Multiple Sclerosis Hub

BERLIN—European registry data do not support the hypothesis that exposure to interferon beta before conception or during pregnancy adversely affects pregnancy outcome or infant outcome, according to an analysis presented at ECTRIMS 2018.

In women, diagnosis of multiple sclerosis (MS) and treatment initiation often occur during childbearing years, but neurologists have not reached consensus about treatment before or during pregnancy. The European Interferon Beta Pregnancy Registry was created to gather evidence about the effect of this treatment on maternal and fetal outcomes. A separate population-based cohort study examined health care registry data from Finland and Sweden (ie, Nordic registries) for the same purpose.

An Analysis of Prospective Data

Kerstin Hellwig, MD, Senior Consultant Neurologist and researcher at St. Joseph and St. Elizabeth Hospital and Ruhr University in Bochum, Germany, and colleagues examined these databases to evaluate the prevalence of pregnancy and infant outcomes in women with MS who had been exposed to interferon beta. The investigators analyzed 948 pregnancy reports with recorded pregnancy outcomes from the European Interferon Beta Pregnancy Registry. They also examined 875 pregnancy events in the Nordic registries among patients exposed to interferon beta and other treatments and 1,831 events among untreated patients.

Treatment Did Not Affect Birth Weight

Approximately 82% of pregnancies in the European registry had an outcome of live birth without congenital anomalies. The prevalence of spontaneous abortions and live births with congenital anomalies were similar to those reported in the general population.

About 98% of pregnancies in the exposed cohort of the Nordic registries had an outcome of live birth without congenital anomalies. This result is similar to the corresponding 97% rate in the nonexposed cohort. The prevalence of spontaneous abortions and congenital anomalies also were similar between the exposed and nonexposed cohorts of the Nordic registries.

Birth weights ranged from 580 g to 5,160 g in the Nordic registries. The proportion of babies with low or very low birth weight was 5.0% in the interferon-exposed cohort, 4.7% among babies exposed to interferon and other treatments, and 5.8% among nonexposed babies. Mean birth weight was 3,421.2 g in the interferon-exposed cohort, 3,434.3 g in the cohort exposed to interferon and other treatments, and 3,389.3 g in the nonexposed cohort. These weights were consistent with results from the prospective German pregnancy registry, according to the authors. Birth weights were not recorded systematically in the European registry.

“The European Inter­feron Beta Pregnancy Registry showed no evidence that interferon beta exposure before conception or during pregnancy adversely affected pregnancy or infant outcomes,” said Dr. Hellwig and colleagues. “This is consistent with data collected from the Nordic registers.”

This study was supported by Merck in Darmstadt, Germany. Additional funding for analysis, project management, and medical writing was provided by Bayer, Biogen, Merck, and Novartis Pharma.

—Erik Greb

Suggested Reading

Alroughani R, Altintas A, Al Jumah M, et al. Pregnancy and the use of disease-modifying therapies in patients with multiple sclerosis: benefits versus risks. Mult Scler Int. 2016;2016:1034912.

Friend S, Richman S, Bloomgren G, et al. Evaluation of pregnancy outcomes from the Tysabri (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol. 2016;16(1):150.

BERLIN—European registry data do not support the hypothesis that exposure to interferon beta before conception or during pregnancy adversely affects pregnancy outcome or infant outcome, according to an analysis presented at ECTRIMS 2018.

In women, diagnosis of multiple sclerosis (MS) and treatment initiation often occur during childbearing years, but neurologists have not reached consensus about treatment before or during pregnancy. The European Interferon Beta Pregnancy Registry was created to gather evidence about the effect of this treatment on maternal and fetal outcomes. A separate population-based cohort study examined health care registry data from Finland and Sweden (ie, Nordic registries) for the same purpose.

An Analysis of Prospective Data

Kerstin Hellwig, MD, Senior Consultant Neurologist and researcher at St. Joseph and St. Elizabeth Hospital and Ruhr University in Bochum, Germany, and colleagues examined these databases to evaluate the prevalence of pregnancy and infant outcomes in women with MS who had been exposed to interferon beta. The investigators analyzed 948 pregnancy reports with recorded pregnancy outcomes from the European Interferon Beta Pregnancy Registry. They also examined 875 pregnancy events in the Nordic registries among patients exposed to interferon beta and other treatments and 1,831 events among untreated patients.

Treatment Did Not Affect Birth Weight

Approximately 82% of pregnancies in the European registry had an outcome of live birth without congenital anomalies. The prevalence of spontaneous abortions and live births with congenital anomalies were similar to those reported in the general population.

About 98% of pregnancies in the exposed cohort of the Nordic registries had an outcome of live birth without congenital anomalies. This result is similar to the corresponding 97% rate in the nonexposed cohort. The prevalence of spontaneous abortions and congenital anomalies also were similar between the exposed and nonexposed cohorts of the Nordic registries.

Birth weights ranged from 580 g to 5,160 g in the Nordic registries. The proportion of babies with low or very low birth weight was 5.0% in the interferon-exposed cohort, 4.7% among babies exposed to interferon and other treatments, and 5.8% among nonexposed babies. Mean birth weight was 3,421.2 g in the interferon-exposed cohort, 3,434.3 g in the cohort exposed to interferon and other treatments, and 3,389.3 g in the nonexposed cohort. These weights were consistent with results from the prospective German pregnancy registry, according to the authors. Birth weights were not recorded systematically in the European registry.

“The European Inter­feron Beta Pregnancy Registry showed no evidence that interferon beta exposure before conception or during pregnancy adversely affected pregnancy or infant outcomes,” said Dr. Hellwig and colleagues. “This is consistent with data collected from the Nordic registers.”

This study was supported by Merck in Darmstadt, Germany. Additional funding for analysis, project management, and medical writing was provided by Bayer, Biogen, Merck, and Novartis Pharma.

—Erik Greb

Suggested Reading

Alroughani R, Altintas A, Al Jumah M, et al. Pregnancy and the use of disease-modifying therapies in patients with multiple sclerosis: benefits versus risks. Mult Scler Int. 2016;2016:1034912.

Friend S, Richman S, Bloomgren G, et al. Evaluation of pregnancy outcomes from the Tysabri (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol. 2016;16(1):150.

BERLIN—European registry data do not support the hypothesis that exposure to interferon beta before conception or during pregnancy adversely affects pregnancy outcome or infant outcome, according to an analysis presented at ECTRIMS 2018.

In women, diagnosis of multiple sclerosis (MS) and treatment initiation often occur during childbearing years, but neurologists have not reached consensus about treatment before or during pregnancy. The European Interferon Beta Pregnancy Registry was created to gather evidence about the effect of this treatment on maternal and fetal outcomes. A separate population-based cohort study examined health care registry data from Finland and Sweden (ie, Nordic registries) for the same purpose.

An Analysis of Prospective Data

Kerstin Hellwig, MD, Senior Consultant Neurologist and researcher at St. Joseph and St. Elizabeth Hospital and Ruhr University in Bochum, Germany, and colleagues examined these databases to evaluate the prevalence of pregnancy and infant outcomes in women with MS who had been exposed to interferon beta. The investigators analyzed 948 pregnancy reports with recorded pregnancy outcomes from the European Interferon Beta Pregnancy Registry. They also examined 875 pregnancy events in the Nordic registries among patients exposed to interferon beta and other treatments and 1,831 events among untreated patients.

Treatment Did Not Affect Birth Weight

Approximately 82% of pregnancies in the European registry had an outcome of live birth without congenital anomalies. The prevalence of spontaneous abortions and live births with congenital anomalies were similar to those reported in the general population.

About 98% of pregnancies in the exposed cohort of the Nordic registries had an outcome of live birth without congenital anomalies. This result is similar to the corresponding 97% rate in the nonexposed cohort. The prevalence of spontaneous abortions and congenital anomalies also were similar between the exposed and nonexposed cohorts of the Nordic registries.

Birth weights ranged from 580 g to 5,160 g in the Nordic registries. The proportion of babies with low or very low birth weight was 5.0% in the interferon-exposed cohort, 4.7% among babies exposed to interferon and other treatments, and 5.8% among nonexposed babies. Mean birth weight was 3,421.2 g in the interferon-exposed cohort, 3,434.3 g in the cohort exposed to interferon and other treatments, and 3,389.3 g in the nonexposed cohort. These weights were consistent with results from the prospective German pregnancy registry, according to the authors. Birth weights were not recorded systematically in the European registry.

“The European Inter­feron Beta Pregnancy Registry showed no evidence that interferon beta exposure before conception or during pregnancy adversely affected pregnancy or infant outcomes,” said Dr. Hellwig and colleagues. “This is consistent with data collected from the Nordic registers.”

This study was supported by Merck in Darmstadt, Germany. Additional funding for analysis, project management, and medical writing was provided by Bayer, Biogen, Merck, and Novartis Pharma.

—Erik Greb

Suggested Reading

Alroughani R, Altintas A, Al Jumah M, et al. Pregnancy and the use of disease-modifying therapies in patients with multiple sclerosis: benefits versus risks. Mult Scler Int. 2016;2016:1034912.

Friend S, Richman S, Bloomgren G, et al. Evaluation of pregnancy outcomes from the Tysabri (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol. 2016;16(1):150.

Daclizumab beta has benefits over interferon beta-1a on measures of disability and function in patients with relapsing-remitting multiple sclerosis (MS), according to research published in the December 2018 issue of the Multiple Sclerosis Journal. The benefits are observed in the overall patient population, as well as in subgroups of patients based on demographic and disease characteristics.

Biogen and AbbVie, the manufacturers of daclizumab beta, voluntarily removed the therapy from the market in March 2018 because of safety concerns that included reports of severe liver damage and conditions associated with the immune system.

The phase 3 DECIDE study (NCT01064401) compared the safety and efficacy of subcutaneous daclizumab beta (150 mg) every 4 weeks with those of intramuscular interferon beta-1a (30 mcg) once weekly in patients with relapsing-remitting MS. Daclizumab beta reduced the risk of 24-week confirmed disability progression as assessed by the Expanded Disability Status Scale (EDSS) by 27%, compared with interferon beta-1a. Daclizumab beta also was associated with a greater median change from baseline to week 96 in MS Functional Composite (MSFC) score and a 24% reduction in the risk of clinically meaningful worsening on the physical impact subscale of the patient-reported 29-Item MS Impact Scale (MSIS-29 PHYS).

To shed light on the treatment’s effects in various demographic groups and in patients with specific clinical characteristics, Stanley L. Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore., and colleagues conducted a post hoc analysis of DECIDE data to examine the treatment effects of daclizumab beta and interferon beta-1a on patient disability or impairment in specific patient subgroups. The investigators examined results according to demographic characteristics, such as age (that is, 35 years or younger and older than 35 years) and sex. They also examined results in subgroups with the following baseline disease characteristics: disability (as defined by EDSS score), relapses in the previous 12 months, disease duration, presence of gadolinium enhancing lesions, T2 hyperintense lesion volume, disease activity, prior use of disease-modifying treatment, and prior use of interferon beta.

Dr. Cohan and colleagues focused on the following three outcome measures: 24-week confirmed disability progression (as measured by EDSS), 24-week sustained worsening on the MSFC, and the proportion of patients with clinically meaningful worsening in MSIS-29 PHYS at week 96. The researchers defined 24-week confirmed disability progression as an increase in the EDSS score of one or more points from a baseline score of 1 or higher or 1.5 points or more from a baseline score of 0 as confirmed after 24 weeks. They defined 24-week sustained worsening on the MSFC as worsening of 20% or more on the Timed 25-Foot Walk, worsening of 20% or more on Nine-Hole Peg Test, or a decrease of four or more points on the Symbol Digit Modalities Test sustained for 24 weeks.

Of the 1,841 patients enrolled in DECIDE, 922 were randomized to interferon beta-1a, and 919 were randomized to daclizumab beta. The treatment groups were well balanced in terms of demographic characteristics. Patients’ mean age was approximately 36 years, 68% of participants were female, and 90% of patients were white. Mean time since diagnosis at baseline was about 4 years, mean number of relapses in the previous year was 1.6, and mean baseline EDSS score was 2.5.

Daclizumab beta was associated with a lower risk of 24-week confirmed disability progression, compared with interferon beta-1a, in all subgroups. Patients aged 35 years or younger had the greatest risk reduction.

The proportion of patients who had 24-week sustained worsening on the MSFC at week 96 was 24% for daclizumab beta and 28% for interferon beta-1a. In the whole study population, daclizumab beta reduced the risk of this outcome by 20%, compared with interferon beta-1a. Daclizumab beta resulted in improved outcomes among all subgroups, compared with interferon beta-1a.

In addition, daclizumab beta reduced the risk of a clinically meaningful worsening of MSIS-29 PHYS at week 96 by 24%, compared with interferon beta-1a. The investigators observed trends favoring daclizumab beta in all subgroups.

