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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
First-in-class antipsychotic linked to lower cardiometabolic risk
A recently approved first-in-class antipsychotic appears to have fewer adverse cardiometabolic effects than standard care with risperidone, new research suggests.
In post hoc analyses of two short-term randomized controlled trials plus an open-label long-term study, patients with schizophrenia on lumateperone (Caplyta, Intra-Cellular Therapies) had reduced rates of metabolic syndrome, compared with their counterparts taking placebo or the antipsychotic risperidone.
In the short-term studies, rates of metabolic syndrome were similar between groups at baseline, but by the end of 4 and 6 weeks of treatment, 25% of patients taking lumateperone no longer met criteria for metabolic syndrome. A similar finding occurred in 36% of patients in the 1-year open label study.
“One of the major advantages that we found during the drug’s development was that it has a very favorable profile with regard to changes in weight, and other [parameters] associated with cardiovascular disease risk, such as elevated glucose and lipids,” study investigator Andrew Satlin, MD, chief medical officer at Intra-Cellular Therapies, New York, told this news organization.
“So we went back to our data and looked to see whether the changes that we saw had an impact on either the development or the resolution of metabolic syndrome in the patients who came into our studies,” he said.
The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
Reduced cholesterol
Lumateperone was approved in December by the Food and Drug Administration. The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems.
The short-term studies included 511 patients randomly assigned to receive lumateperone 42 mg (n = 256 patients) or risperidone 4 mg (n = 255 patients).
At baseline, rates of metabolic syndrome were 16% in the lumateperone group and 19% in the risperidone group. At the end of treatment, metabolic syndrome was less common in the lumateperone group (13%) vs. those receiving risperidone (25%).
In addition, 46% of lumateperone patients with metabolic syndrome at baseline no longer had it at the end of the study period. This compared with 25% of patients on risperidone.
The differences in metabolic syndrome conversion rates appeared to be driven by greater reductions in total cholesterol with lumateperone, compared with risperidone (–2.8 mg/dL with lumateperone vs. 4.8 mg/dL with risperidone) and triglycerides (–0.7 mg/dL with lumateperone vs. 20.4 mg/dL with risperidone).
Greater increases in blood glucose were also seen with risperidone (7.7 mg/dL) than with lumateperone (0.9 mg/dL).
The long-term study included 602 patients with stable schizophrenia. All received lumateperone 42 mg, and 197 patients (33%) had metabolic syndrome at baseline.
At the end of the 1-year study, 72 of these patients (36%) no longer met criteria for metabolic syndrome.
“Safest antipsychotic so far”
“Lumateperone seems to be the safest antipsychotic we have seen so far,” Christoph U. Correll, MD, professor of child and adolescent psychiatry, Charité Universitatsmedizin, Berlin, who was also involved in clinical trials of lumateperone, told this news organization.
“It seems to be very safe when it comes to cardiometabolic parameters, and it shows similar reduction in symptoms as risperidone. It is certainly an agent one should consider, particularly when a patient cannot tolerate other medications or may not be in full adherence,” said Dr. Correll, who has a joint appointment as professor of psychiatry and molecular medicine at the Zucker School of Medicine at Hofstra University in Hempstead, New York.
The drug’s safety and efficacy profile would make it a good candidate in patients initiating antipsychotic treatment, but reimbursement issues may be a barrier, at least for now, he added.
He said that the drug may prevent the onset of metabolic side effects and added that once payers are willing to reimburse the drug it should become the “first-line standard of care.”
It is well known that atypical antipsychotics are associated with adverse and rapid metabolic changes. Dr. Correll noted that particularly early-phase and first-episode patients can be “very sensitive” to the side effects of these drugs and often experience rapid weight gain and other adverse metabolic changes. Lumateperone, he added, may help avoid some of this cardiometabolic risk.
Time will tell
Jessica M. Gannon, MD, a psychiatrist at the University of Pittsburgh said in commenting on the findings that the drug’s favorable metabolic profile has previously been reported.
She also noted that there has been some interest in lumateperone because of possible “downstream effects on NMDA-type glutamate receptor activity, a larger binding ratio at dopamine-2:5HT1A receptors than other atypical antipsychotics, and presynaptic D2 partial agonism and a postsynaptic D2 antagonism.”
“This latter feature may explain the reported low extrapyramidal symptom incidence in the clinical trials,” she said .
“While I think future studies and clinical use can help determine how clinically efficacious this medication will be for our patients when compared to others on the market, its favorable metabolic and EPS profile do make it of interest,” added Gannon, who was not involved in researching the drug.
The study was funded by Intra-Cellular Therapies. Dr. Satlin is chief medical officer of Intracellular Therapies. Dr. Correll has been a consultant or advisor to and has received honoraria from Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva.
A version of this article originally appeared on Medscape.com.
A recently approved first-in-class antipsychotic appears to have fewer adverse cardiometabolic effects than standard care with risperidone, new research suggests.
In post hoc analyses of two short-term randomized controlled trials plus an open-label long-term study, patients with schizophrenia on lumateperone (Caplyta, Intra-Cellular Therapies) had reduced rates of metabolic syndrome, compared with their counterparts taking placebo or the antipsychotic risperidone.
In the short-term studies, rates of metabolic syndrome were similar between groups at baseline, but by the end of 4 and 6 weeks of treatment, 25% of patients taking lumateperone no longer met criteria for metabolic syndrome. A similar finding occurred in 36% of patients in the 1-year open label study.
“One of the major advantages that we found during the drug’s development was that it has a very favorable profile with regard to changes in weight, and other [parameters] associated with cardiovascular disease risk, such as elevated glucose and lipids,” study investigator Andrew Satlin, MD, chief medical officer at Intra-Cellular Therapies, New York, told this news organization.
“So we went back to our data and looked to see whether the changes that we saw had an impact on either the development or the resolution of metabolic syndrome in the patients who came into our studies,” he said.
The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
Reduced cholesterol
Lumateperone was approved in December by the Food and Drug Administration. The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems.
The short-term studies included 511 patients randomly assigned to receive lumateperone 42 mg (n = 256 patients) or risperidone 4 mg (n = 255 patients).
At baseline, rates of metabolic syndrome were 16% in the lumateperone group and 19% in the risperidone group. At the end of treatment, metabolic syndrome was less common in the lumateperone group (13%) vs. those receiving risperidone (25%).
In addition, 46% of lumateperone patients with metabolic syndrome at baseline no longer had it at the end of the study period. This compared with 25% of patients on risperidone.
The differences in metabolic syndrome conversion rates appeared to be driven by greater reductions in total cholesterol with lumateperone, compared with risperidone (–2.8 mg/dL with lumateperone vs. 4.8 mg/dL with risperidone) and triglycerides (–0.7 mg/dL with lumateperone vs. 20.4 mg/dL with risperidone).
Greater increases in blood glucose were also seen with risperidone (7.7 mg/dL) than with lumateperone (0.9 mg/dL).
The long-term study included 602 patients with stable schizophrenia. All received lumateperone 42 mg, and 197 patients (33%) had metabolic syndrome at baseline.
At the end of the 1-year study, 72 of these patients (36%) no longer met criteria for metabolic syndrome.
“Safest antipsychotic so far”
“Lumateperone seems to be the safest antipsychotic we have seen so far,” Christoph U. Correll, MD, professor of child and adolescent psychiatry, Charité Universitatsmedizin, Berlin, who was also involved in clinical trials of lumateperone, told this news organization.
“It seems to be very safe when it comes to cardiometabolic parameters, and it shows similar reduction in symptoms as risperidone. It is certainly an agent one should consider, particularly when a patient cannot tolerate other medications or may not be in full adherence,” said Dr. Correll, who has a joint appointment as professor of psychiatry and molecular medicine at the Zucker School of Medicine at Hofstra University in Hempstead, New York.
The drug’s safety and efficacy profile would make it a good candidate in patients initiating antipsychotic treatment, but reimbursement issues may be a barrier, at least for now, he added.
He said that the drug may prevent the onset of metabolic side effects and added that once payers are willing to reimburse the drug it should become the “first-line standard of care.”
It is well known that atypical antipsychotics are associated with adverse and rapid metabolic changes. Dr. Correll noted that particularly early-phase and first-episode patients can be “very sensitive” to the side effects of these drugs and often experience rapid weight gain and other adverse metabolic changes. Lumateperone, he added, may help avoid some of this cardiometabolic risk.
Time will tell
Jessica M. Gannon, MD, a psychiatrist at the University of Pittsburgh said in commenting on the findings that the drug’s favorable metabolic profile has previously been reported.
She also noted that there has been some interest in lumateperone because of possible “downstream effects on NMDA-type glutamate receptor activity, a larger binding ratio at dopamine-2:5HT1A receptors than other atypical antipsychotics, and presynaptic D2 partial agonism and a postsynaptic D2 antagonism.”
“This latter feature may explain the reported low extrapyramidal symptom incidence in the clinical trials,” she said .
“While I think future studies and clinical use can help determine how clinically efficacious this medication will be for our patients when compared to others on the market, its favorable metabolic and EPS profile do make it of interest,” added Gannon, who was not involved in researching the drug.
The study was funded by Intra-Cellular Therapies. Dr. Satlin is chief medical officer of Intracellular Therapies. Dr. Correll has been a consultant or advisor to and has received honoraria from Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva.
A version of this article originally appeared on Medscape.com.
A recently approved first-in-class antipsychotic appears to have fewer adverse cardiometabolic effects than standard care with risperidone, new research suggests.
In post hoc analyses of two short-term randomized controlled trials plus an open-label long-term study, patients with schizophrenia on lumateperone (Caplyta, Intra-Cellular Therapies) had reduced rates of metabolic syndrome, compared with their counterparts taking placebo or the antipsychotic risperidone.
In the short-term studies, rates of metabolic syndrome were similar between groups at baseline, but by the end of 4 and 6 weeks of treatment, 25% of patients taking lumateperone no longer met criteria for metabolic syndrome. A similar finding occurred in 36% of patients in the 1-year open label study.
“One of the major advantages that we found during the drug’s development was that it has a very favorable profile with regard to changes in weight, and other [parameters] associated with cardiovascular disease risk, such as elevated glucose and lipids,” study investigator Andrew Satlin, MD, chief medical officer at Intra-Cellular Therapies, New York, told this news organization.
“So we went back to our data and looked to see whether the changes that we saw had an impact on either the development or the resolution of metabolic syndrome in the patients who came into our studies,” he said.
The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
Reduced cholesterol
Lumateperone was approved in December by the Food and Drug Administration. The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems.
The short-term studies included 511 patients randomly assigned to receive lumateperone 42 mg (n = 256 patients) or risperidone 4 mg (n = 255 patients).
At baseline, rates of metabolic syndrome were 16% in the lumateperone group and 19% in the risperidone group. At the end of treatment, metabolic syndrome was less common in the lumateperone group (13%) vs. those receiving risperidone (25%).
In addition, 46% of lumateperone patients with metabolic syndrome at baseline no longer had it at the end of the study period. This compared with 25% of patients on risperidone.
The differences in metabolic syndrome conversion rates appeared to be driven by greater reductions in total cholesterol with lumateperone, compared with risperidone (–2.8 mg/dL with lumateperone vs. 4.8 mg/dL with risperidone) and triglycerides (–0.7 mg/dL with lumateperone vs. 20.4 mg/dL with risperidone).
Greater increases in blood glucose were also seen with risperidone (7.7 mg/dL) than with lumateperone (0.9 mg/dL).
The long-term study included 602 patients with stable schizophrenia. All received lumateperone 42 mg, and 197 patients (33%) had metabolic syndrome at baseline.
At the end of the 1-year study, 72 of these patients (36%) no longer met criteria for metabolic syndrome.
“Safest antipsychotic so far”
“Lumateperone seems to be the safest antipsychotic we have seen so far,” Christoph U. Correll, MD, professor of child and adolescent psychiatry, Charité Universitatsmedizin, Berlin, who was also involved in clinical trials of lumateperone, told this news organization.
“It seems to be very safe when it comes to cardiometabolic parameters, and it shows similar reduction in symptoms as risperidone. It is certainly an agent one should consider, particularly when a patient cannot tolerate other medications or may not be in full adherence,” said Dr. Correll, who has a joint appointment as professor of psychiatry and molecular medicine at the Zucker School of Medicine at Hofstra University in Hempstead, New York.
The drug’s safety and efficacy profile would make it a good candidate in patients initiating antipsychotic treatment, but reimbursement issues may be a barrier, at least for now, he added.
He said that the drug may prevent the onset of metabolic side effects and added that once payers are willing to reimburse the drug it should become the “first-line standard of care.”
It is well known that atypical antipsychotics are associated with adverse and rapid metabolic changes. Dr. Correll noted that particularly early-phase and first-episode patients can be “very sensitive” to the side effects of these drugs and often experience rapid weight gain and other adverse metabolic changes. Lumateperone, he added, may help avoid some of this cardiometabolic risk.
Time will tell
Jessica M. Gannon, MD, a psychiatrist at the University of Pittsburgh said in commenting on the findings that the drug’s favorable metabolic profile has previously been reported.
She also noted that there has been some interest in lumateperone because of possible “downstream effects on NMDA-type glutamate receptor activity, a larger binding ratio at dopamine-2:5HT1A receptors than other atypical antipsychotics, and presynaptic D2 partial agonism and a postsynaptic D2 antagonism.”
“This latter feature may explain the reported low extrapyramidal symptom incidence in the clinical trials,” she said .
“While I think future studies and clinical use can help determine how clinically efficacious this medication will be for our patients when compared to others on the market, its favorable metabolic and EPS profile do make it of interest,” added Gannon, who was not involved in researching the drug.
The study was funded by Intra-Cellular Therapies. Dr. Satlin is chief medical officer of Intracellular Therapies. Dr. Correll has been a consultant or advisor to and has received honoraria from Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva.
A version of this article originally appeared on Medscape.com.
Most rheumatology drugs don’t increase COVID-19 hospitalization risk
The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.
“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”
Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.
In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.
The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.
“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.
As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.
Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.
Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.
“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”
“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”
It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.
“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.
The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.
Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.
Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.
“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”
This article first appeared on Medscape.com.
The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.
“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”
Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.
In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.
The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.
“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.
As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.
Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.
Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.
“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”
“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”
It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.
“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.
The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.
Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.
Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.
“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”
This article first appeared on Medscape.com.
The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.
“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”
Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.
In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.
The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.
“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.
As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.
Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.
Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.
“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”
“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”
It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.
“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.
The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.
Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.
Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.
“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”
This article first appeared on Medscape.com.
A bumpy virtual #ASCO20; Returning to Chicago in 2021?
Called ‘incredibly boring,’ Praised as ‘special’
CYBERSPACE – Hope Rugo, MD, was one of the would-be attendees of the American Society of Clinical Oncology annual meeting who could not access the online event on its first day, Friday, May 29.
“Such a shame – virtual ASCO is nonexistent,” tweeted Rugo, who is from the University of California, San Francisco.
The breast cancer specialist tried for more than hour before finally gaining entry in the late morning.
Not everyone was as successful.
That same day, Arjun Balar, MD, of NYU Langone Health in New York announced on Twitter that he’d quit for the day. “I give up @ASCO. Time for a cocktail.”
Don Dizon, MD, of Brown University in Providence, Rhode Island, tried repeatedly to join the meeting as a live broadcast, using his desktop and laptop computers as well as an iPad. Nothing worked. Limited to seeing data and discussions “after the fact,” Dizon looked to next year, tweeting hopefully: “... fingers crossed for an inperson #ASCO21.”
ASCO did not respond to a request for further information about the technical difficulties of the meeting’s first day.
This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10.
Despite those technical glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing.
At the same time, a Medscape Oncology online meeting poll indicated that nearly half (48%) of the 335 respondents said “no,” they do not envision themselves in person at the real thing in Chicago in 2021. About one fifth (21%) said, “yes, if there is a vaccine.” Roughly 15% said “yes,” and another 15% said “not sure right now.”
What did oncologists miss most with virtual ASCO?
Many said face-to-face (F2F) interactions. Collaboration, networking, and catching up with old friends were some of the stock F2F moments cited as losses.
Others described more idiosyncratic disappointments, including Riyaz Shah, MD, of the Kent Oncology Centre in the UK, who dismissed a future with exclusively virtual meetings.
