Administration] for first-episode psychosis, but there are numerous publications in the literature by academic psychiatrists showing that they are quite beneficial, and they reduce the two destructive processes during psychosis, which are neuroinflammation and oxidative stress, or free radicals,” he said. “Those two supplements can help in the acute phase of the illness.”

Another option for clinicians is to begin a patient with first-episode psychosis on oral aripiprazole at a dose of 5 mg per day for 2 days, increasing the dose to 7.5 mg per day for 2 days, then increasing to 10 mg per day. “It is not extended-release, so you have to start with low doses to protect the patient from side effects,” Dr. Nasrallah explained. “Some patients may need 15 or 20 [mg], but most first-episode patients may do well on 10 [mg] without risking side effects.”
 

Planning for discharge

Patients who tolerate aripiprazole can start the long-acting aripiprazole lauroxil at discharge, and clinicians have two options to choose from. One formulation “requires 2 weeks of oral supplementation, which you can do in the hospital if you start the patient on oral aripiprazole, and then you can give that injection prior to discharge.” Another option involves giving the patient “any antipsychotic you like and then switch[ing] the patient to aripiprazole lauroxil. The full dose can be given without oral supplementation on the day of discharge.”

Dr. Nasrallah emphasized the use of LAIs in patients discharged for first-episode psychosis. In a study published in JAMA Psychiatry, researchers found use of LAI risperidone in patients with first-episode psychosis significantly reduced the risk of psychotic exacerbation and relapse compared with patients who were given oral risperidone (JAMA Psychiatry. 2015;72:822-9).

“This kind of well-done study shows you that you can do a great job protecting your patient from the very beginning by giving long-acting injectables,” Dr. Nasrallah explained. “That’s why you have to develop rapport with the patient. That’s why you have to convince the patient to take the injectable, and that’s why you have to educate the patient about the hazards of psychosis to the brain, and the fact that it’s very hard to remember to take the pills, because the illness itself can interfere with that due to cognitive impairment [and] negative symptoms.” Another reason for nonadherence is that the patients might not believe they are sick, he added.

After 2 or 3 weeks, if a patient with first-episode psychosis has a minimal response or does not response at all to an LAI, clozapine is an “aggressive” option that may help nonresponders. For patients with schizophrenia, “about 65%-70% would respond to a dopamine antagonist and the remaining 30% are going to need clozapine sooner or later,” Dr. Nasrallah said. “For clozapine after one or two failures [on LAIs] with an adequate dose and adequate duration, don’t wait. Give the patient clozapine, give them an opportunity to regain their life. I’ve seen some very gratifying results with clozapine in those who respond to it.

“The outcome of schizophrenia may be far less malignant than the perception out there if we actually ensure adherence very early and manage the first-episode aggressively, like cardiologists manage the first heart attack,” he said. “[Cardiologists] do everything in their power to protect the patient from a second heart attack, and I regard psychosis as a ‘brain attack.’ ”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reported that he has received research grants from Acadia; served as a consultant for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim; and is on the speakers bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.

A draft guideline for the management of patients with juvenile idiopathic arthritis reflects changes in therapy away from reliance on NSAIDs and glucocorticoids and toward earlier introduction of biologic disease-modifying antirheumatic drugs (DMARDs).

The guideline, described in an oral session during the virtual annual meeting of the American College of Rheumatology, contains weighted recommendations for the treatment of JIA, including therapeutic approaches for oligoarthritis, tempromandibular joint (TMJ) arthritis, and systemic JIA (sJIA). The recommendations were the result of expert consensus and literature review using GRADE methodology, with input from clinicians, as well as patients and parents.

“Although evidence remains very low and many recommendations are conditional, the inclusion of parents and patients in the decision-making process strengthens their validity,” said project principal investigator Karen Onel, MD, of the Hospital for Special Surgery and Weill Cornell Medicine, both in New York.

She added that “it’s important to remember that these guidelines are meant to be guidelines; clinical care remains in the hands of the provider and the patient, and we endorse the importance of shared decision-making in coming to these agreements.”

Dr. Onel outlined key recommendations for patients for whom a diagnosis of JIA has already been made and who have no contraindications to recommended therapies. The strength of the recommendations (strong or conditional) and evidence levels (high, moderate, low, very low) were also reported.
 

Oligoarthritis with fewer than five involved joints

For these patients, intra-articular glucocorticoids (IAGC) are recommended as a part of initial therapy (strong, very low evidence).

Triamcinolone acetonide is the preferred agent in this situation (strong, low evidence).

The guideline also has a conditional recommendation (very low evidence) for a trial of consistent NSAIDS as part of initial therapy and a conditional recommendation against oral glucocorticoids for initial therapy (very low evidence).

Patients with no or incomplete responses or intolerance to NSAIDS and/or IAGC may be tried on a nonbiologic DMARD (strong, very low evidence), with methotrexate as the preferred agent (conditional, low evidence).

If the patient has no response or an inadequate response to at least one nonbiologic DMARD, biologic DMARDs are recommended (strong, very low evidence), with no preferred agent.

The guideline also conditionally recommends (all with very low evidence) using risk factors and validated disease activity measures to guide treatment decisions, as well as imaging guidance of joints that are difficult to access or to localize the distribution of inflammation.
 

TMJ arthritis

For patients with temporomandibular joint arthritis, isolated or not, IAGCs are conditionally recommended as part of initial therapy (very low evidence) with no preferred agents. The guideline also conditionally recommends in favor of a trial of consistent NSAIDs, and against oral glucocorticoids in initial therapy (evidence for both very low).

Recommendations for patients with TMJ with no or an incomplete response to the initial therapy are the same as for patients with oligoarthritis, with no preferred agent.
 

sJIA without macrophage activation syndrome

For patients with sJIA without macrophage activation syndrome (MAS), NSAIDS are conditionally recommended as initial monotherapy (very low evidence). Biologic DMARDS (including interleukin-1 and IL-6 inhibitors) are also recommended, conditionally, as initial monotherapy, with no preferred agent.

If the patient has an inadequate response or intolerance to NSAIDS and at least one nonbiologic DMARD, a single biologic DMARD is recommended over a combination of nonbiologic therapies (strong, very low evidence).

“However, there have been reports of emergent, highly severe lung disease associated with the use of biologics in children with systemic JIA, especially in those who are young, with chronic macrophage activation syndrome, and those with trisomy 21. More information is needed to clarify the safety of these agents,” Dr. Onel said.

There is a conditional recommendation against oral glucocorticoids as initial monotherapy, and strong recommendation against nonbiologic DMARDs as initial monotherapy (both very low evidence).

sJIA with MAS

“Macrophage activation syndrome is a major cause of morbidity and mortality for children with sJIA. Cytokine storm and secondary hemophagocytic syndrome can be seen with any rheumatic disease, but are most commonly seen with sJIA,” she said.

The features of MAS include fever, high ferritin levels, cytopenias, elevated liver-function test results, and high triglyceride levels.

For these patients, glucocorticoids are recommended as initial monotherapy (conditional, very low evidence). Biologic DMARDs (IL-1 and IL-6 inhibitors) are recommended over calcineurin inhibitors for achieving inactive disease and resolution of MAS (conditional, very low evidence). There is no preferred agent.

For patients with residual arthritis and an incomplete response to IL-1 or IL-6 inhibitors, biologic and nonbiologic DMARDs are recommended over chronic glucocorticoids (strong, very low evidence). There is no preferred agent.

After an MAS inactive disease state has been attained, the guideline recommends tapering and discontinuing glucocorticoids (strong, very low evidence) and the same for biologic DMARDs (conditional, very low evidence).
 

All children with JIA

In addition to the recommendations on specific clinical situations, the guideline includes recommendations for all children with JIA on medication monitoring, laboratory testing, and infection screening, as well as immunization and nonpharmacologic management.

A rheumatologist who was not involved in development of the guidelines commented on the importance of optimal management of JIA.

“Children are not immune from devastating rheumatic diseases, and the largest group is juvenile idiopathic arthritis. In my clinic, I have patients in their 30s, 40s, and 50s who have adult persistence of their arthritis from JIA who have permanent joint damage and even ongoing hard-to-control disease, and it has to do with the lack of therapies in the 1990s,” said Donald Thomas, MD, from Arthritis and Pain Associates of Prince George’s County (Md.).

“Today when we get a young adult transitioned from the pediatric clinic they’re usually in remission or have low disease activity because these treatments have paralleled those of our adult RA patients. Yet they do [provide clinicians with] unique challenges, with stunting of growth, macrophage activiation syndrome, and having to work with family members of the patient,” he said at a press briefing he moderated following the presentation of RA and JIA guidelines.

Eyal Muscal, MD, associate professor of pediatrics and rheumatology at Baylor College of Medicine, Houston, said in an interview that the guidelines clarify recommendations about earlier use of targeted therapies, primarily biologics.

“This will not change care, but hopefully remind all to adopt such strategies. Yet earlier utilization of often expensive biologic agents is delayed by administrative and insurance hurdles in the U.S. and access to these medications globally. I hope the guidelines will enhance advocacy on a state, national, and global stage,” he said when asked for comment.

The guideline development process is supported by ACR. Dr. Onel, Dr. Thomas, and Dr. Muscal reported no relevant conflicts of interest.

SOURCE: Onel K et al. ACR 2020, Presented November 8.

A draft guideline for the management of patients with juvenile idiopathic arthritis reflects changes in therapy away from reliance on NSAIDs and glucocorticoids and toward earlier introduction of biologic disease-modifying antirheumatic drugs (DMARDs).

The guideline, described in an oral session during the virtual annual meeting of the American College of Rheumatology, contains weighted recommendations for the treatment of JIA, including therapeutic approaches for oligoarthritis, tempromandibular joint (TMJ) arthritis, and systemic JIA (sJIA). The recommendations were the result of expert consensus and literature review using GRADE methodology, with input from clinicians, as well as patients and parents.

“Although evidence remains very low and many recommendations are conditional, the inclusion of parents and patients in the decision-making process strengthens their validity,” said project principal investigator Karen Onel, MD, of the Hospital for Special Surgery and Weill Cornell Medicine, both in New York.

She added that “it’s important to remember that these guidelines are meant to be guidelines; clinical care remains in the hands of the provider and the patient, and we endorse the importance of shared decision-making in coming to these agreements.”

Dr. Onel outlined key recommendations for patients for whom a diagnosis of JIA has already been made and who have no contraindications to recommended therapies. The strength of the recommendations (strong or conditional) and evidence levels (high, moderate, low, very low) were also reported.
 

Oligoarthritis with fewer than five involved joints

For these patients, intra-articular glucocorticoids (IAGC) are recommended as a part of initial therapy (strong, very low evidence).

Triamcinolone acetonide is the preferred agent in this situation (strong, low evidence).

The guideline also has a conditional recommendation (very low evidence) for a trial of consistent NSAIDS as part of initial therapy and a conditional recommendation against oral glucocorticoids for initial therapy (very low evidence).

Patients with no or incomplete responses or intolerance to NSAIDS and/or IAGC may be tried on a nonbiologic DMARD (strong, very low evidence), with methotrexate as the preferred agent (conditional, low evidence).

If the patient has no response or an inadequate response to at least one nonbiologic DMARD, biologic DMARDs are recommended (strong, very low evidence), with no preferred agent.

The guideline also conditionally recommends (all with very low evidence) using risk factors and validated disease activity measures to guide treatment decisions, as well as imaging guidance of joints that are difficult to access or to localize the distribution of inflammation.
 

TMJ arthritis

For patients with temporomandibular joint arthritis, isolated or not, IAGCs are conditionally recommended as part of initial therapy (very low evidence) with no preferred agents. The guideline also conditionally recommends in favor of a trial of consistent NSAIDs, and against oral glucocorticoids in initial therapy (evidence for both very low).

Recommendations for patients with TMJ with no or an incomplete response to the initial therapy are the same as for patients with oligoarthritis, with no preferred agent.
 

sJIA without macrophage activation syndrome

For patients with sJIA without macrophage activation syndrome (MAS), NSAIDS are conditionally recommended as initial monotherapy (very low evidence). Biologic DMARDS (including interleukin-1 and IL-6 inhibitors) are also recommended, conditionally, as initial monotherapy, with no preferred agent.

If the patient has an inadequate response or intolerance to NSAIDS and at least one nonbiologic DMARD, a single biologic DMARD is recommended over a combination of nonbiologic therapies (strong, very low evidence).

“However, there have been reports of emergent, highly severe lung disease associated with the use of biologics in children with systemic JIA, especially in those who are young, with chronic macrophage activation syndrome, and those with trisomy 21. More information is needed to clarify the safety of these agents,” Dr. Onel said.

There is a conditional recommendation against oral glucocorticoids as initial monotherapy, and strong recommendation against nonbiologic DMARDs as initial monotherapy (both very low evidence).

sJIA with MAS

“Macrophage activation syndrome is a major cause of morbidity and mortality for children with sJIA. Cytokine storm and secondary hemophagocytic syndrome can be seen with any rheumatic disease, but are most commonly seen with sJIA,” she said.

The features of MAS include fever, high ferritin levels, cytopenias, elevated liver-function test results, and high triglyceride levels.

For these patients, glucocorticoids are recommended as initial monotherapy (conditional, very low evidence). Biologic DMARDs (IL-1 and IL-6 inhibitors) are recommended over calcineurin inhibitors for achieving inactive disease and resolution of MAS (conditional, very low evidence). There is no preferred agent.

For patients with residual arthritis and an incomplete response to IL-1 or IL-6 inhibitors, biologic and nonbiologic DMARDs are recommended over chronic glucocorticoids (strong, very low evidence). There is no preferred agent.

After an MAS inactive disease state has been attained, the guideline recommends tapering and discontinuing glucocorticoids (strong, very low evidence) and the same for biologic DMARDs (conditional, very low evidence).
 

All children with JIA

In addition to the recommendations on specific clinical situations, the guideline includes recommendations for all children with JIA on medication monitoring, laboratory testing, and infection screening, as well as immunization and nonpharmacologic management.

A rheumatologist who was not involved in development of the guidelines commented on the importance of optimal management of JIA.

“Children are not immune from devastating rheumatic diseases, and the largest group is juvenile idiopathic arthritis. In my clinic, I have patients in their 30s, 40s, and 50s who have adult persistence of their arthritis from JIA who have permanent joint damage and even ongoing hard-to-control disease, and it has to do with the lack of therapies in the 1990s,” said Donald Thomas, MD, from Arthritis and Pain Associates of Prince George’s County (Md.).

“Today when we get a young adult transitioned from the pediatric clinic they’re usually in remission or have low disease activity because these treatments have paralleled those of our adult RA patients. Yet they do [provide clinicians with] unique challenges, with stunting of growth, macrophage activiation syndrome, and having to work with family members of the patient,” he said at a press briefing he moderated following the presentation of RA and JIA guidelines.

Eyal Muscal, MD, associate professor of pediatrics and rheumatology at Baylor College of Medicine, Houston, said in an interview that the guidelines clarify recommendations about earlier use of targeted therapies, primarily biologics.

“This will not change care, but hopefully remind all to adopt such strategies. Yet earlier utilization of often expensive biologic agents is delayed by administrative and insurance hurdles in the U.S. and access to these medications globally. I hope the guidelines will enhance advocacy on a state, national, and global stage,” he said when asked for comment.

The guideline development process is supported by ACR. Dr. Onel, Dr. Thomas, and Dr. Muscal reported no relevant conflicts of interest.

SOURCE: Onel K et al. ACR 2020, Presented November 8.

A draft guideline for the management of patients with juvenile idiopathic arthritis reflects changes in therapy away from reliance on NSAIDs and glucocorticoids and toward earlier introduction of biologic disease-modifying antirheumatic drugs (DMARDs).

The guideline, described in an oral session during the virtual annual meeting of the American College of Rheumatology, contains weighted recommendations for the treatment of JIA, including therapeutic approaches for oligoarthritis, tempromandibular joint (TMJ) arthritis, and systemic JIA (sJIA). The recommendations were the result of expert consensus and literature review using GRADE methodology, with input from clinicians, as well as patients and parents.

“Although evidence remains very low and many recommendations are conditional, the inclusion of parents and patients in the decision-making process strengthens their validity,” said project principal investigator Karen Onel, MD, of the Hospital for Special Surgery and Weill Cornell Medicine, both in New York.

She added that “it’s important to remember that these guidelines are meant to be guidelines; clinical care remains in the hands of the provider and the patient, and we endorse the importance of shared decision-making in coming to these agreements.”

Dr. Onel outlined key recommendations for patients for whom a diagnosis of JIA has already been made and who have no contraindications to recommended therapies. The strength of the recommendations (strong or conditional) and evidence levels (high, moderate, low, very low) were also reported.
 

Oligoarthritis with fewer than five involved joints

For these patients, intra-articular glucocorticoids (IAGC) are recommended as a part of initial therapy (strong, very low evidence).

Triamcinolone acetonide is the preferred agent in this situation (strong, low evidence).

The guideline also has a conditional recommendation (very low evidence) for a trial of consistent NSAIDS as part of initial therapy and a conditional recommendation against oral glucocorticoids for initial therapy (very low evidence).

Patients with no or incomplete responses or intolerance to NSAIDS and/or IAGC may be tried on a nonbiologic DMARD (strong, very low evidence), with methotrexate as the preferred agent (conditional, low evidence).

If the patient has no response or an inadequate response to at least one nonbiologic DMARD, biologic DMARDs are recommended (strong, very low evidence), with no preferred agent.

The guideline also conditionally recommends (all with very low evidence) using risk factors and validated disease activity measures to guide treatment decisions, as well as imaging guidance of joints that are difficult to access or to localize the distribution of inflammation.
 

TMJ arthritis

For patients with temporomandibular joint arthritis, isolated or not, IAGCs are conditionally recommended as part of initial therapy (very low evidence) with no preferred agents. The guideline also conditionally recommends in favor of a trial of consistent NSAIDs, and against oral glucocorticoids in initial therapy (evidence for both very low).

Recommendations for patients with TMJ with no or an incomplete response to the initial therapy are the same as for patients with oligoarthritis, with no preferred agent.
 

sJIA without macrophage activation syndrome

For patients with sJIA without macrophage activation syndrome (MAS), NSAIDS are conditionally recommended as initial monotherapy (very low evidence). Biologic DMARDS (including interleukin-1 and IL-6 inhibitors) are also recommended, conditionally, as initial monotherapy, with no preferred agent.

If the patient has an inadequate response or intolerance to NSAIDS and at least one nonbiologic DMARD, a single biologic DMARD is recommended over a combination of nonbiologic therapies (strong, very low evidence).

“However, there have been reports of emergent, highly severe lung disease associated with the use of biologics in children with systemic JIA, especially in those who are young, with chronic macrophage activation syndrome, and those with trisomy 21. More information is needed to clarify the safety of these agents,” Dr. Onel said.

There is a conditional recommendation against oral glucocorticoids as initial monotherapy, and strong recommendation against nonbiologic DMARDs as initial monotherapy (both very low evidence).

sJIA with MAS

“Macrophage activation syndrome is a major cause of morbidity and mortality for children with sJIA. Cytokine storm and secondary hemophagocytic syndrome can be seen with any rheumatic disease, but are most commonly seen with sJIA,” she said.

