Conference Coverage

The popular antipsychotic quetiapine (Seroquel) seems to calm patients with multiple sclerosis (MS) who develop psychiatric distress after taking corticosteroids, a new case review says.

“Our case-report study observed that quetiapine was effective at decreasing irritability, reducing psychological distress, and improving sleep in patients with MS who experienced psychosis symptoms compared with patients who received no treatment. This has changed our practice as we now counsel all patients about the potential side effect of steroid-induced psychosis and discuss treatment options,” said Olinka Hrebicek, MD, medical director of Vancouver Island Multiple Sclerosis Clinic in Victoria, B.C., who was scheduled to present the study findings at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

According to Dr. Hrebicek, who spoke in an interview, nursing staff and neurologists at the Canadian clinic had typically attributed symptoms such as irritability, anger, insomnia, and psychological distress to the stress of experiencing a relapse. The treatment often was a prescription for a benzodiazepine or zopiclone.

In fact, she and colleagues wrote in their report, psychosis following treatment with high-dose corticosteroids for MS may be underreported.

“The purpose of the study was to determine whether quetiapine was effective for treating symptoms of steroid-induced psychosis in patients with MS,” study coauthor and clinic research assistant Niall Murphy said in an interview. “We also wanted to highlight the importance of looking for symptoms of steroid-induced psychosis as this is likely not the primary concern when treating patients for a relapse. In addition, nurses and neurologists may have less experience with the spectrum of clinical symptoms of psychosis than psychiatrists.”

For the case review, researchers examined 10 reports (8 female) of patients who had signs of psychiatric distress after treatment with steroids. Eight of the patients were treated with quetiapine (six female, two male).

All those who took quetiapine experienced benefits, while the two others didn’t improve.

Commenting on the study, E. Sherwood Brown, MD, PhD, MBA, professor of psychiatry at the University of Texas Southwestern Medical Center, Dallas, said in an interview that psychosis may not appear as expected in patients who develop it as a result of corticosteroid use. “Typically, psychosis refers to delusions, hallucinations, or disorganized thought processes. However, with corticosteroids severe mood and cognitive changes [for example, delirium] are also often included in the definition. Mild mood and memory changes appear to be fairly common with prescription corticosteroids. More severe symptoms are less common.”

Higher doses of corticosteroids – like those used in MS – boost the risk of psychosis, said Dr. Brown, who was not involved in the study.

As for quetiapine, Dr. Brown said it could be a good treatment option. “The use of quetiapine, a drug approved for schizophrenia and mania, is consistent with the idea suggested in the literature that the symptoms with corticosteroids tend to be similar to those of bipolar disorder and that they respond to medications for bipolar disorder,” he said. “A potential concern is that both corticosteroids and quetiapine can cause weight gain. However, this may not be a major problem with a brief course of the corticosteroids. It would be great to see a randomized, controlled trial.”

In British Columbia, the Victoria clinic has changed policy as a result of the analysis, Dr. Hrebicek said. “Nurses and physicians now ask more specific questions to decide if patients are experiencing symptoms of steroid-induced psychosis and whether they should be treated with an antipsychotic medication.”

And now, report coauthor Mr. Murphy said, “our clinic proactively offers patients a prescription for quetiapine that they can fill if they are experiencing symptoms of steroid psychosis.”

Dr. Brown supported the new policy of alerting patients to the psychosis risk. “Counseling patients about common side effects is a good idea,” he said. “I have seen data suggesting that patients may be hesitant to report psychiatric symptoms with corticosteroids to their physicians. Letting them know about the potential for these kinds of side effects might make them more forthcoming in reporting this side effect.”

No study funding is reported. The study authors reported no disclosures. Dr. Brown has a National Institutes of Health grant for studying the effect of corticosteroids on the brain.
 

The popular antipsychotic quetiapine (Seroquel) seems to calm patients with multiple sclerosis (MS) who develop psychiatric distress after taking corticosteroids, a new case review says.

“Our case-report study observed that quetiapine was effective at decreasing irritability, reducing psychological distress, and improving sleep in patients with MS who experienced psychosis symptoms compared with patients who received no treatment. This has changed our practice as we now counsel all patients about the potential side effect of steroid-induced psychosis and discuss treatment options,” said Olinka Hrebicek, MD, medical director of Vancouver Island Multiple Sclerosis Clinic in Victoria, B.C., who was scheduled to present the study findings at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

According to Dr. Hrebicek, who spoke in an interview, nursing staff and neurologists at the Canadian clinic had typically attributed symptoms such as irritability, anger, insomnia, and psychological distress to the stress of experiencing a relapse. The treatment often was a prescription for a benzodiazepine or zopiclone.

In fact, she and colleagues wrote in their report, psychosis following treatment with high-dose corticosteroids for MS may be underreported.

“The purpose of the study was to determine whether quetiapine was effective for treating symptoms of steroid-induced psychosis in patients with MS,” study coauthor and clinic research assistant Niall Murphy said in an interview. “We also wanted to highlight the importance of looking for symptoms of steroid-induced psychosis as this is likely not the primary concern when treating patients for a relapse. In addition, nurses and neurologists may have less experience with the spectrum of clinical symptoms of psychosis than psychiatrists.”

For the case review, researchers examined 10 reports (8 female) of patients who had signs of psychiatric distress after treatment with steroids. Eight of the patients were treated with quetiapine (six female, two male).

All those who took quetiapine experienced benefits, while the two others didn’t improve.

Commenting on the study, E. Sherwood Brown, MD, PhD, MBA, professor of psychiatry at the University of Texas Southwestern Medical Center, Dallas, said in an interview that psychosis may not appear as expected in patients who develop it as a result of corticosteroid use. “Typically, psychosis refers to delusions, hallucinations, or disorganized thought processes. However, with corticosteroids severe mood and cognitive changes [for example, delirium] are also often included in the definition. Mild mood and memory changes appear to be fairly common with prescription corticosteroids. More severe symptoms are less common.”

Higher doses of corticosteroids – like those used in MS – boost the risk of psychosis, said Dr. Brown, who was not involved in the study.

As for quetiapine, Dr. Brown said it could be a good treatment option. “The use of quetiapine, a drug approved for schizophrenia and mania, is consistent with the idea suggested in the literature that the symptoms with corticosteroids tend to be similar to those of bipolar disorder and that they respond to medications for bipolar disorder,” he said. “A potential concern is that both corticosteroids and quetiapine can cause weight gain. However, this may not be a major problem with a brief course of the corticosteroids. It would be great to see a randomized, controlled trial.”

In British Columbia, the Victoria clinic has changed policy as a result of the analysis, Dr. Hrebicek said. “Nurses and physicians now ask more specific questions to decide if patients are experiencing symptoms of steroid-induced psychosis and whether they should be treated with an antipsychotic medication.”

And now, report coauthor Mr. Murphy said, “our clinic proactively offers patients a prescription for quetiapine that they can fill if they are experiencing symptoms of steroid psychosis.”

Dr. Brown supported the new policy of alerting patients to the psychosis risk. “Counseling patients about common side effects is a good idea,” he said. “I have seen data suggesting that patients may be hesitant to report psychiatric symptoms with corticosteroids to their physicians. Letting them know about the potential for these kinds of side effects might make them more forthcoming in reporting this side effect.”

No study funding is reported. The study authors reported no disclosures. Dr. Brown has a National Institutes of Health grant for studying the effect of corticosteroids on the brain.
 

The popular antipsychotic quetiapine (Seroquel) seems to calm patients with multiple sclerosis (MS) who develop psychiatric distress after taking corticosteroids, a new case review says.

“Our case-report study observed that quetiapine was effective at decreasing irritability, reducing psychological distress, and improving sleep in patients with MS who experienced psychosis symptoms compared with patients who received no treatment. This has changed our practice as we now counsel all patients about the potential side effect of steroid-induced psychosis and discuss treatment options,” said Olinka Hrebicek, MD, medical director of Vancouver Island Multiple Sclerosis Clinic in Victoria, B.C., who was scheduled to present the study findings at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

According to Dr. Hrebicek, who spoke in an interview, nursing staff and neurologists at the Canadian clinic had typically attributed symptoms such as irritability, anger, insomnia, and psychological distress to the stress of experiencing a relapse. The treatment often was a prescription for a benzodiazepine or zopiclone.

In fact, she and colleagues wrote in their report, psychosis following treatment with high-dose corticosteroids for MS may be underreported.

“The purpose of the study was to determine whether quetiapine was effective for treating symptoms of steroid-induced psychosis in patients with MS,” study coauthor and clinic research assistant Niall Murphy said in an interview. “We also wanted to highlight the importance of looking for symptoms of steroid-induced psychosis as this is likely not the primary concern when treating patients for a relapse. In addition, nurses and neurologists may have less experience with the spectrum of clinical symptoms of psychosis than psychiatrists.”

For the case review, researchers examined 10 reports (8 female) of patients who had signs of psychiatric distress after treatment with steroids. Eight of the patients were treated with quetiapine (six female, two male).

All those who took quetiapine experienced benefits, while the two others didn’t improve.

Commenting on the study, E. Sherwood Brown, MD, PhD, MBA, professor of psychiatry at the University of Texas Southwestern Medical Center, Dallas, said in an interview that psychosis may not appear as expected in patients who develop it as a result of corticosteroid use. “Typically, psychosis refers to delusions, hallucinations, or disorganized thought processes. However, with corticosteroids severe mood and cognitive changes [for example, delirium] are also often included in the definition. Mild mood and memory changes appear to be fairly common with prescription corticosteroids. More severe symptoms are less common.”

Higher doses of corticosteroids – like those used in MS – boost the risk of psychosis, said Dr. Brown, who was not involved in the study.

As for quetiapine, Dr. Brown said it could be a good treatment option. “The use of quetiapine, a drug approved for schizophrenia and mania, is consistent with the idea suggested in the literature that the symptoms with corticosteroids tend to be similar to those of bipolar disorder and that they respond to medications for bipolar disorder,” he said. “A potential concern is that both corticosteroids and quetiapine can cause weight gain. However, this may not be a major problem with a brief course of the corticosteroids. It would be great to see a randomized, controlled trial.”

In British Columbia, the Victoria clinic has changed policy as a result of the analysis, Dr. Hrebicek said. “Nurses and physicians now ask more specific questions to decide if patients are experiencing symptoms of steroid-induced psychosis and whether they should be treated with an antipsychotic medication.”

And now, report coauthor Mr. Murphy said, “our clinic proactively offers patients a prescription for quetiapine that they can fill if they are experiencing symptoms of steroid psychosis.”

Dr. Brown supported the new policy of alerting patients to the psychosis risk. “Counseling patients about common side effects is a good idea,” he said. “I have seen data suggesting that patients may be hesitant to report psychiatric symptoms with corticosteroids to their physicians. Letting them know about the potential for these kinds of side effects might make them more forthcoming in reporting this side effect.”

No study funding is reported. The study authors reported no disclosures. Dr. Brown has a National Institutes of Health grant for studying the effect of corticosteroids on the brain.
 

Several antiepileptic drugs (AEDs) are associated with an increased risk for priapism, new research suggests.

©Thinkstock

After analyzing U.S. adverse event reporting data, investigators found that among nearly 200 cases of priapism, a persistent, often painful erection unrelated to sexual interest or stimulation that lasts more than 4 hours, eight AEDs were associated with a positive “safety signal” for priapism.

These included valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine. Of these, valpromide had the largest association.

“Based on our results, we would recommend to clinicians to be cautious about the possibility of encountering priapism” in patients receiving the eight AEDs identified, lead researcher Ana Pejcic, PhD, department of pharmacology and toxicology, University of Kragujevac, Serbia, told meeting attendees.

If clinicians encounter such cases, they should be “reported to the regulatory authorities,” Dr. Pejcic added.

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

Noteworthy limitations

Dr. Pejcic told this news organization that the safety signal with AEDs “does not directly mean that a medicine has caused the reported adverse event” because an illness or other drug taken by the patient could be responsible instead.

She also noted that the U.S. Food and Drug Administration’s Adverse Event Reporting System relies on “spontaneous reports of adverse events,” which have multiple limitations.

These limitations include that the FDA “does not require that a causal relationship between a drug and event be proven, and reports do not always have enough information to properly evaluate an event.”

Nevertheless, Dr. Pejcic added that if a causal relationship was to be shown, the underlying mechanism could be linked to the pharmacological properties of the individual antiepileptic, such as altered alpha-1 adrenergic receptor expression or increased dopamine release.

Still, that would require “further evaluation in larger pharmacoepidemiological studies, with adjustment for potential confounding variables,” she said.
 

Replication needed

Priapism has recently been observed in case reports in association with the use of some AEDs. In addition, use of the drugs has been associated with hypo- and hypersexuality, as well as erectile and ejaculatory dysfunction.

Because the relationship between priapism and AED use “has not been well characterized,” the researchers mined data from the FDA’s Adverse Event Reporting System.

They examined entries from the first quarter of 2004 and the third quarter of 2020, focusing on 47 AEDs from the N03A subgroup of the Anatomical Therapeutic Chemical Classification System.

The researchers identified 8,122,037 cases for data analysis, of which 1,936 involved priapism as an adverse event. In total, 16 antiepileptic medications had at least one case of an adverse event involving priapism.

A positive safety signal was defined as a Proportional Reporting Ratio (PRR) of at least two, a chi-squared of at least four, or three or more cases. The signal was detected for valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine.

The largest association with priapism was with valpromide, at a PRR of 61.79. That was followed by PRR of 9.61 for brivaracetam, 7.28 for valproic acid, and 3.23 for topiramate.

“Considering that the proportionality analysis we applied in our study is used for hypothesis generation, our results will need to confirm in large cohorts and case-control studies,” said Dr. Pejcic.
 

New and important hypothesis?

Commenting on the study, Daniel Goldenholz, MD, PhD, instructor in the Division of Epilepsy, Beth Israel Deaconess Medical Center, Boston, said priapism is not something that practicing epileptologists are instructed “to look for.”

He noted that “the idea of looking for a hidden signal in a massive database like this is very appealing” because it could reveal patterns that were previously undetected.

However, the event rate in the study suggests priapism, which “in the right context would be considered a medical emergency, [is] relatively uncommon,” said Dr. Goldenholz, who was not involved with the research.

He noted that medications that could cause priapism, “such as antidepressants, blood pressure meds, and anticoagulants,” are commonly used by many people – including those with epilepsy.

It is consequently possible that “the finding from this study can be explained by comorbid medical problems,” Dr. Goldenholz said. This is particularly likely because many of the AEDs in question “have been on the market for decades,” he added.

“If a seemingly dangerous symptom would be happening as a result of one of these medications, it is quite surprising that it has not been noticed sooner,” he said.

Still, Dr. Goldenholz noted that it is “possible that these authors have a new and important hypothesis which must now be tested: Does priapism occur in patients with antiseizure medications when other causes are already ruled out?”

The investigators and Dr. Goldenholz have disclosed no relevant financial relationships.

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

Several antiepileptic drugs (AEDs) are associated with an increased risk for priapism, new research suggests.

©Thinkstock

After analyzing U.S. adverse event reporting data, investigators found that among nearly 200 cases of priapism, a persistent, often painful erection unrelated to sexual interest or stimulation that lasts more than 4 hours, eight AEDs were associated with a positive “safety signal” for priapism.

These included valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine. Of these, valpromide had the largest association.

“Based on our results, we would recommend to clinicians to be cautious about the possibility of encountering priapism” in patients receiving the eight AEDs identified, lead researcher Ana Pejcic, PhD, department of pharmacology and toxicology, University of Kragujevac, Serbia, told meeting attendees.