He tweeted: “Not sustainable. We need to meet F2F. Oncology is an odd one. Exposed to human distress daily (if not hourly). [Very] few people understand what we do, fewer would do it. There aren’t many people we can talk to. I love chewing the cud with my colleagues who are close friends.”
The virtual meeting inspired more social media engagement, but fewer oncologists participated, according to data from social media analytics firm Symplur. This year, 1K users identified as oncologists generated 17.75K tweets. In 2019, 1.3K oncologists put out 15.2K tweets.
Virtual meeting ‘like homework’
George Sledge, MD, of Stanford University, California, asked his 1700 Twitter followers to discuss the virtual ASCO experience, including the spotty functionality of presenter videos (a con) and eating dinner between talks (a pro).
One of his criticisms struck a nerve – that the online meeting was “like homework.”
“ ‘Feels like homework’ is the best expression I [have] read so far!” tweeted Gustavo Gössling, MD, from the Kaplan Oncology Institute in Porto Alegre, Brazil.
Yes, it feels “like studying alone,” agreed Stanford’s Lidia Schapira, MD, in a tweet.
“It’s incredibly boring – let’s bring back F2F next year,” tweeted Ioannis Gounaris, MD, Merck Group, Cambridge, UK, in response to Sledge’s request.
Sledge joined many others in saying that, ultimately, the future should include – and will demand – both virtual and in-person meetings.
What will happen with ASCO next year?
Medscape Medical News asked some virtual attendees whether they envisioned going in person to the ASCO meeting next year in Chicago.
“Counting on it,” said Harold Burstein, MD, PhD, Dana-Farber Cancer Institute, Boston. “But I also recognize that it fully depends on what happens between now and then. Vaccines. Safety of travel. Safety of large, indoor, crowded spaces.”
Despite acknowledging the uncertainty of how things will “play out,” Burstein advised: “Put it on your calendar and make reservations, and make sure the reservations are fully refundable.”
Ahmad Tarhini, MD, from the Moffitt Cancer Center in Tampa, Florida, sounded similarly optimistic: “Hopefully we will have a vaccine by then. I expect the ASCO annual meeting will happen in person in 2021.”
Moffitt colleague Michelle Echevarria Colon, MD, said, “I could see myself attending ... in Chicago in 2021.” And she added: “I think we’ll get to a point where it could happen.”
Others were uncertain.
Ishwaria Subbiah, MD, University of Texas MD Anderson Cancer Center, Houston, said: “If someone told us 6 months ago that our ‘new normal’ would be in this near-total virtual existence, most of us would not have believed them. So it is hard to imagine what our reality will be in a year from now at ASCO 2021.”
Jack West, MD, from City of Hope Comprehensive Cancer Center in Duarte, California, thinks the meeting will be changed for a long time, even if 2021 is a live event.
“While I think that there MIGHT be a live conference, I think it will be many years, if ever, before we see it return to its prior magnitude,” he wrote in an email, echoing remarks previously made by other healthcare professionals about medical meetings in any post–COVID-19 world.
A year from now, said West, “I strongly suspect that we will still be contending with risk of exposure” and that means clinician attendees might, in turn, expose their cancer patients back home.
Despite his wistful “fingers crossed” tweet during ASCO 2020, Brown’s Dizon also recently commented on Medscape that “I wonder whether I will ever sit in a crowded auditorium at an ASCO annual meeting again.”
Sagar Sardesai, MBBS, Ohio State Comprehensive Cancer Center, Columbus, responded: “Unless we have a vaccine that is successful or we can demonstrate enough herd immunity in the United States, I can’t imagine that such large gatherings are a real possibility. We need to protect our vulnerable populations.”
City of Hope’s Cary Presant, MD, acknowledged he is one of those vulnerable people. “In 2021, if the environment is safe for oncologists of my age, I will be in Chicago,” he said. “But with COVID-19 still a threat, I might have to attend only virtually.”
“This year was special”
On social media, MD Anderson’s Vivek Subbiah, MD, did not speculate about next year’s meeting but observed the uniqueness of the current moment.
He tweeted: “The last 8 years of @asco are a blur in my memory. This year #ASCO was special, and I’m sure we will all remember where we were for this year’s meeting.”
Other oncologists praised the accessibility of the virtual meeting.
“The power of a virtual meeting is it creates an unlimited number of seats at the oncology research table. Anyone globally can be involved and that is really special,” said Suneel Kamath, MD, Cleveland Clinic, Ohio.
“Virtual ASCO levels the playing field for oncologists everywhere,” says Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Canada. In a Medscape Commentary, he notes that “attending a typical ASCO meeting is astonishingly cost-prohibitive, especially for colleagues from low- and middle-income countries ... now everybody has the same access to the meeting.”
ASCO made the best out of a bad situation with the expanded virtual meeting, suggested David Henry, MD, Pennsylvania Hospital, Philadelphia, host of MDEdge’s Blood and Cancer podcast, part of the Medscape Professional Network. In an interview with ASCO president Skip Burris, MD, before the meeting, Henry said: “Making lemonade out of lemons. It’ll give us something new and different. What an amazing turn of events.”
With additional reporting by Zosia Chustecka , Liz Neporent, Neil Osterweil, and Jennifer Smith. This article first appeared on Medscape.com.
Called ‘incredibly boring,’ Praised as ‘special’
Called ‘incredibly boring,’ Praised as ‘special’
CYBERSPACE – Hope Rugo, MD, was one of the would-be attendees of the American Society of Clinical Oncology annual meeting who could not access the online event on its first day, Friday, May 29.
“Such a shame – virtual ASCO is nonexistent,” tweeted Rugo, who is from the University of California, San Francisco.
The breast cancer specialist tried for more than hour before finally gaining entry in the late morning.
Not everyone was as successful.
That same day, Arjun Balar, MD, of NYU Langone Health in New York announced on Twitter that he’d quit for the day. “I give up @ASCO. Time for a cocktail.”
Don Dizon, MD, of Brown University in Providence, Rhode Island, tried repeatedly to join the meeting as a live broadcast, using his desktop and laptop computers as well as an iPad. Nothing worked. Limited to seeing data and discussions “after the fact,” Dizon looked to next year, tweeting hopefully: “... fingers crossed for an inperson #ASCO21.”
ASCO did not respond to a request for further information about the technical difficulties of the meeting’s first day.
This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10.
Despite those technical glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing.
At the same time, a Medscape Oncology online meeting poll indicated that nearly half (48%) of the 335 respondents said “no,” they do not envision themselves in person at the real thing in Chicago in 2021. About one fifth (21%) said, “yes, if there is a vaccine.” Roughly 15% said “yes,” and another 15% said “not sure right now.”
What did oncologists miss most with virtual ASCO?
Many said face-to-face (F2F) interactions. Collaboration, networking, and catching up with old friends were some of the stock F2F moments cited as losses.
Others described more idiosyncratic disappointments, including Riyaz Shah, MD, of the Kent Oncology Centre in the UK, who dismissed a future with exclusively virtual meetings.
He tweeted: “Not sustainable. We need to meet F2F. Oncology is an odd one. Exposed to human distress daily (if not hourly). [Very] few people understand what we do, fewer would do it. There aren’t many people we can talk to. I love chewing the cud with my colleagues who are close friends.”
The virtual meeting inspired more social media engagement, but fewer oncologists participated, according to data from social media analytics firm Symplur. This year, 1K users identified as oncologists generated 17.75K tweets. In 2019, 1.3K oncologists put out 15.2K tweets.
Virtual meeting ‘like homework’
George Sledge, MD, of Stanford University, California, asked his 1700 Twitter followers to discuss the virtual ASCO experience, including the spotty functionality of presenter videos (a con) and eating dinner between talks (a pro).
One of his criticisms struck a nerve – that the online meeting was “like homework.”
“ ‘Feels like homework’ is the best expression I [have] read so far!” tweeted Gustavo Gössling, MD, from the Kaplan Oncology Institute in Porto Alegre, Brazil.
Yes, it feels “like studying alone,” agreed Stanford’s Lidia Schapira, MD, in a tweet.
“It’s incredibly boring – let’s bring back F2F next year,” tweeted Ioannis Gounaris, MD, Merck Group, Cambridge, UK, in response to Sledge’s request.
Sledge joined many others in saying that, ultimately, the future should include – and will demand – both virtual and in-person meetings.
What will happen with ASCO next year?
Medscape Medical News asked some virtual attendees whether they envisioned going in person to the ASCO meeting next year in Chicago.
“Counting on it,” said Harold Burstein, MD, PhD, Dana-Farber Cancer Institute, Boston. “But I also recognize that it fully depends on what happens between now and then. Vaccines. Safety of travel. Safety of large, indoor, crowded spaces.”
Despite acknowledging the uncertainty of how things will “play out,” Burstein advised: “Put it on your calendar and make reservations, and make sure the reservations are fully refundable.”
Ahmad Tarhini, MD, from the Moffitt Cancer Center in Tampa, Florida, sounded similarly optimistic: “Hopefully we will have a vaccine by then. I expect the ASCO annual meeting will happen in person in 2021.”
Moffitt colleague Michelle Echevarria Colon, MD, said, “I could see myself attending ... in Chicago in 2021.” And she added: “I think we’ll get to a point where it could happen.”
Others were uncertain.
Ishwaria Subbiah, MD, University of Texas MD Anderson Cancer Center, Houston, said: “If someone told us 6 months ago that our ‘new normal’ would be in this near-total virtual existence, most of us would not have believed them. So it is hard to imagine what our reality will be in a year from now at ASCO 2021.”
Jack West, MD, from City of Hope Comprehensive Cancer Center in Duarte, California, thinks the meeting will be changed for a long time, even if 2021 is a live event.
“While I think that there MIGHT be a live conference, I think it will be many years, if ever, before we see it return to its prior magnitude,” he wrote in an email, echoing remarks previously made by other healthcare professionals about medical meetings in any post–COVID-19 world.
A year from now, said West, “I strongly suspect that we will still be contending with risk of exposure” and that means clinician attendees might, in turn, expose their cancer patients back home.
Despite his wistful “fingers crossed” tweet during ASCO 2020, Brown’s Dizon also recently commented on Medscape that “I wonder whether I will ever sit in a crowded auditorium at an ASCO annual meeting again.”
Sagar Sardesai, MBBS, Ohio State Comprehensive Cancer Center, Columbus, responded: “Unless we have a vaccine that is successful or we can demonstrate enough herd immunity in the United States, I can’t imagine that such large gatherings are a real possibility. We need to protect our vulnerable populations.”
City of Hope’s Cary Presant, MD, acknowledged he is one of those vulnerable people. “In 2021, if the environment is safe for oncologists of my age, I will be in Chicago,” he said. “But with COVID-19 still a threat, I might have to attend only virtually.”
“This year was special”
On social media, MD Anderson’s Vivek Subbiah, MD, did not speculate about next year’s meeting but observed the uniqueness of the current moment.
He tweeted: “The last 8 years of @asco are a blur in my memory. This year #ASCO was special, and I’m sure we will all remember where we were for this year’s meeting.”
Other oncologists praised the accessibility of the virtual meeting.
“The power of a virtual meeting is it creates an unlimited number of seats at the oncology research table. Anyone globally can be involved and that is really special,” said Suneel Kamath, MD, Cleveland Clinic, Ohio.
“Virtual ASCO levels the playing field for oncologists everywhere,” says Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Canada. In a Medscape Commentary, he notes that “attending a typical ASCO meeting is astonishingly cost-prohibitive, especially for colleagues from low- and middle-income countries ... now everybody has the same access to the meeting.”
ASCO made the best out of a bad situation with the expanded virtual meeting, suggested David Henry, MD, Pennsylvania Hospital, Philadelphia, host of MDEdge’s Blood and Cancer podcast, part of the Medscape Professional Network. In an interview with ASCO president Skip Burris, MD, before the meeting, Henry said: “Making lemonade out of lemons. It’ll give us something new and different. What an amazing turn of events.”
With additional reporting by Zosia Chustecka , Liz Neporent, Neil Osterweil, and Jennifer Smith. This article first appeared on Medscape.com.
CYBERSPACE – Hope Rugo, MD, was one of the would-be attendees of the American Society of Clinical Oncology annual meeting who could not access the online event on its first day, Friday, May 29.
“Such a shame – virtual ASCO is nonexistent,” tweeted Rugo, who is from the University of California, San Francisco.
The breast cancer specialist tried for more than hour before finally gaining entry in the late morning.
Not everyone was as successful.
That same day, Arjun Balar, MD, of NYU Langone Health in New York announced on Twitter that he’d quit for the day. “I give up @ASCO. Time for a cocktail.”
Don Dizon, MD, of Brown University in Providence, Rhode Island, tried repeatedly to join the meeting as a live broadcast, using his desktop and laptop computers as well as an iPad. Nothing worked. Limited to seeing data and discussions “after the fact,” Dizon looked to next year, tweeting hopefully: “... fingers crossed for an inperson #ASCO21.”
ASCO did not respond to a request for further information about the technical difficulties of the meeting’s first day.
This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10.
Despite those technical glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing.
At the same time, a Medscape Oncology online meeting poll indicated that nearly half (48%) of the 335 respondents said “no,” they do not envision themselves in person at the real thing in Chicago in 2021. About one fifth (21%) said, “yes, if there is a vaccine.” Roughly 15% said “yes,” and another 15% said “not sure right now.”
What did oncologists miss most with virtual ASCO?
Many said face-to-face (F2F) interactions. Collaboration, networking, and catching up with old friends were some of the stock F2F moments cited as losses.
Others described more idiosyncratic disappointments, including Riyaz Shah, MD, of the Kent Oncology Centre in the UK, who dismissed a future with exclusively virtual meetings.
He tweeted: “Not sustainable. We need to meet F2F. Oncology is an odd one. Exposed to human distress daily (if not hourly). [Very] few people understand what we do, fewer would do it. There aren’t many people we can talk to. I love chewing the cud with my colleagues who are close friends.”
The virtual meeting inspired more social media engagement, but fewer oncologists participated, according to data from social media analytics firm Symplur. This year, 1K users identified as oncologists generated 17.75K tweets. In 2019, 1.3K oncologists put out 15.2K tweets.
Virtual meeting ‘like homework’
George Sledge, MD, of Stanford University, California, asked his 1700 Twitter followers to discuss the virtual ASCO experience, including the spotty functionality of presenter videos (a con) and eating dinner between talks (a pro).
One of his criticisms struck a nerve – that the online meeting was “like homework.”
“ ‘Feels like homework’ is the best expression I [have] read so far!” tweeted Gustavo Gössling, MD, from the Kaplan Oncology Institute in Porto Alegre, Brazil.
Yes, it feels “like studying alone,” agreed Stanford’s Lidia Schapira, MD, in a tweet.
“It’s incredibly boring – let’s bring back F2F next year,” tweeted Ioannis Gounaris, MD, Merck Group, Cambridge, UK, in response to Sledge’s request.
Sledge joined many others in saying that, ultimately, the future should include – and will demand – both virtual and in-person meetings.
What will happen with ASCO next year?
Medscape Medical News asked some virtual attendees whether they envisioned going in person to the ASCO meeting next year in Chicago.
“Counting on it,” said Harold Burstein, MD, PhD, Dana-Farber Cancer Institute, Boston. “But I also recognize that it fully depends on what happens between now and then. Vaccines. Safety of travel. Safety of large, indoor, crowded spaces.”
Despite acknowledging the uncertainty of how things will “play out,” Burstein advised: “Put it on your calendar and make reservations, and make sure the reservations are fully refundable.”
Ahmad Tarhini, MD, from the Moffitt Cancer Center in Tampa, Florida, sounded similarly optimistic: “Hopefully we will have a vaccine by then. I expect the ASCO annual meeting will happen in person in 2021.”
Moffitt colleague Michelle Echevarria Colon, MD, said, “I could see myself attending ... in Chicago in 2021.” And she added: “I think we’ll get to a point where it could happen.”
Others were uncertain.
Ishwaria Subbiah, MD, University of Texas MD Anderson Cancer Center, Houston, said: “If someone told us 6 months ago that our ‘new normal’ would be in this near-total virtual existence, most of us would not have believed them. So it is hard to imagine what our reality will be in a year from now at ASCO 2021.”
Jack West, MD, from City of Hope Comprehensive Cancer Center in Duarte, California, thinks the meeting will be changed for a long time, even if 2021 is a live event.