The features of MAS include fever, high ferritin levels, cytopenias, elevated liver-function test results, and high triglyceride levels.

For these patients, glucocorticoids are recommended as initial monotherapy (conditional, very low evidence). Biologic DMARDs (IL-1 and IL-6 inhibitors) are recommended over calcineurin inhibitors for achieving inactive disease and resolution of MAS (conditional, very low evidence). There is no preferred agent.

For patients with residual arthritis and an incomplete response to IL-1 or IL-6 inhibitors, biologic and nonbiologic DMARDs are recommended over chronic glucocorticoids (strong, very low evidence). There is no preferred agent.

After an MAS inactive disease state has been attained, the guideline recommends tapering and discontinuing glucocorticoids (strong, very low evidence) and the same for biologic DMARDs (conditional, very low evidence).
 

All children with JIA

In addition to the recommendations on specific clinical situations, the guideline includes recommendations for all children with JIA on medication monitoring, laboratory testing, and infection screening, as well as immunization and nonpharmacologic management.

A rheumatologist who was not involved in development of the guidelines commented on the importance of optimal management of JIA.

“Children are not immune from devastating rheumatic diseases, and the largest group is juvenile idiopathic arthritis. In my clinic, I have patients in their 30s, 40s, and 50s who have adult persistence of their arthritis from JIA who have permanent joint damage and even ongoing hard-to-control disease, and it has to do with the lack of therapies in the 1990s,” said Donald Thomas, MD, from Arthritis and Pain Associates of Prince George’s County (Md.).

“Today when we get a young adult transitioned from the pediatric clinic they’re usually in remission or have low disease activity because these treatments have paralleled those of our adult RA patients. Yet they do [provide clinicians with] unique challenges, with stunting of growth, macrophage activiation syndrome, and having to work with family members of the patient,” he said at a press briefing he moderated following the presentation of RA and JIA guidelines.

Eyal Muscal, MD, associate professor of pediatrics and rheumatology at Baylor College of Medicine, Houston, said in an interview that the guidelines clarify recommendations about earlier use of targeted therapies, primarily biologics.

“This will not change care, but hopefully remind all to adopt such strategies. Yet earlier utilization of often expensive biologic agents is delayed by administrative and insurance hurdles in the U.S. and access to these medications globally. I hope the guidelines will enhance advocacy on a state, national, and global stage,” he said when asked for comment.

The guideline development process is supported by ACR. Dr. Onel, Dr. Thomas, and Dr. Muscal reported no relevant conflicts of interest.

SOURCE: Onel K et al. ACR 2020, Presented November 8.

Febuxostat (Uloric) emerged as noninferior to allopurinol regarding risk of cardiovascular death among people 60 years and older with gout and at least one additional cardiovascular risk factor, results of the Febuxostat versus Allopurinol Streamlined Trial (FAST) suggest.

This primary outcome of the FAST trial stands in contrast to results of the CARES trial in 2018. The CARES researchers previously reported a 4.3% increased risk of cardiovascular death associated with febuxostat, compared with a 3.2% rate with allopurinol, a statistically significant 34% increase in the relative risk.

“In contrast to previous studies, there was no evidence of increased mortality with febuxostat, and we believe the regulators should review febuxostat licensing restrictions,” senior author Thomas MacDonald, MD, of the University of Dundee (Scotland), said during a late-breaking abstract session at the virtual annual meeting of the American College of Rheumatology.

The results of the FAST trial were simultaneously published online in The Lancet.

Both febuxostat and allopurinol treat gout by lowering urate levels. Concerns about the cardiovascular safety of febuxostat led to two post-licensing studies: the Cardiovascular Safety of Febuxostat and Allopurinol in Participants with Gout and Cardiovascular Comorbidities (CARES) study, mandated by the U.S. Food and Drug Administration, and FAST, requested by the European Medicines Agency. In February 2019, the FDA added a warning about elevated cardiovascular death and death risk associated with febuxostat.

“When CARES was published, it was somewhat of a threat to our study,” Dr. MacDonald said. “After hearing from our data-monitoring committee, we were told we could continue the trial.”
 

Some switched from allopurinol to febuxostat

So Dr. MacDonald, lead author Isla Mackenzie, MBChB, and their colleagues enrolled 6,128 people with gout in the United Kingdom, Sweden, and Denmark between December 2011 and January 2018. They followed patients for a median of 4 years. Participants had a mean age of 71 years, 85% were men, and 33% had a history of cardiovascular disease. The investigators excluded anyone with a stroke or myocardial infarction in the previous 6 months.

All participants were being treated with allopurinol. The investigators titrated those not at target up to an ideal dose that achieved a serum urate concentration of less than 0.357 mmol/L (< 6 mg/dL). Next, they randomly assigned 3,065 people to continue allopurinol and another 3,063 to switch to 80-120 mg of febuxostat.

The primary outcome of the multicenter, prospective, randomized, open-label FAST trial was a composite of hospitalization for nonfatal MI or biomarker positive for acute coronary syndrome, nonfatal stroke, or cardiovascular death.
 

Key findings

“There was definitely a noninferior primary outcome,” Dr. MacDonald said. In the on-treatment analysis, 172 patients in the febuxostat group reached the composite endpoint versus 241 patients in the allopurinol group. There were 1.72 events per 100 patient-years in the febuxostat group versus 2.05 events in the allopurinol group (adjusted hazard ratio, 0.85; 95% confidence interval, 0.70-1.03). An intent-to-treat analysis also found that febuxostat was noninferior to allopurinol on this measure.

Urate levels were approximately 80 micromoles lower in the febuxostat group versus the allopurinol group each year of the study, Dr. MacDonald said.

At least one gout flare was experienced by 1,017 patients in the febuxostat group and by 1,044 participants in the allopurinol group. “However, there was no placebo group, so we don’t know the effectiveness of either of these agents at preventing flares” based on this research, he said.

Both the on-treatment and intention-to-treat (ITT) secondary analyses demonstrated the noninferiority of febuxostat, compared with allopurinol, for all-cause death, each individual component of the composite primary outcome – cardiovascular death, hospitalization for heart failure, and hospitalization for new, unstable, or worsening angina.

In contrast, the ITT analysis revealed a “nominally significant increase” in hospitalization for arrhythmia with no evidence of ischemia in the febuxostat group. The 0.583 events per 100 patient-years in this group versus 0.385 events in the allopurinol cohort generated an adjusted HR of 1.51 (95% CI, 1.05-2.17).

In terms of all-cause mortality, 222 participants (7.2%) in the febuxostat group died, compared with 263 people (8.6%) in the allopurinol group.

Adverse events and withdrawals

A total 1,720 participants (57.3%) in the febuxostat group experienced at least one serious adverse event, as did 1,812 participants (59.4%) in the allopurinol group. Less than 1% of serious adverse events in each group were considered treatment-related.

Dr. MacDonald said that 6.2% of the febuxostat patients and 5.5% of the allopurinol group withdrew from the study. “We had pretty good follow-up [94%],” Dr. MacDonald said. “I don’t want to criticize CARES, but 47% did drop out of that study, and they could not follow them anymore.”

Limitations of FAST include its open-label design and lack of a placebo group, although Dr. MacDonald pointed out that a placebo group would have been unethical. Strengths included its large randomized trial design and good external validity, he added. “This is what will happen in clinical practice if you switch people from allopurinol to febuxostat.”

When asked how he would treat people with gout now given the FAST findings, Dr. MacDonald said, “I’m not a rheumatologist, I’m a cardiovascular physician. But I would say from the evidence from the FAST trial, it appears to be safe to give patients febuxostat whether or not they have cardiovascular risk factors or prior cardiovascular disease.”

“The FAST study indicates that febuxostat is similar to allopurinol in terms of cardiovascular events during the treatment period. The strengths of this study are its large sample size, excellent follow-up rate, and the relatively long follow-up time,” session moderator Shervin Assassi, MD, said when asked for comment. Dr. Assassi, director of the division of rheumatology at the University of Texas Health Science Center at Houston, was not involved in the research.

Menarini, Ipsen, and Teijin Pharma funded the study. The University of Dundee receives research funds from Menarini. Dr. MacDonald disclosed that he received speaker or consultant fees from Menarini. Dr. Assassi had no relevant disclosures.

SOURCE: MacDonald T et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract L08.

Febuxostat (Uloric) emerged as noninferior to allopurinol regarding risk of cardiovascular death among people 60 years and older with gout and at least one additional cardiovascular risk factor, results of the Febuxostat versus Allopurinol Streamlined Trial (FAST) suggest.

This primary outcome of the FAST trial stands in contrast to results of the CARES trial in 2018. The CARES researchers previously reported a 4.3% increased risk of cardiovascular death associated with febuxostat, compared with a 3.2% rate with allopurinol, a statistically significant 34% increase in the relative risk.

“In contrast to previous studies, there was no evidence of increased mortality with febuxostat, and we believe the regulators should review febuxostat licensing restrictions,” senior author Thomas MacDonald, MD, of the University of Dundee (Scotland), said during a late-breaking abstract session at the virtual annual meeting of the American College of Rheumatology.

The results of the FAST trial were simultaneously published online in The Lancet.

Both febuxostat and allopurinol treat gout by lowering urate levels. Concerns about the cardiovascular safety of febuxostat led to two post-licensing studies: the Cardiovascular Safety of Febuxostat and Allopurinol in Participants with Gout and Cardiovascular Comorbidities (CARES) study, mandated by the U.S. Food and Drug Administration, and FAST, requested by the European Medicines Agency. In February 2019, the FDA added a warning about elevated cardiovascular death and death risk associated with febuxostat.

“When CARES was published, it was somewhat of a threat to our study,” Dr. MacDonald said. “After hearing from our data-monitoring committee, we were told we could continue the trial.”
 

Some switched from allopurinol to febuxostat

So Dr. MacDonald, lead author Isla Mackenzie, MBChB, and their colleagues enrolled 6,128 people with gout in the United Kingdom, Sweden, and Denmark between December 2011 and January 2018. They followed patients for a median of 4 years. Participants had a mean age of 71 years, 85% were men, and 33% had a history of cardiovascular disease. The investigators excluded anyone with a stroke or myocardial infarction in the previous 6 months.

All participants were being treated with allopurinol. The investigators titrated those not at target up to an ideal dose that achieved a serum urate concentration of less than 0.357 mmol/L (< 6 mg/dL). Next, they randomly assigned 3,065 people to continue allopurinol and another 3,063 to switch to 80-120 mg of febuxostat.

The primary outcome of the multicenter, prospective, randomized, open-label FAST trial was a composite of hospitalization for nonfatal MI or biomarker positive for acute coronary syndrome, nonfatal stroke, or cardiovascular death.
 

Key findings

“There was definitely a noninferior primary outcome,” Dr. MacDonald said. In the on-treatment analysis, 172 patients in the febuxostat group reached the composite endpoint versus 241 patients in the allopurinol group. There were 1.72 events per 100 patient-years in the febuxostat group versus 2.05 events in the allopurinol group (adjusted hazard ratio, 0.85; 95% confidence interval, 0.70-1.03). An intent-to-treat analysis also found that febuxostat was noninferior to allopurinol on this measure.

Urate levels were approximately 80 micromoles lower in the febuxostat group versus the allopurinol group each year of the study, Dr. MacDonald said.

At least one gout flare was experienced by 1,017 patients in the febuxostat group and by 1,044 participants in the allopurinol group. “However, there was no placebo group, so we don’t know the effectiveness of either of these agents at preventing flares” based on this research, he said.

Both the on-treatment and intention-to-treat (ITT) secondary analyses demonstrated the noninferiority of febuxostat, compared with allopurinol, for all-cause death, each individual component of the composite primary outcome – cardiovascular death, hospitalization for heart failure, and hospitalization for new, unstable, or worsening angina.

In contrast, the ITT analysis revealed a “nominally significant increase” in hospitalization for arrhythmia with no evidence of ischemia in the febuxostat group. The 0.583 events per 100 patient-years in this group versus 0.385 events in the allopurinol cohort generated an adjusted HR of 1.51 (95% CI, 1.05-2.17).

In terms of all-cause mortality, 222 participants (7.2%) in the febuxostat group died, compared with 263 people (8.6%) in the allopurinol group.

Adverse events and withdrawals

A total 1,720 participants (57.3%) in the febuxostat group experienced at least one serious adverse event, as did 1,812 participants (59.4%) in the allopurinol group. Less than 1% of serious adverse events in each group were considered treatment-related.

Dr. MacDonald said that 6.2% of the febuxostat patients and 5.5% of the allopurinol group withdrew from the study. “We had pretty good follow-up [94%],” Dr. MacDonald said. “I don’t want to criticize CARES, but 47% did drop out of that study, and they could not follow them anymore.”

Limitations of FAST include its open-label design and lack of a placebo group, although Dr. MacDonald pointed out that a placebo group would have been unethical. Strengths included its large randomized trial design and good external validity, he added. “This is what will happen in clinical practice if you switch people from allopurinol to febuxostat.”

When asked how he would treat people with gout now given the FAST findings, Dr. MacDonald said, “I’m not a rheumatologist, I’m a cardiovascular physician. But I would say from the evidence from the FAST trial, it appears to be safe to give patients febuxostat whether or not they have cardiovascular risk factors or prior cardiovascular disease.”

“The FAST study indicates that febuxostat is similar to allopurinol in terms of cardiovascular events during the treatment period. The strengths of this study are its large sample size, excellent follow-up rate, and the relatively long follow-up time,” session moderator Shervin Assassi, MD, said when asked for comment. Dr. Assassi, director of the division of rheumatology at the University of Texas Health Science Center at Houston, was not involved in the research.

Menarini, Ipsen, and Teijin Pharma funded the study. The University of Dundee receives research funds from Menarini. Dr. MacDonald disclosed that he received speaker or consultant fees from Menarini. Dr. Assassi had no relevant disclosures.

SOURCE: MacDonald T et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract L08.

Febuxostat (Uloric) emerged as noninferior to allopurinol regarding risk of cardiovascular death among people 60 years and older with gout and at least one additional cardiovascular risk factor, results of the Febuxostat versus Allopurinol Streamlined Trial (FAST) suggest.

This primary outcome of the FAST trial stands in contrast to results of the CARES trial in 2018. The CARES researchers previously reported a 4.3% increased risk of cardiovascular death associated with febuxostat, compared with a 3.2% rate with allopurinol, a statistically significant 34% increase in the relative risk.

“In contrast to previous studies, there was no evidence of increased mortality with febuxostat, and we believe the regulators should review febuxostat licensing restrictions,” senior author Thomas MacDonald, MD, of the University of Dundee (Scotland), said during a late-breaking abstract session at the virtual annual meeting of the American College of Rheumatology.

The results of the FAST trial were simultaneously published online in The Lancet.

Both febuxostat and allopurinol treat gout by lowering urate levels. Concerns about the cardiovascular safety of febuxostat led to two post-licensing studies: the Cardiovascular Safety of Febuxostat and Allopurinol in Participants with Gout and Cardiovascular Comorbidities (CARES) study, mandated by the U.S. Food and Drug Administration, and FAST, requested by the European Medicines Agency. In February 2019, the FDA added a warning about elevated cardiovascular death and death risk associated with febuxostat.

“When CARES was published, it was somewhat of a threat to our study,” Dr. MacDonald said. “After hearing from our data-monitoring committee, we were told we could continue the trial.”
 

Some switched from allopurinol to febuxostat

So Dr. MacDonald, lead author Isla Mackenzie, MBChB, and their colleagues enrolled 6,128 people with gout in the United Kingdom, Sweden, and Denmark between December 2011 and January 2018. They followed patients for a median of 4 years. Participants had a mean age of 71 years, 85% were men, and 33% had a history of cardiovascular disease. The investigators excluded anyone with a stroke or myocardial infarction in the previous 6 months.

All participants were being treated with allopurinol. The investigators titrated those not at target up to an ideal dose that achieved a serum urate concentration of less than 0.357 mmol/L (< 6 mg/dL). Next, they randomly assigned 3,065 people to continue allopurinol and another 3,063 to switch to 80-120 mg of febuxostat.

The primary outcome of the multicenter, prospective, randomized, open-label FAST trial was a composite of hospitalization for nonfatal MI or biomarker positive for acute coronary syndrome, nonfatal stroke, or cardiovascular death.
 

Key findings

“There was definitely a noninferior primary outcome,” Dr. MacDonald said. In the on-treatment analysis, 172 patients in the febuxostat group reached the composite endpoint versus 241 patients in the allopurinol group. There were 1.72 events per 100 patient-years in the febuxostat group versus 2.05 events in the allopurinol group (adjusted hazard ratio, 0.85; 95% confidence interval, 0.70-1.03). An intent-to-treat analysis also found that febuxostat was noninferior to allopurinol on this measure.

Urate levels were approximately 80 micromoles lower in the febuxostat group versus the allopurinol group each year of the study, Dr. MacDonald said.

At least one gout flare was experienced by 1,017 patients in the febuxostat group and by 1,044 participants in the allopurinol group. “However, there was no placebo group, so we don’t know the effectiveness of either of these agents at preventing flares” based on this research, he said.

Both the on-treatment and intention-to-treat (ITT) secondary analyses demonstrated the noninferiority of febuxostat, compared with allopurinol, for all-cause death, each individual component of the composite primary outcome – cardiovascular death, hospitalization for heart failure, and hospitalization for new, unstable, or worsening angina.

In contrast, the ITT analysis revealed a “nominally significant increase” in hospitalization for arrhythmia with no evidence of ischemia in the febuxostat group. The 0.583 events per 100 patient-years in this group versus 0.385 events in the allopurinol cohort generated an adjusted HR of 1.51 (95% CI, 1.05-2.17).

In terms of all-cause mortality, 222 participants (7.2%) in the febuxostat group died, compared with 263 people (8.6%) in the allopurinol group.

Adverse events and withdrawals

A total 1,720 participants (57.3%) in the febuxostat group experienced at least one serious adverse event, as did 1,812 participants (59.4%) in the allopurinol group. Less than 1% of serious adverse events in each group were considered treatment-related.

Dr. MacDonald said that 6.2% of the febuxostat patients and 5.5% of the allopurinol group withdrew from the study. “We had pretty good follow-up [94%],” Dr. MacDonald said. “I don’t want to criticize CARES, but 47% did drop out of that study, and they could not follow them anymore.”

Limitations of FAST include its open-label design and lack of a placebo group, although Dr. MacDonald pointed out that a placebo group would have been unethical. Strengths included its large randomized trial design and good external validity, he added. “This is what will happen in clinical practice if you switch people from allopurinol to febuxostat.”

When asked how he would treat people with gout now given the FAST findings, Dr. MacDonald said, “I’m not a rheumatologist, I’m a cardiovascular physician. But I would say from the evidence from the FAST trial, it appears to be safe to give patients febuxostat whether or not they have cardiovascular risk factors or prior cardiovascular disease.”

“The FAST study indicates that febuxostat is similar to allopurinol in terms of cardiovascular events during the treatment period. The strengths of this study are its large sample size, excellent follow-up rate, and the relatively long follow-up time,” session moderator Shervin Assassi, MD, said when asked for comment. Dr. Assassi, director of the division of rheumatology at the University of Texas Health Science Center at Houston, was not involved in the research.