If clinicians encounter such cases, they should be “reported to the regulatory authorities,” Dr. Pejcic added.

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

Noteworthy limitations

Dr. Pejcic told this news organization that the safety signal with AEDs “does not directly mean that a medicine has caused the reported adverse event” because an illness or other drug taken by the patient could be responsible instead.

She also noted that the U.S. Food and Drug Administration’s Adverse Event Reporting System relies on “spontaneous reports of adverse events,” which have multiple limitations.

These limitations include that the FDA “does not require that a causal relationship between a drug and event be proven, and reports do not always have enough information to properly evaluate an event.”

Nevertheless, Dr. Pejcic added that if a causal relationship was to be shown, the underlying mechanism could be linked to the pharmacological properties of the individual antiepileptic, such as altered alpha-1 adrenergic receptor expression or increased dopamine release.

Still, that would require “further evaluation in larger pharmacoepidemiological studies, with adjustment for potential confounding variables,” she said.
 

Replication needed

Priapism has recently been observed in case reports in association with the use of some AEDs. In addition, use of the drugs has been associated with hypo- and hypersexuality, as well as erectile and ejaculatory dysfunction.

Because the relationship between priapism and AED use “has not been well characterized,” the researchers mined data from the FDA’s Adverse Event Reporting System.

They examined entries from the first quarter of 2004 and the third quarter of 2020, focusing on 47 AEDs from the N03A subgroup of the Anatomical Therapeutic Chemical Classification System.

The researchers identified 8,122,037 cases for data analysis, of which 1,936 involved priapism as an adverse event. In total, 16 antiepileptic medications had at least one case of an adverse event involving priapism.

A positive safety signal was defined as a Proportional Reporting Ratio (PRR) of at least two, a chi-squared of at least four, or three or more cases. The signal was detected for valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine.

The largest association with priapism was with valpromide, at a PRR of 61.79. That was followed by PRR of 9.61 for brivaracetam, 7.28 for valproic acid, and 3.23 for topiramate.

“Considering that the proportionality analysis we applied in our study is used for hypothesis generation, our results will need to confirm in large cohorts and case-control studies,” said Dr. Pejcic.
 

New and important hypothesis?

Commenting on the study, Daniel Goldenholz, MD, PhD, instructor in the Division of Epilepsy, Beth Israel Deaconess Medical Center, Boston, said priapism is not something that practicing epileptologists are instructed “to look for.”

He noted that “the idea of looking for a hidden signal in a massive database like this is very appealing” because it could reveal patterns that were previously undetected.

However, the event rate in the study suggests priapism, which “in the right context would be considered a medical emergency, [is] relatively uncommon,” said Dr. Goldenholz, who was not involved with the research.

He noted that medications that could cause priapism, “such as antidepressants, blood pressure meds, and anticoagulants,” are commonly used by many people – including those with epilepsy.

It is consequently possible that “the finding from this study can be explained by comorbid medical problems,” Dr. Goldenholz said. This is particularly likely because many of the AEDs in question “have been on the market for decades,” he added.

“If a seemingly dangerous symptom would be happening as a result of one of these medications, it is quite surprising that it has not been noticed sooner,” he said.

Still, Dr. Goldenholz noted that it is “possible that these authors have a new and important hypothesis which must now be tested: Does priapism occur in patients with antiseizure medications when other causes are already ruled out?”

The investigators and Dr. Goldenholz have disclosed no relevant financial relationships.

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

Several antiepileptic drugs (AEDs) are associated with an increased risk for priapism, new research suggests.

©Thinkstock

After analyzing U.S. adverse event reporting data, investigators found that among nearly 200 cases of priapism, a persistent, often painful erection unrelated to sexual interest or stimulation that lasts more than 4 hours, eight AEDs were associated with a positive “safety signal” for priapism.

These included valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine. Of these, valpromide had the largest association.

“Based on our results, we would recommend to clinicians to be cautious about the possibility of encountering priapism” in patients receiving the eight AEDs identified, lead researcher Ana Pejcic, PhD, department of pharmacology and toxicology, University of Kragujevac, Serbia, told meeting attendees.

If clinicians encounter such cases, they should be “reported to the regulatory authorities,” Dr. Pejcic added.

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

Noteworthy limitations

Dr. Pejcic told this news organization that the safety signal with AEDs “does not directly mean that a medicine has caused the reported adverse event” because an illness or other drug taken by the patient could be responsible instead.

She also noted that the U.S. Food and Drug Administration’s Adverse Event Reporting System relies on “spontaneous reports of adverse events,” which have multiple limitations.

These limitations include that the FDA “does not require that a causal relationship between a drug and event be proven, and reports do not always have enough information to properly evaluate an event.”

Nevertheless, Dr. Pejcic added that if a causal relationship was to be shown, the underlying mechanism could be linked to the pharmacological properties of the individual antiepileptic, such as altered alpha-1 adrenergic receptor expression or increased dopamine release.

Still, that would require “further evaluation in larger pharmacoepidemiological studies, with adjustment for potential confounding variables,” she said.
 

Replication needed

Priapism has recently been observed in case reports in association with the use of some AEDs. In addition, use of the drugs has been associated with hypo- and hypersexuality, as well as erectile and ejaculatory dysfunction.

Because the relationship between priapism and AED use “has not been well characterized,” the researchers mined data from the FDA’s Adverse Event Reporting System.

They examined entries from the first quarter of 2004 and the third quarter of 2020, focusing on 47 AEDs from the N03A subgroup of the Anatomical Therapeutic Chemical Classification System.

The researchers identified 8,122,037 cases for data analysis, of which 1,936 involved priapism as an adverse event. In total, 16 antiepileptic medications had at least one case of an adverse event involving priapism.

A positive safety signal was defined as a Proportional Reporting Ratio (PRR) of at least two, a chi-squared of at least four, or three or more cases. The signal was detected for valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine.

The largest association with priapism was with valpromide, at a PRR of 61.79. That was followed by PRR of 9.61 for brivaracetam, 7.28 for valproic acid, and 3.23 for topiramate.

“Considering that the proportionality analysis we applied in our study is used for hypothesis generation, our results will need to confirm in large cohorts and case-control studies,” said Dr. Pejcic.
 

New and important hypothesis?

Commenting on the study, Daniel Goldenholz, MD, PhD, instructor in the Division of Epilepsy, Beth Israel Deaconess Medical Center, Boston, said priapism is not something that practicing epileptologists are instructed “to look for.”

He noted that “the idea of looking for a hidden signal in a massive database like this is very appealing” because it could reveal patterns that were previously undetected.

However, the event rate in the study suggests priapism, which “in the right context would be considered a medical emergency, [is] relatively uncommon,” said Dr. Goldenholz, who was not involved with the research.

He noted that medications that could cause priapism, “such as antidepressants, blood pressure meds, and anticoagulants,” are commonly used by many people – including those with epilepsy.

It is consequently possible that “the finding from this study can be explained by comorbid medical problems,” Dr. Goldenholz said. This is particularly likely because many of the AEDs in question “have been on the market for decades,” he added.

“If a seemingly dangerous symptom would be happening as a result of one of these medications, it is quite surprising that it has not been noticed sooner,” he said.

Still, Dr. Goldenholz noted that it is “possible that these authors have a new and important hypothesis which must now be tested: Does priapism occur in patients with antiseizure medications when other causes are already ruled out?”

The investigators and Dr. Goldenholz have disclosed no relevant financial relationships.

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

Most patients with advanced chronic kidney disease (CKD) and non–ST-elevation myocardial infarction (NSTEMI) fare better with coronary angiography with and without revascularization than with medical therapy, a large nationwide study suggests.

Bruce Jancin/MDedge News

“Invasive management was associated with lower mortality, major adverse cardiovascular events (MACE), and need for revascularization, with a minimal increased risk of in-hospital, postprocedural acute kidney injury (AKI) requiring dialysis and major bleeding,” said lead researcher Ankur Kalra, MD, Cleveland Clinic.

Also, similar post-discharge safety outcomes were seen at 6 months, he said in an online presentation of “key abstracts” released in advance of next month’s Transcatheter Cardiovascular Therapeutics (TCT) 2021 hybrid meeting.

Advanced CKD is an independent predictor of mortality and morbidity in patients with NSTEMI. In CKD, however, current guidelines lack evidence on the efficacy and safety of invasive versus medical management, he noted.

A rare randomized clinical trial in this high-risk population, ISCHEMIA-CKD, recently found no benefit and an increase in stroke with initial invasive management compared with optimal medical therapy.

Session co-moderator Ziad A. Ali, MD, DPhil, St. Francis Hospital & Heart Center, New York, said the current study is “incredibly clinically impactful and answers a question that’s very difficult to answer because these patients aren’t randomized in randomized controlled trials, and there’s a general avoidance, which we’ve now coined ‘renalism,’ like racism, where people don’t really want to touch these patients.”

He questioned, however, how the authors reconcile the results of ISCHEMIA-CKD, a “small but meaningful randomized controlled trial,” with their findings from a large dataset. “Perhaps this is all selection bias, even though the numbers are very large.”

Dr. Kalra replied that ISCHEMIA-CKD examined stable ischemic heart disease, whereas they looked at NSTEMI. “Even though it may fall under the same rubric, I truly believe it is a different set of patients – they are at a heightened risk for future cardiovascular events and have had an acute coronary event.”

For the study, ICD-10 coding data from 2016-2018 in the Nationwide Readmission Database was used to identify NSTEMI patients with CKD stages 3, 4, 5, and end-stage renal disease (ESRD). A total of 141,052 patients were available for in-hospital outcomes and 133,642 patients for post-discharge outcomes.

In-hospital and 6-month mortality – the study’s primary outcome – favored invasive management across all CKD stages and ESRD but did not achieve statistical significance for CKD stage 5. The number needed to treat (NNT) for CKD stages 3, 4, 5, and ESRD were 26, 56, 48, and 18, respectively.

Six-month MACE, including mortality, MI, stroke, and heart failure readmission, was significantly better in all groups with invasive management.

Kaplan-Meier curves for mortality showed similar benefits with an invasive strategy across CKD stages, again barring stage 5 disease. 

With regard to in-hospital safety, stroke rates were not significantly different between the two treatment strategies across all groups.

Rates of AKI requiring dialysis, however, were lower with medical versus invasive management for CKD stage 3 (0.43% vs. 0.6%; hazard ratio, 1.39; P = .016), stage 4 (1.2% vs. 2.0%; HR 1.87; P < .001), and stage 5 (3.7% vs. 4.3%; HR 1.17; P = .527). The number needed to harm (NNH) was 588 for CKD 3 and 125 for CKD 4.

Major bleeding, defined as requiring transfusion, was lower with medical management for all CKD stages but not for ESRD. The rates are as follows:

• CKD stage 3: 2.5% vs. 2.8% (HR, 1.11; P = .078; NNH = 333)
• CKD stage 4: 2.9% vs. 4.0% (HR, 1.42; P < .001; NNH = 91)
• CKD stage 5: 2.2% vs. 4.7% (HR, 2.17; P = .008; NNH = 40)
• ESRD: 3.4% vs. 3.3% (HR, 0.97; P = .709)

“The risk of AKI requiring dialysis and bleeding, as has been shown previously in other studies, was high, but the number needed to harm was also high,” observed Dr. Kalra.

A separate analysis showed no difference in rates of AKI requiring dialysis among patients with CKD stages 3 and 4 who underwent angiography without revascularization and their peers who were medically managed.

Rates of the composite safety outcome of vascular complications, major bleeding, AKI, or stroke readmission at 6 months were not significantly different for invasive versus medical management for CKD stage 3 (both 3.3%), stage 4 (4.5% and 4.2%), stage 5 (3.9% vs. 4.3%), and ESRD (2.3% vs. 2.1%).

Besides the inherent limitations of observational studies and potential for selection bias, Dr. Kalra pointed out that the analysis relied on coding data for exact glomerular filtration rates and lacked information on contrast use, crystalloids before the procedure, and nephrotoxic medication use before or during admission. Out-of-hospital mortality was also not available in the database.

Co-moderator Allen Jeremias, MD, also with St. Francis Hospital & Heart Center, said one of the study’s strengths was that it included all comers, unlike randomized trials that typically exclude the highest risk patients.

“So, when we do these trials it’s very difficult to find the right balance, whereas this is a real-world analysis including everybody, and I think the benefits are clearly demonstrated,” he said. “So I think I’m bullish on doing complex [percutaneous coronary intervention] PCI in this patient population.”

Dr. Kalra reports having no relevant financial relationships.

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

Most patients with advanced chronic kidney disease (CKD) and non–ST-elevation myocardial infarction (NSTEMI) fare better with coronary angiography with and without revascularization than with medical therapy, a large nationwide study suggests.

Bruce Jancin/MDedge News

“Invasive management was associated with lower mortality, major adverse cardiovascular events (MACE), and need for revascularization, with a minimal increased risk of in-hospital, postprocedural acute kidney injury (AKI) requiring dialysis and major bleeding,” said lead researcher Ankur Kalra, MD, Cleveland Clinic.

Also, similar post-discharge safety outcomes were seen at 6 months, he said in an online presentation of “key abstracts” released in advance of next month’s Transcatheter Cardiovascular Therapeutics (TCT) 2021 hybrid meeting.

Advanced CKD is an independent predictor of mortality and morbidity in patients with NSTEMI. In CKD, however, current guidelines lack evidence on the efficacy and safety of invasive versus medical management, he noted.

A rare randomized clinical trial in this high-risk population, ISCHEMIA-CKD, recently found no benefit and an increase in stroke with initial invasive management compared with optimal medical therapy.

Session co-moderator Ziad A. Ali, MD, DPhil, St. Francis Hospital & Heart Center, New York, said the current study is “incredibly clinically impactful and answers a question that’s very difficult to answer because these patients aren’t randomized in randomized controlled trials, and there’s a general avoidance, which we’ve now coined ‘renalism,’ like racism, where people don’t really want to touch these patients.”

He questioned, however, how the authors reconcile the results of ISCHEMIA-CKD, a “small but meaningful randomized controlled trial,” with their findings from a large dataset. “Perhaps this is all selection bias, even though the numbers are very large.”

Dr. Kalra replied that ISCHEMIA-CKD examined stable ischemic heart disease, whereas they looked at NSTEMI. “Even though it may fall under the same rubric, I truly believe it is a different set of patients – they are at a heightened risk for future cardiovascular events and have had an acute coronary event.”

For the study, ICD-10 coding data from 2016-2018 in the Nationwide Readmission Database was used to identify NSTEMI patients with CKD stages 3, 4, 5, and end-stage renal disease (ESRD). A total of 141,052 patients were available for in-hospital outcomes and 133,642 patients for post-discharge outcomes.

In-hospital and 6-month mortality – the study’s primary outcome – favored invasive management across all CKD stages and ESRD but did not achieve statistical significance for CKD stage 5. The number needed to treat (NNT) for CKD stages 3, 4, 5, and ESRD were 26, 56, 48, and 18, respectively.

Six-month MACE, including mortality, MI, stroke, and heart failure readmission, was significantly better in all groups with invasive management.

Kaplan-Meier curves for mortality showed similar benefits with an invasive strategy across CKD stages, again barring stage 5 disease. 

With regard to in-hospital safety, stroke rates were not significantly different between the two treatment strategies across all groups.

Rates of AKI requiring dialysis, however, were lower with medical versus invasive management for CKD stage 3 (0.43% vs. 0.6%; hazard ratio, 1.39; P = .016), stage 4 (1.2% vs. 2.0%; HR 1.87; P < .001), and stage 5 (3.7% vs. 4.3%; HR 1.17; P = .527). The number needed to harm (NNH) was 588 for CKD 3 and 125 for CKD 4.