“These analyses should be interpreted as exploratory and hypothesis-generating for future studies,” said Dr. Cohan and colleagues. They observed that some of the subgroups analyzed had small sample sizes and that no adjustments were made for multiple testing. Nevertheless, the results suggest that daclizumab beta has superior efficacy, compared with interferon beta-1a, regardless of patients’ demographic and disease characteristics, they concluded.

Biogen and AbbVie Biotherapeutics supported the study.

[email protected]

SOURCE: Cohan S et al. Mult Scler J. 2018. doi: 10.1177/1352458517735190.

This article was updated on 3/22/19.

Daclizumab beta has benefits over interferon beta-1a on measures of disability and function in patients with relapsing-remitting multiple sclerosis (MS), according to research published in the December 2018 issue of the Multiple Sclerosis Journal. The benefits are observed in the overall patient population, as well as in subgroups of patients based on demographic and disease characteristics.

Biogen and AbbVie, the manufacturers of daclizumab beta, voluntarily removed the therapy from the market in March 2018 because of safety concerns that included reports of severe liver damage and conditions associated with the immune system.

The phase 3 DECIDE study (NCT01064401) compared the safety and efficacy of subcutaneous daclizumab beta (150 mg) every 4 weeks with those of intramuscular interferon beta-1a (30 mcg) once weekly in patients with relapsing-remitting MS. Daclizumab beta reduced the risk of 24-week confirmed disability progression as assessed by the Expanded Disability Status Scale (EDSS) by 27%, compared with interferon beta-1a. Daclizumab beta also was associated with a greater median change from baseline to week 96 in MS Functional Composite (MSFC) score and a 24% reduction in the risk of clinically meaningful worsening on the physical impact subscale of the patient-reported 29-Item MS Impact Scale (MSIS-29 PHYS).

To shed light on the treatment’s effects in various demographic groups and in patients with specific clinical characteristics, Stanley L. Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore., and colleagues conducted a post hoc analysis of DECIDE data to examine the treatment effects of daclizumab beta and interferon beta-1a on patient disability or impairment in specific patient subgroups. The investigators examined results according to demographic characteristics, such as age (that is, 35 years or younger and older than 35 years) and sex. They also examined results in subgroups with the following baseline disease characteristics: disability (as defined by EDSS score), relapses in the previous 12 months, disease duration, presence of gadolinium enhancing lesions, T2 hyperintense lesion volume, disease activity, prior use of disease-modifying treatment, and prior use of interferon beta.

Dr. Cohan and colleagues focused on the following three outcome measures: 24-week confirmed disability progression (as measured by EDSS), 24-week sustained worsening on the MSFC, and the proportion of patients with clinically meaningful worsening in MSIS-29 PHYS at week 96. The researchers defined 24-week confirmed disability progression as an increase in the EDSS score of one or more points from a baseline score of 1 or higher or 1.5 points or more from a baseline score of 0 as confirmed after 24 weeks. They defined 24-week sustained worsening on the MSFC as worsening of 20% or more on the Timed 25-Foot Walk, worsening of 20% or more on Nine-Hole Peg Test, or a decrease of four or more points on the Symbol Digit Modalities Test sustained for 24 weeks.

Of the 1,841 patients enrolled in DECIDE, 922 were randomized to interferon beta-1a, and 919 were randomized to daclizumab beta. The treatment groups were well balanced in terms of demographic characteristics. Patients’ mean age was approximately 36 years, 68% of participants were female, and 90% of patients were white. Mean time since diagnosis at baseline was about 4 years, mean number of relapses in the previous year was 1.6, and mean baseline EDSS score was 2.5.

Daclizumab beta was associated with a lower risk of 24-week confirmed disability progression, compared with interferon beta-1a, in all subgroups. Patients aged 35 years or younger had the greatest risk reduction.

The proportion of patients who had 24-week sustained worsening on the MSFC at week 96 was 24% for daclizumab beta and 28% for interferon beta-1a. In the whole study population, daclizumab beta reduced the risk of this outcome by 20%, compared with interferon beta-1a. Daclizumab beta resulted in improved outcomes among all subgroups, compared with interferon beta-1a.

In addition, daclizumab beta reduced the risk of a clinically meaningful worsening of MSIS-29 PHYS at week 96 by 24%, compared with interferon beta-1a. The investigators observed trends favoring daclizumab beta in all subgroups.

“These analyses should be interpreted as exploratory and hypothesis-generating for future studies,” said Dr. Cohan and colleagues. They observed that some of the subgroups analyzed had small sample sizes and that no adjustments were made for multiple testing. Nevertheless, the results suggest that daclizumab beta has superior efficacy, compared with interferon beta-1a, regardless of patients’ demographic and disease characteristics, they concluded.

Biogen and AbbVie Biotherapeutics supported the study.

[email protected]

SOURCE: Cohan S et al. Mult Scler J. 2018. doi: 10.1177/1352458517735190.

This article was updated on 3/22/19.

Daclizumab beta has benefits over interferon beta-1a on measures of disability and function in patients with relapsing-remitting multiple sclerosis (MS), according to research published in the December 2018 issue of the Multiple Sclerosis Journal. The benefits are observed in the overall patient population, as well as in subgroups of patients based on demographic and disease characteristics.

Biogen and AbbVie, the manufacturers of daclizumab beta, voluntarily removed the therapy from the market in March 2018 because of safety concerns that included reports of severe liver damage and conditions associated with the immune system.

The phase 3 DECIDE study (NCT01064401) compared the safety and efficacy of subcutaneous daclizumab beta (150 mg) every 4 weeks with those of intramuscular interferon beta-1a (30 mcg) once weekly in patients with relapsing-remitting MS. Daclizumab beta reduced the risk of 24-week confirmed disability progression as assessed by the Expanded Disability Status Scale (EDSS) by 27%, compared with interferon beta-1a. Daclizumab beta also was associated with a greater median change from baseline to week 96 in MS Functional Composite (MSFC) score and a 24% reduction in the risk of clinically meaningful worsening on the physical impact subscale of the patient-reported 29-Item MS Impact Scale (MSIS-29 PHYS).

To shed light on the treatment’s effects in various demographic groups and in patients with specific clinical characteristics, Stanley L. Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore., and colleagues conducted a post hoc analysis of DECIDE data to examine the treatment effects of daclizumab beta and interferon beta-1a on patient disability or impairment in specific patient subgroups. The investigators examined results according to demographic characteristics, such as age (that is, 35 years or younger and older than 35 years) and sex. They also examined results in subgroups with the following baseline disease characteristics: disability (as defined by EDSS score), relapses in the previous 12 months, disease duration, presence of gadolinium enhancing lesions, T2 hyperintense lesion volume, disease activity, prior use of disease-modifying treatment, and prior use of interferon beta.

Dr. Cohan and colleagues focused on the following three outcome measures: 24-week confirmed disability progression (as measured by EDSS), 24-week sustained worsening on the MSFC, and the proportion of patients with clinically meaningful worsening in MSIS-29 PHYS at week 96. The researchers defined 24-week confirmed disability progression as an increase in the EDSS score of one or more points from a baseline score of 1 or higher or 1.5 points or more from a baseline score of 0 as confirmed after 24 weeks. They defined 24-week sustained worsening on the MSFC as worsening of 20% or more on the Timed 25-Foot Walk, worsening of 20% or more on Nine-Hole Peg Test, or a decrease of four or more points on the Symbol Digit Modalities Test sustained for 24 weeks.

Of the 1,841 patients enrolled in DECIDE, 922 were randomized to interferon beta-1a, and 919 were randomized to daclizumab beta. The treatment groups were well balanced in terms of demographic characteristics. Patients’ mean age was approximately 36 years, 68% of participants were female, and 90% of patients were white. Mean time since diagnosis at baseline was about 4 years, mean number of relapses in the previous year was 1.6, and mean baseline EDSS score was 2.5.

Daclizumab beta was associated with a lower risk of 24-week confirmed disability progression, compared with interferon beta-1a, in all subgroups. Patients aged 35 years or younger had the greatest risk reduction.

The proportion of patients who had 24-week sustained worsening on the MSFC at week 96 was 24% for daclizumab beta and 28% for interferon beta-1a. In the whole study population, daclizumab beta reduced the risk of this outcome by 20%, compared with interferon beta-1a. Daclizumab beta resulted in improved outcomes among all subgroups, compared with interferon beta-1a.

In addition, daclizumab beta reduced the risk of a clinically meaningful worsening of MSIS-29 PHYS at week 96 by 24%, compared with interferon beta-1a. The investigators observed trends favoring daclizumab beta in all subgroups.

“These analyses should be interpreted as exploratory and hypothesis-generating for future studies,” said Dr. Cohan and colleagues. They observed that some of the subgroups analyzed had small sample sizes and that no adjustments were made for multiple testing. Nevertheless, the results suggest that daclizumab beta has superior efficacy, compared with interferon beta-1a, regardless of patients’ demographic and disease characteristics, they concluded.

Biogen and AbbVie Biotherapeutics supported the study.

[email protected]

SOURCE: Cohan S et al. Mult Scler J. 2018. doi: 10.1177/1352458517735190.

This article was updated on 3/22/19.

Patients with secondary progressive multiple sclerosis (MS) who are treated with rituximab have significantly lower Expanded Disability Status Scale (EDSS) scores during follow-up and significantly delayed confirmed disability progression, compared with matched controls, according to a retrospective analysis published online Jan. 7 in JAMA Neurology.

The results suggest that “B-cell depletion by rituximab may be therapeutically beneficial in these patients,” said study author Yvonne Naegelin, MD, of the department of neurology at University Hospital Basel, Switzerland, and her colleagues. “A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.”

Research indicates that B cells play a role in the pathogenesis of relapsing-remitting and secondary progressive MS, and rituximab, a monoclonal CD20 antibody, may deplete B cells in the peripheral immune system and CNS. “Owing to the limited treatment options for secondary progressive MS and the extrapolation of results in relapsing-remitting MS and primary progressive MS, rituximab was used off-label for the treatment of secondary progressive MS,” the authors said. They compared disability progression in patients who were treated with rituximab at MS centers in Switzerland with disability of control patients with secondary progressive MS who did not receive rituximab. The control patients were part of an observational cohort study at MS centers in Switzerland and the Netherlands. Data for the present analysis were collected between 2004 and 2017.

The investigators matched rituximab-treated and control patients 1:1 using propensity scores. Matching variables were sex, age, EDSS score, and disease duration at baseline. Rituximab-treated patients had a mean age of 49.7 years, mean disease duration of 18.2 years, and mean EDSS score of 5.9; 59% were women. Controls had a mean age of 51.3 years, mean disease duration of 19.4 years, and mean EDSS score of 5.7; 61% were women.

A covariate-adjusted analysis of the matched set found that rituximab-treated patients had a significantly lower EDSS score during a mean follow-up of 3.5 years (mean difference, –0.52). In addition, time to confirmed disability progression was delayed in the rituximab-treated group (hazard ratio, 0.49). “Approximately 75% of untreated and 50% of treated individuals in our cohorts developed clinically significant confirmed progression for the 10-year period,” Dr. Naegelin and her colleagues reported. Complications, mainly related to infections, occurred in five cases during treatment. The researchers did not identify major safety concerns, however.

Dr. Naegelin had no conflict of interest disclosures. Several coauthors disclosed research support and compensation from pharmaceutical companies.

[email protected]

SOURCE: Naegelin Y et al. JAMA Neurol. 2019 Jan 7. doi: 10.1001/jamaneurol.2018.4239.

Patients with secondary progressive multiple sclerosis (MS) who are treated with rituximab have significantly lower Expanded Disability Status Scale (EDSS) scores during follow-up and significantly delayed confirmed disability progression, compared with matched controls, according to a retrospective analysis published online Jan. 7 in JAMA Neurology.

The results suggest that “B-cell depletion by rituximab may be therapeutically beneficial in these patients,” said study author Yvonne Naegelin, MD, of the department of neurology at University Hospital Basel, Switzerland, and her colleagues. “A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.”

Research indicates that B cells play a role in the pathogenesis of relapsing-remitting and secondary progressive MS, and rituximab, a monoclonal CD20 antibody, may deplete B cells in the peripheral immune system and CNS. “Owing to the limited treatment options for secondary progressive MS and the extrapolation of results in relapsing-remitting MS and primary progressive MS, rituximab was used off-label for the treatment of secondary progressive MS,” the authors said. They compared disability progression in patients who were treated with rituximab at MS centers in Switzerland with disability of control patients with secondary progressive MS who did not receive rituximab. The control patients were part of an observational cohort study at MS centers in Switzerland and the Netherlands. Data for the present analysis were collected between 2004 and 2017.

The investigators matched rituximab-treated and control patients 1:1 using propensity scores. Matching variables were sex, age, EDSS score, and disease duration at baseline. Rituximab-treated patients had a mean age of 49.7 years, mean disease duration of 18.2 years, and mean EDSS score of 5.9; 59% were women. Controls had a mean age of 51.3 years, mean disease duration of 19.4 years, and mean EDSS score of 5.7; 61% were women.