Menarini, Ipsen, and Teijin Pharma funded the study. The University of Dundee receives research funds from Menarini. Dr. MacDonald disclosed that he received speaker or consultant fees from Menarini. Dr. Assassi had no relevant disclosures.

SOURCE: MacDonald T et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract L08.

New data show that new CFTR modulator therapies for cystic fibrosis may be driving down hospitalizations in this patient population.

The triple combination therapy elexacaftor/tezacaftor/ivacaftor was associated with a near elimination of hospital stays in one hospital in Oregon, according to a new report. The hospital savings still weren’t nearly enough to pay for the cost of therapy, but the study underscores what many institutions have observed and adds a new layer to the view of quality of life improvements that the new therapy brings.

“After we started prescribing it, we noticed pretty quickly that hospitalizations appeared to be declining after patients started triple combination therapy, and we were hearing [similar reports] from other centers as well. We wanted to quantify this,” Eric C. Walter, MD, a pulmonologist at the Kaiser Permanente Cystic Fibrosis Clinic in Portland, Ore., said during a presentation of the results at the virtual North American Cystic Fibrosis Conference.

“We’re seeing that across the board in real practice, the number of cystic fibrosis patients that have to be hospitalized since starting this triple combination has gone down,” Robert Giusti, MD, said in an interview. “When they’ve had pulmonary exacerbations in the past, it was frequently because they failed outpatient antibiotics, but I think with triple combination therapy, if they do get sick, the likelihood is they will respond to oral antibiotics, so they may not need that prolonged IV course in the hospital.” Dr. Giusti is clinical professor of pediatrics at New York University and director of the Pediatric Cystic Fibrosis Center. He was not involved in the study.

The therapy gained Food and Drug Administration approval in 2019 for the treatment of individuals with CF who are aged 12 years and older, and who have at least one copy of the F508del mutation. Its cost is about $317,000 per year within the Kaiser Permanente system, according to Dr. Walter. His group compared hospitalization days for CF-related diagnoses from Jan. 1 through Aug. 31, 2020, before and after initiation of triple combination therapy.

Of 47 eligible patients, 32 initiated therapy during the study period; 38% had severe lung disease, defined by forced expiratory volume in 1 second (FEV₁₎ value less than 40%. In 2020, before initiation of therapy, there were an average of 27 hospital days per month, all among patients with severe lung disease.

Among the therapy group, there were no hospitalizations after initiation of therapy through Aug. 31. Dr. Walter noted that the first hospitalization of a patient on triple combination therapy didn’t occur until early October.

At an average daily cost of $6,700, the researchers calculated that triple combination therapy saved about $189,000 per month in this group of patients. Comparing numbers to previous years, in which some patients with FEV₁ greater than 40% were hospitalized, the researchers calculated that the therapy saved about $151,000 per month among individuals with severe lung disease: Patients with severe lung disease contributed about 80% to total hospital costs.

The drug itself for the whole group cost $845,000, dwarfing the $189,000 savings overall. But among patients with severe disease, hospitalization savings were about $151,000 per month, while the drug cost in this group was $316,800 per month.

Cost savings are important, but the improvement in quality of life for a patient – avoiding hospitalization, fewer impacts on work and education – should not be overlooked, according to Ryan Perkins, MD, a pediatric and adult pulmonary fellow at Boston Children’s Hospital and Brigham and Women’s Hospital, who moderated the session. “Some of these aren’t things people typically quantify and assign a price tag to,” Dr. Perkins said in an interview.

A big limitation of the work is that it was conducted during the COVID-19 pandemic, which may have reduced hospitalizations. “We did have patients that called in, told us they were sick, that they needed to be treated for an exacerbation but didn’t want to go to the hospital,” said Dr. Walter. To help adjust for this, Dr. Walter’s team plans to compare intravenous antibiotic exposure before and after triple combination therapy, reasoning that it could help clarify the pandemic’s impact on hospitalizations.

Dr. Walter, Dr. Giusti, and Dr. Perkins have no relevant financial disclosures.

SOURCE: Walter E et al. NACFC 2020. Abstract 795.

New data show that new CFTR modulator therapies for cystic fibrosis may be driving down hospitalizations in this patient population.

The triple combination therapy elexacaftor/tezacaftor/ivacaftor was associated with a near elimination of hospital stays in one hospital in Oregon, according to a new report. The hospital savings still weren’t nearly enough to pay for the cost of therapy, but the study underscores what many institutions have observed and adds a new layer to the view of quality of life improvements that the new therapy brings.

“After we started prescribing it, we noticed pretty quickly that hospitalizations appeared to be declining after patients started triple combination therapy, and we were hearing [similar reports] from other centers as well. We wanted to quantify this,” Eric C. Walter, MD, a pulmonologist at the Kaiser Permanente Cystic Fibrosis Clinic in Portland, Ore., said during a presentation of the results at the virtual North American Cystic Fibrosis Conference.

“We’re seeing that across the board in real practice, the number of cystic fibrosis patients that have to be hospitalized since starting this triple combination has gone down,” Robert Giusti, MD, said in an interview. “When they’ve had pulmonary exacerbations in the past, it was frequently because they failed outpatient antibiotics, but I think with triple combination therapy, if they do get sick, the likelihood is they will respond to oral antibiotics, so they may not need that prolonged IV course in the hospital.” Dr. Giusti is clinical professor of pediatrics at New York University and director of the Pediatric Cystic Fibrosis Center. He was not involved in the study.

The therapy gained Food and Drug Administration approval in 2019 for the treatment of individuals with CF who are aged 12 years and older, and who have at least one copy of the F508del mutation. Its cost is about $317,000 per year within the Kaiser Permanente system, according to Dr. Walter. His group compared hospitalization days for CF-related diagnoses from Jan. 1 through Aug. 31, 2020, before and after initiation of triple combination therapy.

Of 47 eligible patients, 32 initiated therapy during the study period; 38% had severe lung disease, defined by forced expiratory volume in 1 second (FEV₁₎ value less than 40%. In 2020, before initiation of therapy, there were an average of 27 hospital days per month, all among patients with severe lung disease.

Among the therapy group, there were no hospitalizations after initiation of therapy through Aug. 31. Dr. Walter noted that the first hospitalization of a patient on triple combination therapy didn’t occur until early October.

At an average daily cost of $6,700, the researchers calculated that triple combination therapy saved about $189,000 per month in this group of patients. Comparing numbers to previous years, in which some patients with FEV₁ greater than 40% were hospitalized, the researchers calculated that the therapy saved about $151,000 per month among individuals with severe lung disease: Patients with severe lung disease contributed about 80% to total hospital costs.

The drug itself for the whole group cost $845,000, dwarfing the $189,000 savings overall. But among patients with severe disease, hospitalization savings were about $151,000 per month, while the drug cost in this group was $316,800 per month.

Cost savings are important, but the improvement in quality of life for a patient – avoiding hospitalization, fewer impacts on work and education – should not be overlooked, according to Ryan Perkins, MD, a pediatric and adult pulmonary fellow at Boston Children’s Hospital and Brigham and Women’s Hospital, who moderated the session. “Some of these aren’t things people typically quantify and assign a price tag to,” Dr. Perkins said in an interview.

A big limitation of the work is that it was conducted during the COVID-19 pandemic, which may have reduced hospitalizations. “We did have patients that called in, told us they were sick, that they needed to be treated for an exacerbation but didn’t want to go to the hospital,” said Dr. Walter. To help adjust for this, Dr. Walter’s team plans to compare intravenous antibiotic exposure before and after triple combination therapy, reasoning that it could help clarify the pandemic’s impact on hospitalizations.

Dr. Walter, Dr. Giusti, and Dr. Perkins have no relevant financial disclosures.

SOURCE: Walter E et al. NACFC 2020. Abstract 795.

New data show that new CFTR modulator therapies for cystic fibrosis may be driving down hospitalizations in this patient population.

The triple combination therapy elexacaftor/tezacaftor/ivacaftor was associated with a near elimination of hospital stays in one hospital in Oregon, according to a new report. The hospital savings still weren’t nearly enough to pay for the cost of therapy, but the study underscores what many institutions have observed and adds a new layer to the view of quality of life improvements that the new therapy brings.

“After we started prescribing it, we noticed pretty quickly that hospitalizations appeared to be declining after patients started triple combination therapy, and we were hearing [similar reports] from other centers as well. We wanted to quantify this,” Eric C. Walter, MD, a pulmonologist at the Kaiser Permanente Cystic Fibrosis Clinic in Portland, Ore., said during a presentation of the results at the virtual North American Cystic Fibrosis Conference.

“We’re seeing that across the board in real practice, the number of cystic fibrosis patients that have to be hospitalized since starting this triple combination has gone down,” Robert Giusti, MD, said in an interview. “When they’ve had pulmonary exacerbations in the past, it was frequently because they failed outpatient antibiotics, but I think with triple combination therapy, if they do get sick, the likelihood is they will respond to oral antibiotics, so they may not need that prolonged IV course in the hospital.” Dr. Giusti is clinical professor of pediatrics at New York University and director of the Pediatric Cystic Fibrosis Center. He was not involved in the study.

The therapy gained Food and Drug Administration approval in 2019 for the treatment of individuals with CF who are aged 12 years and older, and who have at least one copy of the F508del mutation. Its cost is about $317,000 per year within the Kaiser Permanente system, according to Dr. Walter. His group compared hospitalization days for CF-related diagnoses from Jan. 1 through Aug. 31, 2020, before and after initiation of triple combination therapy.

Of 47 eligible patients, 32 initiated therapy during the study period; 38% had severe lung disease, defined by forced expiratory volume in 1 second (FEV₁₎ value less than 40%. In 2020, before initiation of therapy, there were an average of 27 hospital days per month, all among patients with severe lung disease.

Among the therapy group, there were no hospitalizations after initiation of therapy through Aug. 31. Dr. Walter noted that the first hospitalization of a patient on triple combination therapy didn’t occur until early October.

At an average daily cost of $6,700, the researchers calculated that triple combination therapy saved about $189,000 per month in this group of patients. Comparing numbers to previous years, in which some patients with FEV₁ greater than 40% were hospitalized, the researchers calculated that the therapy saved about $151,000 per month among individuals with severe lung disease: Patients with severe lung disease contributed about 80% to total hospital costs.

The drug itself for the whole group cost $845,000, dwarfing the $189,000 savings overall. But among patients with severe disease, hospitalization savings were about $151,000 per month, while the drug cost in this group was $316,800 per month.

Cost savings are important, but the improvement in quality of life for a patient – avoiding hospitalization, fewer impacts on work and education – should not be overlooked, according to Ryan Perkins, MD, a pediatric and adult pulmonary fellow at Boston Children’s Hospital and Brigham and Women’s Hospital, who moderated the session. “Some of these aren’t things people typically quantify and assign a price tag to,” Dr. Perkins said in an interview.

A big limitation of the work is that it was conducted during the COVID-19 pandemic, which may have reduced hospitalizations. “We did have patients that called in, told us they were sick, that they needed to be treated for an exacerbation but didn’t want to go to the hospital,” said Dr. Walter. To help adjust for this, Dr. Walter’s team plans to compare intravenous antibiotic exposure before and after triple combination therapy, reasoning that it could help clarify the pandemic’s impact on hospitalizations.

Dr. Walter, Dr. Giusti, and Dr. Perkins have no relevant financial disclosures.

SOURCE: Walter E et al. NACFC 2020. Abstract 795.

New data support genetic testing in breast cancer patients older than 65 years, according to researchers.

The prevalence of pathogenic variants in genes predisposing women to breast cancer was 3.18% among women with breast cancer and 1.48% among women without breast cancer in a case-control study of 26,707 women older than 65 years.

Variants in BRCA1/2, CHEK2, and PALB2 were significantly associated with increased breast cancer risk. The residual risk of breast cancer for women aged 66-85 years was 18.3% for BRCA1, 18.6% for BRCA2, 14.9% for CHEK2, and 15.8% for PALB2. In comparison, the residual risk of breast cancer for the general population was 6.8%, according to Surveillance, Epidemiology, and End Results data.

The investigators noted that women who develop breast cancer beyond 65 years of age – a large percentage of the breast cancer population – do not often qualify for genetic testing, but the frequency of pathogenic variants “is not negligible in this population” and significantly elevates remaining lifetime risk.

The data from this study “can be used to reevaluate cancer screening and additional risk management strategies for women over the age of 65,” investigator Nicholas Boddicker, PhD, of the Mayo Clinic in Rochester, Minn., and colleagues wrote in a poster presentation.

The researchers presented their findings at the American Society of Human Genetics Virtual Meeting 2020.
 

Results may inform guidelines

National guidelines generally recommend screening for genetic variants when women develop breast cancer early in life or if they have a family history of breast cancer, but there has been controversy about whether those screening recommendations should be expanded, Dr. Boddicker and colleagues noted. The team thinks data from their study should help inform the discussion.

“We had an idea that the prevalence of these mutations in this population was not going to be zero, but I am not sure we were thinking that it was going to be over 3%. We believe these data will assist with reassessing genetic testing guidelines,” Dr. Boddicker said in an interview.

He said expanding genetic screening to include older women would have clinical implications. Women found to have pathogenic variants could perhaps undergo MRI surveillance in addition to mammography. If they are especially high risk, prophylactic mastectomy could be considered. Also, newer treatments hinge on the presence of pathogenic variants, such as PARP inhibitors for HER2-negative metastatic breast cancer with BRCA mutations.
 

Current testing limits ‘ridiculous’

“This is an excellent study and shows that even women over 65 have significant risk of breast cancer if they have a pathogenic variant. The variant could absolutely affect their treatment,” said Peter Beitsch, MD, a breast cancer surgical oncologist at the Dallas Surgical Group.

Dr. Beitsch was the lead author of a study, published in the Journal of Clinical Oncology in 2019, that showed that nearly half of breast cancer patients with a clinically actionable pathogenic variant were missed by current testing guidelines.

“All patients with a diagnosis of breast cancer [should] undergo expanded panel testing,” Dr. Beitsch and colleagues concluded in the paper.

Dr. Beitsch said current limitations on genetic screening make “no common sense. It’s OK to genetically test a woman who is 64 years and 11 months, but not 1 month later? Obviously ridiculous,” he said when asked for comment on the new report.

“The bigger impact is on their relatives,” Dr. Beitsch added. “Identifying people (men and women) with the same pathogenic variant can potentially save lives from more intensive screening or even prevent a cancer by doing prophylactic mastectomies. Male relatives have increased incidence of cancers with pathogenic variants in many of these genes.”

Screening for those variants could “lead to earlier detection or prevention,” Dr. Beitsch said.

As Dr. Boddicker noted, however, there is the question of who would pay for expanded screening and how to counsel patients who, despite increased risk, may never develop cancer.
 

Study details and next steps

The study included 13,762 women with breast cancer who were older than 65 years and 12,945 age-matched controls without breast cancer. A multigene amplicon-based panel was used to identify 12 known pathogenic variants in breast cancer–predisposing genes.

The women were part of the CARRIERS consortium, which pools breast cancer patients from case-control studies. Overall, 82.6% of subjects were non-Hispanic White, 25.6% of breast cancer patients and 17.9% of control subjects had a positive family history, and the mean age was 72.8 years (range, 66-94.3 years).

Across the entire study population, 0.48% of subjects had variants in ATM, 0.18% in BRCA1, 0.49% in BRCA2, 0.67% in CHEK2, and 0.23% in PALB2.

After adjustment for age, race, and family history, pathogenic variants in BRCA1 increased the risk of cancer more than threefold (odds ratio, 3.37), with similar findings for BRCA2 (OR, 2.64), PALB2 (OR, 3.09), and CHEK2 (OR, 2.13). ATM variants were not associated with a significantly increased risk of breast cancer (OR, 1.38).

Dr. Boddicker said the researchers’ next steps are to incorporate polygenic risk scores into the analyses and further investigate the impact of race.

The study is funded by the National Institutes of Health. Dr. Boddicker and Dr. Beitsch didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Boddicker NJ et al. ASHG 2020, Abstract 2412.

New data support genetic testing in breast cancer patients older than 65 years, according to researchers.

The prevalence of pathogenic variants in genes predisposing women to breast cancer was 3.18% among women with breast cancer and 1.48% among women without breast cancer in a case-control study of 26,707 women older than 65 years.

Variants in BRCA1/2, CHEK2, and PALB2 were significantly associated with increased breast cancer risk. The residual risk of breast cancer for women aged 66-85 years was 18.3% for BRCA1, 18.6% for BRCA2, 14.9% for CHEK2, and 15.8% for PALB2. In comparison, the residual risk of breast cancer for the general population was 6.8%, according to Surveillance, Epidemiology, and End Results data.

The investigators noted that women who develop breast cancer beyond 65 years of age – a large percentage of the breast cancer population – do not often qualify for genetic testing, but the frequency of pathogenic variants “is not negligible in this population” and significantly elevates remaining lifetime risk.

The data from this study “can be used to reevaluate cancer screening and additional risk management strategies for women over the age of 65,” investigator Nicholas Boddicker, PhD, of the Mayo Clinic in Rochester, Minn., and colleagues wrote in a poster presentation.

The researchers presented their findings at the American Society of Human Genetics Virtual Meeting 2020.
 

Results may inform guidelines

National guidelines generally recommend screening for genetic variants when women develop breast cancer early in life or if they have a family history of breast cancer, but there has been controversy about whether those screening recommendations should be expanded, Dr. Boddicker and colleagues noted. The team thinks data from their study should help inform the discussion.

“We had an idea that the prevalence of these mutations in this population was not going to be zero, but I am not sure we were thinking that it was going to be over 3%. We believe these data will assist with reassessing genetic testing guidelines,” Dr. Boddicker said in an interview.

He said expanding genetic screening to include older women would have clinical implications. Women found to have pathogenic variants could perhaps undergo MRI surveillance in addition to mammography. If they are especially high risk, prophylactic mastectomy could be considered. Also, newer treatments hinge on the presence of pathogenic variants, such as PARP inhibitors for HER2-negative metastatic breast cancer with BRCA mutations.
 

Current testing limits ‘ridiculous’

“This is an excellent study and shows that even women over 65 have significant risk of breast cancer if they have a pathogenic variant. The variant could absolutely affect their treatment,” said Peter Beitsch, MD, a breast cancer surgical oncologist at the Dallas Surgical Group.

Dr. Beitsch was the lead author of a study, published in the Journal of Clinical Oncology in 2019, that showed that nearly half of breast cancer patients with a clinically actionable pathogenic variant were missed by current testing guidelines.

“All patients with a diagnosis of breast cancer [should] undergo expanded panel testing,” Dr. Beitsch and colleagues concluded in the paper.

Dr. Beitsch said current limitations on genetic screening make “no common sense. It’s OK to genetically test a woman who is 64 years and 11 months, but not 1 month later? Obviously ridiculous,” he said when asked for comment on the new report.

“The bigger impact is on their relatives,” Dr. Beitsch added. “Identifying people (men and women) with the same pathogenic variant can potentially save lives from more intensive screening or even prevent a cancer by doing prophylactic mastectomies. Male relatives have increased incidence of cancers with pathogenic variants in many of these genes.”

Screening for those variants could “lead to earlier detection or prevention,” Dr. Beitsch said.

As Dr. Boddicker noted, however, there is the question of who would pay for expanded screening and how to counsel patients who, despite increased risk, may never develop cancer.
 