Major bleeding, defined as requiring transfusion, was lower with medical management for all CKD stages but not for ESRD. The rates are as follows:

• CKD stage 3: 2.5% vs. 2.8% (HR, 1.11; P = .078; NNH = 333)
• CKD stage 4: 2.9% vs. 4.0% (HR, 1.42; P < .001; NNH = 91)
• CKD stage 5: 2.2% vs. 4.7% (HR, 2.17; P = .008; NNH = 40)
• ESRD: 3.4% vs. 3.3% (HR, 0.97; P = .709)

“The risk of AKI requiring dialysis and bleeding, as has been shown previously in other studies, was high, but the number needed to harm was also high,” observed Dr. Kalra.

A separate analysis showed no difference in rates of AKI requiring dialysis among patients with CKD stages 3 and 4 who underwent angiography without revascularization and their peers who were medically managed.

Rates of the composite safety outcome of vascular complications, major bleeding, AKI, or stroke readmission at 6 months were not significantly different for invasive versus medical management for CKD stage 3 (both 3.3%), stage 4 (4.5% and 4.2%), stage 5 (3.9% vs. 4.3%), and ESRD (2.3% vs. 2.1%).

Besides the inherent limitations of observational studies and potential for selection bias, Dr. Kalra pointed out that the analysis relied on coding data for exact glomerular filtration rates and lacked information on contrast use, crystalloids before the procedure, and nephrotoxic medication use before or during admission. Out-of-hospital mortality was also not available in the database.

Co-moderator Allen Jeremias, MD, also with St. Francis Hospital & Heart Center, said one of the study’s strengths was that it included all comers, unlike randomized trials that typically exclude the highest risk patients.

“So, when we do these trials it’s very difficult to find the right balance, whereas this is a real-world analysis including everybody, and I think the benefits are clearly demonstrated,” he said. “So I think I’m bullish on doing complex [percutaneous coronary intervention] PCI in this patient population.”

Dr. Kalra reports having no relevant financial relationships.

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

Most patients with advanced chronic kidney disease (CKD) and non–ST-elevation myocardial infarction (NSTEMI) fare better with coronary angiography with and without revascularization than with medical therapy, a large nationwide study suggests.

Bruce Jancin/MDedge News

“Invasive management was associated with lower mortality, major adverse cardiovascular events (MACE), and need for revascularization, with a minimal increased risk of in-hospital, postprocedural acute kidney injury (AKI) requiring dialysis and major bleeding,” said lead researcher Ankur Kalra, MD, Cleveland Clinic.

Also, similar post-discharge safety outcomes were seen at 6 months, he said in an online presentation of “key abstracts” released in advance of next month’s Transcatheter Cardiovascular Therapeutics (TCT) 2021 hybrid meeting.

Advanced CKD is an independent predictor of mortality and morbidity in patients with NSTEMI. In CKD, however, current guidelines lack evidence on the efficacy and safety of invasive versus medical management, he noted.

A rare randomized clinical trial in this high-risk population, ISCHEMIA-CKD, recently found no benefit and an increase in stroke with initial invasive management compared with optimal medical therapy.

Session co-moderator Ziad A. Ali, MD, DPhil, St. Francis Hospital & Heart Center, New York, said the current study is “incredibly clinically impactful and answers a question that’s very difficult to answer because these patients aren’t randomized in randomized controlled trials, and there’s a general avoidance, which we’ve now coined ‘renalism,’ like racism, where people don’t really want to touch these patients.”

He questioned, however, how the authors reconcile the results of ISCHEMIA-CKD, a “small but meaningful randomized controlled trial,” with their findings from a large dataset. “Perhaps this is all selection bias, even though the numbers are very large.”

Dr. Kalra replied that ISCHEMIA-CKD examined stable ischemic heart disease, whereas they looked at NSTEMI. “Even though it may fall under the same rubric, I truly believe it is a different set of patients – they are at a heightened risk for future cardiovascular events and have had an acute coronary event.”

For the study, ICD-10 coding data from 2016-2018 in the Nationwide Readmission Database was used to identify NSTEMI patients with CKD stages 3, 4, 5, and end-stage renal disease (ESRD). A total of 141,052 patients were available for in-hospital outcomes and 133,642 patients for post-discharge outcomes.

In-hospital and 6-month mortality – the study’s primary outcome – favored invasive management across all CKD stages and ESRD but did not achieve statistical significance for CKD stage 5. The number needed to treat (NNT) for CKD stages 3, 4, 5, and ESRD were 26, 56, 48, and 18, respectively.

Six-month MACE, including mortality, MI, stroke, and heart failure readmission, was significantly better in all groups with invasive management.

Kaplan-Meier curves for mortality showed similar benefits with an invasive strategy across CKD stages, again barring stage 5 disease. 

With regard to in-hospital safety, stroke rates were not significantly different between the two treatment strategies across all groups.

Rates of AKI requiring dialysis, however, were lower with medical versus invasive management for CKD stage 3 (0.43% vs. 0.6%; hazard ratio, 1.39; P = .016), stage 4 (1.2% vs. 2.0%; HR 1.87; P < .001), and stage 5 (3.7% vs. 4.3%; HR 1.17; P = .527). The number needed to harm (NNH) was 588 for CKD 3 and 125 for CKD 4.

Major bleeding, defined as requiring transfusion, was lower with medical management for all CKD stages but not for ESRD. The rates are as follows:

• CKD stage 3: 2.5% vs. 2.8% (HR, 1.11; P = .078; NNH = 333)
• CKD stage 4: 2.9% vs. 4.0% (HR, 1.42; P < .001; NNH = 91)
• CKD stage 5: 2.2% vs. 4.7% (HR, 2.17; P = .008; NNH = 40)
• ESRD: 3.4% vs. 3.3% (HR, 0.97; P = .709)

“The risk of AKI requiring dialysis and bleeding, as has been shown previously in other studies, was high, but the number needed to harm was also high,” observed Dr. Kalra.

A separate analysis showed no difference in rates of AKI requiring dialysis among patients with CKD stages 3 and 4 who underwent angiography without revascularization and their peers who were medically managed.

Rates of the composite safety outcome of vascular complications, major bleeding, AKI, or stroke readmission at 6 months were not significantly different for invasive versus medical management for CKD stage 3 (both 3.3%), stage 4 (4.5% and 4.2%), stage 5 (3.9% vs. 4.3%), and ESRD (2.3% vs. 2.1%).

Besides the inherent limitations of observational studies and potential for selection bias, Dr. Kalra pointed out that the analysis relied on coding data for exact glomerular filtration rates and lacked information on contrast use, crystalloids before the procedure, and nephrotoxic medication use before or during admission. Out-of-hospital mortality was also not available in the database.

Co-moderator Allen Jeremias, MD, also with St. Francis Hospital & Heart Center, said one of the study’s strengths was that it included all comers, unlike randomized trials that typically exclude the highest risk patients.

“So, when we do these trials it’s very difficult to find the right balance, whereas this is a real-world analysis including everybody, and I think the benefits are clearly demonstrated,” he said. “So I think I’m bullish on doing complex [percutaneous coronary intervention] PCI in this patient population.”

Dr. Kalra reports having no relevant financial relationships.

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

Autologous hematopoietic stem cell transplantation for the treatment of active secondary progressive multiple sclerosis (MS) is associated with better disability outcomes than other immunotherapies, a new Italian study suggests.

In the study, stem cell transplant was associated with a slowing of disability progression and a higher likelihood of disability improvement in patients with secondary progressive MS compared with other disease-modifying therapies.

“Our study shows that, although limited, sustained disability improvement is still possible during early active secondary progressive MS and seems to be more likely with stem cell transplant than other disease-modifying treatments,” said lead author Giacomo Boffa, MD, University of Genoa, Italy.

“Brain penetrating–intent immune suppression in long-term immunological reconstitution within the central nervous system could be responsible for this clinical efficacy,” he added.

Dr. Boffa presented the research at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

He explained that compartmentalized inflation in the brain parenchyma, left meninges, and the cerebral spinal fluid (CSF) is a key driver of disability worsening in secondary progressive MS.

Although initial studies did not reveal an effect of disease-modifying therapies in secondary progressive MS, recent randomized trials have established some benefit of siponimod in reducing the risk of disability worsening, and consistent with this finding, observational studies have suggested that other available immunotherapies may also be beneficial for active secondary progressive MS, Dr. Boffa noted.

“Autologous hematopoietic stem cell transplantation has been widely investigated for the treatment of refractory MS, and although the ideal candidate for this procedure is a young patient with relapsing-remitting MS, there is some evidence to suggest that the procedure could also slow down neurological disability in patients with secondary progressive MS,” Dr. Boffa said.

“Indeed, all the drugs used in the transplant technology share the ability to cross the blood-brain barrier and exert a strong immunosuppressant effect within the brain parenchyma and CSF,” he added.  
 

Comparing treatment regimens

The aim of the current study was to compare the effect of autologous hematopoietic stem cell transplantation with other immunotherapies on disability worsening in patients with active secondary progressive MS.

Study endpoints included the Expanded Disability Status Scale (EDSS) score, 6-month worsening and improvement in disability, and sustained disability improvement over time.

The researchers studied patients with secondary progressive MS who had received autologous hematopoietic stem cell transplantation and were included in the Italian Bone Marrow Transplant Group. They were compared with a control group of patients in the Italian MS registry who had started a nontransplant disease-modifying therapy after the diagnosis of secondary progressive MS.

To control for many different variables, two separate analyses were preformed. One analyses was a propensity-score approach (patients were matched based on their propensity to receive bone marrow transplant or one of the other disease-modifying therapies). The other analysis used an overlap weighting approach (each patient was given a weight proportional to the probability of them belonging to the other treatment group).

The final cohort consisted of 79 bone marrow transplant recipients and 1,975 patients who had received other disease-modifying therapies.

Before matching, patients in the control group were older, had a longer disease duration, and had a lower annualized relapse rate than transplanted patients.

After propensity-score matching, there were 69 transplanted patients and 217 control patients who were well balanced in terms of clinical and demographic characteristics. After overlap weighting, the entire cohort was also well balanced for these variables.

In terms of the primary endpoint, stem cell transplant stabilized the EDSS score over time, while patients treated with other disease-modifying therapies had continuous progression of the EDSS score over time.

In the propensity-matched analysis, the EDSS score improved by 0.013 points per year in the stem cell transplant group compared with a worsening of 0.157 points per year in the control group. Similar results were seen in the overlap-weighting analysis.  

The effect of stem cell transplant on EDSS score translated into a significantly delayed time to confirmed disability progression in the stem cell transplant group compared with the control group (HR, 0.5; P = .005), Dr. Boffa reported.

Five years after the procedure, 62% of the transplant group were free of disability progression, compared with around 20% of the control group.  

Patients in the transplanted group were also more likely to show disability improvement over time. Five years after the procedure, almost 20% of the stem cell transplant group still maintained a disability improvement compared with only 4% of patients treated with other disease-modifying therapies.

“Our study population was composed of relatively young patients (average age 38 years) with clinical activity during secondary progressive MS, and the results of this study would not be applicable to patients with secondary progressive MS patients without signs of inflammatory activity,” Dr. Boffa commented.

“But on the other hand, our results reinforce the notion that ongoing inflammation during progressive MS requires adequate immunotherapy,” he added.   

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

Autologous hematopoietic stem cell transplantation for the treatment of active secondary progressive multiple sclerosis (MS) is associated with better disability outcomes than other immunotherapies, a new Italian study suggests.

In the study, stem cell transplant was associated with a slowing of disability progression and a higher likelihood of disability improvement in patients with secondary progressive MS compared with other disease-modifying therapies.

“Our study shows that, although limited, sustained disability improvement is still possible during early active secondary progressive MS and seems to be more likely with stem cell transplant than other disease-modifying treatments,” said lead author Giacomo Boffa, MD, University of Genoa, Italy.

“Brain penetrating–intent immune suppression in long-term immunological reconstitution within the central nervous system could be responsible for this clinical efficacy,” he added.

Dr. Boffa presented the research at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

He explained that compartmentalized inflation in the brain parenchyma, left meninges, and the cerebral spinal fluid (CSF) is a key driver of disability worsening in secondary progressive MS.

Although initial studies did not reveal an effect of disease-modifying therapies in secondary progressive MS, recent randomized trials have established some benefit of siponimod in reducing the risk of disability worsening, and consistent with this finding, observational studies have suggested that other available immunotherapies may also be beneficial for active secondary progressive MS, Dr. Boffa noted.

“Autologous hematopoietic stem cell transplantation has been widely investigated for the treatment of refractory MS, and although the ideal candidate for this procedure is a young patient with relapsing-remitting MS, there is some evidence to suggest that the procedure could also slow down neurological disability in patients with secondary progressive MS,” Dr. Boffa said.

“Indeed, all the drugs used in the transplant technology share the ability to cross the blood-brain barrier and exert a strong immunosuppressant effect within the brain parenchyma and CSF,” he added.  
 

Comparing treatment regimens

The aim of the current study was to compare the effect of autologous hematopoietic stem cell transplantation with other immunotherapies on disability worsening in patients with active secondary progressive MS.

Study endpoints included the Expanded Disability Status Scale (EDSS) score, 6-month worsening and improvement in disability, and sustained disability improvement over time.

The researchers studied patients with secondary progressive MS who had received autologous hematopoietic stem cell transplantation and were included in the Italian Bone Marrow Transplant Group. They were compared with a control group of patients in the Italian MS registry who had started a nontransplant disease-modifying therapy after the diagnosis of secondary progressive MS.

To control for many different variables, two separate analyses were preformed. One analyses was a propensity-score approach (patients were matched based on their propensity to receive bone marrow transplant or one of the other disease-modifying therapies). The other analysis used an overlap weighting approach (each patient was given a weight proportional to the probability of them belonging to the other treatment group).

The final cohort consisted of 79 bone marrow transplant recipients and 1,975 patients who had received other disease-modifying therapies.

Before matching, patients in the control group were older, had a longer disease duration, and had a lower annualized relapse rate than transplanted patients.

After propensity-score matching, there were 69 transplanted patients and 217 control patients who were well balanced in terms of clinical and demographic characteristics. After overlap weighting, the entire cohort was also well balanced for these variables.

In terms of the primary endpoint, stem cell transplant stabilized the EDSS score over time, while patients treated with other disease-modifying therapies had continuous progression of the EDSS score over time.

In the propensity-matched analysis, the EDSS score improved by 0.013 points per year in the stem cell transplant group compared with a worsening of 0.157 points per year in the control group. Similar results were seen in the overlap-weighting analysis.  

The effect of stem cell transplant on EDSS score translated into a significantly delayed time to confirmed disability progression in the stem cell transplant group compared with the control group (HR, 0.5; P = .005), Dr. Boffa reported.

Five years after the procedure, 62% of the transplant group were free of disability progression, compared with around 20% of the control group.  

Patients in the transplanted group were also more likely to show disability improvement over time. Five years after the procedure, almost 20% of the stem cell transplant group still maintained a disability improvement compared with only 4% of patients treated with other disease-modifying therapies.

“Our study population was composed of relatively young patients (average age 38 years) with clinical activity during secondary progressive MS, and the results of this study would not be applicable to patients with secondary progressive MS patients without signs of inflammatory activity,” Dr. Boffa commented.

“But on the other hand, our results reinforce the notion that ongoing inflammation during progressive MS requires adequate immunotherapy,” he added.   