A covariate-adjusted analysis of the matched set found that rituximab-treated patients had a significantly lower EDSS score during a mean follow-up of 3.5 years (mean difference, –0.52). In addition, time to confirmed disability progression was delayed in the rituximab-treated group (hazard ratio, 0.49). “Approximately 75% of untreated and 50% of treated individuals in our cohorts developed clinically significant confirmed progression for the 10-year period,” Dr. Naegelin and her colleagues reported. Complications, mainly related to infections, occurred in five cases during treatment. The researchers did not identify major safety concerns, however.

Dr. Naegelin had no conflict of interest disclosures. Several coauthors disclosed research support and compensation from pharmaceutical companies.

[email protected]

SOURCE: Naegelin Y et al. JAMA Neurol. 2019 Jan 7. doi: 10.1001/jamaneurol.2018.4239.

Patients with secondary progressive multiple sclerosis (MS) who are treated with rituximab have significantly lower Expanded Disability Status Scale (EDSS) scores during follow-up and significantly delayed confirmed disability progression, compared with matched controls, according to a retrospective analysis published online Jan. 7 in JAMA Neurology.

The results suggest that “B-cell depletion by rituximab may be therapeutically beneficial in these patients,” said study author Yvonne Naegelin, MD, of the department of neurology at University Hospital Basel, Switzerland, and her colleagues. “A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.”

Research indicates that B cells play a role in the pathogenesis of relapsing-remitting and secondary progressive MS, and rituximab, a monoclonal CD20 antibody, may deplete B cells in the peripheral immune system and CNS. “Owing to the limited treatment options for secondary progressive MS and the extrapolation of results in relapsing-remitting MS and primary progressive MS, rituximab was used off-label for the treatment of secondary progressive MS,” the authors said. They compared disability progression in patients who were treated with rituximab at MS centers in Switzerland with disability of control patients with secondary progressive MS who did not receive rituximab. The control patients were part of an observational cohort study at MS centers in Switzerland and the Netherlands. Data for the present analysis were collected between 2004 and 2017.

The investigators matched rituximab-treated and control patients 1:1 using propensity scores. Matching variables were sex, age, EDSS score, and disease duration at baseline. Rituximab-treated patients had a mean age of 49.7 years, mean disease duration of 18.2 years, and mean EDSS score of 5.9; 59% were women. Controls had a mean age of 51.3 years, mean disease duration of 19.4 years, and mean EDSS score of 5.7; 61% were women.

A covariate-adjusted analysis of the matched set found that rituximab-treated patients had a significantly lower EDSS score during a mean follow-up of 3.5 years (mean difference, –0.52). In addition, time to confirmed disability progression was delayed in the rituximab-treated group (hazard ratio, 0.49). “Approximately 75% of untreated and 50% of treated individuals in our cohorts developed clinically significant confirmed progression for the 10-year period,” Dr. Naegelin and her colleagues reported. Complications, mainly related to infections, occurred in five cases during treatment. The researchers did not identify major safety concerns, however.

Dr. Naegelin had no conflict of interest disclosures. Several coauthors disclosed research support and compensation from pharmaceutical companies.

[email protected]

SOURCE: Naegelin Y et al. JAMA Neurol. 2019 Jan 7. doi: 10.1001/jamaneurol.2018.4239.

Cladribine tablets (3.5 mg/kg) have a favorable adverse event profile and are safe as monotherapy for relapsing remitting multiple sclerosis, according to an integrated analysis of several clinical trials published in Multiple Sclerosis and Related Disorders.

The drug causes transient lymphopenia, as is to be expected from its mechanism of action, but most patients who receive cladribine do not have grade 3 or 4 lymphopenia, the authors wrote. In general, cladribine is not associated with an increased risk of infections or malignancy.

Data indicate that cladribine’s mechanism of action contributes to its durable clinical effect, despite the brief treatment periods. Clinical trials have provided information about the treatment’s safety and tolerability. To examine the treatment’s long-term safety, Stuart Cook, MD, of New Jersey Medical School, Newark, and his colleagues pooled data for patients with multiple sclerosis (MS) treated with cladribine tablets (3.5 mg/kg) as monotherapy or placebo in three phase 3 clinical trials (CLARITY, CLARITY Extension, and ORACLE-MS) and followed up in the PREMIERE registry. The investigators called these patients the monotherapy oral cohort.

To investigate the potential associations between cladribine and rarer adverse events such as malignancies, Dr. Cook and his colleagues examined data from patients with MS who received cladribine, regardless of the formulation or route of administration, or placebo (the all-exposed cohort). This cohort included data from the ONWARD trial, in which patients received cladribine tablets or placebo in combination with interferon-beta, as well as data from five trials in which patients received parenteral cladribine or placebo.

The monotherapy oral cohort included 923 patients who received cladribine and 641 who received placebo. The median age at enrollment in this cohort was approximately 36 years. The majority of patients were women and disease characteristics were balanced between arms. The all-exposed cohort included 1,926 patients who received cladribine and 802 who received placebo. The demographic characteristics of this cohort were similar to those of the monotherapy oral cohort.

In the monotherapy oral cohort, the incidence rate of treatment-emergent adverse events, in adjusted adverse events per 100 patient-years, was 103.29 for the active group versus 94.26 for controls. Lymphopenia (7.94 vs. 1.06) and decreased lymphocyte count (0.78 vs. 0.10) occurred more frequently in the active group than in the placebo group.

Herpes zoster also occurred more frequently in the cladribine group (0.83 vs. 0.20). However, cladribine was not associated with systemic serious disseminated herpes zoster. Furthermore, the investigators found no overall increased risk of infections, including opportunistic infections, with cladribine tablets versus placebo, except for herpes zoster.

In addition, Dr. Cook and his colleagues found no increase in malignancy rates among patients who received cladribine, compared with those who received placebo. They also found no increase in the incidence of malignancies over time in the cladribine group.

The adverse event profile for cladribine tablets (3.5 mg/kg) as monotherapy has been well characterized, the investigators wrote. The results of this analysis are broadly similar to the short-term adverse event results reported in the individual trials.

EMD Serono and Merck Serono, two affiliates of Merck in Darmstadt, Germany, sponsored the study. Merck manufactures cladribine.

[email protected]

SOURCE: Cook S et al. Mult Scler Relat Disord. 2018 Nov 18. doi: 10.1016/j.msard.2018.11.021.

Cladribine tablets (3.5 mg/kg) have a favorable adverse event profile and are safe as monotherapy for relapsing remitting multiple sclerosis, according to an integrated analysis of several clinical trials published in Multiple Sclerosis and Related Disorders.

The drug causes transient lymphopenia, as is to be expected from its mechanism of action, but most patients who receive cladribine do not have grade 3 or 4 lymphopenia, the authors wrote. In general, cladribine is not associated with an increased risk of infections or malignancy.

Data indicate that cladribine’s mechanism of action contributes to its durable clinical effect, despite the brief treatment periods. Clinical trials have provided information about the treatment’s safety and tolerability. To examine the treatment’s long-term safety, Stuart Cook, MD, of New Jersey Medical School, Newark, and his colleagues pooled data for patients with multiple sclerosis (MS) treated with cladribine tablets (3.5 mg/kg) as monotherapy or placebo in three phase 3 clinical trials (CLARITY, CLARITY Extension, and ORACLE-MS) and followed up in the PREMIERE registry. The investigators called these patients the monotherapy oral cohort.

To investigate the potential associations between cladribine and rarer adverse events such as malignancies, Dr. Cook and his colleagues examined data from patients with MS who received cladribine, regardless of the formulation or route of administration, or placebo (the all-exposed cohort). This cohort included data from the ONWARD trial, in which patients received cladribine tablets or placebo in combination with interferon-beta, as well as data from five trials in which patients received parenteral cladribine or placebo.

The monotherapy oral cohort included 923 patients who received cladribine and 641 who received placebo. The median age at enrollment in this cohort was approximately 36 years. The majority of patients were women and disease characteristics were balanced between arms. The all-exposed cohort included 1,926 patients who received cladribine and 802 who received placebo. The demographic characteristics of this cohort were similar to those of the monotherapy oral cohort.

In the monotherapy oral cohort, the incidence rate of treatment-emergent adverse events, in adjusted adverse events per 100 patient-years, was 103.29 for the active group versus 94.26 for controls. Lymphopenia (7.94 vs. 1.06) and decreased lymphocyte count (0.78 vs. 0.10) occurred more frequently in the active group than in the placebo group.

Herpes zoster also occurred more frequently in the cladribine group (0.83 vs. 0.20). However, cladribine was not associated with systemic serious disseminated herpes zoster. Furthermore, the investigators found no overall increased risk of infections, including opportunistic infections, with cladribine tablets versus placebo, except for herpes zoster.

In addition, Dr. Cook and his colleagues found no increase in malignancy rates among patients who received cladribine, compared with those who received placebo. They also found no increase in the incidence of malignancies over time in the cladribine group.

The adverse event profile for cladribine tablets (3.5 mg/kg) as monotherapy has been well characterized, the investigators wrote. The results of this analysis are broadly similar to the short-term adverse event results reported in the individual trials.

EMD Serono and Merck Serono, two affiliates of Merck in Darmstadt, Germany, sponsored the study. Merck manufactures cladribine.

[email protected]

SOURCE: Cook S et al. Mult Scler Relat Disord. 2018 Nov 18. doi: 10.1016/j.msard.2018.11.021.

Cladribine tablets (3.5 mg/kg) have a favorable adverse event profile and are safe as monotherapy for relapsing remitting multiple sclerosis, according to an integrated analysis of several clinical trials published in Multiple Sclerosis and Related Disorders.

The drug causes transient lymphopenia, as is to be expected from its mechanism of action, but most patients who receive cladribine do not have grade 3 or 4 lymphopenia, the authors wrote. In general, cladribine is not associated with an increased risk of infections or malignancy.

Data indicate that cladribine’s mechanism of action contributes to its durable clinical effect, despite the brief treatment periods. Clinical trials have provided information about the treatment’s safety and tolerability. To examine the treatment’s long-term safety, Stuart Cook, MD, of New Jersey Medical School, Newark, and his colleagues pooled data for patients with multiple sclerosis (MS) treated with cladribine tablets (3.5 mg/kg) as monotherapy or placebo in three phase 3 clinical trials (CLARITY, CLARITY Extension, and ORACLE-MS) and followed up in the PREMIERE registry. The investigators called these patients the monotherapy oral cohort.

To investigate the potential associations between cladribine and rarer adverse events such as malignancies, Dr. Cook and his colleagues examined data from patients with MS who received cladribine, regardless of the formulation or route of administration, or placebo (the all-exposed cohort). This cohort included data from the ONWARD trial, in which patients received cladribine tablets or placebo in combination with interferon-beta, as well as data from five trials in which patients received parenteral cladribine or placebo.

The monotherapy oral cohort included 923 patients who received cladribine and 641 who received placebo. The median age at enrollment in this cohort was approximately 36 years. The majority of patients were women and disease characteristics were balanced between arms. The all-exposed cohort included 1,926 patients who received cladribine and 802 who received placebo. The demographic characteristics of this cohort were similar to those of the monotherapy oral cohort.

In the monotherapy oral cohort, the incidence rate of treatment-emergent adverse events, in adjusted adverse events per 100 patient-years, was 103.29 for the active group versus 94.26 for controls. Lymphopenia (7.94 vs. 1.06) and decreased lymphocyte count (0.78 vs. 0.10) occurred more frequently in the active group than in the placebo group.

Herpes zoster also occurred more frequently in the cladribine group (0.83 vs. 0.20). However, cladribine was not associated with systemic serious disseminated herpes zoster. Furthermore, the investigators found no overall increased risk of infections, including opportunistic infections, with cladribine tablets versus placebo, except for herpes zoster.

In addition, Dr. Cook and his colleagues found no increase in malignancy rates among patients who received cladribine, compared with those who received placebo. They also found no increase in the incidence of malignancies over time in the cladribine group.

The adverse event profile for cladribine tablets (3.5 mg/kg) as monotherapy has been well characterized, the investigators wrote. The results of this analysis are broadly similar to the short-term adverse event results reported in the individual trials.

EMD Serono and Merck Serono, two affiliates of Merck in Darmstadt, Germany, sponsored the study. Merck manufactures cladribine.

[email protected]

SOURCE: Cook S et al. Mult Scler Relat Disord. 2018 Nov 18. doi: 10.1016/j.msard.2018.11.021.

Patients with multiple sclerosis (MS) and food allergies had more relapses and gadolinium-enhancing lesions than patients with MS but no food allergies, according to a recent analysis of a longitudinal study.

Patients with food allergies had a 1.3-times higher rate for cumulative number of attacks and a 2.5-times higher likelihood of enhancing lesions on brain MRI in the analysis of patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB).

By contrast, there were no significant differences in relapse or lesion rates for patients with environmental or drug allergies when compared with those without allergies, reported Tanuja Chitnis, MD, of Partners Multiple Sclerosis Center at Brigham and Women’s Hospital, Boston, and her coinvestigators.