Study details and next steps

The study included 13,762 women with breast cancer who were older than 65 years and 12,945 age-matched controls without breast cancer. A multigene amplicon-based panel was used to identify 12 known pathogenic variants in breast cancer–predisposing genes.

The women were part of the CARRIERS consortium, which pools breast cancer patients from case-control studies. Overall, 82.6% of subjects were non-Hispanic White, 25.6% of breast cancer patients and 17.9% of control subjects had a positive family history, and the mean age was 72.8 years (range, 66-94.3 years).

Across the entire study population, 0.48% of subjects had variants in ATM, 0.18% in BRCA1, 0.49% in BRCA2, 0.67% in CHEK2, and 0.23% in PALB2.

After adjustment for age, race, and family history, pathogenic variants in BRCA1 increased the risk of cancer more than threefold (odds ratio, 3.37), with similar findings for BRCA2 (OR, 2.64), PALB2 (OR, 3.09), and CHEK2 (OR, 2.13). ATM variants were not associated with a significantly increased risk of breast cancer (OR, 1.38).

Dr. Boddicker said the researchers’ next steps are to incorporate polygenic risk scores into the analyses and further investigate the impact of race.

The study is funded by the National Institutes of Health. Dr. Boddicker and Dr. Beitsch didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Boddicker NJ et al. ASHG 2020, Abstract 2412.

New data support genetic testing in breast cancer patients older than 65 years, according to researchers.

The prevalence of pathogenic variants in genes predisposing women to breast cancer was 3.18% among women with breast cancer and 1.48% among women without breast cancer in a case-control study of 26,707 women older than 65 years.

Variants in BRCA1/2, CHEK2, and PALB2 were significantly associated with increased breast cancer risk. The residual risk of breast cancer for women aged 66-85 years was 18.3% for BRCA1, 18.6% for BRCA2, 14.9% for CHEK2, and 15.8% for PALB2. In comparison, the residual risk of breast cancer for the general population was 6.8%, according to Surveillance, Epidemiology, and End Results data.

The investigators noted that women who develop breast cancer beyond 65 years of age – a large percentage of the breast cancer population – do not often qualify for genetic testing, but the frequency of pathogenic variants “is not negligible in this population” and significantly elevates remaining lifetime risk.

The data from this study “can be used to reevaluate cancer screening and additional risk management strategies for women over the age of 65,” investigator Nicholas Boddicker, PhD, of the Mayo Clinic in Rochester, Minn., and colleagues wrote in a poster presentation.

The researchers presented their findings at the American Society of Human Genetics Virtual Meeting 2020.
 

Results may inform guidelines

National guidelines generally recommend screening for genetic variants when women develop breast cancer early in life or if they have a family history of breast cancer, but there has been controversy about whether those screening recommendations should be expanded, Dr. Boddicker and colleagues noted. The team thinks data from their study should help inform the discussion.

“We had an idea that the prevalence of these mutations in this population was not going to be zero, but I am not sure we were thinking that it was going to be over 3%. We believe these data will assist with reassessing genetic testing guidelines,” Dr. Boddicker said in an interview.

He said expanding genetic screening to include older women would have clinical implications. Women found to have pathogenic variants could perhaps undergo MRI surveillance in addition to mammography. If they are especially high risk, prophylactic mastectomy could be considered. Also, newer treatments hinge on the presence of pathogenic variants, such as PARP inhibitors for HER2-negative metastatic breast cancer with BRCA mutations.
 

Current testing limits ‘ridiculous’

“This is an excellent study and shows that even women over 65 have significant risk of breast cancer if they have a pathogenic variant. The variant could absolutely affect their treatment,” said Peter Beitsch, MD, a breast cancer surgical oncologist at the Dallas Surgical Group.

Dr. Beitsch was the lead author of a study, published in the Journal of Clinical Oncology in 2019, that showed that nearly half of breast cancer patients with a clinically actionable pathogenic variant were missed by current testing guidelines.

“All patients with a diagnosis of breast cancer [should] undergo expanded panel testing,” Dr. Beitsch and colleagues concluded in the paper.

Dr. Beitsch said current limitations on genetic screening make “no common sense. It’s OK to genetically test a woman who is 64 years and 11 months, but not 1 month later? Obviously ridiculous,” he said when asked for comment on the new report.

“The bigger impact is on their relatives,” Dr. Beitsch added. “Identifying people (men and women) with the same pathogenic variant can potentially save lives from more intensive screening or even prevent a cancer by doing prophylactic mastectomies. Male relatives have increased incidence of cancers with pathogenic variants in many of these genes.”

Screening for those variants could “lead to earlier detection or prevention,” Dr. Beitsch said.

As Dr. Boddicker noted, however, there is the question of who would pay for expanded screening and how to counsel patients who, despite increased risk, may never develop cancer.
 

Study details and next steps

The study included 13,762 women with breast cancer who were older than 65 years and 12,945 age-matched controls without breast cancer. A multigene amplicon-based panel was used to identify 12 known pathogenic variants in breast cancer–predisposing genes.

The women were part of the CARRIERS consortium, which pools breast cancer patients from case-control studies. Overall, 82.6% of subjects were non-Hispanic White, 25.6% of breast cancer patients and 17.9% of control subjects had a positive family history, and the mean age was 72.8 years (range, 66-94.3 years).

Across the entire study population, 0.48% of subjects had variants in ATM, 0.18% in BRCA1, 0.49% in BRCA2, 0.67% in CHEK2, and 0.23% in PALB2.

After adjustment for age, race, and family history, pathogenic variants in BRCA1 increased the risk of cancer more than threefold (odds ratio, 3.37), with similar findings for BRCA2 (OR, 2.64), PALB2 (OR, 3.09), and CHEK2 (OR, 2.13). ATM variants were not associated with a significantly increased risk of breast cancer (OR, 1.38).

Dr. Boddicker said the researchers’ next steps are to incorporate polygenic risk scores into the analyses and further investigate the impact of race.

The study is funded by the National Institutes of Health. Dr. Boddicker and Dr. Beitsch didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Boddicker NJ et al. ASHG 2020, Abstract 2412.

You have a responsibility to screen families for food insecurity, intervene to help them, and advocate on behalf of those experiencing or at risk of food insecurity, according to Kofi Essel, MD, MPH, a pediatrician at Children’s National Hospital in Washington.

YES Market Media/Shutterstock

More than one in four adults are dealing with food access hardships during the pandemic, Dr. Essel said at the virtual annual meeting of the American Academy of Pediatrics. Food insecurity is often interchangeable with hunger and refers to limited or uncertain availability of foods that are nutritious and safe.

“Food insecurity is as much about the threat of deprivation as it is about deprivation itself: A food-insecure life means a life lived in fear of hunger, and the psychological toll that takes,” according to a 2020 New York Times photo feature on food insecurity by Brenda Ann Kenneally that Dr. Essel quoted.

The lived experience of food insecure households includes food anxiety, a preoccupation with being able to get enough food that takes up cognitive bandwidth and prevents people from being able to focus on other important things. Another feature of food-insecure homes is a monotony of diet, which often involves an increase in caloric density and decrease in nutritional quality. As food insecurity grows more dire, adults’ food intake decreases, and then children’s intake decreases as adults seek out any way to get food, including “socially unacceptable” ways, which can include food pantries and bartering for food.

Food insecurity is associated with a wide range of negative outcomes even after accounting for other confounders, including decreased overall health, mental health, and educational outcomes. It’s also associated with an increase in developmental delays, hospitalizations, iron deficiency, asthma, and birth defects, among other problems. Somewhat paradoxically, it’s associated with both an increase and a decrease in obesity in the research.

Megan J. Gray, MD, MPH, assistant professor of pediatrics and population health at Dell Medical School at the The University of Texas at Austin, attended Dr. Essel’s session because food insecurity during COVID-19 now affects about half her patients, according to screening research she’s conducted.

“I wanted to learn more about the nuances of screening and using language and talking points that are helpful with families and with staff in building a culture of discussing food insecurity in our clinics,” Dr. Gray said in an interview. “What I’ve learned in my clinic is that if we don’t ask about it, families aren’t telling us – food insecurity is hiding in plain sight.”

She particularly appreciated Dr. Essel’s slides on the progression of food insecurity and how they acknowledged the mental health burden of food insecurity among parents.

“Right now during COVID-19, I see more patients I would call ‘socially complex’ rather than ‘medically complex,’ ” she said. “We all need to get a crash course in social work and Dr. Essel’s presentation is a great starting place.”

Screening for food insecurity

Beginning in 2015, an AAP policy statement charged pediatricians to “screen and intervene” with regard to food insecurity and their patients, Dr. Essel said. The statement also called for pediatricians to advocate for programs and policies that end childhood food insecurity.

The policy statement recommended a validated two-question screening tool called the Hunger Vital Sign:

1. “Within the past 12 months, we worried whether our food would run out before we got money to buy more.”

2. “Within the past 12 months, the food that we bought just didn’t last and we didn’t have money to get more.”

But in screening, you need to be conscious of how dignity intersects with food insecurity concerns, Dr. Essel said.

“We need to create dignity for our families,” he said. “We need to create a safe environment for our families and use appropriate tools when necessary to be able to identify families that are struggling with food insecurity.”

That need is seen in research on food screening. The Hunger Vital Signs questions can be asked with a dichotomous variable, as a yes/no question, or on a Likert scale, though the latter is a more complex way to ask.

A 2017 study found, however, that asking with “yes/no” answers missed more than a quarter of at-risk families. In the AAP survey using “yes/no” answers, 31% of families screened positive for being at risk of food insecurity, compared with 46% when the same question was asked on a Likert scale. It seems the ability to answer with “sometimes” feels “safer” than answering “yes,” Dr. Essel said.

Another factor that potentially affects answers is how doctors ask. In a March 2020 study at a single primary care practice, 16% of families screened positive with yes/no responses to a food insecurity screen when the questions were written, compared with 10% of positive screens with verbal responses (P < .001).

Epidemiology of food insecurity

The most updated United States Department of Agriculture report on food insecurity released in September shows the United States finally reached prerecession levels in 2019, with 11% of families designated as “food insecure.” But 2019 data cannot show what has occurred since the pandemic.

Further, the numbers are higher in households with children: Fourteen percent, or one in seven households with children, are experiencing food insecurity. Racial and ethnic disparities in food insecurity have remained consistent over the past 2 decades, with about twice as many Black and Hispanic homes experiencing food insecurity as White homes.

More recent research using Census Household Pulse Surveys has found a tremendous increase in food insecurity for children in 2020. One in three Black children and one in four Hispanic children are food insecure, according to these surveys. The rates are one in six for Asian households and one in ten for White households.

“The disparity is consistent,” Dr. Essel said. “We see what COVID has done. We once may have described it as a great equalizer – everyone is touched in the same way – but the reality is, this is actually a great magnifier. It’s revealing to us and magnifying disparities that have existed for far too long and has really allowed us to see it in a new way.”

A big part of disparities in food insecurity is disparities in wealth, “the safety net or cushion for families when things go wrong,” Dr. Essel said. The median wealth of White Americans in 2016 was $171,000, compared to $20,700 among Latinx Americans and $17,600 among Black Americans, according to the Federal Reserve Board Survey of Consumer Finances.
 

Food insecurity interventions

Federal nutrition programs – such as Supplemental Nutrition Assistance Program (SNAP), the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), and school meal programs – are key to addressing food insecurity, Dr. Essel said.

“They have a long track record of rescuing families out of poverty, of rescuing families from food security and improving overall health of families,” he said.

But emergency food relief programs are important as well. Four in 10 families currently coming into food pantries are new recipients, and these resources have seen a 60% increase in clients, he said.

“This is utterly unreasonable for them to be able to manage,” he said. “Food pantries are essential but inadequate to compensate for large numbers of families,” even while they also may be the only option for families unable or unwilling to access federal programs. For example, for every one meal that food banks can provide, SNAP can provide nine meals, Dr. Essel said. Further, during times of economic downtown, every SNAP $1 spent generates $1.50 to $2 in economic activity.

Currently, the Pandemic Electronic Benefit Transfer (P-EBT) program provides benefits to families for school breakfast and lunch and has been extended through December 2021. Another federal pandemic response was to increase SNAP to the maximum household benefit for families, about $646 for a family of four, although 40% of households were already receiving the maximum benefit.
 

Food insecurity advocacy

You can advocate for any one of multiple pillars when it comes to food insecurity, Dr. Essel said. “Food cannot solve food insecurity by itself,” he said. “We have to think about root causes – systemic causes – and think about unemployment, livable wage, systemic racism, oppression, an inequitable food system. All of these things are pillars that any of you can advocate for when recognizing a family that is struggling with food insecurity.”

He offered several suggestions for advocacy:

• Join your local AAP chapter and prioritize food insecurity.
• Join a local antihunger task force.
• Make your clinical environment as safe as possible for families to respond to questions about food insecurity.
• Know what’s happening in your community immigrant populations.
• Provide up-to-date information to families about eligibility for federal programs.
• Share stories through op-eds and letters to the editor, and by contacting congressional representatives and providing expert testimony to school boards and city councils.
• Educate others about food insecurity through the above channels and on social media.

Jessica Lazerov, MD, a general pediatrician at Children’s National Anacostia and assistant professor of pediatrics at George Washington University, Washington, said the session was fantastic.

“Dr. Essel went beyond the basics of food insecurity, delving into the root causes, potential solutions, and important considerations when screening for food insecurity in practice,” Dr. Lazerov said in an interview. “I enjoyed his focus on advocacy, as well as the fact that he spent a bit of time reviewing how the COVID pandemic has affected food insecurity. I truly felt empowered to take my advocacy efforts a step further as Dr. Essel laid out concrete, actionable next steps, as well as a review of the most relevant and current information about food insecurity.”

Dr. Essel, Dr. Lazerov, and Dr. Gray have no relevant financial disclosures.

You have a responsibility to screen families for food insecurity, intervene to help them, and advocate on behalf of those experiencing or at risk of food insecurity, according to Kofi Essel, MD, MPH, a pediatrician at Children’s National Hospital in Washington.

YES Market Media/Shutterstock

More than one in four adults are dealing with food access hardships during the pandemic, Dr. Essel said at the virtual annual meeting of the American Academy of Pediatrics. Food insecurity is often interchangeable with hunger and refers to limited or uncertain availability of foods that are nutritious and safe.

“Food insecurity is as much about the threat of deprivation as it is about deprivation itself: A food-insecure life means a life lived in fear of hunger, and the psychological toll that takes,” according to a 2020 New York Times photo feature on food insecurity by Brenda Ann Kenneally that Dr. Essel quoted.

The lived experience of food insecure households includes food anxiety, a preoccupation with being able to get enough food that takes up cognitive bandwidth and prevents people from being able to focus on other important things. Another feature of food-insecure homes is a monotony of diet, which often involves an increase in caloric density and decrease in nutritional quality. As food insecurity grows more dire, adults’ food intake decreases, and then children’s intake decreases as adults seek out any way to get food, including “socially unacceptable” ways, which can include food pantries and bartering for food.

Food insecurity is associated with a wide range of negative outcomes even after accounting for other confounders, including decreased overall health, mental health, and educational outcomes. It’s also associated with an increase in developmental delays, hospitalizations, iron deficiency, asthma, and birth defects, among other problems. Somewhat paradoxically, it’s associated with both an increase and a decrease in obesity in the research.

Megan J. Gray, MD, MPH, assistant professor of pediatrics and population health at Dell Medical School at the The University of Texas at Austin, attended Dr. Essel’s session because food insecurity during COVID-19 now affects about half her patients, according to screening research she’s conducted.

“I wanted to learn more about the nuances of screening and using language and talking points that are helpful with families and with staff in building a culture of discussing food insecurity in our clinics,” Dr. Gray said in an interview. “What I’ve learned in my clinic is that if we don’t ask about it, families aren’t telling us – food insecurity is hiding in plain sight.”

She particularly appreciated Dr. Essel’s slides on the progression of food insecurity and how they acknowledged the mental health burden of food insecurity among parents.

“Right now during COVID-19, I see more patients I would call ‘socially complex’ rather than ‘medically complex,’ ” she said. “We all need to get a crash course in social work and Dr. Essel’s presentation is a great starting place.”

Screening for food insecurity

Beginning in 2015, an AAP policy statement charged pediatricians to “screen and intervene” with regard to food insecurity and their patients, Dr. Essel said. The statement also called for pediatricians to advocate for programs and policies that end childhood food insecurity.

The policy statement recommended a validated two-question screening tool called the Hunger Vital Sign:

1. “Within the past 12 months, we worried whether our food would run out before we got money to buy more.”

2. “Within the past 12 months, the food that we bought just didn’t last and we didn’t have money to get more.”

But in screening, you need to be conscious of how dignity intersects with food insecurity concerns, Dr. Essel said.

“We need to create dignity for our families,” he said. “We need to create a safe environment for our families and use appropriate tools when necessary to be able to identify families that are struggling with food insecurity.”

That need is seen in research on food screening. The Hunger Vital Signs questions can be asked with a dichotomous variable, as a yes/no question, or on a Likert scale, though the latter is a more complex way to ask.

A 2017 study found, however, that asking with “yes/no” answers missed more than a quarter of at-risk families. In the AAP survey using “yes/no” answers, 31% of families screened positive for being at risk of food insecurity, compared with 46% when the same question was asked on a Likert scale. It seems the ability to answer with “sometimes” feels “safer” than answering “yes,” Dr. Essel said.

Another factor that potentially affects answers is how doctors ask. In a March 2020 study at a single primary care practice, 16% of families screened positive with yes/no responses to a food insecurity screen when the questions were written, compared with 10% of positive screens with verbal responses (P < .001).

Epidemiology of food insecurity

The most updated United States Department of Agriculture report on food insecurity released in September shows the United States finally reached prerecession levels in 2019, with 11% of families designated as “food insecure.” But 2019 data cannot show what has occurred since the pandemic.

Further, the numbers are higher in households with children: Fourteen percent, or one in seven households with children, are experiencing food insecurity. Racial and ethnic disparities in food insecurity have remained consistent over the past 2 decades, with about twice as many Black and Hispanic homes experiencing food insecurity as White homes.

More recent research using Census Household Pulse Surveys has found a tremendous increase in food insecurity for children in 2020. One in three Black children and one in four Hispanic children are food insecure, according to these surveys. The rates are one in six for Asian households and one in ten for White households.

“The disparity is consistent,” Dr. Essel said. “We see what COVID has done. We once may have described it as a great equalizer – everyone is touched in the same way – but the reality is, this is actually a great magnifier. It’s revealing to us and magnifying disparities that have existed for far too long and has really allowed us to see it in a new way.”

A big part of disparities in food insecurity is disparities in wealth, “the safety net or cushion for families when things go wrong,” Dr. Essel said. The median wealth of White Americans in 2016 was $171,000, compared to $20,700 among Latinx Americans and $17,600 among Black Americans, according to the Federal Reserve Board Survey of Consumer Finances.
 

Food insecurity interventions

Federal nutrition programs – such as Supplemental Nutrition Assistance Program (SNAP), the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), and school meal programs – are key to addressing food insecurity, Dr. Essel said.

“They have a long track record of rescuing families out of poverty, of rescuing families from food security and improving overall health of families,” he said.