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

Autologous hematopoietic stem cell transplantation for the treatment of active secondary progressive multiple sclerosis (MS) is associated with better disability outcomes than other immunotherapies, a new Italian study suggests.

In the study, stem cell transplant was associated with a slowing of disability progression and a higher likelihood of disability improvement in patients with secondary progressive MS compared with other disease-modifying therapies.

“Our study shows that, although limited, sustained disability improvement is still possible during early active secondary progressive MS and seems to be more likely with stem cell transplant than other disease-modifying treatments,” said lead author Giacomo Boffa, MD, University of Genoa, Italy.

“Brain penetrating–intent immune suppression in long-term immunological reconstitution within the central nervous system could be responsible for this clinical efficacy,” he added.

Dr. Boffa presented the research at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

He explained that compartmentalized inflation in the brain parenchyma, left meninges, and the cerebral spinal fluid (CSF) is a key driver of disability worsening in secondary progressive MS.

Although initial studies did not reveal an effect of disease-modifying therapies in secondary progressive MS, recent randomized trials have established some benefit of siponimod in reducing the risk of disability worsening, and consistent with this finding, observational studies have suggested that other available immunotherapies may also be beneficial for active secondary progressive MS, Dr. Boffa noted.

“Autologous hematopoietic stem cell transplantation has been widely investigated for the treatment of refractory MS, and although the ideal candidate for this procedure is a young patient with relapsing-remitting MS, there is some evidence to suggest that the procedure could also slow down neurological disability in patients with secondary progressive MS,” Dr. Boffa said.

“Indeed, all the drugs used in the transplant technology share the ability to cross the blood-brain barrier and exert a strong immunosuppressant effect within the brain parenchyma and CSF,” he added.  
 

Comparing treatment regimens

The aim of the current study was to compare the effect of autologous hematopoietic stem cell transplantation with other immunotherapies on disability worsening in patients with active secondary progressive MS.

Study endpoints included the Expanded Disability Status Scale (EDSS) score, 6-month worsening and improvement in disability, and sustained disability improvement over time.

The researchers studied patients with secondary progressive MS who had received autologous hematopoietic stem cell transplantation and were included in the Italian Bone Marrow Transplant Group. They were compared with a control group of patients in the Italian MS registry who had started a nontransplant disease-modifying therapy after the diagnosis of secondary progressive MS.

To control for many different variables, two separate analyses were preformed. One analyses was a propensity-score approach (patients were matched based on their propensity to receive bone marrow transplant or one of the other disease-modifying therapies). The other analysis used an overlap weighting approach (each patient was given a weight proportional to the probability of them belonging to the other treatment group).

The final cohort consisted of 79 bone marrow transplant recipients and 1,975 patients who had received other disease-modifying therapies.

Before matching, patients in the control group were older, had a longer disease duration, and had a lower annualized relapse rate than transplanted patients.

After propensity-score matching, there were 69 transplanted patients and 217 control patients who were well balanced in terms of clinical and demographic characteristics. After overlap weighting, the entire cohort was also well balanced for these variables.

In terms of the primary endpoint, stem cell transplant stabilized the EDSS score over time, while patients treated with other disease-modifying therapies had continuous progression of the EDSS score over time.

In the propensity-matched analysis, the EDSS score improved by 0.013 points per year in the stem cell transplant group compared with a worsening of 0.157 points per year in the control group. Similar results were seen in the overlap-weighting analysis.  

The effect of stem cell transplant on EDSS score translated into a significantly delayed time to confirmed disability progression in the stem cell transplant group compared with the control group (HR, 0.5; P = .005), Dr. Boffa reported.

Five years after the procedure, 62% of the transplant group were free of disability progression, compared with around 20% of the control group.  

Patients in the transplanted group were also more likely to show disability improvement over time. Five years after the procedure, almost 20% of the stem cell transplant group still maintained a disability improvement compared with only 4% of patients treated with other disease-modifying therapies.

“Our study population was composed of relatively young patients (average age 38 years) with clinical activity during secondary progressive MS, and the results of this study would not be applicable to patients with secondary progressive MS patients without signs of inflammatory activity,” Dr. Boffa commented.

“But on the other hand, our results reinforce the notion that ongoing inflammation during progressive MS requires adequate immunotherapy,” he added.   

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

Maternal mortality is a public health crisis for all women, said Elizabeth A. Howell, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the virtual Advancing NIH Research on the Health of Women conference sponsored by the National Institutes of Health.

The maternal mortality rate in the United States in 2018 was 17.4 maternal deaths per 100,000 live births, according to data from the Centers for Disease Control and Prevention, Dr. Howell said. Maternal mortality is defined as death during pregnancy or within 42 days of delivery; pregnancy-related mortality includes death during pregnancy or within 1 year of pregnancy, from pregnancy or as a result of any cause related to, or aggravated by, pregnancy, according to the CDC.

However, “Black women are two to three times more likely than White women to die from a pregnancy-related cause,” Dr. Howell said. These disparities are even more marked in some cities; data show that Black women in New York City are eight times more likely than White women to die from a pregnancy-related cause, she noted.

Pregnancy-related mortality persists regardless of education level, and remains significantly higher in Black women, compared with White women with at least a college degree, Dr. Howell added.

In her presentation, Dr. Howell reviewed some top causes of maternal mortality overall, and potential factors driving disparities. Data from the CDC show cardiomyopathy, cardiovascular conditions, and preeclampsia/eclampsia as the top three underlying causes of pregnancy-related deaths among non-Hispanic Black women, compared with mental health conditions, cardiovascular conditions, and hemorrhage in non-Hispanic White women, Dr. Howell said.

To help prevent maternal mortality across all populations, “It is important for us to think about the timing of deaths so we can better understand the causes,” said Dr. Howell.

CDC Vital Signs data show that approximately one-third of pregnancy-related deaths occur during pregnancy, but approximately 20% occur between 43 and 365 days postpartum, she said.

Although cardiovascular conditions top the list of clinical causes of pregnancy-related maternal mortality, maternal self-harm should not be discounted, and is likely underreported, Dr. Howell said. Data show that the peak incidence of maternal suicide occurs between 9 and 12 months’ postpartum, and risk factors include major depression, substance use disorder, and intimate partner violence, she noted.

Dr. Howell then shared the results of studies she conducted in 2020 and 2016 on racial disparities, hospital quality, and maternal mortality. One of her key findings in the 2020 study, presented at this year’s virtual meeting of the American College of Obstetricians and Gynecologists, showed that women delivering in the lowest-ranked hospitals had six times the rate of severe maternal morbidity, and an accompanying simulation/thought exercise showed that the hospital of delivery accounted for approximately half of the disparity in severe maternal morbidity between Black and White women. An earlier study she published in 2016 of between-hospital differences in New York City showed that Black and Latina women were significantly more likely than White women to deliver in hospitals with higher rates of severe maternal mortality.

These findings illustrate that “racial segregation in neighborhoods is also part of the story,” of maternal mortality, Dr. Howell said.

Dr. Howell outlined ways the health care community can reduce severe maternal morbidity and mortality for all women, including promoting contraception and preconception health, improving postpartum management, eliminating bias, and using patient navigators as needed to enhance communication among the care team,

“Think about ways to engage the community,” in support of women’s pregnancy health, Dr. Howell said. She also emphasized the need to enroll more pregnant women in clinical trials.
 

Don’t exclude pregnant women from trials

In a follow-up session, Cynthia Gyamfi-Bannerman, MD, of the University of California, San Diego, expanded on opportunities to include pregnant women in clinical research.

Clinical trials for pregnant people fall into two categories, she noted; those studying interventions to improve pregnancy outcomes and those studying interventions for common medical conditions that coexist with pregnancy. These trials are either initiated by the investigators, conducted under contract, or federally funded, Dr. Gyamfi-Bannerman said. Currently, the only obstetric clinical trials research network is the Maternal-Fetal Medicine Units Network, established in 1986 by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The MFMU has conducted significant and life-saving research, but “we need more networks to focus on researching pregnancy complications,” Dr. Gyamfi-Bannerman said. Once the infrastructure exists in multiple settings, the ability to conduct trials will improve, she said.

Dr. Gyamfi-Bannerman stressed the need to engage and involve community-based physicians in clinical trials; using those relationships to enroll a more diverse population for whom working with their local physician would be more feasible than traveling to a larger clinical trial center.

She also commented on the need to include pregnant women in nonobstetric clinical trials. The exclusion of pregnant women from COVID-19 vaccine trials left clinicians with no information for guiding pregnant patients, she said. “It is important to think about why we are excluding pregnant women,” she said.

Finally, Dr. Gyamfi-Bannerman recommended a national effort to coordinate and leverage EHR data, which could have an effect on reducing maternal morbidity by facilitating the study of nonobstetric interventions in pregnancy, such as behavior interventions and mental health care.

Dr. Howell and Dr. Gyamfi-Bannerman had no financial conflicts to disclose.
 

Maternal mortality is a public health crisis for all women, said Elizabeth A. Howell, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the virtual Advancing NIH Research on the Health of Women conference sponsored by the National Institutes of Health.

The maternal mortality rate in the United States in 2018 was 17.4 maternal deaths per 100,000 live births, according to data from the Centers for Disease Control and Prevention, Dr. Howell said. Maternal mortality is defined as death during pregnancy or within 42 days of delivery; pregnancy-related mortality includes death during pregnancy or within 1 year of pregnancy, from pregnancy or as a result of any cause related to, or aggravated by, pregnancy, according to the CDC.

However, “Black women are two to three times more likely than White women to die from a pregnancy-related cause,” Dr. Howell said. These disparities are even more marked in some cities; data show that Black women in New York City are eight times more likely than White women to die from a pregnancy-related cause, she noted.

Pregnancy-related mortality persists regardless of education level, and remains significantly higher in Black women, compared with White women with at least a college degree, Dr. Howell added.

In her presentation, Dr. Howell reviewed some top causes of maternal mortality overall, and potential factors driving disparities. Data from the CDC show cardiomyopathy, cardiovascular conditions, and preeclampsia/eclampsia as the top three underlying causes of pregnancy-related deaths among non-Hispanic Black women, compared with mental health conditions, cardiovascular conditions, and hemorrhage in non-Hispanic White women, Dr. Howell said.

To help prevent maternal mortality across all populations, “It is important for us to think about the timing of deaths so we can better understand the causes,” said Dr. Howell.

CDC Vital Signs data show that approximately one-third of pregnancy-related deaths occur during pregnancy, but approximately 20% occur between 43 and 365 days postpartum, she said.

Although cardiovascular conditions top the list of clinical causes of pregnancy-related maternal mortality, maternal self-harm should not be discounted, and is likely underreported, Dr. Howell said. Data show that the peak incidence of maternal suicide occurs between 9 and 12 months’ postpartum, and risk factors include major depression, substance use disorder, and intimate partner violence, she noted.

Dr. Howell then shared the results of studies she conducted in 2020 and 2016 on racial disparities, hospital quality, and maternal mortality. One of her key findings in the 2020 study, presented at this year’s virtual meeting of the American College of Obstetricians and Gynecologists, showed that women delivering in the lowest-ranked hospitals had six times the rate of severe maternal morbidity, and an accompanying simulation/thought exercise showed that the hospital of delivery accounted for approximately half of the disparity in severe maternal morbidity between Black and White women. An earlier study she published in 2016 of between-hospital differences in New York City showed that Black and Latina women were significantly more likely than White women to deliver in hospitals with higher rates of severe maternal mortality.

These findings illustrate that “racial segregation in neighborhoods is also part of the story,” of maternal mortality, Dr. Howell said.

Dr. Howell outlined ways the health care community can reduce severe maternal morbidity and mortality for all women, including promoting contraception and preconception health, improving postpartum management, eliminating bias, and using patient navigators as needed to enhance communication among the care team,

“Think about ways to engage the community,” in support of women’s pregnancy health, Dr. Howell said. She also emphasized the need to enroll more pregnant women in clinical trials.
 

Don’t exclude pregnant women from trials

In a follow-up session, Cynthia Gyamfi-Bannerman, MD, of the University of California, San Diego, expanded on opportunities to include pregnant women in clinical research.

Clinical trials for pregnant people fall into two categories, she noted; those studying interventions to improve pregnancy outcomes and those studying interventions for common medical conditions that coexist with pregnancy. These trials are either initiated by the investigators, conducted under contract, or federally funded, Dr. Gyamfi-Bannerman said. Currently, the only obstetric clinical trials research network is the Maternal-Fetal Medicine Units Network, established in 1986 by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The MFMU has conducted significant and life-saving research, but “we need more networks to focus on researching pregnancy complications,” Dr. Gyamfi-Bannerman said. Once the infrastructure exists in multiple settings, the ability to conduct trials will improve, she said.

Dr. Gyamfi-Bannerman stressed the need to engage and involve community-based physicians in clinical trials; using those relationships to enroll a more diverse population for whom working with their local physician would be more feasible than traveling to a larger clinical trial center.

She also commented on the need to include pregnant women in nonobstetric clinical trials. The exclusion of pregnant women from COVID-19 vaccine trials left clinicians with no information for guiding pregnant patients, she said. “It is important to think about why we are excluding pregnant women,” she said.

Finally, Dr. Gyamfi-Bannerman recommended a national effort to coordinate and leverage EHR data, which could have an effect on reducing maternal morbidity by facilitating the study of nonobstetric interventions in pregnancy, such as behavior interventions and mental health care.

Dr. Howell and Dr. Gyamfi-Bannerman had no financial conflicts to disclose.
 

Maternal mortality is a public health crisis for all women, said Elizabeth A. Howell, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the virtual Advancing NIH Research on the Health of Women conference sponsored by the National Institutes of Health.

The maternal mortality rate in the United States in 2018 was 17.4 maternal deaths per 100,000 live births, according to data from the Centers for Disease Control and Prevention, Dr. Howell said. Maternal mortality is defined as death during pregnancy or within 42 days of delivery; pregnancy-related mortality includes death during pregnancy or within 1 year of pregnancy, from pregnancy or as a result of any cause related to, or aggravated by, pregnancy, according to the CDC.

However, “Black women are two to three times more likely than White women to die from a pregnancy-related cause,” Dr. Howell said. These disparities are even more marked in some cities; data show that Black women in New York City are eight times more likely than White women to die from a pregnancy-related cause, she noted.

Pregnancy-related mortality persists regardless of education level, and remains significantly higher in Black women, compared with White women with at least a college degree, Dr. Howell added.

In her presentation, Dr. Howell reviewed some top causes of maternal mortality overall, and potential factors driving disparities. Data from the CDC show cardiomyopathy, cardiovascular conditions, and preeclampsia/eclampsia as the top three underlying causes of pregnancy-related deaths among non-Hispanic Black women, compared with mental health conditions, cardiovascular conditions, and hemorrhage in non-Hispanic White women, Dr. Howell said.

To help prevent maternal mortality across all populations, “It is important for us to think about the timing of deaths so we can better understand the causes,” said Dr. Howell.

CDC Vital Signs data show that approximately one-third of pregnancy-related deaths occur during pregnancy, but approximately 20% occur between 43 and 365 days postpartum, she said.

Although cardiovascular conditions top the list of clinical causes of pregnancy-related maternal mortality, maternal self-harm should not be discounted, and is likely underreported, Dr. Howell said. Data show that the peak incidence of maternal suicide occurs between 9 and 12 months’ postpartum, and risk factors include major depression, substance use disorder, and intimate partner violence, she noted.