“Our findings suggest that MS patients with allergies have more active disease than those without allergies, and that this effect is driven by food allergies,” Dr. Tanuja and her coauthors wrote in their report, which appeared in the Journal of Neurology, Neurosurgery and Psychiatry.

Previous investigations have looked at whether allergy history increases risk of developing MS, with conflicting results, they added, noting a meta-analysis of 10 observational studies suggesting no such link.

By contrast, whether allergies lead to more or less intense MS activity has not been addressed, according to investigators, who said this is the first study tying allergy history to MS disease course using clinical and MRI variables.

Their study was based on a subset of 1,349 patients with a diagnosis of MS who were enrolled in CLIMB and completed a self-administered questionnaire on food, environmental, and drug allergies. Of those patients, 922 reported allergies, while 427 reported no known allergies.

Patients with food allergies had a significantly increased rate of cumulative number of attacks, compared with those with no allergies, according to investigators, even after adjusting the analysis for gender, age at symptom onset, disease category, and time on treatment (relapse rate ratio, 1.274; 95% confidence interval, 1.023-1.587; P = .0305).

Food allergy patients were more than twice as likely as no-allergy patients were to have gadolinium-enhancing lesions on brain MRI after adjusting for other covariates (odds ratio, 2.53; 95% CI, 1.25-5.11; P = .0096), they added.

Patients with environmental and drug allergies also appeared to have more relapses, compared with patients with no allergies, in univariate analysis, but the differences were not significant in the adjusted analysis, investigators said. Likewise, there were trends toward a link between number of lesions and presence of environmental or drug allergies that did not hold up on multivariate analysis.

It is unknown what underlying biological mechanisms might potentially link food allergies to MS disease severity; however, findings of experimental studies support the hypothesis that gut microbiota might affect the risk and course of MS, Dr. Chitnis and her coauthors wrote in their report.

The CLIMB study was supported by Merck Serono and the National MS Society Nancy Davis Center Without Walls. Dr. Chitnis reported consulting fees from Biogen Idec, Novartis, Sanofi, Bayer, and Celgene outside the submitted work. Coauthors provided additional disclosures related to Merck Serono, Genentech, Verily Life Sciences, EMD Serono, Biogen, Teva, Sanofi, and Novartis, among others.

SOURCE: Fakih R et al. J Neurol Neurosurg Psychiatry. 2018 Dec 18. doi: 10.1136/jnnp-2018-319301.

Patients with multiple sclerosis (MS) and food allergies had more relapses and gadolinium-enhancing lesions than patients with MS but no food allergies, according to a recent analysis of a longitudinal study.

Patients with food allergies had a 1.3-times higher rate for cumulative number of attacks and a 2.5-times higher likelihood of enhancing lesions on brain MRI in the analysis of patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB).

By contrast, there were no significant differences in relapse or lesion rates for patients with environmental or drug allergies when compared with those without allergies, reported Tanuja Chitnis, MD, of Partners Multiple Sclerosis Center at Brigham and Women’s Hospital, Boston, and her coinvestigators.

“Our findings suggest that MS patients with allergies have more active disease than those without allergies, and that this effect is driven by food allergies,” Dr. Tanuja and her coauthors wrote in their report, which appeared in the Journal of Neurology, Neurosurgery and Psychiatry.

Previous investigations have looked at whether allergy history increases risk of developing MS, with conflicting results, they added, noting a meta-analysis of 10 observational studies suggesting no such link.

By contrast, whether allergies lead to more or less intense MS activity has not been addressed, according to investigators, who said this is the first study tying allergy history to MS disease course using clinical and MRI variables.

Their study was based on a subset of 1,349 patients with a diagnosis of MS who were enrolled in CLIMB and completed a self-administered questionnaire on food, environmental, and drug allergies. Of those patients, 922 reported allergies, while 427 reported no known allergies.

Patients with food allergies had a significantly increased rate of cumulative number of attacks, compared with those with no allergies, according to investigators, even after adjusting the analysis for gender, age at symptom onset, disease category, and time on treatment (relapse rate ratio, 1.274; 95% confidence interval, 1.023-1.587; P = .0305).

Food allergy patients were more than twice as likely as no-allergy patients were to have gadolinium-enhancing lesions on brain MRI after adjusting for other covariates (odds ratio, 2.53; 95% CI, 1.25-5.11; P = .0096), they added.

Patients with environmental and drug allergies also appeared to have more relapses, compared with patients with no allergies, in univariate analysis, but the differences were not significant in the adjusted analysis, investigators said. Likewise, there were trends toward a link between number of lesions and presence of environmental or drug allergies that did not hold up on multivariate analysis.

It is unknown what underlying biological mechanisms might potentially link food allergies to MS disease severity; however, findings of experimental studies support the hypothesis that gut microbiota might affect the risk and course of MS, Dr. Chitnis and her coauthors wrote in their report.

The CLIMB study was supported by Merck Serono and the National MS Society Nancy Davis Center Without Walls. Dr. Chitnis reported consulting fees from Biogen Idec, Novartis, Sanofi, Bayer, and Celgene outside the submitted work. Coauthors provided additional disclosures related to Merck Serono, Genentech, Verily Life Sciences, EMD Serono, Biogen, Teva, Sanofi, and Novartis, among others.

SOURCE: Fakih R et al. J Neurol Neurosurg Psychiatry. 2018 Dec 18. doi: 10.1136/jnnp-2018-319301.

Patients with multiple sclerosis (MS) and food allergies had more relapses and gadolinium-enhancing lesions than patients with MS but no food allergies, according to a recent analysis of a longitudinal study.

Patients with food allergies had a 1.3-times higher rate for cumulative number of attacks and a 2.5-times higher likelihood of enhancing lesions on brain MRI in the analysis of patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB).

By contrast, there were no significant differences in relapse or lesion rates for patients with environmental or drug allergies when compared with those without allergies, reported Tanuja Chitnis, MD, of Partners Multiple Sclerosis Center at Brigham and Women’s Hospital, Boston, and her coinvestigators.

“Our findings suggest that MS patients with allergies have more active disease than those without allergies, and that this effect is driven by food allergies,” Dr. Tanuja and her coauthors wrote in their report, which appeared in the Journal of Neurology, Neurosurgery and Psychiatry.

Previous investigations have looked at whether allergy history increases risk of developing MS, with conflicting results, they added, noting a meta-analysis of 10 observational studies suggesting no such link.

By contrast, whether allergies lead to more or less intense MS activity has not been addressed, according to investigators, who said this is the first study tying allergy history to MS disease course using clinical and MRI variables.

Their study was based on a subset of 1,349 patients with a diagnosis of MS who were enrolled in CLIMB and completed a self-administered questionnaire on food, environmental, and drug allergies. Of those patients, 922 reported allergies, while 427 reported no known allergies.

Patients with food allergies had a significantly increased rate of cumulative number of attacks, compared with those with no allergies, according to investigators, even after adjusting the analysis for gender, age at symptom onset, disease category, and time on treatment (relapse rate ratio, 1.274; 95% confidence interval, 1.023-1.587; P = .0305).

Food allergy patients were more than twice as likely as no-allergy patients were to have gadolinium-enhancing lesions on brain MRI after adjusting for other covariates (odds ratio, 2.53; 95% CI, 1.25-5.11; P = .0096), they added.

Patients with environmental and drug allergies also appeared to have more relapses, compared with patients with no allergies, in univariate analysis, but the differences were not significant in the adjusted analysis, investigators said. Likewise, there were trends toward a link between number of lesions and presence of environmental or drug allergies that did not hold up on multivariate analysis.

It is unknown what underlying biological mechanisms might potentially link food allergies to MS disease severity; however, findings of experimental studies support the hypothesis that gut microbiota might affect the risk and course of MS, Dr. Chitnis and her coauthors wrote in their report.

The CLIMB study was supported by Merck Serono and the National MS Society Nancy Davis Center Without Walls. Dr. Chitnis reported consulting fees from Biogen Idec, Novartis, Sanofi, Bayer, and Celgene outside the submitted work. Coauthors provided additional disclosures related to Merck Serono, Genentech, Verily Life Sciences, EMD Serono, Biogen, Teva, Sanofi, and Novartis, among others.

SOURCE: Fakih R et al. J Neurol Neurosurg Psychiatry. 2018 Dec 18. doi: 10.1136/jnnp-2018-319301.

BERLIN – Real-world data from six postmarketing surveillance studies suggest that currently available disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) have long-lasting effects that are matched by reasonable tolerability.

solitude72/iStockphoto

Long-term efficacy and safety data on natalizumab (Tysabri), fingolimod (Gilenya), alemtuzumab (Lemtrada), dimethyl fumarate (Tecfidera), and teriflunomide (Aubagio) from four Swedish studies, one French study, and one international study were reported during a poster session on long-term treatment monitoring at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

The IMSE 1 study with natalizumab

The Immunomodulation and Multiple Sclerosis Epidemiology (IMSE) studies are Swedish postmarketing surveillance studies that were started with the launch of various DMTs in Sweden: natalizumab since 2006 (IMSE 1), fingolimod in 2015 (IMSE 2), alemtuzumab in 2014 (IMSE 3), and dimethyl fumarate in 2014 (IMSE 5).

“Postmarketing surveillance is important for determination of long-term safety and effectiveness in a real-world setting,” Stina Kågström and her associates observed in their poster reporting some findings of the IMSE 1 study with natalizumab (Mult Scler. 2018;24[S2]:699-700, Abstract P1232).

Ms. Kågström of the department of clinical neuroscience at the Karolinska Institute in Stockholm and her colleagues reported that data on 3,108 patients who were seen at 54 Swedish clinics had been collated via the nationwide Swedish Quality Registry for Neurological Care (NEUROreg). NEUROreg started out as an MS register but has since widened its remit to include other neurologic diagnoses.

For the IMSE 1 study, prospectively recorded data regarding natalizumab treatment, adverse events, JC-virus (JCV) status and clinical effectiveness measures were obtained from NEUROreg for 2,225 women and 883 men. Just over one-third (37%, n = 1,150) were still receiving natalizumab at the time of the analysis.


The mean age at which natalizumab was started was 39 years, with treatment primarily given for RRMS (81% of patients) and less often for secondary progressive multiple sclerosis (SPMS, 15%) and rarely for other types of progressive MS. The mean treatment duration was just under 4 years (47.6 months).

JCV testing was introduced in 2011 in Sweden, and this “has led to fewer treated JCV-positive patients,” the IMSE 1 study investigators reported. “This likely explains a reduced incidence of PML [progressive multifocal leukoencephalopathy],” they suggested. There were nine PML cases diagnosed in Sweden from 2008 to the data cut-off point in 2018, one of which was fatal.

JCV status from 2011 onward was available for 1,269 patients, of whom 39% were JCV positive and 61% were JCV negative. The overall drug survival rate was 72% for JCV-negative and 14% for JCV-positive patients. Improved health status was seen, as measured by the Expanded Disability Status Scale (EDSS), the Multiple Sclerosis Severity Score (MSSS), and the physical and psychological Multiple Sclerosis Impact Scale–29 (MSIS-29) components.

A total of 644 of 1,269 patients discontinued treatment with natalizumab at some point, of whom 67% discontinued because of being JCV positive. The main reason for discontinuation in JCV-negative patients was pregnancy or planning a pregnancy (38%), with lack of effect (10%) and adverse events (11%) as other key reasons for stopping natalizumab.

Ms. Kågström and her associates concluded that natalizumab was “generally well tolerated with sustained effectiveness.”

The IMSE 2 study with fingolimod

Data on the long-term safety and efficacy of fingolimod were reported from the IMSE 2 study (Mult Scler. 2018;24[S2]:696-7, Abstract P1228). Lead author Anna Fält, also of the Karolinska Institute, and her associates analyzed data for 1,634 patients who had been treated with fingolimod from June 2015 to September 2018.

Most patients were older than 30 years (79%), and those aged 30 and older were predominantly female (69%), had an RRMS diagnosis (88%), and been treated for a mean of about 3 years (37 months). A total of 829 were being treated with fingolimod at the time of the analysis, with 844 having discontinued treatment at some point. The main reason for discontinuing treatment with fingolimod was a lack of effect (42% of cases) or an adverse effect (34%). The IMSE 2 study authors reported in their abstract that most patients were switched to rituximab after discontinuing fingolimod.

The number of relapses per 1,000 patient-years was reduced by fingolimod treatment from 280 to 82, comparing before and during treatment for all age groups studied. Relapse rate dropped from 694 per 1,000 patient-years before treatment to 138 during treatment in patients aged 20 years or younger, from 454 to 122 in those aged 21-30 years, and from 257 to 72 in those older than 31 years.

After 1 year of treatment, improvements were seen in the health status of patients as measured by various scales, including the EDSS, MSSS, MSIS-29 Physical, and MSIS-29 Psychological. When the researchers analyzed data by age groups, significant improvements were seen in patients aged 21-30 years and older than 30 years.