But emergency food relief programs are important as well. Four in 10 families currently coming into food pantries are new recipients, and these resources have seen a 60% increase in clients, he said.

“This is utterly unreasonable for them to be able to manage,” he said. “Food pantries are essential but inadequate to compensate for large numbers of families,” even while they also may be the only option for families unable or unwilling to access federal programs. For example, for every one meal that food banks can provide, SNAP can provide nine meals, Dr. Essel said. Further, during times of economic downtown, every SNAP $1 spent generates $1.50 to $2 in economic activity.

Currently, the Pandemic Electronic Benefit Transfer (P-EBT) program provides benefits to families for school breakfast and lunch and has been extended through December 2021. Another federal pandemic response was to increase SNAP to the maximum household benefit for families, about $646 for a family of four, although 40% of households were already receiving the maximum benefit.
 

Food insecurity advocacy

You can advocate for any one of multiple pillars when it comes to food insecurity, Dr. Essel said. “Food cannot solve food insecurity by itself,” he said. “We have to think about root causes – systemic causes – and think about unemployment, livable wage, systemic racism, oppression, an inequitable food system. All of these things are pillars that any of you can advocate for when recognizing a family that is struggling with food insecurity.”

He offered several suggestions for advocacy:

• Join your local AAP chapter and prioritize food insecurity.
• Join a local antihunger task force.
• Make your clinical environment as safe as possible for families to respond to questions about food insecurity.
• Know what’s happening in your community immigrant populations.
• Provide up-to-date information to families about eligibility for federal programs.
• Share stories through op-eds and letters to the editor, and by contacting congressional representatives and providing expert testimony to school boards and city councils.
• Educate others about food insecurity through the above channels and on social media.

Jessica Lazerov, MD, a general pediatrician at Children’s National Anacostia and assistant professor of pediatrics at George Washington University, Washington, said the session was fantastic.

“Dr. Essel went beyond the basics of food insecurity, delving into the root causes, potential solutions, and important considerations when screening for food insecurity in practice,” Dr. Lazerov said in an interview. “I enjoyed his focus on advocacy, as well as the fact that he spent a bit of time reviewing how the COVID pandemic has affected food insecurity. I truly felt empowered to take my advocacy efforts a step further as Dr. Essel laid out concrete, actionable next steps, as well as a review of the most relevant and current information about food insecurity.”

Dr. Essel, Dr. Lazerov, and Dr. Gray have no relevant financial disclosures.

You have a responsibility to screen families for food insecurity, intervene to help them, and advocate on behalf of those experiencing or at risk of food insecurity, according to Kofi Essel, MD, MPH, a pediatrician at Children’s National Hospital in Washington.

YES Market Media/Shutterstock

More than one in four adults are dealing with food access hardships during the pandemic, Dr. Essel said at the virtual annual meeting of the American Academy of Pediatrics. Food insecurity is often interchangeable with hunger and refers to limited or uncertain availability of foods that are nutritious and safe.

“Food insecurity is as much about the threat of deprivation as it is about deprivation itself: A food-insecure life means a life lived in fear of hunger, and the psychological toll that takes,” according to a 2020 New York Times photo feature on food insecurity by Brenda Ann Kenneally that Dr. Essel quoted.

The lived experience of food insecure households includes food anxiety, a preoccupation with being able to get enough food that takes up cognitive bandwidth and prevents people from being able to focus on other important things. Another feature of food-insecure homes is a monotony of diet, which often involves an increase in caloric density and decrease in nutritional quality. As food insecurity grows more dire, adults’ food intake decreases, and then children’s intake decreases as adults seek out any way to get food, including “socially unacceptable” ways, which can include food pantries and bartering for food.

Food insecurity is associated with a wide range of negative outcomes even after accounting for other confounders, including decreased overall health, mental health, and educational outcomes. It’s also associated with an increase in developmental delays, hospitalizations, iron deficiency, asthma, and birth defects, among other problems. Somewhat paradoxically, it’s associated with both an increase and a decrease in obesity in the research.

Megan J. Gray, MD, MPH, assistant professor of pediatrics and population health at Dell Medical School at the The University of Texas at Austin, attended Dr. Essel’s session because food insecurity during COVID-19 now affects about half her patients, according to screening research she’s conducted.

“I wanted to learn more about the nuances of screening and using language and talking points that are helpful with families and with staff in building a culture of discussing food insecurity in our clinics,” Dr. Gray said in an interview. “What I’ve learned in my clinic is that if we don’t ask about it, families aren’t telling us – food insecurity is hiding in plain sight.”

She particularly appreciated Dr. Essel’s slides on the progression of food insecurity and how they acknowledged the mental health burden of food insecurity among parents.

“Right now during COVID-19, I see more patients I would call ‘socially complex’ rather than ‘medically complex,’ ” she said. “We all need to get a crash course in social work and Dr. Essel’s presentation is a great starting place.”

Screening for food insecurity

Beginning in 2015, an AAP policy statement charged pediatricians to “screen and intervene” with regard to food insecurity and their patients, Dr. Essel said. The statement also called for pediatricians to advocate for programs and policies that end childhood food insecurity.

The policy statement recommended a validated two-question screening tool called the Hunger Vital Sign:

1. “Within the past 12 months, we worried whether our food would run out before we got money to buy more.”

2. “Within the past 12 months, the food that we bought just didn’t last and we didn’t have money to get more.”

But in screening, you need to be conscious of how dignity intersects with food insecurity concerns, Dr. Essel said.

“We need to create dignity for our families,” he said. “We need to create a safe environment for our families and use appropriate tools when necessary to be able to identify families that are struggling with food insecurity.”

That need is seen in research on food screening. The Hunger Vital Signs questions can be asked with a dichotomous variable, as a yes/no question, or on a Likert scale, though the latter is a more complex way to ask.

A 2017 study found, however, that asking with “yes/no” answers missed more than a quarter of at-risk families. In the AAP survey using “yes/no” answers, 31% of families screened positive for being at risk of food insecurity, compared with 46% when the same question was asked on a Likert scale. It seems the ability to answer with “sometimes” feels “safer” than answering “yes,” Dr. Essel said.

Another factor that potentially affects answers is how doctors ask. In a March 2020 study at a single primary care practice, 16% of families screened positive with yes/no responses to a food insecurity screen when the questions were written, compared with 10% of positive screens with verbal responses (P < .001).

Epidemiology of food insecurity

The most updated United States Department of Agriculture report on food insecurity released in September shows the United States finally reached prerecession levels in 2019, with 11% of families designated as “food insecure.” But 2019 data cannot show what has occurred since the pandemic.

Further, the numbers are higher in households with children: Fourteen percent, or one in seven households with children, are experiencing food insecurity. Racial and ethnic disparities in food insecurity have remained consistent over the past 2 decades, with about twice as many Black and Hispanic homes experiencing food insecurity as White homes.

More recent research using Census Household Pulse Surveys has found a tremendous increase in food insecurity for children in 2020. One in three Black children and one in four Hispanic children are food insecure, according to these surveys. The rates are one in six for Asian households and one in ten for White households.

“The disparity is consistent,” Dr. Essel said. “We see what COVID has done. We once may have described it as a great equalizer – everyone is touched in the same way – but the reality is, this is actually a great magnifier. It’s revealing to us and magnifying disparities that have existed for far too long and has really allowed us to see it in a new way.”

A big part of disparities in food insecurity is disparities in wealth, “the safety net or cushion for families when things go wrong,” Dr. Essel said. The median wealth of White Americans in 2016 was $171,000, compared to $20,700 among Latinx Americans and $17,600 among Black Americans, according to the Federal Reserve Board Survey of Consumer Finances.
 

Food insecurity interventions

Federal nutrition programs – such as Supplemental Nutrition Assistance Program (SNAP), the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), and school meal programs – are key to addressing food insecurity, Dr. Essel said.

“They have a long track record of rescuing families out of poverty, of rescuing families from food security and improving overall health of families,” he said.

But emergency food relief programs are important as well. Four in 10 families currently coming into food pantries are new recipients, and these resources have seen a 60% increase in clients, he said.

“This is utterly unreasonable for them to be able to manage,” he said. “Food pantries are essential but inadequate to compensate for large numbers of families,” even while they also may be the only option for families unable or unwilling to access federal programs. For example, for every one meal that food banks can provide, SNAP can provide nine meals, Dr. Essel said. Further, during times of economic downtown, every SNAP $1 spent generates $1.50 to $2 in economic activity.

Currently, the Pandemic Electronic Benefit Transfer (P-EBT) program provides benefits to families for school breakfast and lunch and has been extended through December 2021. Another federal pandemic response was to increase SNAP to the maximum household benefit for families, about $646 for a family of four, although 40% of households were already receiving the maximum benefit.
 

Food insecurity advocacy

You can advocate for any one of multiple pillars when it comes to food insecurity, Dr. Essel said. “Food cannot solve food insecurity by itself,” he said. “We have to think about root causes – systemic causes – and think about unemployment, livable wage, systemic racism, oppression, an inequitable food system. All of these things are pillars that any of you can advocate for when recognizing a family that is struggling with food insecurity.”

He offered several suggestions for advocacy:

• Join your local AAP chapter and prioritize food insecurity.
• Join a local antihunger task force.
• Make your clinical environment as safe as possible for families to respond to questions about food insecurity.
• Know what’s happening in your community immigrant populations.
• Provide up-to-date information to families about eligibility for federal programs.
• Share stories through op-eds and letters to the editor, and by contacting congressional representatives and providing expert testimony to school boards and city councils.
• Educate others about food insecurity through the above channels and on social media.

Jessica Lazerov, MD, a general pediatrician at Children’s National Anacostia and assistant professor of pediatrics at George Washington University, Washington, said the session was fantastic.

“Dr. Essel went beyond the basics of food insecurity, delving into the root causes, potential solutions, and important considerations when screening for food insecurity in practice,” Dr. Lazerov said in an interview. “I enjoyed his focus on advocacy, as well as the fact that he spent a bit of time reviewing how the COVID pandemic has affected food insecurity. I truly felt empowered to take my advocacy efforts a step further as Dr. Essel laid out concrete, actionable next steps, as well as a review of the most relevant and current information about food insecurity.”

Dr. Essel, Dr. Lazerov, and Dr. Gray have no relevant financial disclosures.

New proposed guidelines for managing rheumatoid arthritis (RA) recommend that methotrexate (MTX) be used aggressively before other treatment options.

Previous guidelines, last updated in 2015, had not ranked the order of the treatments, said Liana Fraenkel, MD, MPH, principal investigator for the American College of Rheumatology’s treatment guidelines.

“There’s a strong emphasis on maximizing methotrexate using various means before switching to a biologic or JAK [Janus kinase] inhibitor,” she said in a press conference at the virtual annual meeting of the American College of Rheumatology. The guidelines draft was developed collaboratively with clinicians, researchers, and patients. In addition, the authors conducted a comprehensive review of the literature.

Dr. Fraenkel, of Yale University in New Haven, Conn., said the exception for maximizing MTX would be for patients with low disease activity for whom treatments with other medications, such as hydroxychloroquine (HCQ) and sulfasalazine, are feasible, she said.
 

Stop defaulting to prednisone

Another recommendation urges against the use of prednisone as a default treatment.

“We should really be trying to maximize disease-modifying antirheumatic drugs [DMARDs] and try to push the needle away from using prednisone as frequently as we do,” she said.

Dr. Fraenkel said the panel wanted to emphasize that “even lower doses of prednisone can be harmful.”

She noted that patients on the guidelines panel said it’s hard to taper off prednisone.

Don Thomas, MD, who is in private rheumatology practice in Greenbelt, Md., said in an interview he loves the guidelines.

“Most of my patients are not on steroids,” he said, “which is a godsend because of the great therapies we have.”

He said he was glad to see support for exhausting methotrexate options first before trying new treatments.

“Too many of us are not as aggressive as we should be with using methotrexate initially,” he said.
 

Specific recommendations

In the proposed guidelines, MTX alone is strongly recommended over HCQ or sulfasalazine and is conditionally recommended over a conventional synthetic DMARD dual or triple combination. MTX alone is also conditionally recommended over MTX in combination with a tumor necrosis factor (TNF) inhibitor and is strongly recommended over MTX in combination with a non-TNF inhibitor, a biologic, or a targeted synthetic DMARD.

For patients with low disease activity who have not taken DMARDs, HCQ is recommended over other conventional synthetic DMARDs. Sulfasalazine is recommended over MTX, and MTX is recommended over leflunomide.

For initial treatment, oral MTX is conditionally recommended over subcutaneous administration. For patients who are not tolerating the oral version, “recommend split-dose or subcutaneous or increasing folic acid over switching to a new DMARD,” she said.

Dr. Fraenkel said the oral recommendation was based largely on patient preference.
 

Use of glucocorticoids

For patients who need glucocorticoids to remain at target, adding or switching DMARDs is recommended over continuing glucocorticoids, the guidelines indicate.

“For patients on DMARDs and not at target, adding or switching DMARDs with or without the use of intraarticular glucocorticoids is conditionally recommended over the use of intraarticular glucocorticoids alone,” the proposed guidelines advise.
 

Tapering

Tapering should only be considered for patients “who have been at target for at least 6 months,” she said. “In these patients, continuation of all DMARDs at their current dose is conditionally recommended over any dose reduction.”

Dose reduction is recommended over gradual discontinuation, and gradual discontinuation is recommended over abruptly stopping.

Dr. Fraenkel acknowledged that the level of evidence is low to very low for many of the recommendations (only 7 of 44 recommendations were classified as strong), which, she said, underscores the importance of shared decision making for RA.

She added, “We really need trials to address clinically important questions driven by patients and not simply driven by [having] a new molecule to test.”

ACR says the final version of the proposed guidelines is expected to be simultaneously published in Arthritis Care and Research and Arthritis and Rheumatology by the end of the year.

These guidelines are focused on pharmacologic agents. Separate ACR guidelines will address nonpharmacologic management of RA and vaccine recommendations for inflammatory disease.

Dr. Fraenkel and Dr. Thomas have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

New proposed guidelines for managing rheumatoid arthritis (RA) recommend that methotrexate (MTX) be used aggressively before other treatment options.

Previous guidelines, last updated in 2015, had not ranked the order of the treatments, said Liana Fraenkel, MD, MPH, principal investigator for the American College of Rheumatology’s treatment guidelines.

“There’s a strong emphasis on maximizing methotrexate using various means before switching to a biologic or JAK [Janus kinase] inhibitor,” she said in a press conference at the virtual annual meeting of the American College of Rheumatology. The guidelines draft was developed collaboratively with clinicians, researchers, and patients. In addition, the authors conducted a comprehensive review of the literature.

Dr. Fraenkel, of Yale University in New Haven, Conn., said the exception for maximizing MTX would be for patients with low disease activity for whom treatments with other medications, such as hydroxychloroquine (HCQ) and sulfasalazine, are feasible, she said.
 

Stop defaulting to prednisone

Another recommendation urges against the use of prednisone as a default treatment.

“We should really be trying to maximize disease-modifying antirheumatic drugs [DMARDs] and try to push the needle away from using prednisone as frequently as we do,” she said.

Dr. Fraenkel said the panel wanted to emphasize that “even lower doses of prednisone can be harmful.”

She noted that patients on the guidelines panel said it’s hard to taper off prednisone.

Don Thomas, MD, who is in private rheumatology practice in Greenbelt, Md., said in an interview he loves the guidelines.

“Most of my patients are not on steroids,” he said, “which is a godsend because of the great therapies we have.”

He said he was glad to see support for exhausting methotrexate options first before trying new treatments.

“Too many of us are not as aggressive as we should be with using methotrexate initially,” he said.
 

Specific recommendations

In the proposed guidelines, MTX alone is strongly recommended over HCQ or sulfasalazine and is conditionally recommended over a conventional synthetic DMARD dual or triple combination. MTX alone is also conditionally recommended over MTX in combination with a tumor necrosis factor (TNF) inhibitor and is strongly recommended over MTX in combination with a non-TNF inhibitor, a biologic, or a targeted synthetic DMARD.

For patients with low disease activity who have not taken DMARDs, HCQ is recommended over other conventional synthetic DMARDs. Sulfasalazine is recommended over MTX, and MTX is recommended over leflunomide.

For initial treatment, oral MTX is conditionally recommended over subcutaneous administration. For patients who are not tolerating the oral version, “recommend split-dose or subcutaneous or increasing folic acid over switching to a new DMARD,” she said.

Dr. Fraenkel said the oral recommendation was based largely on patient preference.
 

Use of glucocorticoids

For patients who need glucocorticoids to remain at target, adding or switching DMARDs is recommended over continuing glucocorticoids, the guidelines indicate.

“For patients on DMARDs and not at target, adding or switching DMARDs with or without the use of intraarticular glucocorticoids is conditionally recommended over the use of intraarticular glucocorticoids alone,” the proposed guidelines advise.
 

Tapering

Tapering should only be considered for patients “who have been at target for at least 6 months,” she said. “In these patients, continuation of all DMARDs at their current dose is conditionally recommended over any dose reduction.”

Dose reduction is recommended over gradual discontinuation, and gradual discontinuation is recommended over abruptly stopping.

Dr. Fraenkel acknowledged that the level of evidence is low to very low for many of the recommendations (only 7 of 44 recommendations were classified as strong), which, she said, underscores the importance of shared decision making for RA.

She added, “We really need trials to address clinically important questions driven by patients and not simply driven by [having] a new molecule to test.”

ACR says the final version of the proposed guidelines is expected to be simultaneously published in Arthritis Care and Research and Arthritis and Rheumatology by the end of the year.

These guidelines are focused on pharmacologic agents. Separate ACR guidelines will address nonpharmacologic management of RA and vaccine recommendations for inflammatory disease.

Dr. Fraenkel and Dr. Thomas have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

New proposed guidelines for managing rheumatoid arthritis (RA) recommend that methotrexate (MTX) be used aggressively before other treatment options.

Previous guidelines, last updated in 2015, had not ranked the order of the treatments, said Liana Fraenkel, MD, MPH, principal investigator for the American College of Rheumatology’s treatment guidelines.

“There’s a strong emphasis on maximizing methotrexate using various means before switching to a biologic or JAK [Janus kinase] inhibitor,” she said in a press conference at the virtual annual meeting of the American College of Rheumatology. The guidelines draft was developed collaboratively with clinicians, researchers, and patients. In addition, the authors conducted a comprehensive review of the literature.

Dr. Fraenkel, of Yale University in New Haven, Conn., said the exception for maximizing MTX would be for patients with low disease activity for whom treatments with other medications, such as hydroxychloroquine (HCQ) and sulfasalazine, are feasible, she said.
 

Stop defaulting to prednisone

Another recommendation urges against the use of prednisone as a default treatment.

“We should really be trying to maximize disease-modifying antirheumatic drugs [DMARDs] and try to push the needle away from using prednisone as frequently as we do,” she said.

Dr. Fraenkel said the panel wanted to emphasize that “even lower doses of prednisone can be harmful.”

She noted that patients on the guidelines panel said it’s hard to taper off prednisone.

Don Thomas, MD, who is in private rheumatology practice in Greenbelt, Md., said in an interview he loves the guidelines.

“Most of my patients are not on steroids,” he said, “which is a godsend because of the great therapies we have.”

He said he was glad to see support for exhausting methotrexate options first before trying new treatments.