“While I think that there MIGHT be a live conference, I think it will be many years, if ever, before we see it return to its prior magnitude,” he wrote in an email, echoing remarks previously made by other healthcare professionals about medical meetings in any post–COVID-19 world.
A year from now, said West, “I strongly suspect that we will still be contending with risk of exposure” and that means clinician attendees might, in turn, expose their cancer patients back home.
Despite his wistful “fingers crossed” tweet during ASCO 2020, Brown’s Dizon also recently commented on Medscape that “I wonder whether I will ever sit in a crowded auditorium at an ASCO annual meeting again.”
Sagar Sardesai, MBBS, Ohio State Comprehensive Cancer Center, Columbus, responded: “Unless we have a vaccine that is successful or we can demonstrate enough herd immunity in the United States, I can’t imagine that such large gatherings are a real possibility. We need to protect our vulnerable populations.”
City of Hope’s Cary Presant, MD, acknowledged he is one of those vulnerable people. “In 2021, if the environment is safe for oncologists of my age, I will be in Chicago,” he said. “But with COVID-19 still a threat, I might have to attend only virtually.”
“This year was special”
On social media, MD Anderson’s Vivek Subbiah, MD, did not speculate about next year’s meeting but observed the uniqueness of the current moment.
He tweeted: “The last 8 years of @asco are a blur in my memory. This year #ASCO was special, and I’m sure we will all remember where we were for this year’s meeting.”
Other oncologists praised the accessibility of the virtual meeting.
“The power of a virtual meeting is it creates an unlimited number of seats at the oncology research table. Anyone globally can be involved and that is really special,” said Suneel Kamath, MD, Cleveland Clinic, Ohio.
“Virtual ASCO levels the playing field for oncologists everywhere,” says Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Canada. In a Medscape Commentary, he notes that “attending a typical ASCO meeting is astonishingly cost-prohibitive, especially for colleagues from low- and middle-income countries ... now everybody has the same access to the meeting.”
ASCO made the best out of a bad situation with the expanded virtual meeting, suggested David Henry, MD, Pennsylvania Hospital, Philadelphia, host of MDEdge’s Blood and Cancer podcast, part of the Medscape Professional Network. In an interview with ASCO president Skip Burris, MD, before the meeting, Henry said: “Making lemonade out of lemons. It’ll give us something new and different. What an amazing turn of events.”
With additional reporting by Zosia Chustecka , Liz Neporent, Neil Osterweil, and Jennifer Smith. This article first appeared on Medscape.com.
FROM ASCO 2020
Newest oral DMTs haven’t yet made a big impact in the MS world
So far, it’s more like a ripple, according to a study of neurologists’ prescribing patterns. “The recently approved therapies will initially be niched as later-line options,” predicted Virginia R. Schobel, MSc, nephrology franchise head at Spherix Global Insights, an independent market intelligence firm in Exton, Pa.
At the virtual annual meeting of the Consortium of Multiple Sclerosis Centers, Ms. Schobel presented the results of a retrospective chart audit Spherix conducted in February 2020 of 1,006 patients with MS who were switched to a new DMT by 199 U.S. participating neurologists within the previous 3 months. About 72% of the switchers had relapsing remitting MS (RRMS).
Assessing the three new oral DMTs
The purpose of the study was to gain an understanding of the early adoption patterns for the three recently approved oral DMTs: siponimod (Mayzent), cladribine (Mavenclad), and diroximel fumarate (Vumerity).
The first surprise was that only 41% of medication switches to a new DMT among the RRMS group were to oral DMTs; that’s a substantially lower proportion than in prior Spherix chart audits. Instead, the most popular switch was to ocrelizumab (Ocrevus), a monoclonal antibody.
“Things to keep in mind when we see the switch shares for the newer products are just how crowded this market has become and how much Ocrevus has really changed the market,” Ms. Schobel explained in an interview. “Ocrevus has become increasingly dominant in the RRMS segment, so that now there are six oral DMTs competing among themselves for a relatively limited pool of patients.”
Because of grandfathering by the Food and Drug Administration, most of the oral DMTs now share identical indications for clinically isolated syndrome, RRMS, and active secondary progressive MS. Ocrevus, she noted, has the same indications.
Only 1% of MS patients who switched to a different DMT in late 2019 or early 2020 moved to diroximel fumarate. Three percent switched to siponimod, and another 3% switched to cladribine. Switches to the three older, established oral DMTs were collectively five times more common, with 15% of patients moving to dimethyl fumarate (Tecfidera), 11% to fingolimod (Gilenya), and 9% to teriflunomide (Aubagio).
Ms. Schobel said that the three latest oral DMTs offer advantages over the older ones in terms of various combinations of efficacy, dosing schedule, and/or tolerability, which may make them attractive options as first-line therapy. She predicted that, over time as neurologists gain increasing familiarity with these drugs as first line, they will also gradually become more comfortable in turning to them as switch options.
First-time switches to an oral DMT among patients with RRMS were most often made in search of improved efficacy. Neurologists cited this as their main reason for 73% of switches to cladribine and 36% of switches to teriflunomide, with the other oral agents falling at various points in between. A switch to fingolimod was most often driven by a wish for a high-efficacy DMT with once-daily oral dosing. Improved tolerability figured prominently in switches to teriflunomide, and even more so in the relatively few changes to diroximel fumarate.
Drug switching in the pandemic era
Ms. Schobel said Spherix has been serially tracking neurologists’ prescribing for MS during the COVID-19 pandemic, which has clearly had an enormous dampening effect on medication switching. In mid-April, neurologists’ switching volume was down by 70%, compared with prepandemic figures. A slow recovery began in May, but by the end of the month prescription-switching volume was still down by 52%.
Of the neurologist prescriptions that are being run for switching thus far during the pandemic, 82% are being done via telemedicine. Therein hangs a tale, since neurology doesn’t readily lend itself to practice by telemedicine. Indeed, neurologists are using telemedicine to a lesser extent than physicians in the other specialties that Spherix monitors, according to Ms. Schobel. “COVID is definitely changing the MS world. Within MS, drug switching is now much more likely to involve a switch to a DMT that doesn’t impact the immune response and is not immunosuppressant, such as an injectable interferon or glatiramer acetate,” she said. “In this COVID world, safety and conservatism may end up trumping the move toward ‘time is brain’ which we’ve been talking so much about in recent years: the importance of getting patients on high-efficacy DMTs from the start in order to give them the best chance for positive outcomes.”
Ms. Schobel noted that Spherix received no industry funding to conduct these studies.
So far, it’s more like a ripple, according to a study of neurologists’ prescribing patterns. “The recently approved therapies will initially be niched as later-line options,” predicted Virginia R. Schobel, MSc, nephrology franchise head at Spherix Global Insights, an independent market intelligence firm in Exton, Pa.
At the virtual annual meeting of the Consortium of Multiple Sclerosis Centers, Ms. Schobel presented the results of a retrospective chart audit Spherix conducted in February 2020 of 1,006 patients with MS who were switched to a new DMT by 199 U.S. participating neurologists within the previous 3 months. About 72% of the switchers had relapsing remitting MS (RRMS).
Assessing the three new oral DMTs
The purpose of the study was to gain an understanding of the early adoption patterns for the three recently approved oral DMTs: siponimod (Mayzent), cladribine (Mavenclad), and diroximel fumarate (Vumerity).
The first surprise was that only 41% of medication switches to a new DMT among the RRMS group were to oral DMTs; that’s a substantially lower proportion than in prior Spherix chart audits. Instead, the most popular switch was to ocrelizumab (Ocrevus), a monoclonal antibody.
“Things to keep in mind when we see the switch shares for the newer products are just how crowded this market has become and how much Ocrevus has really changed the market,” Ms. Schobel explained in an interview. “Ocrevus has become increasingly dominant in the RRMS segment, so that now there are six oral DMTs competing among themselves for a relatively limited pool of patients.”
Because of grandfathering by the Food and Drug Administration, most of the oral DMTs now share identical indications for clinically isolated syndrome, RRMS, and active secondary progressive MS. Ocrevus, she noted, has the same indications.
Only 1% of MS patients who switched to a different DMT in late 2019 or early 2020 moved to diroximel fumarate. Three percent switched to siponimod, and another 3% switched to cladribine. Switches to the three older, established oral DMTs were collectively five times more common, with 15% of patients moving to dimethyl fumarate (Tecfidera), 11% to fingolimod (Gilenya), and 9% to teriflunomide (Aubagio).
Ms. Schobel said that the three latest oral DMTs offer advantages over the older ones in terms of various combinations of efficacy, dosing schedule, and/or tolerability, which may make them attractive options as first-line therapy. She predicted that, over time as neurologists gain increasing familiarity with these drugs as first line, they will also gradually become more comfortable in turning to them as switch options.
First-time switches to an oral DMT among patients with RRMS were most often made in search of improved efficacy. Neurologists cited this as their main reason for 73% of switches to cladribine and 36% of switches to teriflunomide, with the other oral agents falling at various points in between. A switch to fingolimod was most often driven by a wish for a high-efficacy DMT with once-daily oral dosing. Improved tolerability figured prominently in switches to teriflunomide, and even more so in the relatively few changes to diroximel fumarate.
Drug switching in the pandemic era
Ms. Schobel said Spherix has been serially tracking neurologists’ prescribing for MS during the COVID-19 pandemic, which has clearly had an enormous dampening effect on medication switching. In mid-April, neurologists’ switching volume was down by 70%, compared with prepandemic figures. A slow recovery began in May, but by the end of the month prescription-switching volume was still down by 52%.
Of the neurologist prescriptions that are being run for switching thus far during the pandemic, 82% are being done via telemedicine. Therein hangs a tale, since neurology doesn’t readily lend itself to practice by telemedicine. Indeed, neurologists are using telemedicine to a lesser extent than physicians in the other specialties that Spherix monitors, according to Ms. Schobel. “COVID is definitely changing the MS world. Within MS, drug switching is now much more likely to involve a switch to a DMT that doesn’t impact the immune response and is not immunosuppressant, such as an injectable interferon or glatiramer acetate,” she said. “In this COVID world, safety and conservatism may end up trumping the move toward ‘time is brain’ which we’ve been talking so much about in recent years: the importance of getting patients on high-efficacy DMTs from the start in order to give them the best chance for positive outcomes.”
Ms. Schobel noted that Spherix received no industry funding to conduct these studies.
So far, it’s more like a ripple, according to a study of neurologists’ prescribing patterns. “The recently approved therapies will initially be niched as later-line options,” predicted Virginia R. Schobel, MSc, nephrology franchise head at Spherix Global Insights, an independent market intelligence firm in Exton, Pa.
At the virtual annual meeting of the Consortium of Multiple Sclerosis Centers, Ms. Schobel presented the results of a retrospective chart audit Spherix conducted in February 2020 of 1,006 patients with MS who were switched to a new DMT by 199 U.S. participating neurologists within the previous 3 months. About 72% of the switchers had relapsing remitting MS (RRMS).
Assessing the three new oral DMTs
The purpose of the study was to gain an understanding of the early adoption patterns for the three recently approved oral DMTs: siponimod (Mayzent), cladribine (Mavenclad), and diroximel fumarate (Vumerity).
The first surprise was that only 41% of medication switches to a new DMT among the RRMS group were to oral DMTs; that’s a substantially lower proportion than in prior Spherix chart audits. Instead, the most popular switch was to ocrelizumab (Ocrevus), a monoclonal antibody.
“Things to keep in mind when we see the switch shares for the newer products are just how crowded this market has become and how much Ocrevus has really changed the market,” Ms. Schobel explained in an interview. “Ocrevus has become increasingly dominant in the RRMS segment, so that now there are six oral DMTs competing among themselves for a relatively limited pool of patients.”
Because of grandfathering by the Food and Drug Administration, most of the oral DMTs now share identical indications for clinically isolated syndrome, RRMS, and active secondary progressive MS. Ocrevus, she noted, has the same indications.
Only 1% of MS patients who switched to a different DMT in late 2019 or early 2020 moved to diroximel fumarate. Three percent switched to siponimod, and another 3% switched to cladribine. Switches to the three older, established oral DMTs were collectively five times more common, with 15% of patients moving to dimethyl fumarate (Tecfidera), 11% to fingolimod (Gilenya), and 9% to teriflunomide (Aubagio).
Ms. Schobel said that the three latest oral DMTs offer advantages over the older ones in terms of various combinations of efficacy, dosing schedule, and/or tolerability, which may make them attractive options as first-line therapy. She predicted that, over time as neurologists gain increasing familiarity with these drugs as first line, they will also gradually become more comfortable in turning to them as switch options.
First-time switches to an oral DMT among patients with RRMS were most often made in search of improved efficacy. Neurologists cited this as their main reason for 73% of switches to cladribine and 36% of switches to teriflunomide, with the other oral agents falling at various points in between. A switch to fingolimod was most often driven by a wish for a high-efficacy DMT with once-daily oral dosing. Improved tolerability figured prominently in switches to teriflunomide, and even more so in the relatively few changes to diroximel fumarate.
Drug switching in the pandemic era
Ms. Schobel said Spherix has been serially tracking neurologists’ prescribing for MS during the COVID-19 pandemic, which has clearly had an enormous dampening effect on medication switching. In mid-April, neurologists’ switching volume was down by 70%, compared with prepandemic figures. A slow recovery began in May, but by the end of the month prescription-switching volume was still down by 52%.
Of the neurologist prescriptions that are being run for switching thus far during the pandemic, 82% are being done via telemedicine. Therein hangs a tale, since neurology doesn’t readily lend itself to practice by telemedicine. Indeed, neurologists are using telemedicine to a lesser extent than physicians in the other specialties that Spherix monitors, according to Ms. Schobel. “COVID is definitely changing the MS world. Within MS, drug switching is now much more likely to involve a switch to a DMT that doesn’t impact the immune response and is not immunosuppressant, such as an injectable interferon or glatiramer acetate,” she said. “In this COVID world, safety and conservatism may end up trumping the move toward ‘time is brain’ which we’ve been talking so much about in recent years: the importance of getting patients on high-efficacy DMTs from the start in order to give them the best chance for positive outcomes.”
Ms. Schobel noted that Spherix received no industry funding to conduct these studies.
FROM CMSC 2020
‘Promising’ durvalumab results spark phase 3 trial in mesothelioma
Adding durvalumab to first-line pemetrexed and cisplatin improved survival in patients with unresectable malignant pleural mesothelioma (MPM) in a phase 2 trial, compared with historical controls who received only pemetrexed and cisplatin.
The median overall survival was 20.4 months in patients who received durvalumab plus pemetrexed-cisplatin. This is significantly longer than the median overall survival of 12.1 months (P = .0014) observed with pemetrexed-cisplatin in a prior phase 3 study (J Clin Oncol. 2003 Jul 15;21[14]:2636-44).
The new phase 2 results are “promising,” said lead investigator Patrick Forde, MBBCh, director of the thoracic cancer clinical research program at Johns Hopkins University in Baltimore.
He presented the results as part of the American Society of Clinical Oncology virtual scientific program.
Dr. Forde noted that a phase 3 trial directly comparing pemetrexed-cisplatin plus durvalumab to pemetrexed-cisplatin will begin recruiting this year. The trial is a collaboration between U.S. investigators and Australian researchers who reported their own phase 2 results with durvalumab plus pemetrexed-cisplatin in 2018 (J Thorac Oncol. 2018 Oct;13[10]:S338-339).
Study details
Dr. Forde’s phase 2 study enrolled 55 patients with treatment-naive, unresectable MPM. Their median age was 68 years (range, 35-83 years), and 45 (82%) were men. All had an Eastern Cooperative Oncology Group performance status of 0-1.
Epithelioid mesothelioma was the histologic subtype in three-quarters of patients. “It was a fairly typical mesothelioma population,” Dr. Forde said.
The patients received durvalumab at 1,120 mg plus pemetrexed at 500 mg/m2 and cisplatin at 75 mg/m2 every 3 weeks for up to six cycles. Carboplatin was substituted when cisplatin was contraindicated or patients developed toxicities.
All but one patient had stable or responding disease on radiography and went on to durvalumab maintenance, also given at 1,120 mg every 3 weeks, for up to 1 year from study entry.
Results
Dr. Forde said this study had 90% power to detect a 58% improvement in median overall survival, from the 12.1 months seen in historical controls to 19 months, which was the goal of this study.