Ninety nonserious and 62 serious adverse events were reported in fingolimod-treated patients during the time of analysis. Of the latter, 13 serious adverse events involved cardiac disorders, 12 neoplasms, and 10 infections and infestations.

Overall, the IMSE 2 study investigators said that fingolimod was generally tolerable and reduced disease activity in MS.
 

French experience with fingolimod: The VIRGILE study

Real-world data on the long-term safety and efficacy of fingolimod in France from the VIRGILE study were reported by Christine Lebrun-Frenay, MD, PhD, and her associates (Mult Scler. 2018;24[S2]:698-9, Abstract P1231).

Dr. Lebrun-Frenay of Pasteur 2 Hospital in Nice and her coauthors noted that VIRGILE study included patients starting treatment with fingolimod between January 2014 and February 2016. A total of 1,047 patients were included, and another 330 patients treated with natalizumab were included at the behest of the French health authorities.

The annualized relapse rate after 2 years of follow-up was 0.30 in the fingolimod group. Dr. Lebrun-Frenay and her colleagues noted: “The 3-year data from this interim analysis provide evidence for sustained efficacy of fingolimod.” Indeed, they report that almost 60% of patients did not relapse and 64% had no worsening of disease. On average, EDSS was stable during the 3-year follow-up period.

“Safety and tolerability profiles of fingolimod were in line with previous clinical experience, with lymphopenia being the most frequent AE [adverse event] reported,” they added.
 

The IMSE 3 study with alemtuzumab

Long-term experience with alemtuzumab as a treatment for RRMS in the real-world setting is more limited as it only became available for use for this indication in 2014, but some insight is provided by the results of the IMSE 3 study (Mult Scler. 2018;24[S2]:706-7, Abstract P1240).

In total, there were 113 patients treated with alemtuzumab; the vast majority (94%) had RRMS and were aged a mean of 34 years at the start of treatment. Treatment was for more than 12 months in 101 patients, more than 24 months in 86 patients, and more than 36 months in 36 patients.

“In patients treated for at least 12 months, significant improvements were seen in several clinical parameters,” Dr. Fält and her associates observed in their poster at ECTRIMS. The mean baseline and 12-month values for the EDSS were 2.0 and 1.6, and for the MSSS they were 3.46 and 2.61. The mean baseline and 12-month values for the MSIS-29 Psychological subscale were 35.1 and 30.8, respectively, and for MSIS-29 Physical they were 22.7 and 17.7.

Overall, there were 14 nonserious and 11 serious adverse events, the most common of which were infections and infestations, metabolism and nutrition disorders, and immune system disorders.

“A longer follow-up period is needed to assess the real-world effectiveness and safety of alemtuzumab,” the IMSE 3 study authors noted.
 

The IMSE 5 study with dimethyl fumarate

Similarly, the authors of the IMSE 5 study (Mult Scler. 2018;24[S2]:701-2, Abstract 1234) concluded that a longer follow-up period is need to assess the real-world effectiveness of dimethyl fumarate. Selin Safer Demirbüker, also of the Karolinska Institute, and her associates looked at data on 2,108 patients treated with dimethyl fumarate between March 2014 and April 2018, of whom 1,150 were still receiving treatment at the time of their assessment.

The mean age of patients at the start of treatment was 41 years, 91% had RRMS, and 73% were female. The mean treatment duration was 22.3 months. The majority of patients (n = 867) had been previously treated with interferon and glatiramer acetate (Copaxone) prior to dimethyl fumarate, with 538 being naive to treatment.

“Dimethyl fumarate seems to have a positive effect for patients remaining on treatment,” wrote Ms. Safer Demirbüker and her colleagues. The overall 1-year drug survival reported in their abstract was 74%. Their poster showed a lower 2-year drug survival rate of 63.5% for men and 56.4% for women.

“Swedish patients show cognitive, psychological, and physical benefits after 2 or more years of treatment,” the IMSE 5 study authors further noted. Mean EDSS, MSSS, and MSIS-29 Psychological values all fell from baseline to 2 years.

Overall, 958 (47%) of patients discontinued treatment with dimethyl fumarate at some point, primarily (in 52% of cases) because of adverse events or lack of effect (29% of cases). Most patients (39%) switched to rituximab (15% had no new treatment registered), but 35% of patients continued treatment for 3 or more years.

Twelve-year follow-up of teriflunomide shows continued efficacy, safety

Mark Freedman, MD, of the University of Ottawa and the Ottawa Hospital Research Institute and his associates reported long-term follow-up data on the efficacy and safety of teriflunomide (Aubagio) in relapsing forms of MS (Mult Scler. 2018;24[S2]:700-1, Abstract P1233). After up to 12 years’ follow up, teriflunomide 14 mg was associated with an overall annualized relapse rate of 0.228.

Yearly annualized relapse rates were “low and stable,” Dr. Freedman and his coauthors from the United States, Spain, Italy, France, Germany, England, the Republic of Korea, and Australia noted in their poster.

“As of August 2018, over 93,000 patients were being treated with teriflunomide,” the authors stated. This represented a real-world exposure of approximately 186,000 patient-years up to December 2017, they added.

For the analysis, data from one phase 2 study and three phase 3 studies (TEMSO, TOWER, and TENERE) and their long-term extension studies were pooled. In all, there were 1,696 patients treated with 14 mg of teriflunomide in these studies.

Annualized relapse rates ranged from 0.321 in the first year of follow-up in the studies to 0.080 by the 12th year. The proportions of patients remaining relapse free “were high and stable (ranging from 0.75 in year 1 to 0.93 in years 8 and 9).” EDSS scores were 2.57 at baseline and 2.27 at year 12.

Importantly, no new safety signals were reported, Dr. Freedman and his colleagues wrote, adding that most adverse events were mild to moderate in severity.

Taken together, “these data demonstrate the long-term efficacy and safety of teriflunomide,” they concluded.
 

Study and author disclosures

The teriflunomide analysis was supported by Sanofi. Dr. Freedman disclosed receiving research or educational grant support from Bayer and Genzyme; honoraria/consulting fees from Bayer, Biogen, EMD Canada, Novartis, Sanofi, and Teva; and membership on company advisory boards/boards of directors/other similar groups for Bayer, Biogen, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, and Teva.

The IMSE 1 and 5 studies were supported by Biogen and the IMSE 2 and 3 studies by Novartis. The lead study authors for the IMSE studies – Dr. Kågström, Dr. Fält, and Dr. Safer Demirbüker – had nothing personal to disclose. Other authors included employees of the sponsoring companies or those who had received research funding or honoraria for consultancy work from the companies.

The VIRGILE study was supported by Novartis Pharma AG, Switzerland. Dr. Lebrun-Frenay disclosed receiving consultancy fees from Merck, Novartis, Biogen, MedDay, Roche, Teva, and Genzyme. Coauthors included Novartis employees.

BERLIN – Real-world data from six postmarketing surveillance studies suggest that currently available disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) have long-lasting effects that are matched by reasonable tolerability.

solitude72/iStockphoto

Long-term efficacy and safety data on natalizumab (Tysabri), fingolimod (Gilenya), alemtuzumab (Lemtrada), dimethyl fumarate (Tecfidera), and teriflunomide (Aubagio) from four Swedish studies, one French study, and one international study were reported during a poster session on long-term treatment monitoring at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

The IMSE 1 study with natalizumab

The Immunomodulation and Multiple Sclerosis Epidemiology (IMSE) studies are Swedish postmarketing surveillance studies that were started with the launch of various DMTs in Sweden: natalizumab since 2006 (IMSE 1), fingolimod in 2015 (IMSE 2), alemtuzumab in 2014 (IMSE 3), and dimethyl fumarate in 2014 (IMSE 5).

“Postmarketing surveillance is important for determination of long-term safety and effectiveness in a real-world setting,” Stina Kågström and her associates observed in their poster reporting some findings of the IMSE 1 study with natalizumab (Mult Scler. 2018;24[S2]:699-700, Abstract P1232).

Ms. Kågström of the department of clinical neuroscience at the Karolinska Institute in Stockholm and her colleagues reported that data on 3,108 patients who were seen at 54 Swedish clinics had been collated via the nationwide Swedish Quality Registry for Neurological Care (NEUROreg). NEUROreg started out as an MS register but has since widened its remit to include other neurologic diagnoses.

For the IMSE 1 study, prospectively recorded data regarding natalizumab treatment, adverse events, JC-virus (JCV) status and clinical effectiveness measures were obtained from NEUROreg for 2,225 women and 883 men. Just over one-third (37%, n = 1,150) were still receiving natalizumab at the time of the analysis.


The mean age at which natalizumab was started was 39 years, with treatment primarily given for RRMS (81% of patients) and less often for secondary progressive multiple sclerosis (SPMS, 15%) and rarely for other types of progressive MS. The mean treatment duration was just under 4 years (47.6 months).

JCV testing was introduced in 2011 in Sweden, and this “has led to fewer treated JCV-positive patients,” the IMSE 1 study investigators reported. “This likely explains a reduced incidence of PML [progressive multifocal leukoencephalopathy],” they suggested. There were nine PML cases diagnosed in Sweden from 2008 to the data cut-off point in 2018, one of which was fatal.

JCV status from 2011 onward was available for 1,269 patients, of whom 39% were JCV positive and 61% were JCV negative. The overall drug survival rate was 72% for JCV-negative and 14% for JCV-positive patients. Improved health status was seen, as measured by the Expanded Disability Status Scale (EDSS), the Multiple Sclerosis Severity Score (MSSS), and the physical and psychological Multiple Sclerosis Impact Scale–29 (MSIS-29) components.

A total of 644 of 1,269 patients discontinued treatment with natalizumab at some point, of whom 67% discontinued because of being JCV positive. The main reason for discontinuation in JCV-negative patients was pregnancy or planning a pregnancy (38%), with lack of effect (10%) and adverse events (11%) as other key reasons for stopping natalizumab.

Ms. Kågström and her associates concluded that natalizumab was “generally well tolerated with sustained effectiveness.”

The IMSE 2 study with fingolimod

Data on the long-term safety and efficacy of fingolimod were reported from the IMSE 2 study (Mult Scler. 2018;24[S2]:696-7, Abstract P1228). Lead author Anna Fält, also of the Karolinska Institute, and her associates analyzed data for 1,634 patients who had been treated with fingolimod from June 2015 to September 2018.

Most patients were older than 30 years (79%), and those aged 30 and older were predominantly female (69%), had an RRMS diagnosis (88%), and been treated for a mean of about 3 years (37 months). A total of 829 were being treated with fingolimod at the time of the analysis, with 844 having discontinued treatment at some point. The main reason for discontinuing treatment with fingolimod was a lack of effect (42% of cases) or an adverse effect (34%). The IMSE 2 study authors reported in their abstract that most patients were switched to rituximab after discontinuing fingolimod.

The number of relapses per 1,000 patient-years was reduced by fingolimod treatment from 280 to 82, comparing before and during treatment for all age groups studied. Relapse rate dropped from 694 per 1,000 patient-years before treatment to 138 during treatment in patients aged 20 years or younger, from 454 to 122 in those aged 21-30 years, and from 257 to 72 in those older than 31 years.

After 1 year of treatment, improvements were seen in the health status of patients as measured by various scales, including the EDSS, MSSS, MSIS-29 Physical, and MSIS-29 Psychological. When the researchers analyzed data by age groups, significant improvements were seen in patients aged 21-30 years and older than 30 years.

Ninety nonserious and 62 serious adverse events were reported in fingolimod-treated patients during the time of analysis. Of the latter, 13 serious adverse events involved cardiac disorders, 12 neoplasms, and 10 infections and infestations.

Overall, the IMSE 2 study investigators said that fingolimod was generally tolerable and reduced disease activity in MS.
 

French experience with fingolimod: The VIRGILE study

Real-world data on the long-term safety and efficacy of fingolimod in France from the VIRGILE study were reported by Christine Lebrun-Frenay, MD, PhD, and her associates (Mult Scler. 2018;24[S2]:698-9, Abstract P1231).

Dr. Lebrun-Frenay of Pasteur 2 Hospital in Nice and her coauthors noted that VIRGILE study included patients starting treatment with fingolimod between January 2014 and February 2016. A total of 1,047 patients were included, and another 330 patients treated with natalizumab were included at the behest of the French health authorities.

The annualized relapse rate after 2 years of follow-up was 0.30 in the fingolimod group. Dr. Lebrun-Frenay and her colleagues noted: “The 3-year data from this interim analysis provide evidence for sustained efficacy of fingolimod.” Indeed, they report that almost 60% of patients did not relapse and 64% had no worsening of disease. On average, EDSS was stable during the 3-year follow-up period.

“Safety and tolerability profiles of fingolimod were in line with previous clinical experience, with lymphopenia being the most frequent AE [adverse event] reported,” they added.
 