Dr. Howell then shared the results of studies she conducted in 2020 and 2016 on racial disparities, hospital quality, and maternal mortality. One of her key findings in the 2020 study, presented at this year’s virtual meeting of the American College of Obstetricians and Gynecologists, showed that women delivering in the lowest-ranked hospitals had six times the rate of severe maternal morbidity, and an accompanying simulation/thought exercise showed that the hospital of delivery accounted for approximately half of the disparity in severe maternal morbidity between Black and White women. An earlier study she published in 2016 of between-hospital differences in New York City showed that Black and Latina women were significantly more likely than White women to deliver in hospitals with higher rates of severe maternal mortality.

These findings illustrate that “racial segregation in neighborhoods is also part of the story,” of maternal mortality, Dr. Howell said.

Dr. Howell outlined ways the health care community can reduce severe maternal morbidity and mortality for all women, including promoting contraception and preconception health, improving postpartum management, eliminating bias, and using patient navigators as needed to enhance communication among the care team,

“Think about ways to engage the community,” in support of women’s pregnancy health, Dr. Howell said. She also emphasized the need to enroll more pregnant women in clinical trials.
 

Don’t exclude pregnant women from trials

In a follow-up session, Cynthia Gyamfi-Bannerman, MD, of the University of California, San Diego, expanded on opportunities to include pregnant women in clinical research.

Clinical trials for pregnant people fall into two categories, she noted; those studying interventions to improve pregnancy outcomes and those studying interventions for common medical conditions that coexist with pregnancy. These trials are either initiated by the investigators, conducted under contract, or federally funded, Dr. Gyamfi-Bannerman said. Currently, the only obstetric clinical trials research network is the Maternal-Fetal Medicine Units Network, established in 1986 by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The MFMU has conducted significant and life-saving research, but “we need more networks to focus on researching pregnancy complications,” Dr. Gyamfi-Bannerman said. Once the infrastructure exists in multiple settings, the ability to conduct trials will improve, she said.

Dr. Gyamfi-Bannerman stressed the need to engage and involve community-based physicians in clinical trials; using those relationships to enroll a more diverse population for whom working with their local physician would be more feasible than traveling to a larger clinical trial center.

She also commented on the need to include pregnant women in nonobstetric clinical trials. The exclusion of pregnant women from COVID-19 vaccine trials left clinicians with no information for guiding pregnant patients, she said. “It is important to think about why we are excluding pregnant women,” she said.

Finally, Dr. Gyamfi-Bannerman recommended a national effort to coordinate and leverage EHR data, which could have an effect on reducing maternal morbidity by facilitating the study of nonobstetric interventions in pregnancy, such as behavior interventions and mental health care.

Dr. Howell and Dr. Gyamfi-Bannerman had no financial conflicts to disclose.
 

Updated European guidelines on the treatment of patients with multiple sclerosis (MS) have been announced and include a recommendation for siponimod (Mayzent) in progressive MS, as well as a general emphasis toward earlier and more aggressive treatment.

The updated guidelines were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and are the result of a collaboration between ECTRIMS and the European Academy of Neurology (EAN).

Maria Pia Amato, MD, ECTRIMS president and co-chair of the guidelines steering committee, noted that the European MS treatment guidelines were last published in 2018. “Since then more trials have been published, and we felt this was a good time to incorporate the new evidence into updated guidelines,” she said.

“As before, the updated guidelines contain a number of core questions that address the efficacy of disease-modifying therapies, early treatment decisions, disease/treatment response monitoring and treatment modifications, treatment suspension and disease reactivation, and pregnancy and breastfeeding,” Dr. Amato said.
 

New recommendations

New features of the updated guidelines include a recommendation for siponimod for secondary progressive MS with evidence of disease inflammatory activity; in addition, there is more emphasis on starting treatment early, with greater consideration of higher efficacy drugs, depending on the characteristics of the disease and the patient, Dr. Amato commented.

“We also provided more detailed information on disease-modifying therapy use in pregnancy and breastfeeding and also for women with high disease activity who desire to become pregnant,” she added.

Other new features include the introduction of clinical questions dealing with treatment safety and monitoring (for example, for natalizumab) and also considering the current COVID-19 pandemic scenario; switching strategies with more detailed practical indications on timing; and long lasting effects of drugs such as alemtuzumab and cladribine, Dr. Amato said.

The updated guidelines include the following recommendations:

• The entire spectrum of disease-modifying drugs should be prescribed by a neurologist with expertise in MS and ready access to adequate infrastructure to provide proper monitoring of patents, comprehensive assessment, early detection of side effects, and the capacity to address those side effects promptly.
• Offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) highly suggestive of MS and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS.
• For patients with relapsing-remitting MS, the choice between a wide range of available drugs (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, fingolimod, ozanimod, ponesimod, natalizumab, alemtuzumab, ocrelizumab, rituximab, or ofatumumab), from modestly to highly effective, will depend on factors including: underlying disability progression, disease severity/clinical or radiological activity, patient characteristics and morbidity, drug safety profile, family planning, and patient preferences.

Progressive MS

• For patients with secondary progressive MS with evidence of inflammatory activity (relapses and/or MRI activity), offer treatment with siponimod. Treatment with other therapies used for relapsing remitting MS may also be considered.
• For secondary progressive MS without evidence of inflammatory activity, particularly in young patients and those in whom progression has started recently, consider treatment with siponimod or anti-CD20 monoclonal antibodies, taking into account that there is scarce evidence to support their use in this setting.  
• For patients with active secondary progressive MS when there is no other therapy available, consider treatment with mitoxantrone, taking into account the safety concerns and tolerability issues of this agent. 
• Consider ocrelizumab for patients with primary progressive MS, particularly early and active (clinically and/or radiologically) disease.

Emphasis toward higher-efficacy drugs

• Consider choosing a higher-efficacy disease-modifying drug early on, according to disease activity (either clinically or on MRI).
• Offer a more efficacious drug to patients who show evidence of disease activity with their current treatment.
• When treatment with a high-efficacy drug is stopped, whether because of inefficacy or risk of adverse effects, consider starting another high-efficacy drug, taking into account clinical and MRI disease activity before and during treatment, pharmacokinetics and biological activity of the previous drug, and the potential for resumed disease activity or even rebound syndrome (particularly with natalizumab and S1P modulators).
• In the stable patient (clinically and on MRI) who shows no safety or tolerability issues, consider continuing treatment with disease-modifying therapy, taking into account patient characteristics and comorbidities, drug safety profile, family planning, and patient preferences.

Recommendations for pregnancy and breastfeeding

Recommendations for pregnant women and mothers who choose to breastfeed include:

• Advise women who wish to become pregnant to plan their pregnancy beforehand.
• Advise women of childbearing potential that MS disease-modifying therapies are not licensed during pregnancy, with the exception of interferons and glatiramer acetate.
• For women planning a pregnancy, offer interferons and glatiramer acetate and consider continuing these agents during pregnancy after assessment of risk and benefits. Consider using dimethyl fumarate until pregnancy is confirmed and stopping during pregnancy after assessment of the risks and benefits. 
• For women with highly active disease who wish to become pregnant, there are a number of therapeutic options:

1)  treatment with long lasting effects such as alemtuzumab or cladribine provided that at least 4 or 6 months respectively have elapsed between the last dose and conception2)  treatment with anti-CD20 drugs before pregnancy with advice to wait for 2-6 months after the last infusion before becoming pregnant and to avoid further infusions during pregnancy, or3) for patients treated with natalizumab, consider continuing treatment during pregnancy using a 6-week extended dosage regimen until the end of the second trimester or up until week 34 and resuming after delivery (in newborns exposed to natalizumab, check for hematological abnormalities and liver function)

• Only interferons and ofatumumab are currently approved during breastfeeding.   
•  

Treatment safety/monitoring

• When treating patients with natalizumab and after a period of stability, consider switching to a 6-week interval regimen in order to minimize the risk of progressive multifocal leukoencephalopathy (PML).
• Consider treatment with high-efficacy drugs including natalizumab in patients with high disease activity, in whom a quick therapeutic effect is required, taking into account the risk of PML in John Cunningham virus (JCV)-positive patients, as well as the therapeutic lag of the different disease-modifying drugs.
• Ideally, prioritize vaccination against COVID-19 before starting immunosuppressive disease-modifying treatments to achieve the highest protection rate possible.
•  

Long-lasting treatments

• When using long-lasting treatments (alemtuzumab or cladribine) in patients who experience disease activity before the treatment is completed (between the first and second cycles), consider waiting until completion of the therapeutic regimen before switching to other drugs.
• Consider offering additional courses of alemtuzumab after the first two cycles at least 1 year apart from each other when disease activity has not remitted completely or reappears after a period of stability, taking into account the balance between the potential benefits and side effects.

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

Updated European guidelines on the treatment of patients with multiple sclerosis (MS) have been announced and include a recommendation for siponimod (Mayzent) in progressive MS, as well as a general emphasis toward earlier and more aggressive treatment.

The updated guidelines were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and are the result of a collaboration between ECTRIMS and the European Academy of Neurology (EAN).

Maria Pia Amato, MD, ECTRIMS president and co-chair of the guidelines steering committee, noted that the European MS treatment guidelines were last published in 2018. “Since then more trials have been published, and we felt this was a good time to incorporate the new evidence into updated guidelines,” she said.

“As before, the updated guidelines contain a number of core questions that address the efficacy of disease-modifying therapies, early treatment decisions, disease/treatment response monitoring and treatment modifications, treatment suspension and disease reactivation, and pregnancy and breastfeeding,” Dr. Amato said.
 

New recommendations

New features of the updated guidelines include a recommendation for siponimod for secondary progressive MS with evidence of disease inflammatory activity; in addition, there is more emphasis on starting treatment early, with greater consideration of higher efficacy drugs, depending on the characteristics of the disease and the patient, Dr. Amato commented.

“We also provided more detailed information on disease-modifying therapy use in pregnancy and breastfeeding and also for women with high disease activity who desire to become pregnant,” she added.

Other new features include the introduction of clinical questions dealing with treatment safety and monitoring (for example, for natalizumab) and also considering the current COVID-19 pandemic scenario; switching strategies with more detailed practical indications on timing; and long lasting effects of drugs such as alemtuzumab and cladribine, Dr. Amato said.

The updated guidelines include the following recommendations:

• The entire spectrum of disease-modifying drugs should be prescribed by a neurologist with expertise in MS and ready access to adequate infrastructure to provide proper monitoring of patents, comprehensive assessment, early detection of side effects, and the capacity to address those side effects promptly.
• Offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) highly suggestive of MS and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS.
• For patients with relapsing-remitting MS, the choice between a wide range of available drugs (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, fingolimod, ozanimod, ponesimod, natalizumab, alemtuzumab, ocrelizumab, rituximab, or ofatumumab), from modestly to highly effective, will depend on factors including: underlying disability progression, disease severity/clinical or radiological activity, patient characteristics and morbidity, drug safety profile, family planning, and patient preferences.

Progressive MS

• For patients with secondary progressive MS with evidence of inflammatory activity (relapses and/or MRI activity), offer treatment with siponimod. Treatment with other therapies used for relapsing remitting MS may also be considered.
• For secondary progressive MS without evidence of inflammatory activity, particularly in young patients and those in whom progression has started recently, consider treatment with siponimod or anti-CD20 monoclonal antibodies, taking into account that there is scarce evidence to support their use in this setting.  
• For patients with active secondary progressive MS when there is no other therapy available, consider treatment with mitoxantrone, taking into account the safety concerns and tolerability issues of this agent. 
• Consider ocrelizumab for patients with primary progressive MS, particularly early and active (clinically and/or radiologically) disease.

Emphasis toward higher-efficacy drugs

• Consider choosing a higher-efficacy disease-modifying drug early on, according to disease activity (either clinically or on MRI).
• Offer a more efficacious drug to patients who show evidence of disease activity with their current treatment.
• When treatment with a high-efficacy drug is stopped, whether because of inefficacy or risk of adverse effects, consider starting another high-efficacy drug, taking into account clinical and MRI disease activity before and during treatment, pharmacokinetics and biological activity of the previous drug, and the potential for resumed disease activity or even rebound syndrome (particularly with natalizumab and S1P modulators).
• In the stable patient (clinically and on MRI) who shows no safety or tolerability issues, consider continuing treatment with disease-modifying therapy, taking into account patient characteristics and comorbidities, drug safety profile, family planning, and patient preferences.

Recommendations for pregnancy and breastfeeding

Recommendations for pregnant women and mothers who choose to breastfeed include:

• Advise women who wish to become pregnant to plan their pregnancy beforehand.
• Advise women of childbearing potential that MS disease-modifying therapies are not licensed during pregnancy, with the exception of interferons and glatiramer acetate.
• For women planning a pregnancy, offer interferons and glatiramer acetate and consider continuing these agents during pregnancy after assessment of risk and benefits. Consider using dimethyl fumarate until pregnancy is confirmed and stopping during pregnancy after assessment of the risks and benefits. 
• For women with highly active disease who wish to become pregnant, there are a number of therapeutic options:

1)  treatment with long lasting effects such as alemtuzumab or cladribine provided that at least 4 or 6 months respectively have elapsed between the last dose and conception2)  treatment with anti-CD20 drugs before pregnancy with advice to wait for 2-6 months after the last infusion before becoming pregnant and to avoid further infusions during pregnancy, or3) for patients treated with natalizumab, consider continuing treatment during pregnancy using a 6-week extended dosage regimen until the end of the second trimester or up until week 34 and resuming after delivery (in newborns exposed to natalizumab, check for hematological abnormalities and liver function)

• Only interferons and ofatumumab are currently approved during breastfeeding.   
•  

Treatment safety/monitoring

• When treating patients with natalizumab and after a period of stability, consider switching to a 6-week interval regimen in order to minimize the risk of progressive multifocal leukoencephalopathy (PML).
• Consider treatment with high-efficacy drugs including natalizumab in patients with high disease activity, in whom a quick therapeutic effect is required, taking into account the risk of PML in John Cunningham virus (JCV)-positive patients, as well as the therapeutic lag of the different disease-modifying drugs.
• Ideally, prioritize vaccination against COVID-19 before starting immunosuppressive disease-modifying treatments to achieve the highest protection rate possible.
•  

Long-lasting treatments

• When using long-lasting treatments (alemtuzumab or cladribine) in patients who experience disease activity before the treatment is completed (between the first and second cycles), consider waiting until completion of the therapeutic regimen before switching to other drugs.
• Consider offering additional courses of alemtuzumab after the first two cycles at least 1 year apart from each other when disease activity has not remitted completely or reappears after a period of stability, taking into account the balance between the potential benefits and side effects.

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

Updated European guidelines on the treatment of patients with multiple sclerosis (MS) have been announced and include a recommendation for siponimod (Mayzent) in progressive MS, as well as a general emphasis toward earlier and more aggressive treatment.

The updated guidelines were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and are the result of a collaboration between ECTRIMS and the European Academy of Neurology (EAN).

Maria Pia Amato, MD, ECTRIMS president and co-chair of the guidelines steering committee, noted that the European MS treatment guidelines were last published in 2018. “Since then more trials have been published, and we felt this was a good time to incorporate the new evidence into updated guidelines,” she said.

“As before, the updated guidelines contain a number of core questions that address the efficacy of disease-modifying therapies, early treatment decisions, disease/treatment response monitoring and treatment modifications, treatment suspension and disease reactivation, and pregnancy and breastfeeding,” Dr. Amato said.
 

New recommendations

New features of the updated guidelines include a recommendation for siponimod for secondary progressive MS with evidence of disease inflammatory activity; in addition, there is more emphasis on starting treatment early, with greater consideration of higher efficacy drugs, depending on the characteristics of the disease and the patient, Dr. Amato commented.