It was a positive study, he said, as the median overall survival was 20.4 months (P = .0014).
The overall survival rate was 87.2% at 6 months, 70.4% at 12 months, and 44.2% at 24 months. The progression-free survival rate was 69.1% at 6 months, 16.4% at 12 months, and 10.9% at 24 months.
The overall response rate was 56.4%, which comprised 31 partial responses. Forty percent of patients (n = 22) had stable disease. One patient had progressive disease, and one was not evaluable (1.8% each).
To help with future patient selection, the researchers looked for baseline biomarkers that predicted response. Tumor PD-L1 expression, tumor mutation burden, and other potential candidates haven’t worked out so far, but the work continues, Dr. Forde said.
He noted that many of the adverse events in this trial are those typically seen with platinum-based chemotherapy.
Grade 3/4 treatment-emergent adverse events included anemia (n = 14), fatigue (n = 4), decreased appetite (n = 1), and hypomagnesemia (n = 1).
The most common grade 1/2 adverse events of special interest were hypothyroidism (n = 7), rash (n = 5), pruritus (n = 3), AST elevation (n = 3), and hyperthyroidism (n = 3).
Putting the results in context
Given the role of inflammation in MPM, durvalumab is among several immunotherapies under investigation for the disease.
A phase 3 French trial showed MPM patients had a median overall survival of 18.8 months with pemetrexed-cisplatin plus bevacizumab versus 16.1 months with pemetrexed-cisplatin only (Lancet. 2016 Apr 2;387[10026]:1405-1414).
The higher overall survival in the French study’s pemetrexed-cisplatin arm, compared with the 2003 trial results, is likely due to the use of modern second-line options, said Marjorie Zauderer, MD, codirector of the mesothelioma program at Memorial Sloan Kettering Cancer Center in New York, who was the discussant for Dr. Forde’s presentation.
“I think the improvement in overall survival presented by Dr. Forde is potentially clinically meaningful,” she said, but it was “well within the 95% confidence interval” of the bevacizumab trial. Even so, “I look forward” to the phase 3 results, she said.
Dr. Zauderer also pointed out an April press release from Bristol Myers Squibb that reported improved survival over pemetrexed-cisplatin with two of the company’s immunotherapies, nivolumab and ipilimumab, not as additions but as replacement first-line therapy. However, the randomized trial data haven’t been released yet. “We are all eager to evaluate this option further,” she said.
AstraZeneca, maker of durvalumab, funded the current study. Dr. Forde is an adviser for the company and reported research funding. Dr. Zauderer reported a relationship with Roche, which markets bevacizumab through its subsidiary, Genentech. She also disclosed research funding from Bristol Myers Squibb.
SOURCE: Forde PM et al. ASCO 2020, Abstract 9003.
Adding durvalumab to first-line pemetrexed and cisplatin improved survival in patients with unresectable malignant pleural mesothelioma (MPM) in a phase 2 trial, compared with historical controls who received only pemetrexed and cisplatin.
The median overall survival was 20.4 months in patients who received durvalumab plus pemetrexed-cisplatin. This is significantly longer than the median overall survival of 12.1 months (P = .0014) observed with pemetrexed-cisplatin in a prior phase 3 study (J Clin Oncol. 2003 Jul 15;21[14]:2636-44).
The new phase 2 results are “promising,” said lead investigator Patrick Forde, MBBCh, director of the thoracic cancer clinical research program at Johns Hopkins University in Baltimore.
He presented the results as part of the American Society of Clinical Oncology virtual scientific program.
Dr. Forde noted that a phase 3 trial directly comparing pemetrexed-cisplatin plus durvalumab to pemetrexed-cisplatin will begin recruiting this year. The trial is a collaboration between U.S. investigators and Australian researchers who reported their own phase 2 results with durvalumab plus pemetrexed-cisplatin in 2018 (J Thorac Oncol. 2018 Oct;13[10]:S338-339).
Study details
Dr. Forde’s phase 2 study enrolled 55 patients with treatment-naive, unresectable MPM. Their median age was 68 years (range, 35-83 years), and 45 (82%) were men. All had an Eastern Cooperative Oncology Group performance status of 0-1.
Epithelioid mesothelioma was the histologic subtype in three-quarters of patients. “It was a fairly typical mesothelioma population,” Dr. Forde said.
The patients received durvalumab at 1,120 mg plus pemetrexed at 500 mg/m2 and cisplatin at 75 mg/m2 every 3 weeks for up to six cycles. Carboplatin was substituted when cisplatin was contraindicated or patients developed toxicities.
All but one patient had stable or responding disease on radiography and went on to durvalumab maintenance, also given at 1,120 mg every 3 weeks, for up to 1 year from study entry.
Results
Dr. Forde said this study had 90% power to detect a 58% improvement in median overall survival, from the 12.1 months seen in historical controls to 19 months, which was the goal of this study.
It was a positive study, he said, as the median overall survival was 20.4 months (P = .0014).
The overall survival rate was 87.2% at 6 months, 70.4% at 12 months, and 44.2% at 24 months. The progression-free survival rate was 69.1% at 6 months, 16.4% at 12 months, and 10.9% at 24 months.
The overall response rate was 56.4%, which comprised 31 partial responses. Forty percent of patients (n = 22) had stable disease. One patient had progressive disease, and one was not evaluable (1.8% each).
To help with future patient selection, the researchers looked for baseline biomarkers that predicted response. Tumor PD-L1 expression, tumor mutation burden, and other potential candidates haven’t worked out so far, but the work continues, Dr. Forde said.
He noted that many of the adverse events in this trial are those typically seen with platinum-based chemotherapy.
Grade 3/4 treatment-emergent adverse events included anemia (n = 14), fatigue (n = 4), decreased appetite (n = 1), and hypomagnesemia (n = 1).
The most common grade 1/2 adverse events of special interest were hypothyroidism (n = 7), rash (n = 5), pruritus (n = 3), AST elevation (n = 3), and hyperthyroidism (n = 3).
Putting the results in context
Given the role of inflammation in MPM, durvalumab is among several immunotherapies under investigation for the disease.
A phase 3 French trial showed MPM patients had a median overall survival of 18.8 months with pemetrexed-cisplatin plus bevacizumab versus 16.1 months with pemetrexed-cisplatin only (Lancet. 2016 Apr 2;387[10026]:1405-1414).
The higher overall survival in the French study’s pemetrexed-cisplatin arm, compared with the 2003 trial results, is likely due to the use of modern second-line options, said Marjorie Zauderer, MD, codirector of the mesothelioma program at Memorial Sloan Kettering Cancer Center in New York, who was the discussant for Dr. Forde’s presentation.
“I think the improvement in overall survival presented by Dr. Forde is potentially clinically meaningful,” she said, but it was “well within the 95% confidence interval” of the bevacizumab trial. Even so, “I look forward” to the phase 3 results, she said.
Dr. Zauderer also pointed out an April press release from Bristol Myers Squibb that reported improved survival over pemetrexed-cisplatin with two of the company’s immunotherapies, nivolumab and ipilimumab, not as additions but as replacement first-line therapy. However, the randomized trial data haven’t been released yet. “We are all eager to evaluate this option further,” she said.
AstraZeneca, maker of durvalumab, funded the current study. Dr. Forde is an adviser for the company and reported research funding. Dr. Zauderer reported a relationship with Roche, which markets bevacizumab through its subsidiary, Genentech. She also disclosed research funding from Bristol Myers Squibb.
SOURCE: Forde PM et al. ASCO 2020, Abstract 9003.
Adding durvalumab to first-line pemetrexed and cisplatin improved survival in patients with unresectable malignant pleural mesothelioma (MPM) in a phase 2 trial, compared with historical controls who received only pemetrexed and cisplatin.
The median overall survival was 20.4 months in patients who received durvalumab plus pemetrexed-cisplatin. This is significantly longer than the median overall survival of 12.1 months (P = .0014) observed with pemetrexed-cisplatin in a prior phase 3 study (J Clin Oncol. 2003 Jul 15;21[14]:2636-44).
The new phase 2 results are “promising,” said lead investigator Patrick Forde, MBBCh, director of the thoracic cancer clinical research program at Johns Hopkins University in Baltimore.
He presented the results as part of the American Society of Clinical Oncology virtual scientific program.
Dr. Forde noted that a phase 3 trial directly comparing pemetrexed-cisplatin plus durvalumab to pemetrexed-cisplatin will begin recruiting this year. The trial is a collaboration between U.S. investigators and Australian researchers who reported their own phase 2 results with durvalumab plus pemetrexed-cisplatin in 2018 (J Thorac Oncol. 2018 Oct;13[10]:S338-339).
Study details
Dr. Forde’s phase 2 study enrolled 55 patients with treatment-naive, unresectable MPM. Their median age was 68 years (range, 35-83 years), and 45 (82%) were men. All had an Eastern Cooperative Oncology Group performance status of 0-1.
Epithelioid mesothelioma was the histologic subtype in three-quarters of patients. “It was a fairly typical mesothelioma population,” Dr. Forde said.
The patients received durvalumab at 1,120 mg plus pemetrexed at 500 mg/m2 and cisplatin at 75 mg/m2 every 3 weeks for up to six cycles. Carboplatin was substituted when cisplatin was contraindicated or patients developed toxicities.
All but one patient had stable or responding disease on radiography and went on to durvalumab maintenance, also given at 1,120 mg every 3 weeks, for up to 1 year from study entry.
Results
Dr. Forde said this study had 90% power to detect a 58% improvement in median overall survival, from the 12.1 months seen in historical controls to 19 months, which was the goal of this study.
It was a positive study, he said, as the median overall survival was 20.4 months (P = .0014).
The overall survival rate was 87.2% at 6 months, 70.4% at 12 months, and 44.2% at 24 months. The progression-free survival rate was 69.1% at 6 months, 16.4% at 12 months, and 10.9% at 24 months.
The overall response rate was 56.4%, which comprised 31 partial responses. Forty percent of patients (n = 22) had stable disease. One patient had progressive disease, and one was not evaluable (1.8% each).
To help with future patient selection, the researchers looked for baseline biomarkers that predicted response. Tumor PD-L1 expression, tumor mutation burden, and other potential candidates haven’t worked out so far, but the work continues, Dr. Forde said.
He noted that many of the adverse events in this trial are those typically seen with platinum-based chemotherapy.
Grade 3/4 treatment-emergent adverse events included anemia (n = 14), fatigue (n = 4), decreased appetite (n = 1), and hypomagnesemia (n = 1).
The most common grade 1/2 adverse events of special interest were hypothyroidism (n = 7), rash (n = 5), pruritus (n = 3), AST elevation (n = 3), and hyperthyroidism (n = 3).
Putting the results in context
Given the role of inflammation in MPM, durvalumab is among several immunotherapies under investigation for the disease.
A phase 3 French trial showed MPM patients had a median overall survival of 18.8 months with pemetrexed-cisplatin plus bevacizumab versus 16.1 months with pemetrexed-cisplatin only (Lancet. 2016 Apr 2;387[10026]:1405-1414).
The higher overall survival in the French study’s pemetrexed-cisplatin arm, compared with the 2003 trial results, is likely due to the use of modern second-line options, said Marjorie Zauderer, MD, codirector of the mesothelioma program at Memorial Sloan Kettering Cancer Center in New York, who was the discussant for Dr. Forde’s presentation.
“I think the improvement in overall survival presented by Dr. Forde is potentially clinically meaningful,” she said, but it was “well within the 95% confidence interval” of the bevacizumab trial. Even so, “I look forward” to the phase 3 results, she said.
Dr. Zauderer also pointed out an April press release from Bristol Myers Squibb that reported improved survival over pemetrexed-cisplatin with two of the company’s immunotherapies, nivolumab and ipilimumab, not as additions but as replacement first-line therapy. However, the randomized trial data haven’t been released yet. “We are all eager to evaluate this option further,” she said.
AstraZeneca, maker of durvalumab, funded the current study. Dr. Forde is an adviser for the company and reported research funding. Dr. Zauderer reported a relationship with Roche, which markets bevacizumab through its subsidiary, Genentech. She also disclosed research funding from Bristol Myers Squibb.
SOURCE: Forde PM et al. ASCO 2020, Abstract 9003.
FROM ASCO 2020
Celecoxib ‘should not be used’ as adjuvant therapy for stage III colon cancer
results of the phase 3 CALGB/SWOG 80702 trial showed.
The trial included 2,526 patients randomized to either 6 or 12 cycles of adjuvant FOLFOX with either celecoxib or placebo. The 3-year disease-free survival (DFS) rate was 76.3% for patients on celecoxib and 73.4% for those on placebo. The 5-year overall survival (OS) was 84% and 81.8%, respectively.
“The addition of celecoxib to FOLFOX adjuvant therapy in stage III colon cancer did not significantly improve disease-free or overall survival,” Jeffrey A. Meyerhardt, MD, of the Dana-Farber Cancer Institute in Boston, said while presenting the results as part of the American Society of Clinical Oncology virtual scientific program.
“We did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for disease-free survival. Similarly, we did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for overall survival,” Dr. Meyerhardt said.
“Simply put, celecoxib should not be used for the secondary prevention of colon cancer,” said invited discussant Christopher Lieu, MD, of the University of Colorado Cancer Center, Aurora.
Trial details
The 80702 trial was designed to test whether the COX-2 inhibitor celecoxib could help further reduce the risk of recurrence when added to adjuvant chemotherapy with 3 or 6 months of FOLFOX. Data on the FOLFOX portion of the trial were previously reported as part of the International Duration Evaluation of Adjuvant Therapy collaboration (N Engl J Med. 2018;378:1177-88).
The trial enrolled 2,526 patients with resected stage III colon cancer. They were randomized to receive 3 or 6 months (6 or 12 cycles) of FOLFOX with either concurrent celecoxib at 400 mg daily (n = 1,265) or placebo (n = 1,261) for 3 years from the start of the trial.
The primary endpoint of 3-year DFS did not differ between the groups (hazard ratio, 0.90; P = .16). Likewise, 5-year OS rates did not differ significantly (HR, 0.89; P = .22).
As Dr. Meyerhardt said, there were no significant interactions detected among any subgroups for DFS or OS, including by age, N or T stage, risk group, concurrent low-dose aspirin use, sex, race/ethnicity, baseline performance status, FOLFOX duration, body mass index, or tumor location.
Rates of toxicities were similar between the groups, except for a higher incidence of hypertension of any grade with celecoxib during FOLFOX therapy (14.6% vs. 10.9%, P = .01) and a grade 2 or greater creatinine increase with celecoxib after FOLFOX (1.7% vs. 0.5%, P = .01).
About 40% of patients completed all 3 years of celecoxib or placebo. Reasons for discontinuation included recurrent disease, adverse events, patient withdrawal from the study, physician decision, or other complicating disease.
Why didn’t it work?
Previous studies have indicated that aspirin and cyclooxygenase (COX)-2 inhibitors are associated with a reduced risk of colorectal polyps and cancer, Dr. Lieu said. So why didn’t celecoxib improve survival in the current trial?
“There are obviously COX-1 and COX-independent targets that aspirin hit that celecoxib does not, and its survival impact of affecting these targets is still largely unclear,” Dr. Lieu said.
He added that ongoing trials – including the Add-Aspirin and ASCOLT studies – should provide more insight.
The current trial was sponsored by the Alliance for Clinical Trials in Oncology in collaboration with the National Cancer Institute. Pfizer provided the celecoxib and placebo. Dr. Meyerhardt disclosed relationships with Cota Healthcare, Taiho Pharmaceutical, and Array BioPharma. Dr. Lieu disclosed relationships with Foundation Medicine, Ipsen, Merck, and Immune Design.
SOURCE: Meyerhardt JA et al. ASCO 2020, Abstract 4003.
results of the phase 3 CALGB/SWOG 80702 trial showed.
The trial included 2,526 patients randomized to either 6 or 12 cycles of adjuvant FOLFOX with either celecoxib or placebo. The 3-year disease-free survival (DFS) rate was 76.3% for patients on celecoxib and 73.4% for those on placebo. The 5-year overall survival (OS) was 84% and 81.8%, respectively.
“The addition of celecoxib to FOLFOX adjuvant therapy in stage III colon cancer did not significantly improve disease-free or overall survival,” Jeffrey A. Meyerhardt, MD, of the Dana-Farber Cancer Institute in Boston, said while presenting the results as part of the American Society of Clinical Oncology virtual scientific program.