“Too many of us are not as aggressive as we should be with using methotrexate initially,” he said.
 

Specific recommendations

In the proposed guidelines, MTX alone is strongly recommended over HCQ or sulfasalazine and is conditionally recommended over a conventional synthetic DMARD dual or triple combination. MTX alone is also conditionally recommended over MTX in combination with a tumor necrosis factor (TNF) inhibitor and is strongly recommended over MTX in combination with a non-TNF inhibitor, a biologic, or a targeted synthetic DMARD.

For patients with low disease activity who have not taken DMARDs, HCQ is recommended over other conventional synthetic DMARDs. Sulfasalazine is recommended over MTX, and MTX is recommended over leflunomide.

For initial treatment, oral MTX is conditionally recommended over subcutaneous administration. For patients who are not tolerating the oral version, “recommend split-dose or subcutaneous or increasing folic acid over switching to a new DMARD,” she said.

Dr. Fraenkel said the oral recommendation was based largely on patient preference.
 

Use of glucocorticoids

For patients who need glucocorticoids to remain at target, adding or switching DMARDs is recommended over continuing glucocorticoids, the guidelines indicate.

“For patients on DMARDs and not at target, adding or switching DMARDs with or without the use of intraarticular glucocorticoids is conditionally recommended over the use of intraarticular glucocorticoids alone,” the proposed guidelines advise.
 

Tapering

Tapering should only be considered for patients “who have been at target for at least 6 months,” she said. “In these patients, continuation of all DMARDs at their current dose is conditionally recommended over any dose reduction.”

Dose reduction is recommended over gradual discontinuation, and gradual discontinuation is recommended over abruptly stopping.

Dr. Fraenkel acknowledged that the level of evidence is low to very low for many of the recommendations (only 7 of 44 recommendations were classified as strong), which, she said, underscores the importance of shared decision making for RA.

She added, “We really need trials to address clinically important questions driven by patients and not simply driven by [having] a new molecule to test.”

ACR says the final version of the proposed guidelines is expected to be simultaneously published in Arthritis Care and Research and Arthritis and Rheumatology by the end of the year.

These guidelines are focused on pharmacologic agents. Separate ACR guidelines will address nonpharmacologic management of RA and vaccine recommendations for inflammatory disease.

Dr. Fraenkel and Dr. Thomas have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

“I would argue that the most important reason to care about climate change is because of our children,” Saul Hymes, MD, said at the annual meeting of the American Academy of Pediatrics, held virtually this year.

Cynthia Goldsmith/CDC photo #10073

“Being able to point out to people how climate change harms the health of their children and affects their children’s risk of infections is a particularly effective argument to make,” said Dr. Hymes, a pediatric infectious diseases specialist at Stony Brook (N.Y.) University.

Rachel Boykan, MD, a pediatrician at the university, found Dr. Hymes’ presentation excellent and highly relevant to issues all health care workers treating children face, even beyond infectious disease.

“It was data focused but also understandable for a broad audience,” Dr. Boykan, who was not involved in the presentation, said in an interview. “He explained the science of climate change in a way that all physicians, but especially pediatricians, would find relevant. I suspect if people who were listening didn’t already prioritize the issues of climate change, they certainly did after hearing the talk.”

She also appreciated that Dr. Hymes addressed how climate change affects everyone in both their professional and personal lives.

“We need to be prepared to address the clinical issues that ensue after a natural disaster, and we need to be advocates for change so that we can slow down the climate changes we are all dealing with,” said Dr. Boykan, adding that the presentation was also inspiring. “He presented many different viewpoints and many ways to be involved and to be an advocate. I would think that a good number of people who were there would be energized to do something differently to combat climate change.”
 

The multitudinous impacts of climate change

The impact of climate change on human health is broad and far-reaching, Dr. Hymes said. It doesn’t require much imagination to recognize that rising global temperatures can lead to prolonged extreme heat waves that can cause heat-related deaths and illnesses. But other effects can be more gradual or subtle. Changes in outdoor air quality can affect weather patterns, pollen counts, and air pollution that can increase risk of asthma, allergies, as well as acute and chronic respiratory and cardiovascular disease.

Sea level rise, more frequent and severe hurricanes, storm surges, and extreme precipitation all can lead to contaminated water and destruction of essential infrastructure. In addition to drowning and injuries from the storms themselves, these changes have mental health consequences, and can lead to gastrointestinal and other illnesses, including water-borne infectious disease. The distribution and prevalence of vector-borne diseases also will shift with changes in temperature, precipitation, and other weather patterns.
 

Distribution, prevalence of vector-borne diseases shift with climate change

One of the most common bacteria transmitted by vectors in the United States is Borrelia burgdorferi, the cause of Lyme disease. Transmitted by deer ticks, Lyme disease is listed by the Environmental Protection Agency as an indicator of climate change’s impact on human health and is becoming more common every year. Cases doubled from 1990 to 2014, from 4 to 8 cases per 100,000 people.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

Increases were most dramatic in the Northeast, where Lyme disease is endemic. States such as Maine, Vermont, and New Hampshire all saw increases of 80-100 more cases per 100,000 people. Evidence now shows that Lyme disease is moving north as the climate warms. Toronto, for example, has seen more than a 400% increase in cases in less than a decade, from 128 cases per 100,000 people in 2009 to 700 cases per 100,000 in 2015.

“It’s a known phenomenon that climate change affects more northerly latitudes disproportionately to more than southerly latitudes,” Dr. Hymes said. He shared a 2013 study providing evidence that climate change is expanding the range of Lyme disease. Even when controlling for other confounding factors, the research found that areas being warmed proportionately more by climate change also are experiencing greater Lyme incidence. While Lyme cases declined in several Western and Deep South states, it significantly increased in nearly every Northeast state as well as Idaho, Arizona, and states in the northern Midwest near the Great Lakes.

Courtesy CDC

“We find that this impact of climate change on the movement of vectors like ticks affects more than just Lyme disease,” Dr. Hymes said. Amblyomma americanum, the Lone Star tick, has historically been restricted to the southern United States but is now found further north, even up to New England. It carries bacteria that can cause multiple illnesses, including ehrlichiosis, heartland virus, and tularemia.

An alpha-gal meat allergy associated with this tick can lead to anaphylaxis about 6 hours after a person eats red meat or pork. Prevalence of this allergy, first reported in Georgia in 1989-1991, has been increasing and moving further north, and the Lone Star tick is a particularly heat-tolerant and heat-loving tick.

Climate change also affects how long during the year people are at risk. Lyme disease, for example, typically lasted from April/May to October, when ticks then hibernated during the cold weather. But the warming climate has expanded Lyme season: Local Lyme cases have begun occurring into November through January on Long Island over the past 5 years.

Courtesy Megan Lobdell

The impact of seasonal changes on infectious diseases overall is difficult to predict. The seasons for cold weather diseases such as influenza and respiratory syncytial virus, for example, may become shorter or milder while viruses more common in the summer, such as enteroviruses, may become a risk year-round.
 

Natural disasters pose multiple risks

Natural disasters can pose immediate dangers to families and have a significant impact on mental health, but that’s not their only potential impact.

“Severe weather events such as hurricanes, floods, and tornadoes are well established in the climate change literature as an effect of increased temperatures and more volatile weather systems, but they also have a significant effect on infectious diseases and on children in particular,” Dr. Hymes said. “Hurricanes and flash floods can cause increases in infectious disease outbreaks through a variety of different ways.”

They can bring saltwater, freshwater, and sometimes soil organisms into the food and water supplies, and lead to sewage contamination from overloaded sewers, overflowing storm drains, and loss of power or pumps. Displaced animal vectors, such as rats, can lead to spread of other diseases, such as plague, hantavirus, typhus, and rabies.

Examples of saltwater organisms include Vibrio, Aeromonas, and Mycobacterium marinum, all of which can cause infections in wounds and/or diarrheal illness or bacteremia. Similarly, organisms from freshwater and soil that can cause serious illness or death include Aeromonas, Pseudomonas, Amebiasis, Giardia, and Legionella. Without access to clean water, or with contamination from overflowing sewage, cryptosporidium, Escherichia coli, salmonella, typhoid, norovirus, hepatitis A and E, and even cholera can also become problems as well.

In Houston following Hurricane Harvey, for example, cellulitis cases doubled and included infections from organisms different from the usual suspects. Scrapes and cuts that occurred during the storm also festered sooner.

Cases of disease linked to Hurricane Katrina in a Centers for Disease Control and Prevention report included 6 cases of cholera, 17 cases of other vibrio – including five that resulted in death – and reported cases of norovirus, Escherichia coli, salmonella, and influenza and pneumonia from overcrowding of evacuees.
 

You can help in a variety of ways

You can play several key roles as the world’s climate changes, starting with preparing for the changes. You should familiarize themselves with new and emerging infections, or those that have been around a while but not seen in your areas, such as Lyme, Zika, and Dengue.

“If you haven’t seen them already, you likely will due to movements of vector-borne infections that can occur due to climate change,” Dr. Hymes said. “You also want to expect the usual common diseases, but maybe at unsuspected times,” he added. “If you have a pediatric patient who looks like they have Coxsackie virus but it’s February, if it’s been a warm February, it may very well be Coxsackie virus.”

Following natural disasters such as floods, hurricanes and tornadoes, consider who your patients are. If they’re evacuees, are they living in overcrowded conditions? Do they have access to clean water? If not, explain the need to boil water if they can, or to use iodine tablets or a portable pump filter. Consider that some infections may involve unexpected or odd organisms, such as legionella pneumonia or vibrio cellulitis, and contact your local infectious disease doctor as needed.

You also can make personal lifestyle changes that, while small, can add up in the aggregate in reducing carbon footprints, such as purchasing an electric or hybrid car and converting their homes to solar power.

“For very little money, you can purchase carbon offsets,” Dr. Hymes said, such as $10-$15 a month for wind power offsets with home electricity or $5-$10 a month for car or plane travel.

“But really, the most important thing we can do as pediatricians is educate,” Dr. Hymes said. “Taking opportunities every day in your office to educate your patients and educate your colleagues about the importance of climate change in our patients’ health and our own children’s health is super, super important.”

Dr. Hymes and Dr. Boykan had no relevant financial disclosures.

“I would argue that the most important reason to care about climate change is because of our children,” Saul Hymes, MD, said at the annual meeting of the American Academy of Pediatrics, held virtually this year.

Cynthia Goldsmith/CDC photo #10073

“Being able to point out to people how climate change harms the health of their children and affects their children’s risk of infections is a particularly effective argument to make,” said Dr. Hymes, a pediatric infectious diseases specialist at Stony Brook (N.Y.) University.

Rachel Boykan, MD, a pediatrician at the university, found Dr. Hymes’ presentation excellent and highly relevant to issues all health care workers treating children face, even beyond infectious disease.

“It was data focused but also understandable for a broad audience,” Dr. Boykan, who was not involved in the presentation, said in an interview. “He explained the science of climate change in a way that all physicians, but especially pediatricians, would find relevant. I suspect if people who were listening didn’t already prioritize the issues of climate change, they certainly did after hearing the talk.”

She also appreciated that Dr. Hymes addressed how climate change affects everyone in both their professional and personal lives.

“We need to be prepared to address the clinical issues that ensue after a natural disaster, and we need to be advocates for change so that we can slow down the climate changes we are all dealing with,” said Dr. Boykan, adding that the presentation was also inspiring. “He presented many different viewpoints and many ways to be involved and to be an advocate. I would think that a good number of people who were there would be energized to do something differently to combat climate change.”
 

The multitudinous impacts of climate change

The impact of climate change on human health is broad and far-reaching, Dr. Hymes said. It doesn’t require much imagination to recognize that rising global temperatures can lead to prolonged extreme heat waves that can cause heat-related deaths and illnesses. But other effects can be more gradual or subtle. Changes in outdoor air quality can affect weather patterns, pollen counts, and air pollution that can increase risk of asthma, allergies, as well as acute and chronic respiratory and cardiovascular disease.

Sea level rise, more frequent and severe hurricanes, storm surges, and extreme precipitation all can lead to contaminated water and destruction of essential infrastructure. In addition to drowning and injuries from the storms themselves, these changes have mental health consequences, and can lead to gastrointestinal and other illnesses, including water-borne infectious disease. The distribution and prevalence of vector-borne diseases also will shift with changes in temperature, precipitation, and other weather patterns.
 

Distribution, prevalence of vector-borne diseases shift with climate change

One of the most common bacteria transmitted by vectors in the United States is Borrelia burgdorferi, the cause of Lyme disease. Transmitted by deer ticks, Lyme disease is listed by the Environmental Protection Agency as an indicator of climate change’s impact on human health and is becoming more common every year. Cases doubled from 1990 to 2014, from 4 to 8 cases per 100,000 people.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

Increases were most dramatic in the Northeast, where Lyme disease is endemic. States such as Maine, Vermont, and New Hampshire all saw increases of 80-100 more cases per 100,000 people. Evidence now shows that Lyme disease is moving north as the climate warms. Toronto, for example, has seen more than a 400% increase in cases in less than a decade, from 128 cases per 100,000 people in 2009 to 700 cases per 100,000 in 2015.

“It’s a known phenomenon that climate change affects more northerly latitudes disproportionately to more than southerly latitudes,” Dr. Hymes said. He shared a 2013 study providing evidence that climate change is expanding the range of Lyme disease. Even when controlling for other confounding factors, the research found that areas being warmed proportionately more by climate change also are experiencing greater Lyme incidence. While Lyme cases declined in several Western and Deep South states, it significantly increased in nearly every Northeast state as well as Idaho, Arizona, and states in the northern Midwest near the Great Lakes.

Courtesy CDC

“We find that this impact of climate change on the movement of vectors like ticks affects more than just Lyme disease,” Dr. Hymes said. Amblyomma americanum, the Lone Star tick, has historically been restricted to the southern United States but is now found further north, even up to New England. It carries bacteria that can cause multiple illnesses, including ehrlichiosis, heartland virus, and tularemia.

An alpha-gal meat allergy associated with this tick can lead to anaphylaxis about 6 hours after a person eats red meat or pork. Prevalence of this allergy, first reported in Georgia in 1989-1991, has been increasing and moving further north, and the Lone Star tick is a particularly heat-tolerant and heat-loving tick.

Climate change also affects how long during the year people are at risk. Lyme disease, for example, typically lasted from April/May to October, when ticks then hibernated during the cold weather. But the warming climate has expanded Lyme season: Local Lyme cases have begun occurring into November through January on Long Island over the past 5 years.

Courtesy Megan Lobdell

The impact of seasonal changes on infectious diseases overall is difficult to predict. The seasons for cold weather diseases such as influenza and respiratory syncytial virus, for example, may become shorter or milder while viruses more common in the summer, such as enteroviruses, may become a risk year-round.
 

Natural disasters pose multiple risks

Natural disasters can pose immediate dangers to families and have a significant impact on mental health, but that’s not their only potential impact.

“Severe weather events such as hurricanes, floods, and tornadoes are well established in the climate change literature as an effect of increased temperatures and more volatile weather systems, but they also have a significant effect on infectious diseases and on children in particular,” Dr. Hymes said. “Hurricanes and flash floods can cause increases in infectious disease outbreaks through a variety of different ways.”

They can bring saltwater, freshwater, and sometimes soil organisms into the food and water supplies, and lead to sewage contamination from overloaded sewers, overflowing storm drains, and loss of power or pumps. Displaced animal vectors, such as rats, can lead to spread of other diseases, such as plague, hantavirus, typhus, and rabies.

Examples of saltwater organisms include Vibrio, Aeromonas, and Mycobacterium marinum, all of which can cause infections in wounds and/or diarrheal illness or bacteremia. Similarly, organisms from freshwater and soil that can cause serious illness or death include Aeromonas, Pseudomonas, Amebiasis, Giardia, and Legionella. Without access to clean water, or with contamination from overflowing sewage, cryptosporidium, Escherichia coli, salmonella, typhoid, norovirus, hepatitis A and E, and even cholera can also become problems as well.

In Houston following Hurricane Harvey, for example, cellulitis cases doubled and included infections from organisms different from the usual suspects. Scrapes and cuts that occurred during the storm also festered sooner.

Cases of disease linked to Hurricane Katrina in a Centers for Disease Control and Prevention report included 6 cases of cholera, 17 cases of other vibrio – including five that resulted in death – and reported cases of norovirus, Escherichia coli, salmonella, and influenza and pneumonia from overcrowding of evacuees.
 

You can help in a variety of ways

You can play several key roles as the world’s climate changes, starting with preparing for the changes. You should familiarize themselves with new and emerging infections, or those that have been around a while but not seen in your areas, such as Lyme, Zika, and Dengue.

“If you haven’t seen them already, you likely will due to movements of vector-borne infections that can occur due to climate change,” Dr. Hymes said. “You also want to expect the usual common diseases, but maybe at unsuspected times,” he added. “If you have a pediatric patient who looks like they have Coxsackie virus but it’s February, if it’s been a warm February, it may very well be Coxsackie virus.”

Following natural disasters such as floods, hurricanes and tornadoes, consider who your patients are. If they’re evacuees, are they living in overcrowded conditions? Do they have access to clean water? If not, explain the need to boil water if they can, or to use iodine tablets or a portable pump filter. Consider that some infections may involve unexpected or odd organisms, such as legionella pneumonia or vibrio cellulitis, and contact your local infectious disease doctor as needed.

You also can make personal lifestyle changes that, while small, can add up in the aggregate in reducing carbon footprints, such as purchasing an electric or hybrid car and converting their homes to solar power.

“For very little money, you can purchase carbon offsets,” Dr. Hymes said, such as $10-$15 a month for wind power offsets with home electricity or $5-$10 a month for car or plane travel.

“But really, the most important thing we can do as pediatricians is educate,” Dr. Hymes said. “Taking opportunities every day in your office to educate your patients and educate your colleagues about the importance of climate change in our patients’ health and our own children’s health is super, super important.”

Dr. Hymes and Dr. Boykan had no relevant financial disclosures.

“I would argue that the most important reason to care about climate change is because of our children,” Saul Hymes, MD, said at the annual meeting of the American Academy of Pediatrics, held virtually this year.

Cynthia Goldsmith/CDC photo #10073

“Being able to point out to people how climate change harms the health of their children and affects their children’s risk of infections is a particularly effective argument to make,” said Dr. Hymes, a pediatric infectious diseases specialist at Stony Brook (N.Y.) University.

Rachel Boykan, MD, a pediatrician at the university, found Dr. Hymes’ presentation excellent and highly relevant to issues all health care workers treating children face, even beyond infectious disease.

“It was data focused but also understandable for a broad audience,” Dr. Boykan, who was not involved in the presentation, said in an interview. “He explained the science of climate change in a way that all physicians, but especially pediatricians, would find relevant. I suspect if people who were listening didn’t already prioritize the issues of climate change, they certainly did after hearing the talk.”

She also appreciated that Dr. Hymes addressed how climate change affects everyone in both their professional and personal lives.

“We need to be prepared to address the clinical issues that ensue after a natural disaster, and we need to be advocates for change so that we can slow down the climate changes we are all dealing with,” said Dr. Boykan, adding that the presentation was also inspiring. “He presented many different viewpoints and many ways to be involved and to be an advocate. I would think that a good number of people who were there would be energized to do something differently to combat climate change.”
 