“We also provided more detailed information on disease-modifying therapy use in pregnancy and breastfeeding and also for women with high disease activity who desire to become pregnant,” she added.

Other new features include the introduction of clinical questions dealing with treatment safety and monitoring (for example, for natalizumab) and also considering the current COVID-19 pandemic scenario; switching strategies with more detailed practical indications on timing; and long lasting effects of drugs such as alemtuzumab and cladribine, Dr. Amato said.

The updated guidelines include the following recommendations:

• The entire spectrum of disease-modifying drugs should be prescribed by a neurologist with expertise in MS and ready access to adequate infrastructure to provide proper monitoring of patents, comprehensive assessment, early detection of side effects, and the capacity to address those side effects promptly.
• Offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) highly suggestive of MS and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS.
• For patients with relapsing-remitting MS, the choice between a wide range of available drugs (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, fingolimod, ozanimod, ponesimod, natalizumab, alemtuzumab, ocrelizumab, rituximab, or ofatumumab), from modestly to highly effective, will depend on factors including: underlying disability progression, disease severity/clinical or radiological activity, patient characteristics and morbidity, drug safety profile, family planning, and patient preferences.

Progressive MS

• For patients with secondary progressive MS with evidence of inflammatory activity (relapses and/or MRI activity), offer treatment with siponimod. Treatment with other therapies used for relapsing remitting MS may also be considered.
• For secondary progressive MS without evidence of inflammatory activity, particularly in young patients and those in whom progression has started recently, consider treatment with siponimod or anti-CD20 monoclonal antibodies, taking into account that there is scarce evidence to support their use in this setting.  
• For patients with active secondary progressive MS when there is no other therapy available, consider treatment with mitoxantrone, taking into account the safety concerns and tolerability issues of this agent. 
• Consider ocrelizumab for patients with primary progressive MS, particularly early and active (clinically and/or radiologically) disease.

Emphasis toward higher-efficacy drugs

• Consider choosing a higher-efficacy disease-modifying drug early on, according to disease activity (either clinically or on MRI).
• Offer a more efficacious drug to patients who show evidence of disease activity with their current treatment.
• When treatment with a high-efficacy drug is stopped, whether because of inefficacy or risk of adverse effects, consider starting another high-efficacy drug, taking into account clinical and MRI disease activity before and during treatment, pharmacokinetics and biological activity of the previous drug, and the potential for resumed disease activity or even rebound syndrome (particularly with natalizumab and S1P modulators).
• In the stable patient (clinically and on MRI) who shows no safety or tolerability issues, consider continuing treatment with disease-modifying therapy, taking into account patient characteristics and comorbidities, drug safety profile, family planning, and patient preferences.

Recommendations for pregnancy and breastfeeding

Recommendations for pregnant women and mothers who choose to breastfeed include:

• Advise women who wish to become pregnant to plan their pregnancy beforehand.
• Advise women of childbearing potential that MS disease-modifying therapies are not licensed during pregnancy, with the exception of interferons and glatiramer acetate.
• For women planning a pregnancy, offer interferons and glatiramer acetate and consider continuing these agents during pregnancy after assessment of risk and benefits. Consider using dimethyl fumarate until pregnancy is confirmed and stopping during pregnancy after assessment of the risks and benefits. 
• For women with highly active disease who wish to become pregnant, there are a number of therapeutic options:

1)  treatment with long lasting effects such as alemtuzumab or cladribine provided that at least 4 or 6 months respectively have elapsed between the last dose and conception2)  treatment with anti-CD20 drugs before pregnancy with advice to wait for 2-6 months after the last infusion before becoming pregnant and to avoid further infusions during pregnancy, or3) for patients treated with natalizumab, consider continuing treatment during pregnancy using a 6-week extended dosage regimen until the end of the second trimester or up until week 34 and resuming after delivery (in newborns exposed to natalizumab, check for hematological abnormalities and liver function)

• Only interferons and ofatumumab are currently approved during breastfeeding.   
•  

Treatment safety/monitoring

• When treating patients with natalizumab and after a period of stability, consider switching to a 6-week interval regimen in order to minimize the risk of progressive multifocal leukoencephalopathy (PML).
• Consider treatment with high-efficacy drugs including natalizumab in patients with high disease activity, in whom a quick therapeutic effect is required, taking into account the risk of PML in John Cunningham virus (JCV)-positive patients, as well as the therapeutic lag of the different disease-modifying drugs.
• Ideally, prioritize vaccination against COVID-19 before starting immunosuppressive disease-modifying treatments to achieve the highest protection rate possible.
•  

Long-lasting treatments

• When using long-lasting treatments (alemtuzumab or cladribine) in patients who experience disease activity before the treatment is completed (between the first and second cycles), consider waiting until completion of the therapeutic regimen before switching to other drugs.
• Consider offering additional courses of alemtuzumab after the first two cycles at least 1 year apart from each other when disease activity has not remitted completely or reappears after a period of stability, taking into account the balance between the potential benefits and side effects.

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

Among pediatric patients with multiple sclerosis (MS), some specific clinical characteristics, as well as treatment with disease-modifying therapies (DMTs), are linked to less future disability.

An estimated 3%-10% of MS patients are diagnosed during childhood. These patients experience a higher relapse rate and have higher magnetic resonance imaging (MRI) activity than do adult-onset patients. They have a slower rate of progression, but they reach irreversible disability milestones at an early age, with more than 50% having secondary progressive disease by age 30.

Studies in adults suggest that use of high-efficacy DMTs is most effective when initiated during the early active phase of MS, but little is known about children. “Early recognition of predictors of faster disability in children is crucial for clinicians to make the treatment decisions at the earliest possible time,” Sifat Sharmin, PhD, said during her presentation of the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Dr. Sharmin is a statistician and research fellow at the University of Melbourne.
 

‘Reassuring’ data

“I think the most important observation that was made here is the protective factor of use of high efficacy disease modifying therapies,” said Bruce Cree, MD, PhD, who was asked to comment on the study.

That result wasn’t unexpected, but it should provide reassurance. “For parents of children who are hesitant about use of high efficacy therapies, this study provides supporting evidence for use of these high efficacy therapies early on, to try and prevent irreversible disability from occurring,” said Dr. Cree, professor of clinical neurology and the George A. Zimmermann Endowed Professor in Multiple Sclerosis at the University of California at San Francisco UCSF Weill Institute for Neurosciences.

The study provides real-world data to back up findings from a phase 3 clinical trial that showed fewer relapses and fewer new lesions in pediatric patients with MS who were taking fingolimod versus interferon beta-1a.

“Given a large randomized, controlled trial, and now with this additional real-world data set showing the same thing, the only conclusion to reach is that if you’ve got a kid with MS, they should be treated with fingolimod,” said Dr. Cree. He noted that other DMTs such as natalizumab may also benefit pediatric patients, but fingolimod is the only drug that has been studied in randomized, controlled trials in children.

Real-world data

The researchers analyzed data from 672 patients drawn from the international MSBase Neuroimmunology Registry, who had undergone neurological assessment within 1 year of symptom onset and had at least two annual visits where the Expanded Disability Status Scale (EDSS) was recorded. They sought to identify predictors of Multiple Sclerosis Severity Score (MSSS). A secondary analysis looked at predictors of EDSS sustained worsening at 6 months, defined as an increase of 1.5 if EDSS baseline was 0, 1.0 or more if baseline EDSS was 1.0-5.5, or 0.5 if baseline EDSS was over 5.5.

The researchers also conducted a sensitivity analysis that looked at relapse phenotypes and relapse frequency in the first year, as well as a subgroup analysis of patients with available MRI data from the first year. The researchers adjusted for time on high-efficacy DMTs at each visit.

Among the study participants, 70% were female. The median age of onset was 16 years. The median EDSS score was 1.5 at inclusion, and the median score was 1.0 at follow-up of 3 years. At 6 months, 82 worsening events occurred in 57 patients.

A total of 76% of the patients were treated with DMTs. The most commonly prescribed DMTs were interferon beta (40.63%), natalizumab (8.48%), and fingolimod (6.40%). Seventy-eight percent of those who received DMTs started treatment before age 18. Twenty-seven percent received high-efficacy DMTs.

The analysis showed associations between disability and older age at onset [exp(beta), 1.09; 95% confidence interval, 1.03-1.16], maximum EDSS score during the first year of disease [exp(beta), 1.25; 95% CI, 1.13-1.36], or first-year pyramidal symptoms [exp(beta), 1.34; 95% CI, 1.13-1.58], visual symptoms [exp(beta), 1.28; 95% CI, 1.10-1.48], or cerebellum symptoms [exp(beta), 1.17; 95% CI, 1.00-1.39]. A greater amount of time on high-efficacy DMTs was associated with a lower probability of disability [exp(beta), 0.96; 95% CI, 0.93-0.99].

A complete recovery from the first relapse was associated with a lower probability of relapse, though this association did not reach statistical significance [exp(beta), 0.83; 95% CI, 0.68-1.03].

The secondary analyses found that the only predictor of 6-month EDSS worsening [exp(beta), 1.32; 95% CI, 1.21-1.45] was having a maximum EDSS score in the first year. Sensitivity analyses of complete and incomplete recovery from relapses found that a higher MSSS was associated incomplete recovery [exp(beta), 1.16; 95% CI, 1.02-1.32], and confirmed the primary finding that recovery from first relapse was associated with a lower probability of disability [exp(beta), 0.78; 95% CI, 0.63-0.96].

Among patients with MRI data, a new MRI lesion in year 1 was associated with a lower future MSSS score [exp(beta), 0.81; 95% CI, 0.66-0.99].

The study was funded by the National Health and Medical Research Council of Australia. The study authors disclosed ties with a wide range of pharmaceutical companies, including Biogen and Novartis. Dr. Cree has consulted for Biogen, Novartis, and other pharmaceutical companies.

Among pediatric patients with multiple sclerosis (MS), some specific clinical characteristics, as well as treatment with disease-modifying therapies (DMTs), are linked to less future disability.

An estimated 3%-10% of MS patients are diagnosed during childhood. These patients experience a higher relapse rate and have higher magnetic resonance imaging (MRI) activity than do adult-onset patients. They have a slower rate of progression, but they reach irreversible disability milestones at an early age, with more than 50% having secondary progressive disease by age 30.

Studies in adults suggest that use of high-efficacy DMTs is most effective when initiated during the early active phase of MS, but little is known about children. “Early recognition of predictors of faster disability in children is crucial for clinicians to make the treatment decisions at the earliest possible time,” Sifat Sharmin, PhD, said during her presentation of the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Dr. Sharmin is a statistician and research fellow at the University of Melbourne.
 

‘Reassuring’ data

“I think the most important observation that was made here is the protective factor of use of high efficacy disease modifying therapies,” said Bruce Cree, MD, PhD, who was asked to comment on the study.

That result wasn’t unexpected, but it should provide reassurance. “For parents of children who are hesitant about use of high efficacy therapies, this study provides supporting evidence for use of these high efficacy therapies early on, to try and prevent irreversible disability from occurring,” said Dr. Cree, professor of clinical neurology and the George A. Zimmermann Endowed Professor in Multiple Sclerosis at the University of California at San Francisco UCSF Weill Institute for Neurosciences.

The study provides real-world data to back up findings from a phase 3 clinical trial that showed fewer relapses and fewer new lesions in pediatric patients with MS who were taking fingolimod versus interferon beta-1a.

“Given a large randomized, controlled trial, and now with this additional real-world data set showing the same thing, the only conclusion to reach is that if you’ve got a kid with MS, they should be treated with fingolimod,” said Dr. Cree. He noted that other DMTs such as natalizumab may also benefit pediatric patients, but fingolimod is the only drug that has been studied in randomized, controlled trials in children.

Real-world data

The researchers analyzed data from 672 patients drawn from the international MSBase Neuroimmunology Registry, who had undergone neurological assessment within 1 year of symptom onset and had at least two annual visits where the Expanded Disability Status Scale (EDSS) was recorded. They sought to identify predictors of Multiple Sclerosis Severity Score (MSSS). A secondary analysis looked at predictors of EDSS sustained worsening at 6 months, defined as an increase of 1.5 if EDSS baseline was 0, 1.0 or more if baseline EDSS was 1.0-5.5, or 0.5 if baseline EDSS was over 5.5.

The researchers also conducted a sensitivity analysis that looked at relapse phenotypes and relapse frequency in the first year, as well as a subgroup analysis of patients with available MRI data from the first year. The researchers adjusted for time on high-efficacy DMTs at each visit.

Among the study participants, 70% were female. The median age of onset was 16 years. The median EDSS score was 1.5 at inclusion, and the median score was 1.0 at follow-up of 3 years. At 6 months, 82 worsening events occurred in 57 patients.

A total of 76% of the patients were treated with DMTs. The most commonly prescribed DMTs were interferon beta (40.63%), natalizumab (8.48%), and fingolimod (6.40%). Seventy-eight percent of those who received DMTs started treatment before age 18. Twenty-seven percent received high-efficacy DMTs.

The analysis showed associations between disability and older age at onset [exp(beta), 1.09; 95% confidence interval, 1.03-1.16], maximum EDSS score during the first year of disease [exp(beta), 1.25; 95% CI, 1.13-1.36], or first-year pyramidal symptoms [exp(beta), 1.34; 95% CI, 1.13-1.58], visual symptoms [exp(beta), 1.28; 95% CI, 1.10-1.48], or cerebellum symptoms [exp(beta), 1.17; 95% CI, 1.00-1.39]. A greater amount of time on high-efficacy DMTs was associated with a lower probability of disability [exp(beta), 0.96; 95% CI, 0.93-0.99].

A complete recovery from the first relapse was associated with a lower probability of relapse, though this association did not reach statistical significance [exp(beta), 0.83; 95% CI, 0.68-1.03].

The secondary analyses found that the only predictor of 6-month EDSS worsening [exp(beta), 1.32; 95% CI, 1.21-1.45] was having a maximum EDSS score in the first year. Sensitivity analyses of complete and incomplete recovery from relapses found that a higher MSSS was associated incomplete recovery [exp(beta), 1.16; 95% CI, 1.02-1.32], and confirmed the primary finding that recovery from first relapse was associated with a lower probability of disability [exp(beta), 0.78; 95% CI, 0.63-0.96].

Among patients with MRI data, a new MRI lesion in year 1 was associated with a lower future MSSS score [exp(beta), 0.81; 95% CI, 0.66-0.99].

The study was funded by the National Health and Medical Research Council of Australia. The study authors disclosed ties with a wide range of pharmaceutical companies, including Biogen and Novartis. Dr. Cree has consulted for Biogen, Novartis, and other pharmaceutical companies.

Among pediatric patients with multiple sclerosis (MS), some specific clinical characteristics, as well as treatment with disease-modifying therapies (DMTs), are linked to less future disability.

An estimated 3%-10% of MS patients are diagnosed during childhood. These patients experience a higher relapse rate and have higher magnetic resonance imaging (MRI) activity than do adult-onset patients. They have a slower rate of progression, but they reach irreversible disability milestones at an early age, with more than 50% having secondary progressive disease by age 30.

Studies in adults suggest that use of high-efficacy DMTs is most effective when initiated during the early active phase of MS, but little is known about children. “Early recognition of predictors of faster disability in children is crucial for clinicians to make the treatment decisions at the earliest possible time,” Sifat Sharmin, PhD, said during her presentation of the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Dr. Sharmin is a statistician and research fellow at the University of Melbourne.
 

‘Reassuring’ data

“I think the most important observation that was made here is the protective factor of use of high efficacy disease modifying therapies,” said Bruce Cree, MD, PhD, who was asked to comment on the study.