“We did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for disease-free survival. Similarly, we did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for overall survival,” Dr. Meyerhardt said.
“Simply put, celecoxib should not be used for the secondary prevention of colon cancer,” said invited discussant Christopher Lieu, MD, of the University of Colorado Cancer Center, Aurora.
Trial details
The 80702 trial was designed to test whether the COX-2 inhibitor celecoxib could help further reduce the risk of recurrence when added to adjuvant chemotherapy with 3 or 6 months of FOLFOX. Data on the FOLFOX portion of the trial were previously reported as part of the International Duration Evaluation of Adjuvant Therapy collaboration (N Engl J Med. 2018;378:1177-88).
The trial enrolled 2,526 patients with resected stage III colon cancer. They were randomized to receive 3 or 6 months (6 or 12 cycles) of FOLFOX with either concurrent celecoxib at 400 mg daily (n = 1,265) or placebo (n = 1,261) for 3 years from the start of the trial.
The primary endpoint of 3-year DFS did not differ between the groups (hazard ratio, 0.90; P = .16). Likewise, 5-year OS rates did not differ significantly (HR, 0.89; P = .22).
As Dr. Meyerhardt said, there were no significant interactions detected among any subgroups for DFS or OS, including by age, N or T stage, risk group, concurrent low-dose aspirin use, sex, race/ethnicity, baseline performance status, FOLFOX duration, body mass index, or tumor location.
Rates of toxicities were similar between the groups, except for a higher incidence of hypertension of any grade with celecoxib during FOLFOX therapy (14.6% vs. 10.9%, P = .01) and a grade 2 or greater creatinine increase with celecoxib after FOLFOX (1.7% vs. 0.5%, P = .01).
About 40% of patients completed all 3 years of celecoxib or placebo. Reasons for discontinuation included recurrent disease, adverse events, patient withdrawal from the study, physician decision, or other complicating disease.
Why didn’t it work?
Previous studies have indicated that aspirin and cyclooxygenase (COX)-2 inhibitors are associated with a reduced risk of colorectal polyps and cancer, Dr. Lieu said. So why didn’t celecoxib improve survival in the current trial?
“There are obviously COX-1 and COX-independent targets that aspirin hit that celecoxib does not, and its survival impact of affecting these targets is still largely unclear,” Dr. Lieu said.
He added that ongoing trials – including the Add-Aspirin and ASCOLT studies – should provide more insight.
The current trial was sponsored by the Alliance for Clinical Trials in Oncology in collaboration with the National Cancer Institute. Pfizer provided the celecoxib and placebo. Dr. Meyerhardt disclosed relationships with Cota Healthcare, Taiho Pharmaceutical, and Array BioPharma. Dr. Lieu disclosed relationships with Foundation Medicine, Ipsen, Merck, and Immune Design.
SOURCE: Meyerhardt JA et al. ASCO 2020, Abstract 4003.
results of the phase 3 CALGB/SWOG 80702 trial showed.
The trial included 2,526 patients randomized to either 6 or 12 cycles of adjuvant FOLFOX with either celecoxib or placebo. The 3-year disease-free survival (DFS) rate was 76.3% for patients on celecoxib and 73.4% for those on placebo. The 5-year overall survival (OS) was 84% and 81.8%, respectively.
“The addition of celecoxib to FOLFOX adjuvant therapy in stage III colon cancer did not significantly improve disease-free or overall survival,” Jeffrey A. Meyerhardt, MD, of the Dana-Farber Cancer Institute in Boston, said while presenting the results as part of the American Society of Clinical Oncology virtual scientific program.
“We did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for disease-free survival. Similarly, we did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for overall survival,” Dr. Meyerhardt said.
“Simply put, celecoxib should not be used for the secondary prevention of colon cancer,” said invited discussant Christopher Lieu, MD, of the University of Colorado Cancer Center, Aurora.
Trial details
The 80702 trial was designed to test whether the COX-2 inhibitor celecoxib could help further reduce the risk of recurrence when added to adjuvant chemotherapy with 3 or 6 months of FOLFOX. Data on the FOLFOX portion of the trial were previously reported as part of the International Duration Evaluation of Adjuvant Therapy collaboration (N Engl J Med. 2018;378:1177-88).
The trial enrolled 2,526 patients with resected stage III colon cancer. They were randomized to receive 3 or 6 months (6 or 12 cycles) of FOLFOX with either concurrent celecoxib at 400 mg daily (n = 1,265) or placebo (n = 1,261) for 3 years from the start of the trial.
The primary endpoint of 3-year DFS did not differ between the groups (hazard ratio, 0.90; P = .16). Likewise, 5-year OS rates did not differ significantly (HR, 0.89; P = .22).
As Dr. Meyerhardt said, there were no significant interactions detected among any subgroups for DFS or OS, including by age, N or T stage, risk group, concurrent low-dose aspirin use, sex, race/ethnicity, baseline performance status, FOLFOX duration, body mass index, or tumor location.
Rates of toxicities were similar between the groups, except for a higher incidence of hypertension of any grade with celecoxib during FOLFOX therapy (14.6% vs. 10.9%, P = .01) and a grade 2 or greater creatinine increase with celecoxib after FOLFOX (1.7% vs. 0.5%, P = .01).
About 40% of patients completed all 3 years of celecoxib or placebo. Reasons for discontinuation included recurrent disease, adverse events, patient withdrawal from the study, physician decision, or other complicating disease.
Why didn’t it work?
Previous studies have indicated that aspirin and cyclooxygenase (COX)-2 inhibitors are associated with a reduced risk of colorectal polyps and cancer, Dr. Lieu said. So why didn’t celecoxib improve survival in the current trial?
“There are obviously COX-1 and COX-independent targets that aspirin hit that celecoxib does not, and its survival impact of affecting these targets is still largely unclear,” Dr. Lieu said.
He added that ongoing trials – including the Add-Aspirin and ASCOLT studies – should provide more insight.
The current trial was sponsored by the Alliance for Clinical Trials in Oncology in collaboration with the National Cancer Institute. Pfizer provided the celecoxib and placebo. Dr. Meyerhardt disclosed relationships with Cota Healthcare, Taiho Pharmaceutical, and Array BioPharma. Dr. Lieu disclosed relationships with Foundation Medicine, Ipsen, Merck, and Immune Design.
SOURCE: Meyerhardt JA et al. ASCO 2020, Abstract 4003.
FROM ASCO 2020
Avacopan notches a win in ANCA-associated vasculitis
Avacopan, an investigational oral inhibitor of complement activation, is efficacious and safe for treating antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, based on the results of the pivotal phase 3 ADVOCATE trial.
The trial results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year because of COVID-19.
“Standard of care for induction of remission includes high-dose glucocorticoids with either cyclophosphamide or rituximab. However, glucocorticoids are the major cause of treatment-related harm,” noted lead investigator Peter A. Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia.
The 331 patients in the trial had active ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), either new onset or relapsed, with positivity for either proteinase 3 or myeloperoxidase antibodies and moderate to high disease activity.
They were randomized evenly to double-blind avacopan 30 mg or tapering prednisone from 60 mg/day to zero over 20 weeks, each combined either with rituximab (Rituxan) or with cyclophosphamide followed by azathioprine. Avacopan (formerly called CCX168) is a selective antagonist of the complement C5a receptor that has orphan-drug designation from the Food and Drug Administration for this disease.
Trial results showed that avacopan was noninferior to prednisone with respect to the week 26 rate of remission on the Birmingham Vasculitis Activity Score, with an estimate of common difference of 3.4%. And it was superior to prednisone with respect to the week 52 rate of sustained remission, which required remission from week 26 onward, with an estimate of common difference of 12.5%.
The avacopan group also had less glucocorticoid-related toxicity and, among patients with preexisting renal disease, greater improvement in renal function.
“This large, randomized trial met both of its primary endpoints. Important secondary endpoints were also achieved, with a very acceptable safety profile,” Dr. Merkel summarized.
Making sense of the results
The optimal duration of avacopan therapy is unclear, he noted. “We are still going to be learning how to use this drug, if it’s approved, in routine practice. But the data from the second 6 months – from week 26 to week 52 – implies that there is ongoing benefit to being on avacopan after remission is achieved.”
Avacopan worked similarly well regardless of disease status in ADVOCATE, according to Dr. Merkel. “We have not seen significant differences in efficacy of other drugs in our trials [by disease status], in the trials of ANCA-associated vasculitis. So I think we would treat moderate to serious disease similarly, whether it is new onset or recurrence, in terms of efficacy of the drug.”
“The topline phase 3 data from ADVOCATE sort of even exceeded my expectations in terms of the ability to show not just noninferiority, but superiority of avacopan at week 52 in maintaining sustained remission,” Lindsay S. Lally, MD, assistant professor of medicine at the Hospital for Special Surgery in New York, commented in an interview. “It’s spectacular to treat patients with this serious vasculitis without any steroids or with very minimal steroids, and see superiority at a year. That is really game changing.”
The ADVOCATE findings will likely pass muster with the FDA, according to Dr. Lally. “The bar that was set in terms of the coprimary endpoints was very stringent and in line with other registration trials, particularly the RAVE trial that led to the approval of rituximab,” she elaborated. “I don’t think there is any significant safety signal in the data related to avacopan.
“This study is going to move forward our ability to treat this disease effectively, as we have been able to do in some of our other vasculitis syndromes, by finding drugs that have significant steroid-sparing effects,” Dr. Lally predicted.
Study details
ADVOCATE results reported at the congress showed that the week 26 rate of disease remission was 72.3% with avacopan versus 70.1% with prednisone, with the difference falling within the 20% boundary for noninferiority (P < .0001) but missing the mark for superiority (P = .2387).
However, the week 52 rate of sustained disease remission was 65.7% versus 54.9%, respectively, yielding a difference in favor of avacopan that was statistically both noninferior (P < .0001) and superior (P = .0066).
At week 26, patients in the avacopan group had more favorable Glucocorticoid Toxicity Index scores for cumulative worsening (39.7 vs. 56.6; P = .0002) and for aggregate improvement (11.2 vs. 23.4; P = .008).
Among patients who had renal disease at baseline, those in the avacopan group had a greater increase in estimated glomerular filtration rate at week 52 (7.3 vs. 4.1 mL/min per 1.73 m2; P = .029).
“Particularly interesting is the fact that, even after week 26, when the patients were in remission, there was continued improvement in renal function,” Dr. Merkel noted.
Overall, avacopan had a good safety profile. “This was a sick population with many complications, but there were no important safety signals of the study medication,” he reported.
The avacopan and prednisone groups had a similar rate of severe adverse events (23.5% vs. 25.0%). But the former had lower rates of life-threatening adverse events (4.8% vs. 8.5%), adverse events potentially related to glucocorticoids (66.3% vs. 80.5%), deaths (1.2% vs. 2.4%), and deaths specifically caused by infection (0.6% vs. 1.2%).
The trial was sponsored by ChemoCentryx. Dr. Merkel disclosed receiving grant/research support from and consulting fees from ChemoCentryx, among other disclosures. Dr. Lally disclosed that she was an investigator in the trial.
SOURCE: Merkel PA et al. Ann Rheum Dis. 2020;79[suppl 1]:8, Abstract OP0011.
Avacopan, an investigational oral inhibitor of complement activation, is efficacious and safe for treating antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, based on the results of the pivotal phase 3 ADVOCATE trial.
The trial results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year because of COVID-19.
“Standard of care for induction of remission includes high-dose glucocorticoids with either cyclophosphamide or rituximab. However, glucocorticoids are the major cause of treatment-related harm,” noted lead investigator Peter A. Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia.
The 331 patients in the trial had active ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), either new onset or relapsed, with positivity for either proteinase 3 or myeloperoxidase antibodies and moderate to high disease activity.
They were randomized evenly to double-blind avacopan 30 mg or tapering prednisone from 60 mg/day to zero over 20 weeks, each combined either with rituximab (Rituxan) or with cyclophosphamide followed by azathioprine. Avacopan (formerly called CCX168) is a selective antagonist of the complement C5a receptor that has orphan-drug designation from the Food and Drug Administration for this disease.
Trial results showed that avacopan was noninferior to prednisone with respect to the week 26 rate of remission on the Birmingham Vasculitis Activity Score, with an estimate of common difference of 3.4%. And it was superior to prednisone with respect to the week 52 rate of sustained remission, which required remission from week 26 onward, with an estimate of common difference of 12.5%.
The avacopan group also had less glucocorticoid-related toxicity and, among patients with preexisting renal disease, greater improvement in renal function.
“This large, randomized trial met both of its primary endpoints. Important secondary endpoints were also achieved, with a very acceptable safety profile,” Dr. Merkel summarized.
Making sense of the results
The optimal duration of avacopan therapy is unclear, he noted. “We are still going to be learning how to use this drug, if it’s approved, in routine practice. But the data from the second 6 months – from week 26 to week 52 – implies that there is ongoing benefit to being on avacopan after remission is achieved.”
Avacopan worked similarly well regardless of disease status in ADVOCATE, according to Dr. Merkel. “We have not seen significant differences in efficacy of other drugs in our trials [by disease status], in the trials of ANCA-associated vasculitis. So I think we would treat moderate to serious disease similarly, whether it is new onset or recurrence, in terms of efficacy of the drug.”
“The topline phase 3 data from ADVOCATE sort of even exceeded my expectations in terms of the ability to show not just noninferiority, but superiority of avacopan at week 52 in maintaining sustained remission,” Lindsay S. Lally, MD, assistant professor of medicine at the Hospital for Special Surgery in New York, commented in an interview. “It’s spectacular to treat patients with this serious vasculitis without any steroids or with very minimal steroids, and see superiority at a year. That is really game changing.”
The ADVOCATE findings will likely pass muster with the FDA, according to Dr. Lally. “The bar that was set in terms of the coprimary endpoints was very stringent and in line with other registration trials, particularly the RAVE trial that led to the approval of rituximab,” she elaborated. “I don’t think there is any significant safety signal in the data related to avacopan.
“This study is going to move forward our ability to treat this disease effectively, as we have been able to do in some of our other vasculitis syndromes, by finding drugs that have significant steroid-sparing effects,” Dr. Lally predicted.
Study details
ADVOCATE results reported at the congress showed that the week 26 rate of disease remission was 72.3% with avacopan versus 70.1% with prednisone, with the difference falling within the 20% boundary for noninferiority (P < .0001) but missing the mark for superiority (P = .2387).
However, the week 52 rate of sustained disease remission was 65.7% versus 54.9%, respectively, yielding a difference in favor of avacopan that was statistically both noninferior (P < .0001) and superior (P = .0066).
At week 26, patients in the avacopan group had more favorable Glucocorticoid Toxicity Index scores for cumulative worsening (39.7 vs. 56.6; P = .0002) and for aggregate improvement (11.2 vs. 23.4; P = .008).
Among patients who had renal disease at baseline, those in the avacopan group had a greater increase in estimated glomerular filtration rate at week 52 (7.3 vs. 4.1 mL/min per 1.73 m2; P = .029).
“Particularly interesting is the fact that, even after week 26, when the patients were in remission, there was continued improvement in renal function,” Dr. Merkel noted.
Overall, avacopan had a good safety profile. “This was a sick population with many complications, but there were no important safety signals of the study medication,” he reported.
The avacopan and prednisone groups had a similar rate of severe adverse events (23.5% vs. 25.0%). But the former had lower rates of life-threatening adverse events (4.8% vs. 8.5%), adverse events potentially related to glucocorticoids (66.3% vs. 80.5%), deaths (1.2% vs. 2.4%), and deaths specifically caused by infection (0.6% vs. 1.2%).
The trial was sponsored by ChemoCentryx. Dr. Merkel disclosed receiving grant/research support from and consulting fees from ChemoCentryx, among other disclosures. Dr. Lally disclosed that she was an investigator in the trial.
SOURCE: Merkel PA et al. Ann Rheum Dis. 2020;79[suppl 1]:8, Abstract OP0011.
Avacopan, an investigational oral inhibitor of complement activation, is efficacious and safe for treating antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, based on the results of the pivotal phase 3 ADVOCATE trial.
The trial results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year because of COVID-19.
“Standard of care for induction of remission includes high-dose glucocorticoids with either cyclophosphamide or rituximab. However, glucocorticoids are the major cause of treatment-related harm,” noted lead investigator Peter A. Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia.