The multitudinous impacts of climate change

The impact of climate change on human health is broad and far-reaching, Dr. Hymes said. It doesn’t require much imagination to recognize that rising global temperatures can lead to prolonged extreme heat waves that can cause heat-related deaths and illnesses. But other effects can be more gradual or subtle. Changes in outdoor air quality can affect weather patterns, pollen counts, and air pollution that can increase risk of asthma, allergies, as well as acute and chronic respiratory and cardiovascular disease.

Sea level rise, more frequent and severe hurricanes, storm surges, and extreme precipitation all can lead to contaminated water and destruction of essential infrastructure. In addition to drowning and injuries from the storms themselves, these changes have mental health consequences, and can lead to gastrointestinal and other illnesses, including water-borne infectious disease. The distribution and prevalence of vector-borne diseases also will shift with changes in temperature, precipitation, and other weather patterns.
 

Distribution, prevalence of vector-borne diseases shift with climate change

One of the most common bacteria transmitted by vectors in the United States is Borrelia burgdorferi, the cause of Lyme disease. Transmitted by deer ticks, Lyme disease is listed by the Environmental Protection Agency as an indicator of climate change’s impact on human health and is becoming more common every year. Cases doubled from 1990 to 2014, from 4 to 8 cases per 100,000 people.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

Increases were most dramatic in the Northeast, where Lyme disease is endemic. States such as Maine, Vermont, and New Hampshire all saw increases of 80-100 more cases per 100,000 people. Evidence now shows that Lyme disease is moving north as the climate warms. Toronto, for example, has seen more than a 400% increase in cases in less than a decade, from 128 cases per 100,000 people in 2009 to 700 cases per 100,000 in 2015.

“It’s a known phenomenon that climate change affects more northerly latitudes disproportionately to more than southerly latitudes,” Dr. Hymes said. He shared a 2013 study providing evidence that climate change is expanding the range of Lyme disease. Even when controlling for other confounding factors, the research found that areas being warmed proportionately more by climate change also are experiencing greater Lyme incidence. While Lyme cases declined in several Western and Deep South states, it significantly increased in nearly every Northeast state as well as Idaho, Arizona, and states in the northern Midwest near the Great Lakes.

Courtesy CDC

“We find that this impact of climate change on the movement of vectors like ticks affects more than just Lyme disease,” Dr. Hymes said. Amblyomma americanum, the Lone Star tick, has historically been restricted to the southern United States but is now found further north, even up to New England. It carries bacteria that can cause multiple illnesses, including ehrlichiosis, heartland virus, and tularemia.

An alpha-gal meat allergy associated with this tick can lead to anaphylaxis about 6 hours after a person eats red meat or pork. Prevalence of this allergy, first reported in Georgia in 1989-1991, has been increasing and moving further north, and the Lone Star tick is a particularly heat-tolerant and heat-loving tick.

Climate change also affects how long during the year people are at risk. Lyme disease, for example, typically lasted from April/May to October, when ticks then hibernated during the cold weather. But the warming climate has expanded Lyme season: Local Lyme cases have begun occurring into November through January on Long Island over the past 5 years.

Courtesy Megan Lobdell

The impact of seasonal changes on infectious diseases overall is difficult to predict. The seasons for cold weather diseases such as influenza and respiratory syncytial virus, for example, may become shorter or milder while viruses more common in the summer, such as enteroviruses, may become a risk year-round.
 

Natural disasters pose multiple risks

Natural disasters can pose immediate dangers to families and have a significant impact on mental health, but that’s not their only potential impact.

“Severe weather events such as hurricanes, floods, and tornadoes are well established in the climate change literature as an effect of increased temperatures and more volatile weather systems, but they also have a significant effect on infectious diseases and on children in particular,” Dr. Hymes said. “Hurricanes and flash floods can cause increases in infectious disease outbreaks through a variety of different ways.”

They can bring saltwater, freshwater, and sometimes soil organisms into the food and water supplies, and lead to sewage contamination from overloaded sewers, overflowing storm drains, and loss of power or pumps. Displaced animal vectors, such as rats, can lead to spread of other diseases, such as plague, hantavirus, typhus, and rabies.

Examples of saltwater organisms include Vibrio, Aeromonas, and Mycobacterium marinum, all of which can cause infections in wounds and/or diarrheal illness or bacteremia. Similarly, organisms from freshwater and soil that can cause serious illness or death include Aeromonas, Pseudomonas, Amebiasis, Giardia, and Legionella. Without access to clean water, or with contamination from overflowing sewage, cryptosporidium, Escherichia coli, salmonella, typhoid, norovirus, hepatitis A and E, and even cholera can also become problems as well.

In Houston following Hurricane Harvey, for example, cellulitis cases doubled and included infections from organisms different from the usual suspects. Scrapes and cuts that occurred during the storm also festered sooner.

Cases of disease linked to Hurricane Katrina in a Centers for Disease Control and Prevention report included 6 cases of cholera, 17 cases of other vibrio – including five that resulted in death – and reported cases of norovirus, Escherichia coli, salmonella, and influenza and pneumonia from overcrowding of evacuees.
 

You can help in a variety of ways

You can play several key roles as the world’s climate changes, starting with preparing for the changes. You should familiarize themselves with new and emerging infections, or those that have been around a while but not seen in your areas, such as Lyme, Zika, and Dengue.

“If you haven’t seen them already, you likely will due to movements of vector-borne infections that can occur due to climate change,” Dr. Hymes said. “You also want to expect the usual common diseases, but maybe at unsuspected times,” he added. “If you have a pediatric patient who looks like they have Coxsackie virus but it’s February, if it’s been a warm February, it may very well be Coxsackie virus.”

Following natural disasters such as floods, hurricanes and tornadoes, consider who your patients are. If they’re evacuees, are they living in overcrowded conditions? Do they have access to clean water? If not, explain the need to boil water if they can, or to use iodine tablets or a portable pump filter. Consider that some infections may involve unexpected or odd organisms, such as legionella pneumonia or vibrio cellulitis, and contact your local infectious disease doctor as needed.

You also can make personal lifestyle changes that, while small, can add up in the aggregate in reducing carbon footprints, such as purchasing an electric or hybrid car and converting their homes to solar power.

“For very little money, you can purchase carbon offsets,” Dr. Hymes said, such as $10-$15 a month for wind power offsets with home electricity or $5-$10 a month for car or plane travel.

“But really, the most important thing we can do as pediatricians is educate,” Dr. Hymes said. “Taking opportunities every day in your office to educate your patients and educate your colleagues about the importance of climate change in our patients’ health and our own children’s health is super, super important.”

Dr. Hymes and Dr. Boykan had no relevant financial disclosures.

Adding the immunomodulator mycophenolate mofetil (MMF) to therapy with pegloticase (Krystexxa) may improve outcomes in patients with refractory gout, results of the proof-of-concept RECIPE trial suggest.

In the phase 2 trial, 19 of 22 patients randomized to received pegloticase and MMF achieved the primary outcome of serum uric acid levels below 6 mg/dL at week 12, compared with 4 of 10 patients assigned to pegloticase and placebo, reported Puja Khanna MD, MPH, of the University of Michigan, Ann Arbor, and colleagues.

“The use of MMF was associated with statistically significant and clinically meaningful impact on the proportion of subjects who achieved and maintained a serum urate of less than 6 mg/dL. Short-term concomitant use of MMF with pegloticase was generally well tolerated, and the estimated rates of adverse events were comparable between the groups,” she said during the virtual annual meeting of the American College of Rheumatology.

Pegloticase is a pegylated recombinant form of porcine uricase that has been shown to be effective in the treatment of gout in patients for whom other therapies have failed.

The drug’s use is limited, however, by immunogenicity, with high antipegloticase antibody titers associated with a loss of response.

“The PEG portion of the molecule, the polyethylene glycol component, can initiate an immune response that would cause significant infusion reactions and preclude further use of the medication for our patients,” explained Suleman Bhana, MD, a rheumatologist with Crystal Run Healthcare in New York’s Hudson Valley, who was not involved in the study.

“By trying to attenuate that immune response by whatever means one can, that could reduce the risk of these infusion reactions and lead to longevity and continuing efficacy of the medication,” he said.
 

Study details

The RECIPE trial was designed to test whether concomitant immunomodulation could prolong the efficacy of pegloticase therapy by dampening immune reactions.

Investigators enrolled patients 18 years and older who met 2015 ACR/European League Against Rheumatism gout classification criteria and had chronic refractory disease, defined as having symptoms inadequately controlled with oral urate-lowering therapy or a contraindication to ULT.

A total of 42 patients from five rheumatology practices were screened, and 35 were randomized on a 3:1 basis. In the intention-to-treat analysis of the results, the investigators included 32 patients: 22 in the MMF/pegloticase group and 10 placebo-treated controls who had received at least one dose of pegloticase.

Men comprised approximately 90% of the patients in each study arm, with the mean patient age around 55 years. In both groups, patients had a median of one gout flare in the prior year, and a mean duration of gout of 13 years plus a few months.

The patients’ prior urate-lowering agents included allopurinol and febuxostat, and patients had received colchicine, NSAIDs, and corticosteroids for acute gout.

The mean serum urate levels at baseline were 8.9 mg/dL in the MMF group, and 9.8 mg/dL in the placebo group.

Patients were given either MMF 1 g twice daily or a placebo during a 2-week run-in, with the assigned medications continuing for the first 12 weeks concomitantly with pegloticase. The uricase was given intravenously at a dose of 8 mg every 2 weeks for a total of 12 infusions.

As noted before, 86% of patients in the MMF arm (19 of 22) reached the primary outcome of serum uric acid levels below 6 mg/dL by week 12, compared with 40% (4 of 10) in the placebo arm (P = .01).

Week 24 serum uric acid response, a secondary endpoint, was sustained in 68% of patients in the MMF arm, compared with 30% in the placebo arm (P = .03).

“We found no significant differences between the groups in the absolute change in serum urate from baseline to week 24, or from week 12 to 24. We also did not find any differences between the treatment arms for the PROMIS [Patient Reported Outcomes Measurement Information System] or for the Gout Impact Scale,” Dr. Khanna said.

The most commonly reported adverse events included gout flares in 13% of patients in the MMF group and 3% in the placebo group, cardiac disorders in 3% versus 2%, respectively, and gastrointestinal disorders in 9% versus 2%.

Adverse events that occurred only in the MMF group included infections (3%), musculoskeletal and connective tissue disorders (18%), and respiratory events.

Three patients in the placebo arm had infusion reactions, two of which occurred during the first infusion, and one during the second. One of the reactions was considered serious and required hospitalization, but all infusion reactions resolved and none were fatal. There were no infusion reactions in the MMF arm.

Maybe methotrexate instead?

“The efficacy data for mycophenolate in the RECIPE study are convincing, and suggest that this combination substantially increases the proportion of people who respond to pegloticase,” commented Nicola Dalbeth, MD, professor of medicine at the University of Auckland (New Zealand), who moderated the session where the RECIPE data were reported.

“Previous open-label studies of methotrexate with pegloticase [e.g., the MIRROR study] suggest that methotrexate is another effective option to increase the response to pegloticase. However, at this stage, placebo-controlled trials of methotrexate have not been reported. I think a key consideration will be safety, and which option [methotrexate vs. mycophenolate] is safer, noting that many patients with severe gout have important comorbidities, including chronic kidney disease, diabetes, and liver disease,” she said.

Dr. Bhana also noted that there are multiple factors that might determine the choice of MMF or methotrexate as an immunomodulatory partner for pegloticase.

“Some gout patients have chronic kidney disease or a variety of comorbidities – high uric acid can also cause kidney damage – and if they have a kidney illness, methotrexate may not be a safe medicine because there’s a risk of further toxicity that can lead to bone marrow suppression, which I have seen personally in patients, and in this case mycophenolate would be the preferred option,” he said.

The study was sponsored by the University of Alabama at Birmingham, with collaboration from the University of Michigan, as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Horizon, which makes pegloticase. Dr. Khanna disclosed grant and research support from Dyve, Selecta, and Sobi, and consulting for Sobi and Horizon. Dr. Dalbeth disclosed relationships with AstraZeneca, AbbVie, Arthrosi, Dyve, Selecta, and Janssen. Dr. Bhana disclosed nonbranded consulting work for Horizon.

SOURCE: Khanna P et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 0952.

Adding the immunomodulator mycophenolate mofetil (MMF) to therapy with pegloticase (Krystexxa) may improve outcomes in patients with refractory gout, results of the proof-of-concept RECIPE trial suggest.

In the phase 2 trial, 19 of 22 patients randomized to received pegloticase and MMF achieved the primary outcome of serum uric acid levels below 6 mg/dL at week 12, compared with 4 of 10 patients assigned to pegloticase and placebo, reported Puja Khanna MD, MPH, of the University of Michigan, Ann Arbor, and colleagues.

“The use of MMF was associated with statistically significant and clinically meaningful impact on the proportion of subjects who achieved and maintained a serum urate of less than 6 mg/dL. Short-term concomitant use of MMF with pegloticase was generally well tolerated, and the estimated rates of adverse events were comparable between the groups,” she said during the virtual annual meeting of the American College of Rheumatology.

Pegloticase is a pegylated recombinant form of porcine uricase that has been shown to be effective in the treatment of gout in patients for whom other therapies have failed.

The drug’s use is limited, however, by immunogenicity, with high antipegloticase antibody titers associated with a loss of response.

“The PEG portion of the molecule, the polyethylene glycol component, can initiate an immune response that would cause significant infusion reactions and preclude further use of the medication for our patients,” explained Suleman Bhana, MD, a rheumatologist with Crystal Run Healthcare in New York’s Hudson Valley, who was not involved in the study.

“By trying to attenuate that immune response by whatever means one can, that could reduce the risk of these infusion reactions and lead to longevity and continuing efficacy of the medication,” he said.
 

Study details

The RECIPE trial was designed to test whether concomitant immunomodulation could prolong the efficacy of pegloticase therapy by dampening immune reactions.

Investigators enrolled patients 18 years and older who met 2015 ACR/European League Against Rheumatism gout classification criteria and had chronic refractory disease, defined as having symptoms inadequately controlled with oral urate-lowering therapy or a contraindication to ULT.

A total of 42 patients from five rheumatology practices were screened, and 35 were randomized on a 3:1 basis. In the intention-to-treat analysis of the results, the investigators included 32 patients: 22 in the MMF/pegloticase group and 10 placebo-treated controls who had received at least one dose of pegloticase.

Men comprised approximately 90% of the patients in each study arm, with the mean patient age around 55 years. In both groups, patients had a median of one gout flare in the prior year, and a mean duration of gout of 13 years plus a few months.

The patients’ prior urate-lowering agents included allopurinol and febuxostat, and patients had received colchicine, NSAIDs, and corticosteroids for acute gout.

The mean serum urate levels at baseline were 8.9 mg/dL in the MMF group, and 9.8 mg/dL in the placebo group.

Patients were given either MMF 1 g twice daily or a placebo during a 2-week run-in, with the assigned medications continuing for the first 12 weeks concomitantly with pegloticase. The uricase was given intravenously at a dose of 8 mg every 2 weeks for a total of 12 infusions.

As noted before, 86% of patients in the MMF arm (19 of 22) reached the primary outcome of serum uric acid levels below 6 mg/dL by week 12, compared with 40% (4 of 10) in the placebo arm (P = .01).

Week 24 serum uric acid response, a secondary endpoint, was sustained in 68% of patients in the MMF arm, compared with 30% in the placebo arm (P = .03).

“We found no significant differences between the groups in the absolute change in serum urate from baseline to week 24, or from week 12 to 24. We also did not find any differences between the treatment arms for the PROMIS [Patient Reported Outcomes Measurement Information System] or for the Gout Impact Scale,” Dr. Khanna said.

The most commonly reported adverse events included gout flares in 13% of patients in the MMF group and 3% in the placebo group, cardiac disorders in 3% versus 2%, respectively, and gastrointestinal disorders in 9% versus 2%.

Adverse events that occurred only in the MMF group included infections (3%), musculoskeletal and connective tissue disorders (18%), and respiratory events.

Three patients in the placebo arm had infusion reactions, two of which occurred during the first infusion, and one during the second. One of the reactions was considered serious and required hospitalization, but all infusion reactions resolved and none were fatal. There were no infusion reactions in the MMF arm.

Maybe methotrexate instead?

“The efficacy data for mycophenolate in the RECIPE study are convincing, and suggest that this combination substantially increases the proportion of people who respond to pegloticase,” commented Nicola Dalbeth, MD, professor of medicine at the University of Auckland (New Zealand), who moderated the session where the RECIPE data were reported.

“Previous open-label studies of methotrexate with pegloticase [e.g., the MIRROR study] suggest that methotrexate is another effective option to increase the response to pegloticase. However, at this stage, placebo-controlled trials of methotrexate have not been reported. I think a key consideration will be safety, and which option [methotrexate vs. mycophenolate] is safer, noting that many patients with severe gout have important comorbidities, including chronic kidney disease, diabetes, and liver disease,” she said.

Dr. Bhana also noted that there are multiple factors that might determine the choice of MMF or methotrexate as an immunomodulatory partner for pegloticase.

“Some gout patients have chronic kidney disease or a variety of comorbidities – high uric acid can also cause kidney damage – and if they have a kidney illness, methotrexate may not be a safe medicine because there’s a risk of further toxicity that can lead to bone marrow suppression, which I have seen personally in patients, and in this case mycophenolate would be the preferred option,” he said.

The study was sponsored by the University of Alabama at Birmingham, with collaboration from the University of Michigan, as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Horizon, which makes pegloticase. Dr. Khanna disclosed grant and research support from Dyve, Selecta, and Sobi, and consulting for Sobi and Horizon. Dr. Dalbeth disclosed relationships with AstraZeneca, AbbVie, Arthrosi, Dyve, Selecta, and Janssen. Dr. Bhana disclosed nonbranded consulting work for Horizon.

SOURCE: Khanna P et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 0952.

Adding the immunomodulator mycophenolate mofetil (MMF) to therapy with pegloticase (Krystexxa) may improve outcomes in patients with refractory gout, results of the proof-of-concept RECIPE trial suggest.

In the phase 2 trial, 19 of 22 patients randomized to received pegloticase and MMF achieved the primary outcome of serum uric acid levels below 6 mg/dL at week 12, compared with 4 of 10 patients assigned to pegloticase and placebo, reported Puja Khanna MD, MPH, of the University of Michigan, Ann Arbor, and colleagues.

“The use of MMF was associated with statistically significant and clinically meaningful impact on the proportion of subjects who achieved and maintained a serum urate of less than 6 mg/dL. Short-term concomitant use of MMF with pegloticase was generally well tolerated, and the estimated rates of adverse events were comparable between the groups,” she said during the virtual annual meeting of the American College of Rheumatology.

Pegloticase is a pegylated recombinant form of porcine uricase that has been shown to be effective in the treatment of gout in patients for whom other therapies have failed.

The drug’s use is limited, however, by immunogenicity, with high antipegloticase antibody titers associated with a loss of response.

“The PEG portion of the molecule, the polyethylene glycol component, can initiate an immune response that would cause significant infusion reactions and preclude further use of the medication for our patients,” explained Suleman Bhana, MD, a rheumatologist with Crystal Run Healthcare in New York’s Hudson Valley, who was not involved in the study.