The IMSE 3 study with alemtuzumab

Long-term experience with alemtuzumab as a treatment for RRMS in the real-world setting is more limited as it only became available for use for this indication in 2014, but some insight is provided by the results of the IMSE 3 study (Mult Scler. 2018;24[S2]:706-7, Abstract P1240).

In total, there were 113 patients treated with alemtuzumab; the vast majority (94%) had RRMS and were aged a mean of 34 years at the start of treatment. Treatment was for more than 12 months in 101 patients, more than 24 months in 86 patients, and more than 36 months in 36 patients.

“In patients treated for at least 12 months, significant improvements were seen in several clinical parameters,” Dr. Fält and her associates observed in their poster at ECTRIMS. The mean baseline and 12-month values for the EDSS were 2.0 and 1.6, and for the MSSS they were 3.46 and 2.61. The mean baseline and 12-month values for the MSIS-29 Psychological subscale were 35.1 and 30.8, respectively, and for MSIS-29 Physical they were 22.7 and 17.7.

Overall, there were 14 nonserious and 11 serious adverse events, the most common of which were infections and infestations, metabolism and nutrition disorders, and immune system disorders.

“A longer follow-up period is needed to assess the real-world effectiveness and safety of alemtuzumab,” the IMSE 3 study authors noted.
 

The IMSE 5 study with dimethyl fumarate

Similarly, the authors of the IMSE 5 study (Mult Scler. 2018;24[S2]:701-2, Abstract 1234) concluded that a longer follow-up period is need to assess the real-world effectiveness of dimethyl fumarate. Selin Safer Demirbüker, also of the Karolinska Institute, and her associates looked at data on 2,108 patients treated with dimethyl fumarate between March 2014 and April 2018, of whom 1,150 were still receiving treatment at the time of their assessment.

The mean age of patients at the start of treatment was 41 years, 91% had RRMS, and 73% were female. The mean treatment duration was 22.3 months. The majority of patients (n = 867) had been previously treated with interferon and glatiramer acetate (Copaxone) prior to dimethyl fumarate, with 538 being naive to treatment.

“Dimethyl fumarate seems to have a positive effect for patients remaining on treatment,” wrote Ms. Safer Demirbüker and her colleagues. The overall 1-year drug survival reported in their abstract was 74%. Their poster showed a lower 2-year drug survival rate of 63.5% for men and 56.4% for women.

“Swedish patients show cognitive, psychological, and physical benefits after 2 or more years of treatment,” the IMSE 5 study authors further noted. Mean EDSS, MSSS, and MSIS-29 Psychological values all fell from baseline to 2 years.

Overall, 958 (47%) of patients discontinued treatment with dimethyl fumarate at some point, primarily (in 52% of cases) because of adverse events or lack of effect (29% of cases). Most patients (39%) switched to rituximab (15% had no new treatment registered), but 35% of patients continued treatment for 3 or more years.

Twelve-year follow-up of teriflunomide shows continued efficacy, safety

Mark Freedman, MD, of the University of Ottawa and the Ottawa Hospital Research Institute and his associates reported long-term follow-up data on the efficacy and safety of teriflunomide (Aubagio) in relapsing forms of MS (Mult Scler. 2018;24[S2]:700-1, Abstract P1233). After up to 12 years’ follow up, teriflunomide 14 mg was associated with an overall annualized relapse rate of 0.228.

Yearly annualized relapse rates were “low and stable,” Dr. Freedman and his coauthors from the United States, Spain, Italy, France, Germany, England, the Republic of Korea, and Australia noted in their poster.

“As of August 2018, over 93,000 patients were being treated with teriflunomide,” the authors stated. This represented a real-world exposure of approximately 186,000 patient-years up to December 2017, they added.

For the analysis, data from one phase 2 study and three phase 3 studies (TEMSO, TOWER, and TENERE) and their long-term extension studies were pooled. In all, there were 1,696 patients treated with 14 mg of teriflunomide in these studies.

Annualized relapse rates ranged from 0.321 in the first year of follow-up in the studies to 0.080 by the 12th year. The proportions of patients remaining relapse free “were high and stable (ranging from 0.75 in year 1 to 0.93 in years 8 and 9).” EDSS scores were 2.57 at baseline and 2.27 at year 12.

Importantly, no new safety signals were reported, Dr. Freedman and his colleagues wrote, adding that most adverse events were mild to moderate in severity.

Taken together, “these data demonstrate the long-term efficacy and safety of teriflunomide,” they concluded.
 

Study and author disclosures

The teriflunomide analysis was supported by Sanofi. Dr. Freedman disclosed receiving research or educational grant support from Bayer and Genzyme; honoraria/consulting fees from Bayer, Biogen, EMD Canada, Novartis, Sanofi, and Teva; and membership on company advisory boards/boards of directors/other similar groups for Bayer, Biogen, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, and Teva.

The IMSE 1 and 5 studies were supported by Biogen and the IMSE 2 and 3 studies by Novartis. The lead study authors for the IMSE studies – Dr. Kågström, Dr. Fält, and Dr. Safer Demirbüker – had nothing personal to disclose. Other authors included employees of the sponsoring companies or those who had received research funding or honoraria for consultancy work from the companies.

The VIRGILE study was supported by Novartis Pharma AG, Switzerland. Dr. Lebrun-Frenay disclosed receiving consultancy fees from Merck, Novartis, Biogen, MedDay, Roche, Teva, and Genzyme. Coauthors included Novartis employees.

BERLIN – Real-world data from six postmarketing surveillance studies suggest that currently available disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) have long-lasting effects that are matched by reasonable tolerability.

solitude72/iStockphoto

Long-term efficacy and safety data on natalizumab (Tysabri), fingolimod (Gilenya), alemtuzumab (Lemtrada), dimethyl fumarate (Tecfidera), and teriflunomide (Aubagio) from four Swedish studies, one French study, and one international study were reported during a poster session on long-term treatment monitoring at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

The IMSE 1 study with natalizumab

The Immunomodulation and Multiple Sclerosis Epidemiology (IMSE) studies are Swedish postmarketing surveillance studies that were started with the launch of various DMTs in Sweden: natalizumab since 2006 (IMSE 1), fingolimod in 2015 (IMSE 2), alemtuzumab in 2014 (IMSE 3), and dimethyl fumarate in 2014 (IMSE 5).

“Postmarketing surveillance is important for determination of long-term safety and effectiveness in a real-world setting,” Stina Kågström and her associates observed in their poster reporting some findings of the IMSE 1 study with natalizumab (Mult Scler. 2018;24[S2]:699-700, Abstract P1232).

Ms. Kågström of the department of clinical neuroscience at the Karolinska Institute in Stockholm and her colleagues reported that data on 3,108 patients who were seen at 54 Swedish clinics had been collated via the nationwide Swedish Quality Registry for Neurological Care (NEUROreg). NEUROreg started out as an MS register but has since widened its remit to include other neurologic diagnoses.

For the IMSE 1 study, prospectively recorded data regarding natalizumab treatment, adverse events, JC-virus (JCV) status and clinical effectiveness measures were obtained from NEUROreg for 2,225 women and 883 men. Just over one-third (37%, n = 1,150) were still receiving natalizumab at the time of the analysis.


The mean age at which natalizumab was started was 39 years, with treatment primarily given for RRMS (81% of patients) and less often for secondary progressive multiple sclerosis (SPMS, 15%) and rarely for other types of progressive MS. The mean treatment duration was just under 4 years (47.6 months).

JCV testing was introduced in 2011 in Sweden, and this “has led to fewer treated JCV-positive patients,” the IMSE 1 study investigators reported. “This likely explains a reduced incidence of PML [progressive multifocal leukoencephalopathy],” they suggested. There were nine PML cases diagnosed in Sweden from 2008 to the data cut-off point in 2018, one of which was fatal.

JCV status from 2011 onward was available for 1,269 patients, of whom 39% were JCV positive and 61% were JCV negative. The overall drug survival rate was 72% for JCV-negative and 14% for JCV-positive patients. Improved health status was seen, as measured by the Expanded Disability Status Scale (EDSS), the Multiple Sclerosis Severity Score (MSSS), and the physical and psychological Multiple Sclerosis Impact Scale–29 (MSIS-29) components.

A total of 644 of 1,269 patients discontinued treatment with natalizumab at some point, of whom 67% discontinued because of being JCV positive. The main reason for discontinuation in JCV-negative patients was pregnancy or planning a pregnancy (38%), with lack of effect (10%) and adverse events (11%) as other key reasons for stopping natalizumab.

Ms. Kågström and her associates concluded that natalizumab was “generally well tolerated with sustained effectiveness.”

The IMSE 2 study with fingolimod

Data on the long-term safety and efficacy of fingolimod were reported from the IMSE 2 study (Mult Scler. 2018;24[S2]:696-7, Abstract P1228). Lead author Anna Fält, also of the Karolinska Institute, and her associates analyzed data for 1,634 patients who had been treated with fingolimod from June 2015 to September 2018.

Most patients were older than 30 years (79%), and those aged 30 and older were predominantly female (69%), had an RRMS diagnosis (88%), and been treated for a mean of about 3 years (37 months). A total of 829 were being treated with fingolimod at the time of the analysis, with 844 having discontinued treatment at some point. The main reason for discontinuing treatment with fingolimod was a lack of effect (42% of cases) or an adverse effect (34%). The IMSE 2 study authors reported in their abstract that most patients were switched to rituximab after discontinuing fingolimod.

The number of relapses per 1,000 patient-years was reduced by fingolimod treatment from 280 to 82, comparing before and during treatment for all age groups studied. Relapse rate dropped from 694 per 1,000 patient-years before treatment to 138 during treatment in patients aged 20 years or younger, from 454 to 122 in those aged 21-30 years, and from 257 to 72 in those older than 31 years.

After 1 year of treatment, improvements were seen in the health status of patients as measured by various scales, including the EDSS, MSSS, MSIS-29 Physical, and MSIS-29 Psychological. When the researchers analyzed data by age groups, significant improvements were seen in patients aged 21-30 years and older than 30 years.

Ninety nonserious and 62 serious adverse events were reported in fingolimod-treated patients during the time of analysis. Of the latter, 13 serious adverse events involved cardiac disorders, 12 neoplasms, and 10 infections and infestations.

Overall, the IMSE 2 study investigators said that fingolimod was generally tolerable and reduced disease activity in MS.
 

French experience with fingolimod: The VIRGILE study

Real-world data on the long-term safety and efficacy of fingolimod in France from the VIRGILE study were reported by Christine Lebrun-Frenay, MD, PhD, and her associates (Mult Scler. 2018;24[S2]:698-9, Abstract P1231).

Dr. Lebrun-Frenay of Pasteur 2 Hospital in Nice and her coauthors noted that VIRGILE study included patients starting treatment with fingolimod between January 2014 and February 2016. A total of 1,047 patients were included, and another 330 patients treated with natalizumab were included at the behest of the French health authorities.

The annualized relapse rate after 2 years of follow-up was 0.30 in the fingolimod group. Dr. Lebrun-Frenay and her colleagues noted: “The 3-year data from this interim analysis provide evidence for sustained efficacy of fingolimod.” Indeed, they report that almost 60% of patients did not relapse and 64% had no worsening of disease. On average, EDSS was stable during the 3-year follow-up period.

“Safety and tolerability profiles of fingolimod were in line with previous clinical experience, with lymphopenia being the most frequent AE [adverse event] reported,” they added.
 

The IMSE 3 study with alemtuzumab

Long-term experience with alemtuzumab as a treatment for RRMS in the real-world setting is more limited as it only became available for use for this indication in 2014, but some insight is provided by the results of the IMSE 3 study (Mult Scler. 2018;24[S2]:706-7, Abstract P1240).

In total, there were 113 patients treated with alemtuzumab; the vast majority (94%) had RRMS and were aged a mean of 34 years at the start of treatment. Treatment was for more than 12 months in 101 patients, more than 24 months in 86 patients, and more than 36 months in 36 patients.

“In patients treated for at least 12 months, significant improvements were seen in several clinical parameters,” Dr. Fält and her associates observed in their poster at ECTRIMS. The mean baseline and 12-month values for the EDSS were 2.0 and 1.6, and for the MSSS they were 3.46 and 2.61. The mean baseline and 12-month values for the MSIS-29 Psychological subscale were 35.1 and 30.8, respectively, and for MSIS-29 Physical they were 22.7 and 17.7.

Overall, there were 14 nonserious and 11 serious adverse events, the most common of which were infections and infestations, metabolism and nutrition disorders, and immune system disorders.

“A longer follow-up period is needed to assess the real-world effectiveness and safety of alemtuzumab,” the IMSE 3 study authors noted.
 

The IMSE 5 study with dimethyl fumarate

Similarly, the authors of the IMSE 5 study (Mult Scler. 2018;24[S2]:701-2, Abstract 1234) concluded that a longer follow-up period is need to assess the real-world effectiveness of dimethyl fumarate. Selin Safer Demirbüker, also of the Karolinska Institute, and her associates looked at data on 2,108 patients treated with dimethyl fumarate between March 2014 and April 2018, of whom 1,150 were still receiving treatment at the time of their assessment.