The 331 patients in the trial had active ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), either new onset or relapsed, with positivity for either proteinase 3 or myeloperoxidase antibodies and moderate to high disease activity.
They were randomized evenly to double-blind avacopan 30 mg or tapering prednisone from 60 mg/day to zero over 20 weeks, each combined either with rituximab (Rituxan) or with cyclophosphamide followed by azathioprine. Avacopan (formerly called CCX168) is a selective antagonist of the complement C5a receptor that has orphan-drug designation from the Food and Drug Administration for this disease.
Trial results showed that avacopan was noninferior to prednisone with respect to the week 26 rate of remission on the Birmingham Vasculitis Activity Score, with an estimate of common difference of 3.4%. And it was superior to prednisone with respect to the week 52 rate of sustained remission, which required remission from week 26 onward, with an estimate of common difference of 12.5%.
The avacopan group also had less glucocorticoid-related toxicity and, among patients with preexisting renal disease, greater improvement in renal function.
“This large, randomized trial met both of its primary endpoints. Important secondary endpoints were also achieved, with a very acceptable safety profile,” Dr. Merkel summarized.
Making sense of the results
The optimal duration of avacopan therapy is unclear, he noted. “We are still going to be learning how to use this drug, if it’s approved, in routine practice. But the data from the second 6 months – from week 26 to week 52 – implies that there is ongoing benefit to being on avacopan after remission is achieved.”
Avacopan worked similarly well regardless of disease status in ADVOCATE, according to Dr. Merkel. “We have not seen significant differences in efficacy of other drugs in our trials [by disease status], in the trials of ANCA-associated vasculitis. So I think we would treat moderate to serious disease similarly, whether it is new onset or recurrence, in terms of efficacy of the drug.”
“The topline phase 3 data from ADVOCATE sort of even exceeded my expectations in terms of the ability to show not just noninferiority, but superiority of avacopan at week 52 in maintaining sustained remission,” Lindsay S. Lally, MD, assistant professor of medicine at the Hospital for Special Surgery in New York, commented in an interview. “It’s spectacular to treat patients with this serious vasculitis without any steroids or with very minimal steroids, and see superiority at a year. That is really game changing.”
The ADVOCATE findings will likely pass muster with the FDA, according to Dr. Lally. “The bar that was set in terms of the coprimary endpoints was very stringent and in line with other registration trials, particularly the RAVE trial that led to the approval of rituximab,” she elaborated. “I don’t think there is any significant safety signal in the data related to avacopan.
“This study is going to move forward our ability to treat this disease effectively, as we have been able to do in some of our other vasculitis syndromes, by finding drugs that have significant steroid-sparing effects,” Dr. Lally predicted.
Study details
ADVOCATE results reported at the congress showed that the week 26 rate of disease remission was 72.3% with avacopan versus 70.1% with prednisone, with the difference falling within the 20% boundary for noninferiority (P < .0001) but missing the mark for superiority (P = .2387).
However, the week 52 rate of sustained disease remission was 65.7% versus 54.9%, respectively, yielding a difference in favor of avacopan that was statistically both noninferior (P < .0001) and superior (P = .0066).
At week 26, patients in the avacopan group had more favorable Glucocorticoid Toxicity Index scores for cumulative worsening (39.7 vs. 56.6; P = .0002) and for aggregate improvement (11.2 vs. 23.4; P = .008).
Among patients who had renal disease at baseline, those in the avacopan group had a greater increase in estimated glomerular filtration rate at week 52 (7.3 vs. 4.1 mL/min per 1.73 m2; P = .029).
“Particularly interesting is the fact that, even after week 26, when the patients were in remission, there was continued improvement in renal function,” Dr. Merkel noted.
Overall, avacopan had a good safety profile. “This was a sick population with many complications, but there were no important safety signals of the study medication,” he reported.
The avacopan and prednisone groups had a similar rate of severe adverse events (23.5% vs. 25.0%). But the former had lower rates of life-threatening adverse events (4.8% vs. 8.5%), adverse events potentially related to glucocorticoids (66.3% vs. 80.5%), deaths (1.2% vs. 2.4%), and deaths specifically caused by infection (0.6% vs. 1.2%).
The trial was sponsored by ChemoCentryx. Dr. Merkel disclosed receiving grant/research support from and consulting fees from ChemoCentryx, among other disclosures. Dr. Lally disclosed that she was an investigator in the trial.
SOURCE: Merkel PA et al. Ann Rheum Dis. 2020;79[suppl 1]:8, Abstract OP0011.
FROM EULAR 2020 E-CONGRESS
Study tests a simpler low disease activity measure for lupus
An alternative disease activity index for patients with systemic lupus erythematosus called the SLE-DAS (Disease Activity Score) has shown similar results to the Lupus Low Disease Activity State (LLDAS) in classifying low disease activity but may be easier to potentially apply in daily clinical practice in treat-to-target strategies, according to research presented at the annual European Congress of Rheumatology, held online this year because of COVID-19.
A treat-to-target approach, in which therapies are adjusted and the patient monitored to achieve the desired endpoint, has been proposed for patients with SLE. Clinical remission is the ideal goal, followed by achieving low disease activity (LDA) when clinical remission is unattainable, the first author of the SLE-DAS study, Helena Assunção, MD, of the department of rheumatology at Centro Hospitalar e Universitário de Coimbra (Portugal), said in an interview prior to the presentation of the study at the e-congress.
But to conduct a treat-to-target approach in the clinical setting, clinicians must have reliable, user-friendly targets to assess a patient’s progress, she said. But that’s not available right now. Proposed definitions of LDA, such as the LLDAS, are based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). This index doesn’t address some important manifestations of SLE and it is scored dichotomously – for example, giving a similar score for thrombocytopenia when platelet count is reduced to 100,000 or to 10,000.
To compensate for these limitations, the current LLDAS definition also requires the Physician Global Assessment and other steps, including a review of medication and changes to treatment or clinical status since the previous visit.
“It is not easy to apply,” Dr. Assunção said.
The SLE-DAS is a continuous index involving 17 parameters (4 continuous: arthritis, proteinuria, thrombocytopenia, and leukopenia), assigning higher scores when a manifestation is more severe, and has manifestation information that SLEDAI-2K lacks (cardiopulmonary involvement, lupus enteritis, and hemolytic anemia).
In contrast, the LLDAS is defined as:
- A SLEDAI-2k score of 4 or less with no major organ involvement
- No new disease activity
- A physician global assessment of the patient of 1 or less on a 0-3 scale
- Maintenance on a prednisolone dosage of 7.5 mg/day or less
- Maintenance on a standard immunosuppressive regimen
A previous study validated the SLE-DAS (Ann Rheum Dis. 2019 Mar;78[3]:365-71), and another exploratory study identified a cutoff SLE-DAS value of 3.77 or lower for LDA with SLE-DAS (Ann Rheum Dis. 2019;78:411-2).
Her group compared LDA status as measured with LLDAS versus the SLE-DAS in a cross-sectional study of 292 consecutive patients at their hospital. LDA on the SLE-DAS was defined as a score 3.77 or lower and a prednisolone dose of 7.5 mg/day or less. A total of 85% of patients were in LDA with SLE-DAS and 83.9% with LLDAS, and the agreement between LLDAS and SLE-DAS LDA was very high (Cohen’s kappa coefficient test; kappa = 0.831; P < .01). Out of 292 patients, only 13 were classified differently by the two definitions, 8 of which were classified as LDA by SLE-DAS, and 5 by LLDAS. Overall, 87% of patients were women and had a mean age of nearly 49 years, with a mean disease duration of about 14 years.
Dr. Assunção feels that the SLE-DAS LDA should be sufficient to monitor disease activity without adding the Physician Global Assessment and other steps, which would make it easier to apply than LLDAS. The fact that it is based on a continuous index is also an important difference. “Especially for low disease activity, it’s very good to be able to define it with a continuous index, because you are not that bad, but not that good, you’re in the middle,” she said.
The study should be regarded as exploratory, she said, but the results were encouraging. “We got similar results, and it’s definitely easier to apply.” She can also personally attest that the new model is easier to use, since she personally collected data for LLDAS assignment. “I had to check this, and this, and this … [SLE-DAS] is easier.”
Future work from her group will aim at deriving and validating a more robust definition of LDA, which will again be compared with the current LLDAS definition.
Her colleagues have already developed and validated a definition for clinical remission using SLE-DAS, although those results have not yet been published. They hope to define activity states using SLE-DAS, including mild, moderate, and high disease activity.
The team has produced an online SLE-DAS calculator (http://sle-das.eu/) where clinicians can score the 17 parameters. “You just input the values and it gives a number reflecting disease activity. Using this definition of SLE-DAS LDA you only need that number and to verify that the prednisolone dose is equal to or inferior to 7.5 mg/day,” said Dr. Assunção.
The study received no funding. Dr. Assunção has no financial disclosures, but one coauthor reported receiving grant/research support from Pfizer and AbbVie and serving as a consultant to Pfizer, AbbVie, Roche, Lilly, and Novartis.
SOURCE: Assunção H et al. Ann Rheum Dis 2020;79[suppl 1]:60, Abstract OP0092.
An alternative disease activity index for patients with systemic lupus erythematosus called the SLE-DAS (Disease Activity Score) has shown similar results to the Lupus Low Disease Activity State (LLDAS) in classifying low disease activity but may be easier to potentially apply in daily clinical practice in treat-to-target strategies, according to research presented at the annual European Congress of Rheumatology, held online this year because of COVID-19.
A treat-to-target approach, in which therapies are adjusted and the patient monitored to achieve the desired endpoint, has been proposed for patients with SLE. Clinical remission is the ideal goal, followed by achieving low disease activity (LDA) when clinical remission is unattainable, the first author of the SLE-DAS study, Helena Assunção, MD, of the department of rheumatology at Centro Hospitalar e Universitário de Coimbra (Portugal), said in an interview prior to the presentation of the study at the e-congress.
But to conduct a treat-to-target approach in the clinical setting, clinicians must have reliable, user-friendly targets to assess a patient’s progress, she said. But that’s not available right now. Proposed definitions of LDA, such as the LLDAS, are based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). This index doesn’t address some important manifestations of SLE and it is scored dichotomously – for example, giving a similar score for thrombocytopenia when platelet count is reduced to 100,000 or to 10,000.
To compensate for these limitations, the current LLDAS definition also requires the Physician Global Assessment and other steps, including a review of medication and changes to treatment or clinical status since the previous visit.
“It is not easy to apply,” Dr. Assunção said.
The SLE-DAS is a continuous index involving 17 parameters (4 continuous: arthritis, proteinuria, thrombocytopenia, and leukopenia), assigning higher scores when a manifestation is more severe, and has manifestation information that SLEDAI-2K lacks (cardiopulmonary involvement, lupus enteritis, and hemolytic anemia).
In contrast, the LLDAS is defined as:
- A SLEDAI-2k score of 4 or less with no major organ involvement
- No new disease activity
- A physician global assessment of the patient of 1 or less on a 0-3 scale
- Maintenance on a prednisolone dosage of 7.5 mg/day or less
- Maintenance on a standard immunosuppressive regimen
A previous study validated the SLE-DAS (Ann Rheum Dis. 2019 Mar;78[3]:365-71), and another exploratory study identified a cutoff SLE-DAS value of 3.77 or lower for LDA with SLE-DAS (Ann Rheum Dis. 2019;78:411-2).
Her group compared LDA status as measured with LLDAS versus the SLE-DAS in a cross-sectional study of 292 consecutive patients at their hospital. LDA on the SLE-DAS was defined as a score 3.77 or lower and a prednisolone dose of 7.5 mg/day or less. A total of 85% of patients were in LDA with SLE-DAS and 83.9% with LLDAS, and the agreement between LLDAS and SLE-DAS LDA was very high (Cohen’s kappa coefficient test; kappa = 0.831; P < .01). Out of 292 patients, only 13 were classified differently by the two definitions, 8 of which were classified as LDA by SLE-DAS, and 5 by LLDAS. Overall, 87% of patients were women and had a mean age of nearly 49 years, with a mean disease duration of about 14 years.
Dr. Assunção feels that the SLE-DAS LDA should be sufficient to monitor disease activity without adding the Physician Global Assessment and other steps, which would make it easier to apply than LLDAS. The fact that it is based on a continuous index is also an important difference. “Especially for low disease activity, it’s very good to be able to define it with a continuous index, because you are not that bad, but not that good, you’re in the middle,” she said.
The study should be regarded as exploratory, she said, but the results were encouraging. “We got similar results, and it’s definitely easier to apply.” She can also personally attest that the new model is easier to use, since she personally collected data for LLDAS assignment. “I had to check this, and this, and this … [SLE-DAS] is easier.”
Future work from her group will aim at deriving and validating a more robust definition of LDA, which will again be compared with the current LLDAS definition.
Her colleagues have already developed and validated a definition for clinical remission using SLE-DAS, although those results have not yet been published. They hope to define activity states using SLE-DAS, including mild, moderate, and high disease activity.
The team has produced an online SLE-DAS calculator (http://sle-das.eu/) where clinicians can score the 17 parameters. “You just input the values and it gives a number reflecting disease activity. Using this definition of SLE-DAS LDA you only need that number and to verify that the prednisolone dose is equal to or inferior to 7.5 mg/day,” said Dr. Assunção.
The study received no funding. Dr. Assunção has no financial disclosures, but one coauthor reported receiving grant/research support from Pfizer and AbbVie and serving as a consultant to Pfizer, AbbVie, Roche, Lilly, and Novartis.
SOURCE: Assunção H et al. Ann Rheum Dis 2020;79[suppl 1]:60, Abstract OP0092.
An alternative disease activity index for patients with systemic lupus erythematosus called the SLE-DAS (Disease Activity Score) has shown similar results to the Lupus Low Disease Activity State (LLDAS) in classifying low disease activity but may be easier to potentially apply in daily clinical practice in treat-to-target strategies, according to research presented at the annual European Congress of Rheumatology, held online this year because of COVID-19.
A treat-to-target approach, in which therapies are adjusted and the patient monitored to achieve the desired endpoint, has been proposed for patients with SLE. Clinical remission is the ideal goal, followed by achieving low disease activity (LDA) when clinical remission is unattainable, the first author of the SLE-DAS study, Helena Assunção, MD, of the department of rheumatology at Centro Hospitalar e Universitário de Coimbra (Portugal), said in an interview prior to the presentation of the study at the e-congress.
But to conduct a treat-to-target approach in the clinical setting, clinicians must have reliable, user-friendly targets to assess a patient’s progress, she said. But that’s not available right now. Proposed definitions of LDA, such as the LLDAS, are based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). This index doesn’t address some important manifestations of SLE and it is scored dichotomously – for example, giving a similar score for thrombocytopenia when platelet count is reduced to 100,000 or to 10,000.
To compensate for these limitations, the current LLDAS definition also requires the Physician Global Assessment and other steps, including a review of medication and changes to treatment or clinical status since the previous visit.
“It is not easy to apply,” Dr. Assunção said.
The SLE-DAS is a continuous index involving 17 parameters (4 continuous: arthritis, proteinuria, thrombocytopenia, and leukopenia), assigning higher scores when a manifestation is more severe, and has manifestation information that SLEDAI-2K lacks (cardiopulmonary involvement, lupus enteritis, and hemolytic anemia).
In contrast, the LLDAS is defined as:
- A SLEDAI-2k score of 4 or less with no major organ involvement
- No new disease activity
- A physician global assessment of the patient of 1 or less on a 0-3 scale
- Maintenance on a prednisolone dosage of 7.5 mg/day or less
- Maintenance on a standard immunosuppressive regimen
A previous study validated the SLE-DAS (Ann Rheum Dis. 2019 Mar;78[3]:365-71), and another exploratory study identified a cutoff SLE-DAS value of 3.77 or lower for LDA with SLE-DAS (Ann Rheum Dis. 2019;78:411-2).
Her group compared LDA status as measured with LLDAS versus the SLE-DAS in a cross-sectional study of 292 consecutive patients at their hospital. LDA on the SLE-DAS was defined as a score 3.77 or lower and a prednisolone dose of 7.5 mg/day or less. A total of 85% of patients were in LDA with SLE-DAS and 83.9% with LLDAS, and the agreement between LLDAS and SLE-DAS LDA was very high (Cohen’s kappa coefficient test; kappa = 0.831; P < .01). Out of 292 patients, only 13 were classified differently by the two definitions, 8 of which were classified as LDA by SLE-DAS, and 5 by LLDAS. Overall, 87% of patients were women and had a mean age of nearly 49 years, with a mean disease duration of about 14 years.