“By trying to attenuate that immune response by whatever means one can, that could reduce the risk of these infusion reactions and lead to longevity and continuing efficacy of the medication,” he said.
 

Study details

The RECIPE trial was designed to test whether concomitant immunomodulation could prolong the efficacy of pegloticase therapy by dampening immune reactions.

Investigators enrolled patients 18 years and older who met 2015 ACR/European League Against Rheumatism gout classification criteria and had chronic refractory disease, defined as having symptoms inadequately controlled with oral urate-lowering therapy or a contraindication to ULT.

A total of 42 patients from five rheumatology practices were screened, and 35 were randomized on a 3:1 basis. In the intention-to-treat analysis of the results, the investigators included 32 patients: 22 in the MMF/pegloticase group and 10 placebo-treated controls who had received at least one dose of pegloticase.

Men comprised approximately 90% of the patients in each study arm, with the mean patient age around 55 years. In both groups, patients had a median of one gout flare in the prior year, and a mean duration of gout of 13 years plus a few months.

The patients’ prior urate-lowering agents included allopurinol and febuxostat, and patients had received colchicine, NSAIDs, and corticosteroids for acute gout.

The mean serum urate levels at baseline were 8.9 mg/dL in the MMF group, and 9.8 mg/dL in the placebo group.

Patients were given either MMF 1 g twice daily or a placebo during a 2-week run-in, with the assigned medications continuing for the first 12 weeks concomitantly with pegloticase. The uricase was given intravenously at a dose of 8 mg every 2 weeks for a total of 12 infusions.

As noted before, 86% of patients in the MMF arm (19 of 22) reached the primary outcome of serum uric acid levels below 6 mg/dL by week 12, compared with 40% (4 of 10) in the placebo arm (P = .01).

Week 24 serum uric acid response, a secondary endpoint, was sustained in 68% of patients in the MMF arm, compared with 30% in the placebo arm (P = .03).

“We found no significant differences between the groups in the absolute change in serum urate from baseline to week 24, or from week 12 to 24. We also did not find any differences between the treatment arms for the PROMIS [Patient Reported Outcomes Measurement Information System] or for the Gout Impact Scale,” Dr. Khanna said.

The most commonly reported adverse events included gout flares in 13% of patients in the MMF group and 3% in the placebo group, cardiac disorders in 3% versus 2%, respectively, and gastrointestinal disorders in 9% versus 2%.

Adverse events that occurred only in the MMF group included infections (3%), musculoskeletal and connective tissue disorders (18%), and respiratory events.

Three patients in the placebo arm had infusion reactions, two of which occurred during the first infusion, and one during the second. One of the reactions was considered serious and required hospitalization, but all infusion reactions resolved and none were fatal. There were no infusion reactions in the MMF arm.

Maybe methotrexate instead?

“The efficacy data for mycophenolate in the RECIPE study are convincing, and suggest that this combination substantially increases the proportion of people who respond to pegloticase,” commented Nicola Dalbeth, MD, professor of medicine at the University of Auckland (New Zealand), who moderated the session where the RECIPE data were reported.

“Previous open-label studies of methotrexate with pegloticase [e.g., the MIRROR study] suggest that methotrexate is another effective option to increase the response to pegloticase. However, at this stage, placebo-controlled trials of methotrexate have not been reported. I think a key consideration will be safety, and which option [methotrexate vs. mycophenolate] is safer, noting that many patients with severe gout have important comorbidities, including chronic kidney disease, diabetes, and liver disease,” she said.

Dr. Bhana also noted that there are multiple factors that might determine the choice of MMF or methotrexate as an immunomodulatory partner for pegloticase.

“Some gout patients have chronic kidney disease or a variety of comorbidities – high uric acid can also cause kidney damage – and if they have a kidney illness, methotrexate may not be a safe medicine because there’s a risk of further toxicity that can lead to bone marrow suppression, which I have seen personally in patients, and in this case mycophenolate would be the preferred option,” he said.

The study was sponsored by the University of Alabama at Birmingham, with collaboration from the University of Michigan, as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Horizon, which makes pegloticase. Dr. Khanna disclosed grant and research support from Dyve, Selecta, and Sobi, and consulting for Sobi and Horizon. Dr. Dalbeth disclosed relationships with AstraZeneca, AbbVie, Arthrosi, Dyve, Selecta, and Janssen. Dr. Bhana disclosed nonbranded consulting work for Horizon.

SOURCE: Khanna P et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 0952.

Clinicians treating patients with cystic fibrosis (CF) have had to face the possibility that their patients may be particularly susceptible to SARS-CoV-2 infection and perhaps at greater risk of worse outcomes from COVID-19. But early results suggest that social distance measures and perhaps the younger average age of individuals with CF have prevented a severe impact on this patient population.

Not all of the news is good. Some research suggests that posttransplant individuals may be at greater risk of severe outcomes. However, researchers warned that the data are too sparse to draw firm conclusions, and ongoing analyses of patient registries and other sources should lend greater insight into the burden of COVID-19 among individuals with CF. Those were some of the conclusions presented at a session of the virtual North American Cystic Fibrosis Conference.

D.B. Sanders, MD, who is a pediatric pulmonologist at Riley Hospital for Children and the Indiana University, both in Indianapolis, presented data from the Cystic Fibrosis Foundation’s Patient Registry, which includes patients in the United States. As in other populations, he showed that health care use has gone down among individuals with CF. From April to September 2019, 81% of clinical encounters were in the clinic and 12% in the hospital. Over the same period in 2020, those numbers dropped to 35% and 4%, respectively, with 30% by phone or computer. In-person health care use rebounded somewhat between July 1 and Sept. 16, with 53% of encounters at the clinic, 5% at the hospital, and 28% conducted virtually. There were also dips in forced expiratory volume in one second (FEV₁) and microbiology testing, from about 90% occurring during health encounters at the end of 2019 to fewer than 10% of encounters by April.

As of Aug. 17, Dr. Sanders reported that 3,048 individuals with CF had been tested for COVID-19, with 174 positive results.

Racial and ethnic disparities in positive test results seen in other populations were also observable among individuals with CF. Several groups made up a higher proportion of COVID-19–positive CF patients than the general CF population, including Hispanics (18% vs. 9%), Blacks (7% vs. 5%), and individuals with FEV₁ value less than 40% predicted (14% vs. 8%).

As of Sept. 17, there had been 51 hospitalizations and two deaths in the United States among 212 individuals with CF who tested positive for COVID-19, with increasing numbers that mirror trends in the U.S. population. One death occurred in a patient with advanced lung disease, the other in a post–lung transplant patient. “Thankfully [the numbers are] not higher, but this is being followed very closely,” said Dr. Sanders during his presentation.

One encouraging bit of news was that hospitalizations among individuals with CF have dropped since the start of the pandemic. “I think this shows how good our families are at socially distancing, wearing masks, and now that they not being exposed to viruses, I think we’re seeing the fruits of this with fewer hospitalizations,” said Dr. Sanders. He noted that it’s possible some of the decline could have been to reluctance to go to the hospital, and the introduction of triple combination cystic fibrosis transmembrane conductance regulator modulator therapy has also likely contributed. “We were already seeing fewer hospitalizations even before the pandemic hit,” he said.

At the session, Rebecca Cosgriff, director of data and quality improvement at the Cystic Fibrosis Trust in the United Kingdom, presented an international perspective on COVID-19 cases among individuals with CF. At the beginning of the pandemic, the Cystic Fibrosis Global Registry Harmonization Group recruited country coordinators to collect anonymized data on infections, hospitalizations, and other outcomes. In April, the group published its initial findings from 40 cases in eight countries, which concluded that these cases generally resembled the broader population in clinical course, which assuaged initial fears.

Ms. Cosgriff reported on results from a second round of data collection with a cutoff date of June 19, which expanded to 19 countries and included many from South America and more in Europe. The network encompassed about 85,000 individuals with CF, and tallied 181 cases of COVID-19. A total of 149 cases were nontransplant, and 32 were posttransplant (28 lung only). Fully 15% of the nontransplant group were over age 40 years, compared with 41% in the transplant group. Homozygous F508del mutations were more common in the posttransplant group (59% vs. 36%). However, lung function, as estimated by the best FEV₁ measured in the previous year prior to infection, differed between the nontransplant (73%) and posttransplant (80%) COVID-19 patients.

Across all age groups, hospitalizations were more common in patients with best FEV₁ percentage predicted values less than 70% (P = .001). Ms. Cosgriff also expressed concern about the posttransplant group. “Across all outcomes that might be indicative of infection severity – hospitalization, ICU admission, new supplementary oxygen, and non-invasive ventilation – the proportion of the posttransplant group was higher across the board,” she said during her presentation.

There were seven deaths. Ms. Cosgriff noted that there were too few deaths to analyze trends, but she presented a slide showing characteristics of deceased patients. “Factors like being post–lung transplant, being male, having less FEV₁ than predicted, being over 40, or having CF-related diabetes, all appear pretty frequently amongst the cohort of people who died,” she said.

Overall, the results of these surveys are encouraging, suggesting that early fears that COVID-19 cases could be more severe among individuals with CF may not have been borne out so far. Dr. Sanders noted in his talk that there aren’t enough cases in the U.S. cohort to show links to risk factors with statistical significance. “But thankfully we’re not seeing a host of negative outcomes,” he said.

Dr. Sanders and Ms Cosgriff have no relevant financial disclosures.

Clinicians treating patients with cystic fibrosis (CF) have had to face the possibility that their patients may be particularly susceptible to SARS-CoV-2 infection and perhaps at greater risk of worse outcomes from COVID-19. But early results suggest that social distance measures and perhaps the younger average age of individuals with CF have prevented a severe impact on this patient population.

Not all of the news is good. Some research suggests that posttransplant individuals may be at greater risk of severe outcomes. However, researchers warned that the data are too sparse to draw firm conclusions, and ongoing analyses of patient registries and other sources should lend greater insight into the burden of COVID-19 among individuals with CF. Those were some of the conclusions presented at a session of the virtual North American Cystic Fibrosis Conference.

D.B. Sanders, MD, who is a pediatric pulmonologist at Riley Hospital for Children and the Indiana University, both in Indianapolis, presented data from the Cystic Fibrosis Foundation’s Patient Registry, which includes patients in the United States. As in other populations, he showed that health care use has gone down among individuals with CF. From April to September 2019, 81% of clinical encounters were in the clinic and 12% in the hospital. Over the same period in 2020, those numbers dropped to 35% and 4%, respectively, with 30% by phone or computer. In-person health care use rebounded somewhat between July 1 and Sept. 16, with 53% of encounters at the clinic, 5% at the hospital, and 28% conducted virtually. There were also dips in forced expiratory volume in one second (FEV₁) and microbiology testing, from about 90% occurring during health encounters at the end of 2019 to fewer than 10% of encounters by April.

As of Aug. 17, Dr. Sanders reported that 3,048 individuals with CF had been tested for COVID-19, with 174 positive results.

Racial and ethnic disparities in positive test results seen in other populations were also observable among individuals with CF. Several groups made up a higher proportion of COVID-19–positive CF patients than the general CF population, including Hispanics (18% vs. 9%), Blacks (7% vs. 5%), and individuals with FEV₁ value less than 40% predicted (14% vs. 8%).

As of Sept. 17, there had been 51 hospitalizations and two deaths in the United States among 212 individuals with CF who tested positive for COVID-19, with increasing numbers that mirror trends in the U.S. population. One death occurred in a patient with advanced lung disease, the other in a post–lung transplant patient. “Thankfully [the numbers are] not higher, but this is being followed very closely,” said Dr. Sanders during his presentation.

One encouraging bit of news was that hospitalizations among individuals with CF have dropped since the start of the pandemic. “I think this shows how good our families are at socially distancing, wearing masks, and now that they not being exposed to viruses, I think we’re seeing the fruits of this with fewer hospitalizations,” said Dr. Sanders. He noted that it’s possible some of the decline could have been to reluctance to go to the hospital, and the introduction of triple combination cystic fibrosis transmembrane conductance regulator modulator therapy has also likely contributed. “We were already seeing fewer hospitalizations even before the pandemic hit,” he said.

At the session, Rebecca Cosgriff, director of data and quality improvement at the Cystic Fibrosis Trust in the United Kingdom, presented an international perspective on COVID-19 cases among individuals with CF. At the beginning of the pandemic, the Cystic Fibrosis Global Registry Harmonization Group recruited country coordinators to collect anonymized data on infections, hospitalizations, and other outcomes. In April, the group published its initial findings from 40 cases in eight countries, which concluded that these cases generally resembled the broader population in clinical course, which assuaged initial fears.

Ms. Cosgriff reported on results from a second round of data collection with a cutoff date of June 19, which expanded to 19 countries and included many from South America and more in Europe. The network encompassed about 85,000 individuals with CF, and tallied 181 cases of COVID-19. A total of 149 cases were nontransplant, and 32 were posttransplant (28 lung only). Fully 15% of the nontransplant group were over age 40 years, compared with 41% in the transplant group. Homozygous F508del mutations were more common in the posttransplant group (59% vs. 36%). However, lung function, as estimated by the best FEV₁ measured in the previous year prior to infection, differed between the nontransplant (73%) and posttransplant (80%) COVID-19 patients.

Across all age groups, hospitalizations were more common in patients with best FEV₁ percentage predicted values less than 70% (P = .001). Ms. Cosgriff also expressed concern about the posttransplant group. “Across all outcomes that might be indicative of infection severity – hospitalization, ICU admission, new supplementary oxygen, and non-invasive ventilation – the proportion of the posttransplant group was higher across the board,” she said during her presentation.

There were seven deaths. Ms. Cosgriff noted that there were too few deaths to analyze trends, but she presented a slide showing characteristics of deceased patients. “Factors like being post–lung transplant, being male, having less FEV₁ than predicted, being over 40, or having CF-related diabetes, all appear pretty frequently amongst the cohort of people who died,” she said.

Overall, the results of these surveys are encouraging, suggesting that early fears that COVID-19 cases could be more severe among individuals with CF may not have been borne out so far. Dr. Sanders noted in his talk that there aren’t enough cases in the U.S. cohort to show links to risk factors with statistical significance. “But thankfully we’re not seeing a host of negative outcomes,” he said.

Dr. Sanders and Ms Cosgriff have no relevant financial disclosures.

Clinicians treating patients with cystic fibrosis (CF) have had to face the possibility that their patients may be particularly susceptible to SARS-CoV-2 infection and perhaps at greater risk of worse outcomes from COVID-19. But early results suggest that social distance measures and perhaps the younger average age of individuals with CF have prevented a severe impact on this patient population.

Not all of the news is good. Some research suggests that posttransplant individuals may be at greater risk of severe outcomes. However, researchers warned that the data are too sparse to draw firm conclusions, and ongoing analyses of patient registries and other sources should lend greater insight into the burden of COVID-19 among individuals with CF. Those were some of the conclusions presented at a session of the virtual North American Cystic Fibrosis Conference.

D.B. Sanders, MD, who is a pediatric pulmonologist at Riley Hospital for Children and the Indiana University, both in Indianapolis, presented data from the Cystic Fibrosis Foundation’s Patient Registry, which includes patients in the United States. As in other populations, he showed that health care use has gone down among individuals with CF. From April to September 2019, 81% of clinical encounters were in the clinic and 12% in the hospital. Over the same period in 2020, those numbers dropped to 35% and 4%, respectively, with 30% by phone or computer. In-person health care use rebounded somewhat between July 1 and Sept. 16, with 53% of encounters at the clinic, 5% at the hospital, and 28% conducted virtually. There were also dips in forced expiratory volume in one second (FEV₁) and microbiology testing, from about 90% occurring during health encounters at the end of 2019 to fewer than 10% of encounters by April.

As of Aug. 17, Dr. Sanders reported that 3,048 individuals with CF had been tested for COVID-19, with 174 positive results.

Racial and ethnic disparities in positive test results seen in other populations were also observable among individuals with CF. Several groups made up a higher proportion of COVID-19–positive CF patients than the general CF population, including Hispanics (18% vs. 9%), Blacks (7% vs. 5%), and individuals with FEV₁ value less than 40% predicted (14% vs. 8%).

As of Sept. 17, there had been 51 hospitalizations and two deaths in the United States among 212 individuals with CF who tested positive for COVID-19, with increasing numbers that mirror trends in the U.S. population. One death occurred in a patient with advanced lung disease, the other in a post–lung transplant patient. “Thankfully [the numbers are] not higher, but this is being followed very closely,” said Dr. Sanders during his presentation.

One encouraging bit of news was that hospitalizations among individuals with CF have dropped since the start of the pandemic. “I think this shows how good our families are at socially distancing, wearing masks, and now that they not being exposed to viruses, I think we’re seeing the fruits of this with fewer hospitalizations,” said Dr. Sanders. He noted that it’s possible some of the decline could have been to reluctance to go to the hospital, and the introduction of triple combination cystic fibrosis transmembrane conductance regulator modulator therapy has also likely contributed. “We were already seeing fewer hospitalizations even before the pandemic hit,” he said.

At the session, Rebecca Cosgriff, director of data and quality improvement at the Cystic Fibrosis Trust in the United Kingdom, presented an international perspective on COVID-19 cases among individuals with CF. At the beginning of the pandemic, the Cystic Fibrosis Global Registry Harmonization Group recruited country coordinators to collect anonymized data on infections, hospitalizations, and other outcomes. In April, the group published its initial findings from 40 cases in eight countries, which concluded that these cases generally resembled the broader population in clinical course, which assuaged initial fears.

Ms. Cosgriff reported on results from a second round of data collection with a cutoff date of June 19, which expanded to 19 countries and included many from South America and more in Europe. The network encompassed about 85,000 individuals with CF, and tallied 181 cases of COVID-19. A total of 149 cases were nontransplant, and 32 were posttransplant (28 lung only). Fully 15% of the nontransplant group were over age 40 years, compared with 41% in the transplant group. Homozygous F508del mutations were more common in the posttransplant group (59% vs. 36%). However, lung function, as estimated by the best FEV₁ measured in the previous year prior to infection, differed between the nontransplant (73%) and posttransplant (80%) COVID-19 patients.

Across all age groups, hospitalizations were more common in patients with best FEV₁ percentage predicted values less than 70% (P = .001). Ms. Cosgriff also expressed concern about the posttransplant group. “Across all outcomes that might be indicative of infection severity – hospitalization, ICU admission, new supplementary oxygen, and non-invasive ventilation – the proportion of the posttransplant group was higher across the board,” she said during her presentation.

There were seven deaths. Ms. Cosgriff noted that there were too few deaths to analyze trends, but she presented a slide showing characteristics of deceased patients. “Factors like being post–lung transplant, being male, having less FEV₁ than predicted, being over 40, or having CF-related diabetes, all appear pretty frequently amongst the cohort of people who died,” she said.

Overall, the results of these surveys are encouraging, suggesting that early fears that COVID-19 cases could be more severe among individuals with CF may not have been borne out so far. Dr. Sanders noted in his talk that there aren’t enough cases in the U.S. cohort to show links to risk factors with statistical significance. “But thankfully we’re not seeing a host of negative outcomes,” he said.

Dr. Sanders and Ms Cosgriff have no relevant financial disclosures.