The mean age of patients at the start of treatment was 41 years, 91% had RRMS, and 73% were female. The mean treatment duration was 22.3 months. The majority of patients (n = 867) had been previously treated with interferon and glatiramer acetate (Copaxone) prior to dimethyl fumarate, with 538 being naive to treatment.

“Dimethyl fumarate seems to have a positive effect for patients remaining on treatment,” wrote Ms. Safer Demirbüker and her colleagues. The overall 1-year drug survival reported in their abstract was 74%. Their poster showed a lower 2-year drug survival rate of 63.5% for men and 56.4% for women.

“Swedish patients show cognitive, psychological, and physical benefits after 2 or more years of treatment,” the IMSE 5 study authors further noted. Mean EDSS, MSSS, and MSIS-29 Psychological values all fell from baseline to 2 years.

Overall, 958 (47%) of patients discontinued treatment with dimethyl fumarate at some point, primarily (in 52% of cases) because of adverse events or lack of effect (29% of cases). Most patients (39%) switched to rituximab (15% had no new treatment registered), but 35% of patients continued treatment for 3 or more years.

Twelve-year follow-up of teriflunomide shows continued efficacy, safety

Mark Freedman, MD, of the University of Ottawa and the Ottawa Hospital Research Institute and his associates reported long-term follow-up data on the efficacy and safety of teriflunomide (Aubagio) in relapsing forms of MS (Mult Scler. 2018;24[S2]:700-1, Abstract P1233). After up to 12 years’ follow up, teriflunomide 14 mg was associated with an overall annualized relapse rate of 0.228.

Yearly annualized relapse rates were “low and stable,” Dr. Freedman and his coauthors from the United States, Spain, Italy, France, Germany, England, the Republic of Korea, and Australia noted in their poster.

“As of August 2018, over 93,000 patients were being treated with teriflunomide,” the authors stated. This represented a real-world exposure of approximately 186,000 patient-years up to December 2017, they added.

For the analysis, data from one phase 2 study and three phase 3 studies (TEMSO, TOWER, and TENERE) and their long-term extension studies were pooled. In all, there were 1,696 patients treated with 14 mg of teriflunomide in these studies.

Annualized relapse rates ranged from 0.321 in the first year of follow-up in the studies to 0.080 by the 12th year. The proportions of patients remaining relapse free “were high and stable (ranging from 0.75 in year 1 to 0.93 in years 8 and 9).” EDSS scores were 2.57 at baseline and 2.27 at year 12.

Importantly, no new safety signals were reported, Dr. Freedman and his colleagues wrote, adding that most adverse events were mild to moderate in severity.

Taken together, “these data demonstrate the long-term efficacy and safety of teriflunomide,” they concluded.
 

Study and author disclosures

The teriflunomide analysis was supported by Sanofi. Dr. Freedman disclosed receiving research or educational grant support from Bayer and Genzyme; honoraria/consulting fees from Bayer, Biogen, EMD Canada, Novartis, Sanofi, and Teva; and membership on company advisory boards/boards of directors/other similar groups for Bayer, Biogen, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, and Teva.

The IMSE 1 and 5 studies were supported by Biogen and the IMSE 2 and 3 studies by Novartis. The lead study authors for the IMSE studies – Dr. Kågström, Dr. Fält, and Dr. Safer Demirbüker – had nothing personal to disclose. Other authors included employees of the sponsoring companies or those who had received research funding or honoraria for consultancy work from the companies.

The VIRGILE study was supported by Novartis Pharma AG, Switzerland. Dr. Lebrun-Frenay disclosed receiving consultancy fees from Merck, Novartis, Biogen, MedDay, Roche, Teva, and Genzyme. Coauthors included Novartis employees.

Infusion of allogeneic BK virus-specific T cells may be an effective treatment for patients with progressive multifocal leukoencephalopathy (PML), according to a report in the October 11 New England Journal of Medicine. The infusion cleared JC virus from the CSF of two patients and reduced viral load in the third, reported lead author Muharrem Muftuoglu, MD, of the Department of Stem Cell Transplantation and Cellular Therapy at the University of Texas MD Anderson Cancer Center in Houston, and colleagues. One of the patients completely recovered and returned to work; this outcome was unprecedented in PML therapy.

“Several approaches for the treatment of PML, including the use of antiviral medications and mirtazapine, have been tested, with poor results,” the investigators said. Although virus-specific T-cell infusion is a novel approach to treating PML, this method has been used for other conditions. “Several groups, including ours, have successfully used viral-specific T cells to treat BK virus infection after stem-cell transplantation,” the investigators said. “Because BK virus and JC virus are genetically similar to one another and share a number of immunogenic proteins with a substantial degree of sequence homology ... we hypothesized that T cells developed against BK virus may also be effective against JC virus infection.”

This hypothesis proved correct. The investigators infused three patients with PML with “cryopreserved, third-party–produced, viral-specific T cells that had been designed for the treatment of patients with BK virus infection after stem-cell transplantation.” Each patient presented with a different condition and PML-precipitating therapy. The first patient was a 32-year-old woman with high-risk acute myeloid leukemia who had received a cord-blood transplantation, the second a 73-year-old woman with JAK2-positive myeloproliferative neoplasia on ruxolitinib therapy, and the third a 35-year-old man with HIV who had received highly active antiretroviral therapy.

T-cell infusions cleared JC virus from the CSF of the woman with leukemia (three infusions) and the man with HIV (four infusions). These patients recovered to different degrees.The woman had full resolution of symptoms, while the man had slurred speech and walked with a cane. Treatment reduced JC viral load in the elderly woman with myeloproliferative neoplasia (two infusions), but she did not clear the virus and died about eight months later.

No adverse events occurred, but two patients developed immune reconstitution inflammatory syndrome. This outcome was likely caused by the T-cell infusion, since absolute T-cell counts remained steady and white matter enhancement was detected on MRI within four weeks of treatment. Still, the investigators were optimistic about future potential.

“Third-party–produced, ‘off-the-shelf,’ partially HLA-matched, BK virus–specific T cells may serve as therapy for PML,” the investigators concluded. “Further study in a larger group of patients is required to determine the success rate, durability, and longer-term adverse events associated with this treatment.”

The study was funded by the MD Anderson Cancer Center Moon Shots Program and the National Institutes of Health.

—Will Pass

Suggested Reading

Muftuoglu M, Olson A, Marin D, et al. Allogeneic BK specific T cells for progressive multifocal leukoencephalopathy. N Engl J Med. 2018;379(15):1443-1451.

Infusion of allogeneic BK virus-specific T cells may be an effective treatment for patients with progressive multifocal leukoencephalopathy (PML), according to a report in the October 11 New England Journal of Medicine. The infusion cleared JC virus from the CSF of two patients and reduced viral load in the third, reported lead author Muharrem Muftuoglu, MD, of the Department of Stem Cell Transplantation and Cellular Therapy at the University of Texas MD Anderson Cancer Center in Houston, and colleagues. One of the patients completely recovered and returned to work; this outcome was unprecedented in PML therapy.

“Several approaches for the treatment of PML, including the use of antiviral medications and mirtazapine, have been tested, with poor results,” the investigators said. Although virus-specific T-cell infusion is a novel approach to treating PML, this method has been used for other conditions. “Several groups, including ours, have successfully used viral-specific T cells to treat BK virus infection after stem-cell transplantation,” the investigators said. “Because BK virus and JC virus are genetically similar to one another and share a number of immunogenic proteins with a substantial degree of sequence homology ... we hypothesized that T cells developed against BK virus may also be effective against JC virus infection.”

This hypothesis proved correct. The investigators infused three patients with PML with “cryopreserved, third-party–produced, viral-specific T cells that had been designed for the treatment of patients with BK virus infection after stem-cell transplantation.” Each patient presented with a different condition and PML-precipitating therapy. The first patient was a 32-year-old woman with high-risk acute myeloid leukemia who had received a cord-blood transplantation, the second a 73-year-old woman with JAK2-positive myeloproliferative neoplasia on ruxolitinib therapy, and the third a 35-year-old man with HIV who had received highly active antiretroviral therapy.

T-cell infusions cleared JC virus from the CSF of the woman with leukemia (three infusions) and the man with HIV (four infusions). These patients recovered to different degrees.The woman had full resolution of symptoms, while the man had slurred speech and walked with a cane. Treatment reduced JC viral load in the elderly woman with myeloproliferative neoplasia (two infusions), but she did not clear the virus and died about eight months later.

No adverse events occurred, but two patients developed immune reconstitution inflammatory syndrome. This outcome was likely caused by the T-cell infusion, since absolute T-cell counts remained steady and white matter enhancement was detected on MRI within four weeks of treatment. Still, the investigators were optimistic about future potential.

“Third-party–produced, ‘off-the-shelf,’ partially HLA-matched, BK virus–specific T cells may serve as therapy for PML,” the investigators concluded. “Further study in a larger group of patients is required to determine the success rate, durability, and longer-term adverse events associated with this treatment.”

The study was funded by the MD Anderson Cancer Center Moon Shots Program and the National Institutes of Health.

—Will Pass

Suggested Reading

Muftuoglu M, Olson A, Marin D, et al. Allogeneic BK specific T cells for progressive multifocal leukoencephalopathy. N Engl J Med. 2018;379(15):1443-1451.

Infusion of allogeneic BK virus-specific T cells may be an effective treatment for patients with progressive multifocal leukoencephalopathy (PML), according to a report in the October 11 New England Journal of Medicine. The infusion cleared JC virus from the CSF of two patients and reduced viral load in the third, reported lead author Muharrem Muftuoglu, MD, of the Department of Stem Cell Transplantation and Cellular Therapy at the University of Texas MD Anderson Cancer Center in Houston, and colleagues. One of the patients completely recovered and returned to work; this outcome was unprecedented in PML therapy.

“Several approaches for the treatment of PML, including the use of antiviral medications and mirtazapine, have been tested, with poor results,” the investigators said. Although virus-specific T-cell infusion is a novel approach to treating PML, this method has been used for other conditions. “Several groups, including ours, have successfully used viral-specific T cells to treat BK virus infection after stem-cell transplantation,” the investigators said. “Because BK virus and JC virus are genetically similar to one another and share a number of immunogenic proteins with a substantial degree of sequence homology ... we hypothesized that T cells developed against BK virus may also be effective against JC virus infection.”

This hypothesis proved correct. The investigators infused three patients with PML with “cryopreserved, third-party–produced, viral-specific T cells that had been designed for the treatment of patients with BK virus infection after stem-cell transplantation.” Each patient presented with a different condition and PML-precipitating therapy. The first patient was a 32-year-old woman with high-risk acute myeloid leukemia who had received a cord-blood transplantation, the second a 73-year-old woman with JAK2-positive myeloproliferative neoplasia on ruxolitinib therapy, and the third a 35-year-old man with HIV who had received highly active antiretroviral therapy.

T-cell infusions cleared JC virus from the CSF of the woman with leukemia (three infusions) and the man with HIV (four infusions). These patients recovered to different degrees.The woman had full resolution of symptoms, while the man had slurred speech and walked with a cane. Treatment reduced JC viral load in the elderly woman with myeloproliferative neoplasia (two infusions), but she did not clear the virus and died about eight months later.

No adverse events occurred, but two patients developed immune reconstitution inflammatory syndrome. This outcome was likely caused by the T-cell infusion, since absolute T-cell counts remained steady and white matter enhancement was detected on MRI within four weeks of treatment. Still, the investigators were optimistic about future potential.

“Third-party–produced, ‘off-the-shelf,’ partially HLA-matched, BK virus–specific T cells may serve as therapy for PML,” the investigators concluded. “Further study in a larger group of patients is required to determine the success rate, durability, and longer-term adverse events associated with this treatment.”

The study was funded by the MD Anderson Cancer Center Moon Shots Program and the National Institutes of Health.

—Will Pass

Suggested Reading

Muftuoglu M, Olson A, Marin D, et al. Allogeneic BK specific T cells for progressive multifocal leukoencephalopathy. N Engl J Med. 2018;379(15):1443-1451.

BERLIN – Among a host of potential risk factors for multiple sclerosis (MS), one emerging risk factor – dietary sodium – has accumulating evidence, bolstered by new imaging techniques and emerging research about the mediating effect of the gut microbiome.

Georges Lievre / Fotolia.com

“The word is still out on salt – there’s still some work to do; we are not where we stand with smoking or obesity” and the association with MS, said Ralf Linker, MD, speaking at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

For all potential emerging risk factors for MS, there’s an attractive hypothesis and, often, epidemiologic data, Dr. Linker said. “There are probably good [epidemiologic] data in multiple sclerosis for vitamin D, smoking, obesity, and probably also alcohol,” he said. “The therapeutic consequence, however, is much less clear, the best example of that being, of course, vitamin D.”