Dr. Assunção feels that the SLE-DAS LDA should be sufficient to monitor disease activity without adding the Physician Global Assessment and other steps, which would make it easier to apply than LLDAS. The fact that it is based on a continuous index is also an important difference. “Especially for low disease activity, it’s very good to be able to define it with a continuous index, because you are not that bad, but not that good, you’re in the middle,” she said.
The study should be regarded as exploratory, she said, but the results were encouraging. “We got similar results, and it’s definitely easier to apply.” She can also personally attest that the new model is easier to use, since she personally collected data for LLDAS assignment. “I had to check this, and this, and this … [SLE-DAS] is easier.”
Future work from her group will aim at deriving and validating a more robust definition of LDA, which will again be compared with the current LLDAS definition.
Her colleagues have already developed and validated a definition for clinical remission using SLE-DAS, although those results have not yet been published. They hope to define activity states using SLE-DAS, including mild, moderate, and high disease activity.
The team has produced an online SLE-DAS calculator (http://sle-das.eu/) where clinicians can score the 17 parameters. “You just input the values and it gives a number reflecting disease activity. Using this definition of SLE-DAS LDA you only need that number and to verify that the prednisolone dose is equal to or inferior to 7.5 mg/day,” said Dr. Assunção.
The study received no funding. Dr. Assunção has no financial disclosures, but one coauthor reported receiving grant/research support from Pfizer and AbbVie and serving as a consultant to Pfizer, AbbVie, Roche, Lilly, and Novartis.
SOURCE: Assunção H et al. Ann Rheum Dis 2020;79[suppl 1]:60, Abstract OP0092.
FROM EULAR 2020 E-CONGRESS
Working group proposes MRI definitions of structural lesions indicative of axial spondyloarthritis
What constitutes a structural lesion of the sacroiliac joints on MRI that’s indicative of axial spondyloarthritis (axSpA) has long been a matter of conjecture, but the Assessment of SpondyloArthritis International Society (ASAS) MRI Working Group has developed new definitions that showed a high degree of specificity in identifying such lesions in the disease.
“There is a lack of consensus as to what defines a structural lesion on MRI of the sacroiliac joint [SIJ] typical of axial spondyloarthritis. Previous studies have described structural lesions in different ways, precluding meaningful comparisons between studies. The ASAS MRI group has generated updated consensus lesion definitions that describe each of the MRI lesions in the sacroiliac joint. These definitions have been validated by seven expert readers from the ASAS MRI group on MRI images from the ASAS classification cohort,” Walter P. Maksymowych, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.
Making a definitive diagnosis of axSpA can be difficult because MRI can show a variety of SIJ abnormalities in healthy people as well as those with axSpA, said Dr. Maksymowych, chief medical officer of CARE Arthritis and professor in rheumatology at the University of Alberta in Edmonton, said in an interview prior to his presentation at the e-congress. “People who evaluate MRI scans are looking for clues as to what types of lesions they can be confident are indicative of axSpA.”
That started a process by the ASAS MRI group to evaluate scans from the landmark ASAS Classification Cohort study (Ann Rheum Dis. 2019;78:1550-8). “But,” said Dr. Maksymowych, “the MRI scans from that study were never evaluated.” So that work was handed off to the working group, whose 25 members included 7 expert image readers who evaluated the MRI scans.
The group adopted a standardized approach for evaluating MRIs of the SIJ in 148 cases, dividing each SIJ into quadrants and then evaluating consecutive MRI slices. The readers first documented whether they observed a definite structural lesion on the scan, which they then used as an external reference standard. They then analyzed which lesion, and in how many SIJ quadrants or slices, best reflected this external standard.
The investigators defined an erosion as “a defect in subchondral bone associated with full-thickness loss of a dark appearance of the subchondral cortex at its expected location, with loss of signal on a T1-weighted, non–fat-suppressed sequence, compared with the normal bright appearance of adjacent bone marrow.” They defined a fat lesion or fat metaplasia as a “bright signal seen on a T1-weighted, non–fat-suppressed sequence that is brighter than normal bone marrow which meets the following requirements: It is homogeneously bright, located in a typical anatomical area (specifically subchondral bone), and has a sharply defined border along its nonarticular border with normal bone marrow.”
An erosion in one quadrant isn’t sufficient to define a scan as positive for a definite structural lesion, said Dr. Maksymowych; but an erosion in three quadrants or in two or more consecutive slices meets the group’s designation of a definite structural lesion. “This showed over a 95% specificity for being associated with a definite structural lesion as defined by a majority of the seven experts,” he said.
The group also determined that a fat lesion typical of axSpA has a homogeneous white appearance on T1-weighted scans with a sharply defined border. The group also determined that such a fat lesion with at least 1-cm horizontal depth from the joint margin in at least one SIJ quadrant is strongly indicative of axSpA.
“So we now have definitions for two structural lesions, erosion and fat lesions, that reflect what a majority of experts consider to be a definite structural lesion according to at least 95% specificity,” he said. Sensitivity values were 90% for erosion in three quadrants and 83% for erosions in two or more consecutive slices. and 59% for a fat lesion with at least 1-cm horizontal depth from the joint margin in at least one SIJ quadrant.
The second part of the analysis evaluated the predictive capacity of these lesion definitions for a rheumatologic diagnosis of axSpA at 4.4 years of follow-up. “These lesions predicted SpA with over 95% positive predictive value,” he said. “In other words, if you see them at baseline they’re going to predict SpA with high certainty at follow-up after 4.4 years.”
Three aspects of this study design are unique, Dr. Maksymowych noted. First is the high number of expert MRI readers who evaluated the scans. “There aren’t really too many studies I can think of that used more than two or three expert MRI readers,” he said.
Second is the way in which the study “very precisely and in a very standardized way” applied all the consensus-based ASAS definitions of structural SIJ lesions. “In the past, a variety of ways were used to define these lesions,” he said. “A good example would be the different ways in which erosions have been defined.”
The third novel aspect of the study is that the expert readers’ assessment of what constitutes a definite structural lesion was used as an external reference standard. For example, the study calculated sensitivity and specificity for numbers of SIJ quadrants and consecutive slices with erosion, sclerosis, and fat lesions where a majority of readers agreed on the presence of a structural lesion typical of axSpA with high confidence (3 or greater on a scale of 1-4). “The reason this was put in place is because we recognize sometimes lesions are very subtle and you can’t be certain that they’re reflecting SpA,” he said.
The investigators disclosed relationships with AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novo Nordisk, Novartis, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB.
Maksymowych WP et al. Ann Rheum Dis, 2020;79[suppl 1]:53. Abstract OP0079.
What constitutes a structural lesion of the sacroiliac joints on MRI that’s indicative of axial spondyloarthritis (axSpA) has long been a matter of conjecture, but the Assessment of SpondyloArthritis International Society (ASAS) MRI Working Group has developed new definitions that showed a high degree of specificity in identifying such lesions in the disease.
“There is a lack of consensus as to what defines a structural lesion on MRI of the sacroiliac joint [SIJ] typical of axial spondyloarthritis. Previous studies have described structural lesions in different ways, precluding meaningful comparisons between studies. The ASAS MRI group has generated updated consensus lesion definitions that describe each of the MRI lesions in the sacroiliac joint. These definitions have been validated by seven expert readers from the ASAS MRI group on MRI images from the ASAS classification cohort,” Walter P. Maksymowych, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.
Making a definitive diagnosis of axSpA can be difficult because MRI can show a variety of SIJ abnormalities in healthy people as well as those with axSpA, said Dr. Maksymowych, chief medical officer of CARE Arthritis and professor in rheumatology at the University of Alberta in Edmonton, said in an interview prior to his presentation at the e-congress. “People who evaluate MRI scans are looking for clues as to what types of lesions they can be confident are indicative of axSpA.”
That started a process by the ASAS MRI group to evaluate scans from the landmark ASAS Classification Cohort study (Ann Rheum Dis. 2019;78:1550-8). “But,” said Dr. Maksymowych, “the MRI scans from that study were never evaluated.” So that work was handed off to the working group, whose 25 members included 7 expert image readers who evaluated the MRI scans.
The group adopted a standardized approach for evaluating MRIs of the SIJ in 148 cases, dividing each SIJ into quadrants and then evaluating consecutive MRI slices. The readers first documented whether they observed a definite structural lesion on the scan, which they then used as an external reference standard. They then analyzed which lesion, and in how many SIJ quadrants or slices, best reflected this external standard.
The investigators defined an erosion as “a defect in subchondral bone associated with full-thickness loss of a dark appearance of the subchondral cortex at its expected location, with loss of signal on a T1-weighted, non–fat-suppressed sequence, compared with the normal bright appearance of adjacent bone marrow.” They defined a fat lesion or fat metaplasia as a “bright signal seen on a T1-weighted, non–fat-suppressed sequence that is brighter than normal bone marrow which meets the following requirements: It is homogeneously bright, located in a typical anatomical area (specifically subchondral bone), and has a sharply defined border along its nonarticular border with normal bone marrow.”
An erosion in one quadrant isn’t sufficient to define a scan as positive for a definite structural lesion, said Dr. Maksymowych; but an erosion in three quadrants or in two or more consecutive slices meets the group’s designation of a definite structural lesion. “This showed over a 95% specificity for being associated with a definite structural lesion as defined by a majority of the seven experts,” he said.
The group also determined that a fat lesion typical of axSpA has a homogeneous white appearance on T1-weighted scans with a sharply defined border. The group also determined that such a fat lesion with at least 1-cm horizontal depth from the joint margin in at least one SIJ quadrant is strongly indicative of axSpA.
“So we now have definitions for two structural lesions, erosion and fat lesions, that reflect what a majority of experts consider to be a definite structural lesion according to at least 95% specificity,” he said. Sensitivity values were 90% for erosion in three quadrants and 83% for erosions in two or more consecutive slices. and 59% for a fat lesion with at least 1-cm horizontal depth from the joint margin in at least one SIJ quadrant.
The second part of the analysis evaluated the predictive capacity of these lesion definitions for a rheumatologic diagnosis of axSpA at 4.4 years of follow-up. “These lesions predicted SpA with over 95% positive predictive value,” he said. “In other words, if you see them at baseline they’re going to predict SpA with high certainty at follow-up after 4.4 years.”
Three aspects of this study design are unique, Dr. Maksymowych noted. First is the high number of expert MRI readers who evaluated the scans. “There aren’t really too many studies I can think of that used more than two or three expert MRI readers,” he said.
Second is the way in which the study “very precisely and in a very standardized way” applied all the consensus-based ASAS definitions of structural SIJ lesions. “In the past, a variety of ways were used to define these lesions,” he said. “A good example would be the different ways in which erosions have been defined.”
The third novel aspect of the study is that the expert readers’ assessment of what constitutes a definite structural lesion was used as an external reference standard. For example, the study calculated sensitivity and specificity for numbers of SIJ quadrants and consecutive slices with erosion, sclerosis, and fat lesions where a majority of readers agreed on the presence of a structural lesion typical of axSpA with high confidence (3 or greater on a scale of 1-4). “The reason this was put in place is because we recognize sometimes lesions are very subtle and you can’t be certain that they’re reflecting SpA,” he said.
The investigators disclosed relationships with AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novo Nordisk, Novartis, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB.
Maksymowych WP et al. Ann Rheum Dis, 2020;79[suppl 1]:53. Abstract OP0079.
What constitutes a structural lesion of the sacroiliac joints on MRI that’s indicative of axial spondyloarthritis (axSpA) has long been a matter of conjecture, but the Assessment of SpondyloArthritis International Society (ASAS) MRI Working Group has developed new definitions that showed a high degree of specificity in identifying such lesions in the disease.
“There is a lack of consensus as to what defines a structural lesion on MRI of the sacroiliac joint [SIJ] typical of axial spondyloarthritis. Previous studies have described structural lesions in different ways, precluding meaningful comparisons between studies. The ASAS MRI group has generated updated consensus lesion definitions that describe each of the MRI lesions in the sacroiliac joint. These definitions have been validated by seven expert readers from the ASAS MRI group on MRI images from the ASAS classification cohort,” Walter P. Maksymowych, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.
Making a definitive diagnosis of axSpA can be difficult because MRI can show a variety of SIJ abnormalities in healthy people as well as those with axSpA, said Dr. Maksymowych, chief medical officer of CARE Arthritis and professor in rheumatology at the University of Alberta in Edmonton, said in an interview prior to his presentation at the e-congress. “People who evaluate MRI scans are looking for clues as to what types of lesions they can be confident are indicative of axSpA.”
That started a process by the ASAS MRI group to evaluate scans from the landmark ASAS Classification Cohort study (Ann Rheum Dis. 2019;78:1550-8). “But,” said Dr. Maksymowych, “the MRI scans from that study were never evaluated.” So that work was handed off to the working group, whose 25 members included 7 expert image readers who evaluated the MRI scans.
The group adopted a standardized approach for evaluating MRIs of the SIJ in 148 cases, dividing each SIJ into quadrants and then evaluating consecutive MRI slices. The readers first documented whether they observed a definite structural lesion on the scan, which they then used as an external reference standard. They then analyzed which lesion, and in how many SIJ quadrants or slices, best reflected this external standard.
The investigators defined an erosion as “a defect in subchondral bone associated with full-thickness loss of a dark appearance of the subchondral cortex at its expected location, with loss of signal on a T1-weighted, non–fat-suppressed sequence, compared with the normal bright appearance of adjacent bone marrow.” They defined a fat lesion or fat metaplasia as a “bright signal seen on a T1-weighted, non–fat-suppressed sequence that is brighter than normal bone marrow which meets the following requirements: It is homogeneously bright, located in a typical anatomical area (specifically subchondral bone), and has a sharply defined border along its nonarticular border with normal bone marrow.”
An erosion in one quadrant isn’t sufficient to define a scan as positive for a definite structural lesion, said Dr. Maksymowych; but an erosion in three quadrants or in two or more consecutive slices meets the group’s designation of a definite structural lesion. “This showed over a 95% specificity for being associated with a definite structural lesion as defined by a majority of the seven experts,” he said.
The group also determined that a fat lesion typical of axSpA has a homogeneous white appearance on T1-weighted scans with a sharply defined border. The group also determined that such a fat lesion with at least 1-cm horizontal depth from the joint margin in at least one SIJ quadrant is strongly indicative of axSpA.
“So we now have definitions for two structural lesions, erosion and fat lesions, that reflect what a majority of experts consider to be a definite structural lesion according to at least 95% specificity,” he said. Sensitivity values were 90% for erosion in three quadrants and 83% for erosions in two or more consecutive slices. and 59% for a fat lesion with at least 1-cm horizontal depth from the joint margin in at least one SIJ quadrant.
The second part of the analysis evaluated the predictive capacity of these lesion definitions for a rheumatologic diagnosis of axSpA at 4.4 years of follow-up. “These lesions predicted SpA with over 95% positive predictive value,” he said. “In other words, if you see them at baseline they’re going to predict SpA with high certainty at follow-up after 4.4 years.”
Three aspects of this study design are unique, Dr. Maksymowych noted. First is the high number of expert MRI readers who evaluated the scans. “There aren’t really too many studies I can think of that used more than two or three expert MRI readers,” he said.
Second is the way in which the study “very precisely and in a very standardized way” applied all the consensus-based ASAS definitions of structural SIJ lesions. “In the past, a variety of ways were used to define these lesions,” he said. “A good example would be the different ways in which erosions have been defined.”
The third novel aspect of the study is that the expert readers’ assessment of what constitutes a definite structural lesion was used as an external reference standard. For example, the study calculated sensitivity and specificity for numbers of SIJ quadrants and consecutive slices with erosion, sclerosis, and fat lesions where a majority of readers agreed on the presence of a structural lesion typical of axSpA with high confidence (3 or greater on a scale of 1-4). “The reason this was put in place is because we recognize sometimes lesions are very subtle and you can’t be certain that they’re reflecting SpA,” he said.
The investigators disclosed relationships with AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novo Nordisk, Novartis, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB.
Maksymowych WP et al. Ann Rheum Dis, 2020;79[suppl 1]:53. Abstract OP0079.