That result wasn’t unexpected, but it should provide reassurance. “For parents of children who are hesitant about use of high efficacy therapies, this study provides supporting evidence for use of these high efficacy therapies early on, to try and prevent irreversible disability from occurring,” said Dr. Cree, professor of clinical neurology and the George A. Zimmermann Endowed Professor in Multiple Sclerosis at the University of California at San Francisco UCSF Weill Institute for Neurosciences.

The study provides real-world data to back up findings from a phase 3 clinical trial that showed fewer relapses and fewer new lesions in pediatric patients with MS who were taking fingolimod versus interferon beta-1a.

“Given a large randomized, controlled trial, and now with this additional real-world data set showing the same thing, the only conclusion to reach is that if you’ve got a kid with MS, they should be treated with fingolimod,” said Dr. Cree. He noted that other DMTs such as natalizumab may also benefit pediatric patients, but fingolimod is the only drug that has been studied in randomized, controlled trials in children.

Real-world data

The researchers analyzed data from 672 patients drawn from the international MSBase Neuroimmunology Registry, who had undergone neurological assessment within 1 year of symptom onset and had at least two annual visits where the Expanded Disability Status Scale (EDSS) was recorded. They sought to identify predictors of Multiple Sclerosis Severity Score (MSSS). A secondary analysis looked at predictors of EDSS sustained worsening at 6 months, defined as an increase of 1.5 if EDSS baseline was 0, 1.0 or more if baseline EDSS was 1.0-5.5, or 0.5 if baseline EDSS was over 5.5.

The researchers also conducted a sensitivity analysis that looked at relapse phenotypes and relapse frequency in the first year, as well as a subgroup analysis of patients with available MRI data from the first year. The researchers adjusted for time on high-efficacy DMTs at each visit.

Among the study participants, 70% were female. The median age of onset was 16 years. The median EDSS score was 1.5 at inclusion, and the median score was 1.0 at follow-up of 3 years. At 6 months, 82 worsening events occurred in 57 patients.

A total of 76% of the patients were treated with DMTs. The most commonly prescribed DMTs were interferon beta (40.63%), natalizumab (8.48%), and fingolimod (6.40%). Seventy-eight percent of those who received DMTs started treatment before age 18. Twenty-seven percent received high-efficacy DMTs.

The analysis showed associations between disability and older age at onset [exp(beta), 1.09; 95% confidence interval, 1.03-1.16], maximum EDSS score during the first year of disease [exp(beta), 1.25; 95% CI, 1.13-1.36], or first-year pyramidal symptoms [exp(beta), 1.34; 95% CI, 1.13-1.58], visual symptoms [exp(beta), 1.28; 95% CI, 1.10-1.48], or cerebellum symptoms [exp(beta), 1.17; 95% CI, 1.00-1.39]. A greater amount of time on high-efficacy DMTs was associated with a lower probability of disability [exp(beta), 0.96; 95% CI, 0.93-0.99].

A complete recovery from the first relapse was associated with a lower probability of relapse, though this association did not reach statistical significance [exp(beta), 0.83; 95% CI, 0.68-1.03].

The secondary analyses found that the only predictor of 6-month EDSS worsening [exp(beta), 1.32; 95% CI, 1.21-1.45] was having a maximum EDSS score in the first year. Sensitivity analyses of complete and incomplete recovery from relapses found that a higher MSSS was associated incomplete recovery [exp(beta), 1.16; 95% CI, 1.02-1.32], and confirmed the primary finding that recovery from first relapse was associated with a lower probability of disability [exp(beta), 0.78; 95% CI, 0.63-0.96].

Among patients with MRI data, a new MRI lesion in year 1 was associated with a lower future MSSS score [exp(beta), 0.81; 95% CI, 0.66-0.99].

The study was funded by the National Health and Medical Research Council of Australia. The study authors disclosed ties with a wide range of pharmaceutical companies, including Biogen and Novartis. Dr. Cree has consulted for Biogen, Novartis, and other pharmaceutical companies.

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
 

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

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
 

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

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.

The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.

The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.

“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”

Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
 

Study details

The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.

“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”

After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.

The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).

After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).

Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).

Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.

Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
 

Understanding how it works

To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.

At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.

The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.

“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.

Based on these results, Finch plans to launch a phase 3 trial soon, she said.

The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.

“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.

Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.

Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
 

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

While type 2 diabetes is associated with a greater risk for cardiovascular events than type 1 diabetes, the latter is more associated with chronic kidney complications, according to data from a French observational study.

That’s not to say that type 1 diabetes isn’t also associated with poor heart health that is of concern, according to Denis Angoulvant, MD, of Tours (France) Regional University Hospital and Trousseau Hospital in Paris.

“The difference is that, in the middle or older ages, we suddenly see a surge of cardiovascular events in type 1 diabetic patients,” he said at the annual meeting of the European Association for the Study of Diabetes. “As a cardiologist, I must say that we are barely see these patients ahead of those complications, so we advocate that there’s a gap to be filled here to prevent these events in these patients.”

Few studies have looked at the comparative risks for cardiovascular and renal outcomes between patients with type 1 and type 2 diabetes, Dr. Angoulvant said, so the aim of the study he presented was to look at this in more detail.
 

Comparing cardiovascular and renal outcomes

Data from the French hospital discharge database (PMSI), which covers more than 98% of the country’s population, were used to find all adults with type 1 or type 2 diabetes who had at least 5 years of follow-up data starting from 2013.

Not surprisingly, there were eight times as many individuals with type 2 diabetes (425,207) than those with type 1 diabetes (50,623), and patients with type 2 diabetes tended to be older than those with type 1 diabetes (mean age, 68.6 vs. 61.4 years).

There were many significant differences between the two groups of patients in terms of clinical variables, such as patients with type 2 diabetes having more cardiovascular risk factors or preexisting heart problems, and those with type 1 diabetes more likely to have diabetic eye disease.

Indeed, Dr. Angoulvant pointed out that those with type 2 diabetes were significantly more likely (all P < .0001) than those with type 1 diabetes to have: hypertension (70.8% vs. 50.5%), heart failure (35.7% vs. 16.4%), valvular heart disease (7.2% vs. 3.5%), dilated cardiomyopathy (5.5% vs. 2.7%), coronary artery disease (27.6 vs. 18.6%), previous MI (3.0% vs. 2.4%), peripheral vascular disease (22.0% vs. 15.5%), and ischemic stroke (3.3 vs. 2.2%).

“Regarding more specific microvascular diabetic complications, we had a higher incidence of chronic kidney disease in type 2 diabetes patients [10.2% vs. 9.1%], but a higher incidence of diabetic retinopathy in type 1 diabetes patients [6.6% vs. 12.2%],” Dr. Angoulvant said.

Considering more than 2 million person-years of follow-up, the annual rates of MI, new-onset heart failure, ischemic stroke, and chronic kidney disease for the whole study population were respective 1.4%, 5.4%, 1.2%, and 3.4%. The annual rates for death from any cause was 9.7%, and for a cardiovascular reason was 2.4%.
 

Cardiovascular disease prevalence and event rates

The mean follow-up period was 4.3 years, and over this time the age- and sex-adjusted prevalence of cardiovascular disease was found to be highest in individuals with type 2 diabetes, especially after the age of 40 years.

Looking at the rates of different cardiovascular events showed that both younger (18-29 years) and older (60+ years) people with type 1 diabetes had a 1.2-fold higher risk for MI than similarly aged individuals with type 2 diabetes.

Furthermore, younger and older type 1 diabetes individuals had a 1.1- to 1.4-fold greater risk of new-onset heart failure than those with type 2 diabetes.

“Interestingly, regarding the incidence of ischemic stroke in our population, we found no significant difference between patients with type 1 diabetes, and patients with type 2 diabetes,” Dr. Angoulvant said.
 

Chronic kidney disease and risk for death

Chronic kidney disease was most common in individuals with type 1 diabetes who were aged between 18 and 69 years, with a greater prevalence also seen in those with type 2 diabetes only after age 80.

The risk of new chronic kidney disease was significantly increased in patients with type 1 diabetes, compared with patients with type 2 diabetes, with a 1.1- to 2.4-fold increase seen, first in individuals aged 18-49 years, and then again after the age of 60 years.

Dr. Angoulvant reported that the risk of dying from any cause was 1.1-fold higher in people with type 1 diabetes, compared with those with type 2 diabetes, but after the age of 60 years.

The risk of death from cardiovascular events was also increased in people with type 1 diabetes, but between the ages of 60 and 69 years.

Asked what his take-home message might be, Dr. Angoulvant stressed the importance of heart failure, in all patients with diabetes but particularly in those with type 1 diabetes.

“I think there is room for improvement in terms of assessing who is going to have heart failure, how to assess heart failure, and more importantly, how to prevent heart failure,” perhaps by “introducing those drugs that have shown tremendous benefit regarding hospitalization, such as [sodium-glucose transporter 2] inhibitors” in patients with type 1 diabetes ahead of the events, he said.

Dr. Angoulvant had no conflicts of interest to disclose.

While type 2 diabetes is associated with a greater risk for cardiovascular events than type 1 diabetes, the latter is more associated with chronic kidney complications, according to data from a French observational study.

That’s not to say that type 1 diabetes isn’t also associated with poor heart health that is of concern, according to Denis Angoulvant, MD, of Tours (France) Regional University Hospital and Trousseau Hospital in Paris.

“The difference is that, in the middle or older ages, we suddenly see a surge of cardiovascular events in type 1 diabetic patients,” he said at the annual meeting of the European Association for the Study of Diabetes. “As a cardiologist, I must say that we are barely see these patients ahead of those complications, so we advocate that there’s a gap to be filled here to prevent these events in these patients.”

Few studies have looked at the comparative risks for cardiovascular and renal outcomes between patients with type 1 and type 2 diabetes, Dr. Angoulvant said, so the aim of the study he presented was to look at this in more detail.
 

Comparing cardiovascular and renal outcomes

Data from the French hospital discharge database (PMSI), which covers more than 98% of the country’s population, were used to find all adults with type 1 or type 2 diabetes who had at least 5 years of follow-up data starting from 2013.

Not surprisingly, there were eight times as many individuals with type 2 diabetes (425,207) than those with type 1 diabetes (50,623), and patients with type 2 diabetes tended to be older than those with type 1 diabetes (mean age, 68.6 vs. 61.4 years).

There were many significant differences between the two groups of patients in terms of clinical variables, such as patients with type 2 diabetes having more cardiovascular risk factors or preexisting heart problems, and those with type 1 diabetes more likely to have diabetic eye disease.

Indeed, Dr. Angoulvant pointed out that those with type 2 diabetes were significantly more likely (all P < .0001) than those with type 1 diabetes to have: hypertension (70.8% vs. 50.5%), heart failure (35.7% vs. 16.4%), valvular heart disease (7.2% vs. 3.5%), dilated cardiomyopathy (5.5% vs. 2.7%), coronary artery disease (27.6 vs. 18.6%), previous MI (3.0% vs. 2.4%), peripheral vascular disease (22.0% vs. 15.5%), and ischemic stroke (3.3 vs. 2.2%).

“Regarding more specific microvascular diabetic complications, we had a higher incidence of chronic kidney disease in type 2 diabetes patients [10.2% vs. 9.1%], but a higher incidence of diabetic retinopathy in type 1 diabetes patients [6.6% vs. 12.2%],” Dr. Angoulvant said.

Considering more than 2 million person-years of follow-up, the annual rates of MI, new-onset heart failure, ischemic stroke, and chronic kidney disease for the whole study population were respective 1.4%, 5.4%, 1.2%, and 3.4%. The annual rates for death from any cause was 9.7%, and for a cardiovascular reason was 2.4%.
 

Cardiovascular disease prevalence and event rates

The mean follow-up period was 4.3 years, and over this time the age- and sex-adjusted prevalence of cardiovascular disease was found to be highest in individuals with type 2 diabetes, especially after the age of 40 years.

Looking at the rates of different cardiovascular events showed that both younger (18-29 years) and older (60+ years) people with type 1 diabetes had a 1.2-fold higher risk for MI than similarly aged individuals with type 2 diabetes.

Furthermore, younger and older type 1 diabetes individuals had a 1.1- to 1.4-fold greater risk of new-onset heart failure than those with type 2 diabetes.

“Interestingly, regarding the incidence of ischemic stroke in our population, we found no significant difference between patients with type 1 diabetes, and patients with type 2 diabetes,” Dr. Angoulvant said.
 

Chronic kidney disease and risk for death

Chronic kidney disease was most common in individuals with type 1 diabetes who were aged between 18 and 69 years, with a greater prevalence also seen in those with type 2 diabetes only after age 80.

The risk of new chronic kidney disease was significantly increased in patients with type 1 diabetes, compared with patients with type 2 diabetes, with a 1.1- to 2.4-fold increase seen, first in individuals aged 18-49 years, and then again after the age of 60 years.

Dr. Angoulvant reported that the risk of dying from any cause was 1.1-fold higher in people with type 1 diabetes, compared with those with type 2 diabetes, but after the age of 60 years.

The risk of death from cardiovascular events was also increased in people with type 1 diabetes, but between the ages of 60 and 69 years.

Asked what his take-home message might be, Dr. Angoulvant stressed the importance of heart failure, in all patients with diabetes but particularly in those with type 1 diabetes.

“I think there is room for improvement in terms of assessing who is going to have heart failure, how to assess heart failure, and more importantly, how to prevent heart failure,” perhaps by “introducing those drugs that have shown tremendous benefit regarding hospitalization, such as [sodium-glucose transporter 2] inhibitors” in patients with type 1 diabetes ahead of the events, he said.

Dr. Angoulvant had no conflicts of interest to disclose.

While type 2 diabetes is associated with a greater risk for cardiovascular events than type 1 diabetes, the latter is more associated with chronic kidney complications, according to data from a French observational study.

That’s not to say that type 1 diabetes isn’t also associated with poor heart health that is of concern, according to Denis Angoulvant, MD, of Tours (France) Regional University Hospital and Trousseau Hospital in Paris.

“The difference is that, in the middle or older ages, we suddenly see a surge of cardiovascular events in type 1 diabetic patients,” he said at the annual meeting of the European Association for the Study of Diabetes. “As a cardiologist, I must say that we are barely see these patients ahead of those complications, so we advocate that there’s a gap to be filled here to prevent these events in these patients.”

Few studies have looked at the comparative risks for cardiovascular and renal outcomes between patients with type 1 and type 2 diabetes, Dr. Angoulvant said, so the aim of the study he presented was to look at this in more detail.
 

Comparing cardiovascular and renal outcomes

Data from the French hospital discharge database (PMSI), which covers more than 98% of the country’s population, were used to find all adults with type 1 or type 2 diabetes who had at least 5 years of follow-up data starting from 2013.

Not surprisingly, there were eight times as many individuals with type 2 diabetes (425,207) than those with type 1 diabetes (50,623), and patients with type 2 diabetes tended to be older than those with type 1 diabetes (mean age, 68.6 vs. 61.4 years).

There were many significant differences between the two groups of patients in terms of clinical variables, such as patients with type 2 diabetes having more cardiovascular risk factors or preexisting heart problems, and those with type 1 diabetes more likely to have diabetic eye disease.

Indeed, Dr. Angoulvant pointed out that those with type 2 diabetes were significantly more likely (all P < .0001) than those with type 1 diabetes to have: hypertension (70.8% vs. 50.5%), heart failure (35.7% vs. 16.4%), valvular heart disease (7.2% vs. 3.5%), dilated cardiomyopathy (5.5% vs. 2.7%), coronary artery disease (27.6 vs. 18.6%), previous MI (3.0% vs. 2.4%), peripheral vascular disease (22.0% vs. 15.5%), and ischemic stroke (3.3 vs. 2.2%).