FROM EULAR 2020 E-CONGRESS
Is cannabis gaining acceptance as a treatment for neuropathic pain?
, a recent debate on the topic suggests. During the debate, one expert argued for, and another against, there being sufficient evidence for the use of cannabis to treat neuropathic pain, but in the end, they agreed that some patients do benefit.
The discussion took place at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual online meeting because of the COVID-19 pandemic.
The cannabis plant has 460 constituents. The two main components are tetrahydrocannabinol (THC) and cannabidiol (CBD). It can be consumed by swallowing oil extracts, by the sublingual route, or by smoking or eating the plant. Cannabis medications already in use include oral THC (nabilone, dronabinol) and an oral mucosal spray, nabiximols (Sativex).
Arguing that therapeutic cannabis is helpful for neuropathic pain, Elon Eisenberg, MD, professor of neurology and pain medicine, Israel Institute of Technology, Haifa, cited a number of encouraging randomized, controlled trials and meta-analyses of studies on the subject.
Opioid substitute
Dr. Eisenberg discussed three relevant articles. One was a 2016 viewpoint article published in JAMA that concluded that “cannabis seems to be a substitute, a rather good one, for opioids,” said Dr. Eisenberg.
A “comprehensive” 440-page review, published by the National Academies Press in 2017, evaluated the evidence to that point and “came to the conclusion there is substantial evidence that cannabis is an effective treatment for chronic pain in adults,” said Dr. Eisenberg.
And a 2018 position paper from the European Pain Federation determined that “the quantity and quality of evidence is such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain,” he said.
He noted that the most recent results from an Israeli prospective cohort registry study that is following more than 851 patients who are taking cannabis over 1 year are positive. Analyses show a steady reduction in pain intensity and improvements in catastrophizing and disability. Importantly, he said, participants are using fewer opioids. However, about 40% of patients in that registry study experienced some adverse event, although most were not serious, said Dr. Eisenberg.
Not convinced
Arguing on the other side – that therapeutic cannabis is not helpful for neuropathic pain – was Nadine Attal, MD, PhD, professor of therapeutics and pain at the University Versailles Saint Quentin, France. She questioned the quality of some of the research to date and stressed that studies should consider neuropathic pain as a primary outcome – not spasticity or pain in general. They should also be double-blind, randomized, and placebo controlled, she said.
In addition, she said these studies should enroll at least 10 patients per group and should continue for 3 weeks or longer.
Dr. Attal wondered which of the many plant derivatives (phytocannabinoids) are used in cannabis studies.
She discussed four meta-analyses or reviews on the topic, some of which she said are “heterogeneous” and don’t provide convincing evidence for cannabis use in neuropathic pain.
For example, one review examined only marijuana, and all studies in it were short term. One of the studies in this review was of spasticity. Another review included two studies of cancer pain, and the most positive study in NP used short-term inhaled THC.
“There is no evidence to date that cannabinoids, including nabiximols or oral THC, administered for at least 3 weeks are more effective than placebo in neuropathic pain,” she concluded.
Some responders
However, Dr. Attal acknowledged that cannabis might be effective for some patients. In her experience, which has been borne out by some observational studies, patients with paroxysmal pain, or sudden stabbing pain, seem to get more relief from cannabis. “It’s absolutely possible that there’s a subgroup of symptoms or a subgroup of patients with specific symptoms who are much better responders to cannabis than others,” she said.
Asked if patients experience increased pain after withdrawing from cannabis, Dr. Eisenberg said he has observed that many patients stop taking cannabis when they start feeling better, but he hasn’t seen severe withdrawal symptoms.
However, there are other concerns related to cannabis use, said Dr. Eisenberg. A major concern regards driving a vehicle. In Israel, getting behind the wheel is prohibited within 6 hours of using cannabis.
But Dr. Eisenberg pointed out that published data on the safety of cannabis and driving were based on recreational users. “We need to keep in mind that recreational users typically use other substances, so we’re not sure the data is accurate,” he said.
There are increasing reports of stroke, transient ischemic attack, and MI among cannabis users. This is especially concerning because many of these cases involve young male adults who have no risk factors, said Dr. Eisenberg.
One conference delegate asked whether legal issues make it difficult to properly investigate cannabis in large studies. Dr. Eisenberg noted that legal concerns may help explain why there have not been any new randomized, controlled trials for about 2 years. “In the U.S., you can’t do clinical trials; cannabis is still regarded as schedule I substance,” he said.
Some physicians “are reluctant to deal with cannabis unless they get better data,” he said. “Doing research on cannabis seems to be somehow out of the mainstream.” Moreover, the research is difficult to carry out, owing to the complexity of the cannabis plant, which has many constituents. Perhaps it’s a matter of identifying and adding particular components to better demonstrate reduced pain, said Dr. Eisenberg.
Another complicating factor is that bioavailability differs considerably from one patient to another, “sometimes even by 10-fold,” he said.
Dr. Attal’s group will be starting a study next January that will enroll a large sample of patients with neuropathic pain or spasticity. In that study, cannabis will be dispensed through pharmacies and primary care. The aim of the study is “to see how it works in a real-life setting,” she said
Those participating in the virtual session were asked to vote on which side they agreed with. About 57% voted in favor of cannabis use, 14% voted against, and 28% had no opinion.
Dr. Eisenberg has received research grants from Rafa Laboratories, Saga Medical Ltd., Israel Pain Association, and Teva Israel. Dr. Attal has received support from Merck Sharp & Dohme, Sanofi, Ipsen, Novartis, Aptinyx, Air Liquide, Lilly, and Grunenthal.
A version of this article originally appeared on Medscape.com.
, a recent debate on the topic suggests. During the debate, one expert argued for, and another against, there being sufficient evidence for the use of cannabis to treat neuropathic pain, but in the end, they agreed that some patients do benefit.
The discussion took place at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual online meeting because of the COVID-19 pandemic.
The cannabis plant has 460 constituents. The two main components are tetrahydrocannabinol (THC) and cannabidiol (CBD). It can be consumed by swallowing oil extracts, by the sublingual route, or by smoking or eating the plant. Cannabis medications already in use include oral THC (nabilone, dronabinol) and an oral mucosal spray, nabiximols (Sativex).
Arguing that therapeutic cannabis is helpful for neuropathic pain, Elon Eisenberg, MD, professor of neurology and pain medicine, Israel Institute of Technology, Haifa, cited a number of encouraging randomized, controlled trials and meta-analyses of studies on the subject.
Opioid substitute
Dr. Eisenberg discussed three relevant articles. One was a 2016 viewpoint article published in JAMA that concluded that “cannabis seems to be a substitute, a rather good one, for opioids,” said Dr. Eisenberg.
A “comprehensive” 440-page review, published by the National Academies Press in 2017, evaluated the evidence to that point and “came to the conclusion there is substantial evidence that cannabis is an effective treatment for chronic pain in adults,” said Dr. Eisenberg.
And a 2018 position paper from the European Pain Federation determined that “the quantity and quality of evidence is such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain,” he said.
He noted that the most recent results from an Israeli prospective cohort registry study that is following more than 851 patients who are taking cannabis over 1 year are positive. Analyses show a steady reduction in pain intensity and improvements in catastrophizing and disability. Importantly, he said, participants are using fewer opioids. However, about 40% of patients in that registry study experienced some adverse event, although most were not serious, said Dr. Eisenberg.
Not convinced
Arguing on the other side – that therapeutic cannabis is not helpful for neuropathic pain – was Nadine Attal, MD, PhD, professor of therapeutics and pain at the University Versailles Saint Quentin, France. She questioned the quality of some of the research to date and stressed that studies should consider neuropathic pain as a primary outcome – not spasticity or pain in general. They should also be double-blind, randomized, and placebo controlled, she said.
In addition, she said these studies should enroll at least 10 patients per group and should continue for 3 weeks or longer.
Dr. Attal wondered which of the many plant derivatives (phytocannabinoids) are used in cannabis studies.
She discussed four meta-analyses or reviews on the topic, some of which she said are “heterogeneous” and don’t provide convincing evidence for cannabis use in neuropathic pain.
For example, one review examined only marijuana, and all studies in it were short term. One of the studies in this review was of spasticity. Another review included two studies of cancer pain, and the most positive study in NP used short-term inhaled THC.
“There is no evidence to date that cannabinoids, including nabiximols or oral THC, administered for at least 3 weeks are more effective than placebo in neuropathic pain,” she concluded.
Some responders
However, Dr. Attal acknowledged that cannabis might be effective for some patients. In her experience, which has been borne out by some observational studies, patients with paroxysmal pain, or sudden stabbing pain, seem to get more relief from cannabis. “It’s absolutely possible that there’s a subgroup of symptoms or a subgroup of patients with specific symptoms who are much better responders to cannabis than others,” she said.
Asked if patients experience increased pain after withdrawing from cannabis, Dr. Eisenberg said he has observed that many patients stop taking cannabis when they start feeling better, but he hasn’t seen severe withdrawal symptoms.
However, there are other concerns related to cannabis use, said Dr. Eisenberg. A major concern regards driving a vehicle. In Israel, getting behind the wheel is prohibited within 6 hours of using cannabis.
But Dr. Eisenberg pointed out that published data on the safety of cannabis and driving were based on recreational users. “We need to keep in mind that recreational users typically use other substances, so we’re not sure the data is accurate,” he said.
There are increasing reports of stroke, transient ischemic attack, and MI among cannabis users. This is especially concerning because many of these cases involve young male adults who have no risk factors, said Dr. Eisenberg.
One conference delegate asked whether legal issues make it difficult to properly investigate cannabis in large studies. Dr. Eisenberg noted that legal concerns may help explain why there have not been any new randomized, controlled trials for about 2 years. “In the U.S., you can’t do clinical trials; cannabis is still regarded as schedule I substance,” he said.
Some physicians “are reluctant to deal with cannabis unless they get better data,” he said. “Doing research on cannabis seems to be somehow out of the mainstream.” Moreover, the research is difficult to carry out, owing to the complexity of the cannabis plant, which has many constituents. Perhaps it’s a matter of identifying and adding particular components to better demonstrate reduced pain, said Dr. Eisenberg.
Another complicating factor is that bioavailability differs considerably from one patient to another, “sometimes even by 10-fold,” he said.
Dr. Attal’s group will be starting a study next January that will enroll a large sample of patients with neuropathic pain or spasticity. In that study, cannabis will be dispensed through pharmacies and primary care. The aim of the study is “to see how it works in a real-life setting,” she said
Those participating in the virtual session were asked to vote on which side they agreed with. About 57% voted in favor of cannabis use, 14% voted against, and 28% had no opinion.
Dr. Eisenberg has received research grants from Rafa Laboratories, Saga Medical Ltd., Israel Pain Association, and Teva Israel. Dr. Attal has received support from Merck Sharp & Dohme, Sanofi, Ipsen, Novartis, Aptinyx, Air Liquide, Lilly, and Grunenthal.
A version of this article originally appeared on Medscape.com.
, a recent debate on the topic suggests. During the debate, one expert argued for, and another against, there being sufficient evidence for the use of cannabis to treat neuropathic pain, but in the end, they agreed that some patients do benefit.
The discussion took place at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual online meeting because of the COVID-19 pandemic.
The cannabis plant has 460 constituents. The two main components are tetrahydrocannabinol (THC) and cannabidiol (CBD). It can be consumed by swallowing oil extracts, by the sublingual route, or by smoking or eating the plant. Cannabis medications already in use include oral THC (nabilone, dronabinol) and an oral mucosal spray, nabiximols (Sativex).
Arguing that therapeutic cannabis is helpful for neuropathic pain, Elon Eisenberg, MD, professor of neurology and pain medicine, Israel Institute of Technology, Haifa, cited a number of encouraging randomized, controlled trials and meta-analyses of studies on the subject.
Opioid substitute
Dr. Eisenberg discussed three relevant articles. One was a 2016 viewpoint article published in JAMA that concluded that “cannabis seems to be a substitute, a rather good one, for opioids,” said Dr. Eisenberg.
A “comprehensive” 440-page review, published by the National Academies Press in 2017, evaluated the evidence to that point and “came to the conclusion there is substantial evidence that cannabis is an effective treatment for chronic pain in adults,” said Dr. Eisenberg.
And a 2018 position paper from the European Pain Federation determined that “the quantity and quality of evidence is such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain,” he said.
He noted that the most recent results from an Israeli prospective cohort registry study that is following more than 851 patients who are taking cannabis over 1 year are positive. Analyses show a steady reduction in pain intensity and improvements in catastrophizing and disability. Importantly, he said, participants are using fewer opioids. However, about 40% of patients in that registry study experienced some adverse event, although most were not serious, said Dr. Eisenberg.
Not convinced
Arguing on the other side – that therapeutic cannabis is not helpful for neuropathic pain – was Nadine Attal, MD, PhD, professor of therapeutics and pain at the University Versailles Saint Quentin, France. She questioned the quality of some of the research to date and stressed that studies should consider neuropathic pain as a primary outcome – not spasticity or pain in general. They should also be double-blind, randomized, and placebo controlled, she said.
In addition, she said these studies should enroll at least 10 patients per group and should continue for 3 weeks or longer.
Dr. Attal wondered which of the many plant derivatives (phytocannabinoids) are used in cannabis studies.
She discussed four meta-analyses or reviews on the topic, some of which she said are “heterogeneous” and don’t provide convincing evidence for cannabis use in neuropathic pain.
For example, one review examined only marijuana, and all studies in it were short term. One of the studies in this review was of spasticity. Another review included two studies of cancer pain, and the most positive study in NP used short-term inhaled THC.
“There is no evidence to date that cannabinoids, including nabiximols or oral THC, administered for at least 3 weeks are more effective than placebo in neuropathic pain,” she concluded.
Some responders
However, Dr. Attal acknowledged that cannabis might be effective for some patients. In her experience, which has been borne out by some observational studies, patients with paroxysmal pain, or sudden stabbing pain, seem to get more relief from cannabis. “It’s absolutely possible that there’s a subgroup of symptoms or a subgroup of patients with specific symptoms who are much better responders to cannabis than others,” she said.
Asked if patients experience increased pain after withdrawing from cannabis, Dr. Eisenberg said he has observed that many patients stop taking cannabis when they start feeling better, but he hasn’t seen severe withdrawal symptoms.
However, there are other concerns related to cannabis use, said Dr. Eisenberg. A major concern regards driving a vehicle. In Israel, getting behind the wheel is prohibited within 6 hours of using cannabis.
But Dr. Eisenberg pointed out that published data on the safety of cannabis and driving were based on recreational users. “We need to keep in mind that recreational users typically use other substances, so we’re not sure the data is accurate,” he said.
There are increasing reports of stroke, transient ischemic attack, and MI among cannabis users. This is especially concerning because many of these cases involve young male adults who have no risk factors, said Dr. Eisenberg.
One conference delegate asked whether legal issues make it difficult to properly investigate cannabis in large studies. Dr. Eisenberg noted that legal concerns may help explain why there have not been any new randomized, controlled trials for about 2 years. “In the U.S., you can’t do clinical trials; cannabis is still regarded as schedule I substance,” he said.
Some physicians “are reluctant to deal with cannabis unless they get better data,” he said. “Doing research on cannabis seems to be somehow out of the mainstream.” Moreover, the research is difficult to carry out, owing to the complexity of the cannabis plant, which has many constituents. Perhaps it’s a matter of identifying and adding particular components to better demonstrate reduced pain, said Dr. Eisenberg.
Another complicating factor is that bioavailability differs considerably from one patient to another, “sometimes even by 10-fold,” he said.
Dr. Attal’s group will be starting a study next January that will enroll a large sample of patients with neuropathic pain or spasticity. In that study, cannabis will be dispensed through pharmacies and primary care. The aim of the study is “to see how it works in a real-life setting,” she said
Those participating in the virtual session were asked to vote on which side they agreed with. About 57% voted in favor of cannabis use, 14% voted against, and 28% had no opinion.
Dr. Eisenberg has received research grants from Rafa Laboratories, Saga Medical Ltd., Israel Pain Association, and Teva Israel. Dr. Attal has received support from Merck Sharp & Dohme, Sanofi, Ipsen, Novartis, Aptinyx, Air Liquide, Lilly, and Grunenthal.
A version of this article originally appeared on Medscape.com.
FROM EAN 2020