“Regarding more specific microvascular diabetic complications, we had a higher incidence of chronic kidney disease in type 2 diabetes patients [10.2% vs. 9.1%], but a higher incidence of diabetic retinopathy in type 1 diabetes patients [6.6% vs. 12.2%],” Dr. Angoulvant said.

Considering more than 2 million person-years of follow-up, the annual rates of MI, new-onset heart failure, ischemic stroke, and chronic kidney disease for the whole study population were respective 1.4%, 5.4%, 1.2%, and 3.4%. The annual rates for death from any cause was 9.7%, and for a cardiovascular reason was 2.4%.
 

Cardiovascular disease prevalence and event rates

The mean follow-up period was 4.3 years, and over this time the age- and sex-adjusted prevalence of cardiovascular disease was found to be highest in individuals with type 2 diabetes, especially after the age of 40 years.

Looking at the rates of different cardiovascular events showed that both younger (18-29 years) and older (60+ years) people with type 1 diabetes had a 1.2-fold higher risk for MI than similarly aged individuals with type 2 diabetes.

Furthermore, younger and older type 1 diabetes individuals had a 1.1- to 1.4-fold greater risk of new-onset heart failure than those with type 2 diabetes.

“Interestingly, regarding the incidence of ischemic stroke in our population, we found no significant difference between patients with type 1 diabetes, and patients with type 2 diabetes,” Dr. Angoulvant said.
 

Chronic kidney disease and risk for death

Chronic kidney disease was most common in individuals with type 1 diabetes who were aged between 18 and 69 years, with a greater prevalence also seen in those with type 2 diabetes only after age 80.

The risk of new chronic kidney disease was significantly increased in patients with type 1 diabetes, compared with patients with type 2 diabetes, with a 1.1- to 2.4-fold increase seen, first in individuals aged 18-49 years, and then again after the age of 60 years.

Dr. Angoulvant reported that the risk of dying from any cause was 1.1-fold higher in people with type 1 diabetes, compared with those with type 2 diabetes, but after the age of 60 years.

The risk of death from cardiovascular events was also increased in people with type 1 diabetes, but between the ages of 60 and 69 years.

Asked what his take-home message might be, Dr. Angoulvant stressed the importance of heart failure, in all patients with diabetes but particularly in those with type 1 diabetes.

“I think there is room for improvement in terms of assessing who is going to have heart failure, how to assess heart failure, and more importantly, how to prevent heart failure,” perhaps by “introducing those drugs that have shown tremendous benefit regarding hospitalization, such as [sodium-glucose transporter 2] inhibitors” in patients with type 1 diabetes ahead of the events, he said.

Dr. Angoulvant had no conflicts of interest to disclose.

Motor imagery (MI) is a useful tool in the management of multiple sclerosis (MS), with the potential to improve balance, walking, and even cognitive function and mental health. It’s a technique that many think of as the realm of professional athletes, who use it to help mentally prepare for physical activity. But the underlying mechanism has broad applicability, even in patients with MS who have disability.

The method recruits and employs motor-related areas within the brain, which suggests that it has functional equivalence to carrying out the rehearsed movement. The mental chronometry is also similar between imagined and executed actions, said Barbara Seebacher, PhD, who discussed MI during a presentation at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

MI involves mentally rehearsing movements, and so requires working memory. The patient must also have the fundamental ability to carry out the action, so it isn’t much use having nonambulatory patients imagine themselves walking. “The mental representations need to be available,” said Dr. Seebacher, a researcher at Medical University of Innsbruck in Austria.

During MI, individuals may imagine themselves from a first- or third-person view. The experience may be visual, as in picturing oneself moving, or kinesthetic, as in imagining the feeling of movement. There can be implicit components, such as imagining a projection of the speed and distance of an approaching car, and explicit, such as imagining the personal movement of walking across the street.

The use of MI in MS rehabilitation is a relatively new development, with no reports before 2010. One early, uncontrolled study found improvements in fatigue and quality of life when MI was combined with physical practice in 20 patients. Another study published in 2012 found that MS patients had worse MI accuracy and temporal organization than that of healthy controls, and that MI accuracy was associated with cognitive impairment.

A study in 2012 used visual and rhythmic cues combined with MI, and compared results when those cues were present or absent during MI. The cues produced much better results. Dr. Seebacher’s group has used rhythmic, auditory-cued MI of walking in people with MS. Approaches included music cueing, music and verbal cueing, metronome and verbal cueing, and no cue MI. “We found significant effects after all of these approaches, but the greatest effects were shown after music and verbally-cued MI practice,” said Dr. Seebacher.

MI ability appears to be impaired by longer MS disease duration, more severe disability, depression and anxiety, and cognitive fatigue. “All of this contributes to timing deficits in performing mental movements and to deficits in the spatial organization of imagined movements,” said Dr. Seebacher.

In contrast, studies have shown that MI training improves dynamic balance, walking, perceived walking ability, balance, confidence, cognition, fatigue, anxiety and depression, quality of life, and health-related quality of life.

Rehabilitation specialists can help patients achieve success with MI by letting them select their preferred perspective, first or third person, at least during initial sessions. Patients can also be given the choice to use a more dexterous, more often-used body part, at least in initial MI sessions. External rhythmic, audio, or visual cuing can be offered.

Dr. Seebacher has developed an initial framework for helping patients to improve their MI ability. This includes assessing rhythmicity of single imagined movements to help ensure that MI and movements are functionally equivalent. Another step is to incorporate movements that are meaningful to the patients, to help ensure that they are emotionally engaged with the exercise. Research conducted primarily in stroke patients has shown that embedding physical practice into MI, or adding physical movement to MI, can enhance sensory feedback.

Motor learning principles from neurorehabilitation also apply to MI, such as beginning with simple tasks and progressing to more complex tasks, as well as use of blocked practice before turning to random practice. “All this should help our patients to perform MI more easily and to gain a greater benefit,” said Dr. Seebacher.

The potential of MI piqued the interest of comoderator Hanneke Hulst, PhD, assistant professor of neurology at Amsterdam University Medical Center, during the Q&A session. “It’s actually very intriguing and interesting,” she said, and then asked Dr. Seebacher how difficult MI is to implement in a rehabilitation program, especially for someone who isn’t a rehabilitation specialist.

Dr. Seebacher responded that it can be difficult, especially because patients and therapists usually aren’t familiar with MI. “Whenever I explain MI to patients, I compare it with athletes, because everybody knows that athletes use mental training, together with their physical training. And this is something patients can identify themselves with,” said Dr. Seebacher. It’s also vital that the patient has preserved cognitive function, and is open to a new therapeutic approach. “If somebody just wants to act the same way that they did all the time, it may not be useful for these patients,” said Dr. Seebacher.

MI is also useful for patients who have difficulty with physical training, for example following relapses, or for those who are at greater risk of falling.

Dr. Seebacher has no relevant financial disclosures. Dr. Hulst has consulted with or served on the scientific advisory boards of Biogen, Celgene, Genzyme, Merck, and Roche.

Motor imagery (MI) is a useful tool in the management of multiple sclerosis (MS), with the potential to improve balance, walking, and even cognitive function and mental health. It’s a technique that many think of as the realm of professional athletes, who use it to help mentally prepare for physical activity. But the underlying mechanism has broad applicability, even in patients with MS who have disability.

The method recruits and employs motor-related areas within the brain, which suggests that it has functional equivalence to carrying out the rehearsed movement. The mental chronometry is also similar between imagined and executed actions, said Barbara Seebacher, PhD, who discussed MI during a presentation at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

MI involves mentally rehearsing movements, and so requires working memory. The patient must also have the fundamental ability to carry out the action, so it isn’t much use having nonambulatory patients imagine themselves walking. “The mental representations need to be available,” said Dr. Seebacher, a researcher at Medical University of Innsbruck in Austria.

During MI, individuals may imagine themselves from a first- or third-person view. The experience may be visual, as in picturing oneself moving, or kinesthetic, as in imagining the feeling of movement. There can be implicit components, such as imagining a projection of the speed and distance of an approaching car, and explicit, such as imagining the personal movement of walking across the street.

The use of MI in MS rehabilitation is a relatively new development, with no reports before 2010. One early, uncontrolled study found improvements in fatigue and quality of life when MI was combined with physical practice in 20 patients. Another study published in 2012 found that MS patients had worse MI accuracy and temporal organization than that of healthy controls, and that MI accuracy was associated with cognitive impairment.

A study in 2012 used visual and rhythmic cues combined with MI, and compared results when those cues were present or absent during MI. The cues produced much better results. Dr. Seebacher’s group has used rhythmic, auditory-cued MI of walking in people with MS. Approaches included music cueing, music and verbal cueing, metronome and verbal cueing, and no cue MI. “We found significant effects after all of these approaches, but the greatest effects were shown after music and verbally-cued MI practice,” said Dr. Seebacher.

MI ability appears to be impaired by longer MS disease duration, more severe disability, depression and anxiety, and cognitive fatigue. “All of this contributes to timing deficits in performing mental movements and to deficits in the spatial organization of imagined movements,” said Dr. Seebacher.

In contrast, studies have shown that MI training improves dynamic balance, walking, perceived walking ability, balance, confidence, cognition, fatigue, anxiety and depression, quality of life, and health-related quality of life.

Rehabilitation specialists can help patients achieve success with MI by letting them select their preferred perspective, first or third person, at least during initial sessions. Patients can also be given the choice to use a more dexterous, more often-used body part, at least in initial MI sessions. External rhythmic, audio, or visual cuing can be offered.

Dr. Seebacher has developed an initial framework for helping patients to improve their MI ability. This includes assessing rhythmicity of single imagined movements to help ensure that MI and movements are functionally equivalent. Another step is to incorporate movements that are meaningful to the patients, to help ensure that they are emotionally engaged with the exercise. Research conducted primarily in stroke patients has shown that embedding physical practice into MI, or adding physical movement to MI, can enhance sensory feedback.

Motor learning principles from neurorehabilitation also apply to MI, such as beginning with simple tasks and progressing to more complex tasks, as well as use of blocked practice before turning to random practice. “All this should help our patients to perform MI more easily and to gain a greater benefit,” said Dr. Seebacher.

The potential of MI piqued the interest of comoderator Hanneke Hulst, PhD, assistant professor of neurology at Amsterdam University Medical Center, during the Q&A session. “It’s actually very intriguing and interesting,” she said, and then asked Dr. Seebacher how difficult MI is to implement in a rehabilitation program, especially for someone who isn’t a rehabilitation specialist.

Dr. Seebacher responded that it can be difficult, especially because patients and therapists usually aren’t familiar with MI. “Whenever I explain MI to patients, I compare it with athletes, because everybody knows that athletes use mental training, together with their physical training. And this is something patients can identify themselves with,” said Dr. Seebacher. It’s also vital that the patient has preserved cognitive function, and is open to a new therapeutic approach. “If somebody just wants to act the same way that they did all the time, it may not be useful for these patients,” said Dr. Seebacher.

MI is also useful for patients who have difficulty with physical training, for example following relapses, or for those who are at greater risk of falling.

Dr. Seebacher has no relevant financial disclosures. Dr. Hulst has consulted with or served on the scientific advisory boards of Biogen, Celgene, Genzyme, Merck, and Roche.

Motor imagery (MI) is a useful tool in the management of multiple sclerosis (MS), with the potential to improve balance, walking, and even cognitive function and mental health. It’s a technique that many think of as the realm of professional athletes, who use it to help mentally prepare for physical activity. But the underlying mechanism has broad applicability, even in patients with MS who have disability.

The method recruits and employs motor-related areas within the brain, which suggests that it has functional equivalence to carrying out the rehearsed movement. The mental chronometry is also similar between imagined and executed actions, said Barbara Seebacher, PhD, who discussed MI during a presentation at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

MI involves mentally rehearsing movements, and so requires working memory. The patient must also have the fundamental ability to carry out the action, so it isn’t much use having nonambulatory patients imagine themselves walking. “The mental representations need to be available,” said Dr. Seebacher, a researcher at Medical University of Innsbruck in Austria.

During MI, individuals may imagine themselves from a first- or third-person view. The experience may be visual, as in picturing oneself moving, or kinesthetic, as in imagining the feeling of movement. There can be implicit components, such as imagining a projection of the speed and distance of an approaching car, and explicit, such as imagining the personal movement of walking across the street.

The use of MI in MS rehabilitation is a relatively new development, with no reports before 2010. One early, uncontrolled study found improvements in fatigue and quality of life when MI was combined with physical practice in 20 patients. Another study published in 2012 found that MS patients had worse MI accuracy and temporal organization than that of healthy controls, and that MI accuracy was associated with cognitive impairment.

A study in 2012 used visual and rhythmic cues combined with MI, and compared results when those cues were present or absent during MI. The cues produced much better results. Dr. Seebacher’s group has used rhythmic, auditory-cued MI of walking in people with MS. Approaches included music cueing, music and verbal cueing, metronome and verbal cueing, and no cue MI. “We found significant effects after all of these approaches, but the greatest effects were shown after music and verbally-cued MI practice,” said Dr. Seebacher.

MI ability appears to be impaired by longer MS disease duration, more severe disability, depression and anxiety, and cognitive fatigue. “All of this contributes to timing deficits in performing mental movements and to deficits in the spatial organization of imagined movements,” said Dr. Seebacher.

In contrast, studies have shown that MI training improves dynamic balance, walking, perceived walking ability, balance, confidence, cognition, fatigue, anxiety and depression, quality of life, and health-related quality of life.

Rehabilitation specialists can help patients achieve success with MI by letting them select their preferred perspective, first or third person, at least during initial sessions. Patients can also be given the choice to use a more dexterous, more often-used body part, at least in initial MI sessions. External rhythmic, audio, or visual cuing can be offered.

Dr. Seebacher has developed an initial framework for helping patients to improve their MI ability. This includes assessing rhythmicity of single imagined movements to help ensure that MI and movements are functionally equivalent. Another step is to incorporate movements that are meaningful to the patients, to help ensure that they are emotionally engaged with the exercise. Research conducted primarily in stroke patients has shown that embedding physical practice into MI, or adding physical movement to MI, can enhance sensory feedback.

Motor learning principles from neurorehabilitation also apply to MI, such as beginning with simple tasks and progressing to more complex tasks, as well as use of blocked practice before turning to random practice. “All this should help our patients to perform MI more easily and to gain a greater benefit,” said Dr. Seebacher.

The potential of MI piqued the interest of comoderator Hanneke Hulst, PhD, assistant professor of neurology at Amsterdam University Medical Center, during the Q&A session. “It’s actually very intriguing and interesting,” she said, and then asked Dr. Seebacher how difficult MI is to implement in a rehabilitation program, especially for someone who isn’t a rehabilitation specialist.

Dr. Seebacher responded that it can be difficult, especially because patients and therapists usually aren’t familiar with MI. “Whenever I explain MI to patients, I compare it with athletes, because everybody knows that athletes use mental training, together with their physical training. And this is something patients can identify themselves with,” said Dr. Seebacher. It’s also vital that the patient has preserved cognitive function, and is open to a new therapeutic approach. “If somebody just wants to act the same way that they did all the time, it may not be useful for these patients,” said Dr. Seebacher.

MI is also useful for patients who have difficulty with physical training, for example following relapses, or for those who are at greater risk of falling.

Dr. Seebacher has no relevant financial disclosures. Dr. Hulst has consulted with or served on the scientific advisory boards of Biogen, Celgene, Genzyme, Merck, and Roche.