“The attractive risk factor is not enough to be a hypothesis, although some people seem to believe that nowadays,” said Dr. Linker, chair of the department of neurology at Friedrich-Alexander University, Erlangen, Germany. “Probably it’s better to start with some basic science and some experimental data to get an idea of the mechanism.”

“Today, we need clear associations with clear markers, well-defined cohorts, and proper epidemiological data telling us whether this is a real risk factor. ... If you look at the clinicians – and there are many among us in the room here – your ultimate goal, of course, is to use this as an intervention.”

For salt intake, there’s a clear overlap between high salt consumption in Westernized diets and increasing incidence of MS. The association also holds for many other autoimmune diseases, Dr. Linker added.

“The next step is experimental evidence,” Dr. Linker said. In a rodent model of experimental autoimmune encephalomyelitis (EAE), rats with high salt intake had a worse clinical course, compared with control rats fed a usual diet (Nature. 2013 Apr 25;496[7446]:518-22).

“There were a lot of follow-up studies on that,” with identification of multiple immune cells that are up- or down-regulated via distinct pathways in a high-salt environment, Dr. Linker said.

[email protected]

SOURCE: Linker R. ECTRIMS 2018, Scientific Session 7.

BERLIN – Among a host of potential risk factors for multiple sclerosis (MS), one emerging risk factor – dietary sodium – has accumulating evidence, bolstered by new imaging techniques and emerging research about the mediating effect of the gut microbiome.

Georges Lievre / Fotolia.com

“The word is still out on salt – there’s still some work to do; we are not where we stand with smoking or obesity” and the association with MS, said Ralf Linker, MD, speaking at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

For all potential emerging risk factors for MS, there’s an attractive hypothesis and, often, epidemiologic data, Dr. Linker said. “There are probably good [epidemiologic] data in multiple sclerosis for vitamin D, smoking, obesity, and probably also alcohol,” he said. “The therapeutic consequence, however, is much less clear, the best example of that being, of course, vitamin D.”

“The attractive risk factor is not enough to be a hypothesis, although some people seem to believe that nowadays,” said Dr. Linker, chair of the department of neurology at Friedrich-Alexander University, Erlangen, Germany. “Probably it’s better to start with some basic science and some experimental data to get an idea of the mechanism.”

“Today, we need clear associations with clear markers, well-defined cohorts, and proper epidemiological data telling us whether this is a real risk factor. ... If you look at the clinicians – and there are many among us in the room here – your ultimate goal, of course, is to use this as an intervention.”

For salt intake, there’s a clear overlap between high salt consumption in Westernized diets and increasing incidence of MS. The association also holds for many other autoimmune diseases, Dr. Linker added.

“The next step is experimental evidence,” Dr. Linker said. In a rodent model of experimental autoimmune encephalomyelitis (EAE), rats with high salt intake had a worse clinical course, compared with control rats fed a usual diet (Nature. 2013 Apr 25;496[7446]:518-22).

“There were a lot of follow-up studies on that,” with identification of multiple immune cells that are up- or down-regulated via distinct pathways in a high-salt environment, Dr. Linker said.

[email protected]

SOURCE: Linker R. ECTRIMS 2018, Scientific Session 7.

BERLIN – Among a host of potential risk factors for multiple sclerosis (MS), one emerging risk factor – dietary sodium – has accumulating evidence, bolstered by new imaging techniques and emerging research about the mediating effect of the gut microbiome.

Georges Lievre / Fotolia.com

“The word is still out on salt – there’s still some work to do; we are not where we stand with smoking or obesity” and the association with MS, said Ralf Linker, MD, speaking at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

For all potential emerging risk factors for MS, there’s an attractive hypothesis and, often, epidemiologic data, Dr. Linker said. “There are probably good [epidemiologic] data in multiple sclerosis for vitamin D, smoking, obesity, and probably also alcohol,” he said. “The therapeutic consequence, however, is much less clear, the best example of that being, of course, vitamin D.”

“The attractive risk factor is not enough to be a hypothesis, although some people seem to believe that nowadays,” said Dr. Linker, chair of the department of neurology at Friedrich-Alexander University, Erlangen, Germany. “Probably it’s better to start with some basic science and some experimental data to get an idea of the mechanism.”

“Today, we need clear associations with clear markers, well-defined cohorts, and proper epidemiological data telling us whether this is a real risk factor. ... If you look at the clinicians – and there are many among us in the room here – your ultimate goal, of course, is to use this as an intervention.”

For salt intake, there’s a clear overlap between high salt consumption in Westernized diets and increasing incidence of MS. The association also holds for many other autoimmune diseases, Dr. Linker added.

“The next step is experimental evidence,” Dr. Linker said. In a rodent model of experimental autoimmune encephalomyelitis (EAE), rats with high salt intake had a worse clinical course, compared with control rats fed a usual diet (Nature. 2013 Apr 25;496[7446]:518-22).

“There were a lot of follow-up studies on that,” with identification of multiple immune cells that are up- or down-regulated via distinct pathways in a high-salt environment, Dr. Linker said.

[email protected]

SOURCE: Linker R. ECTRIMS 2018, Scientific Session 7.

BERLIN – In the changing multiple sclerosis landscape, more women are having babies, and more are asking questions. With these women, what’s the best way to address the complicated interplay among pregnancy, relapse risk, breastfeeding, and medication resumption? A starting point is to recognize that “women with MS are very different today than they were 25 years ago,” said Annette Langer-Gould, MD, PhD. Not only have diagnostic criteria changed but also highly effective treatments now exist that were not available when the first pregnancy cohorts were studied, she pointed out, speaking at the annual congress of the European Committee on Treatment and Research in Multiple Sclerosis.

SelectStock/Getty Images

The existing literature, said Dr. Langer-Gould, has addressed one controversy: “Most women with MS can have normal pregnancies – and breastfeed – without incurring harm,” though it’s true that severe rebound relapses are possible if natalizumab (Tysabri) or fingolimod (Gilenya) are stopped before pregnancy. In any case, new small-molecule MS medications need to be stopped during pregnancy and breastfeeding, she pointed out. “We didn’t have to worry about that too much when we only had injectables and monoclonal antibodies because they were larger and didn’t cross the placenta.”

Since the 1980s, the conversation about pregnancy and MS has moved from asking “Is pregnancy bad for women with MS?” to the current MS landscape, in which sicker women are able to become pregnant, Dr. Langer-Gould said, adding that how women with MS fare through pregnancy and in the postpartum period is changing over time as well. She and her colleagues’ experience with pregnancy in a cohort of women with MS in the Kaiser Permanente care system, where she is a clinical neurologist and regional research lead, revealed a relapse rate of 8.4%. “So it was pretty rare for a woman to have a relapse during pregnancy,” Dr. Langer-Gould said.

Most women with MS who become pregnant, whether their care is received in a referral center or is community based, are now doing so while on a disease-modifying therapy (DMT), Dr. Langer-Gould said. On these highly effective treatments, “women who were too sick to get pregnant are now well controlled and having babies.”

As more women with MS become pregnant, more conversations about breastfeeding will inevitably crop up, she said. And the discussion about breastfeeding has now begun to acknowledge the “strong benefits to mom and the baby of not just breastfeeding, but longer breastfeeding,” as well.

“Because of this baby-friendly push in a lot of hospitals in the United States, where they’re trying to encourage all women to breastfeed,” a full 87% of women breastfed their infants at least some of the time, and over a third of women (35%) breastfed exclusively for at least 2 months, Dr. Langer-Gould said.

“There’s no one clear explanation of why the women seem to be healthier and doing better through pregnancy as a group, but it’s probably a combination of having milder disease, breastfeeding more, and they’ve got better controlled disease before pregnancy,” she said.


At least eight studies to date have examined the relationship between postpartum MS relapses and breastfeeding, Dr. Langer-Gould said.

“The thing to take away ... is that, even though we’ve studied this many, many times, no one can show that it’s harmful,” she said. For mothers who want to breastfeed, “you can support them in the breastfeeding choice, because they are not going to have more severe disease because of that.”

Whether breastfeeding is exclusive or not has not always been tracked in studies of childbearing women with MS, but when it was captured in the data, exclusive breastfeeding has exerted a protective effect, with about a 50% reduction in risk for postpartum relapse seen in one study (JAMA Neurol. 2015 Oct;72[10]:1132-8).

There is a hormonal rationale for exclusive breastfeeding exerting a protective effect on MS: With exclusive breastfeeding comes more frequent, intense suckling, with more profound elevations in prolactin, and larger drops in follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol. All these hormonal changes work together to produce more prolonged amenorrhea and anovulation, Dr. Langer-Gould said, with potentially beneficial immunologic effects.

When other, more general maternal and infant health benefits of breastfeeding also are taken into account, there’s strong evidence for the benefits of breastfeeding for women with MS whose medication profile allows them to breastfeed, she said.

However, the “treatment” effect of exclusive breastfeeding is only effective until the infant starts taking regular supplemental feedings, including the introduction of table food at around 6 months of age. “Once regular supplemental feedings are introduced, relapses return,” Dr. Langer-Gould said.

There is some suggestion that, in women without MS, prolonged breastfeeding may be associated with reduced risk of MS. In the MS Sunshine study, breastfeeding for 15 months or longer decreased the risk of later MS by 23%-53% (Nutrients. 2018 Feb 27;10[3]:268). The investigators, led by Dr. Langer-Gould, summed the total months of breastfeeding across all children, so that the 15-month threshold could be reached by breastfeeding one child for 15 months, or three children for 5 months each. “It’s a single study; I wouldn’t make too much out of it,” Dr. Langer-Gould said.

Open questions still remain, she said: “So far, no one has been able to demonstrate a clear beneficial effect in reducing the risk of postpartum relapse if they resume their DMT early in the postpartum period.” Dr. Langer-Gould noted that the literature in this area is hampered by heterogeneity and by the fact that newer, more highly active DMTs have not been well studied.

Also, the link between postpartum relapses and long-term prognosis is not completely delineated. Indirect evidence, she said, points to a postpartum relapse as being “overall, a low-impact event.”

Dr. Langer-Gould reported that she has been the site principal investigator for clinical trials sponsored by Roche and Biogen.

[email protected]

SOURCE: Langer-Gould A. ECTRIMS 2018, Abstract 5.

BERLIN – In the changing multiple sclerosis landscape, more women are having babies, and more are asking questions. With these women, what’s the best way to address the complicated interplay among pregnancy, relapse risk, breastfeeding, and medication resumption? A starting point is to recognize that “women with MS are very different today than they were 25 years ago,” said Annette Langer-Gould, MD, PhD. Not only have diagnostic criteria changed but also highly effective treatments now exist that were not available when the first pregnancy cohorts were studied, she pointed out, speaking at the annual congress of the European Committee on Treatment and Research in Multiple Sclerosis.

SelectStock/Getty Images

The existing literature, said Dr. Langer-Gould, has addressed one controversy: “Most women with MS can have normal pregnancies – and breastfeed – without incurring harm,” though it’s true that severe rebound relapses are possible if natalizumab (Tysabri) or fingolimod (Gilenya) are stopped before pregnancy. In any case, new small-molecule MS medications need to be stopped during pregnancy and breastfeeding, she pointed out. “We didn’t have to worry about that too much when we only had injectables and monoclonal antibodies because they were larger and didn’t cross the placenta.”

Since the 1980s, the conversation about pregnancy and MS has moved from asking “Is pregnancy bad for women with MS?” to the current MS landscape, in which sicker women are able to become pregnant, Dr. Langer-Gould said, adding that how women with MS fare through pregnancy and in the postpartum period is changing over time as well. She and her colleagues’ experience with pregnancy in a cohort of women with MS in the Kaiser Permanente care system, where she is a clinical neurologist and regional research lead, revealed a relapse rate of 8.4%. “So it was pretty rare for a woman to have a relapse during pregnancy,” Dr. Langer-Gould said.

Most women with MS who become pregnant, whether their care is received in a referral center or is community based, are now doing so while on a disease-modifying therapy (DMT), Dr. Langer-Gould said. On these highly effective treatments, “women who were too sick to get pregnant are now well controlled and having babies.”

As more women with MS become pregnant, more conversations about breastfeeding will inevitably crop up, she said. And the discussion about breastfeeding has now begun to acknowledge the “strong benefits to mom and the baby of not just breastfeeding, but longer breastfeeding,” as well.

“Because of this baby-friendly push in a lot of hospitals in the United States, where they’re trying to encourage all women to breastfeed,” a full 87% of women breastfed their infants at least some of the time, and over a third of women (35%) breastfed exclusively for at least 2 months, Dr. Langer-Gould said.

“There’s no one clear explanation of why the women seem to be healthier and doing better through pregnancy as a group, but it’s probably a combination of having milder disease, breastfeeding more, and they’ve got better controlled disease before pregnancy,” she said.


At least eight studies to date have examined the relationship between postpartum MS relapses and breastfeeding, Dr. Langer-Gould said.

“The thing to take away ... is that, even though we’ve studied this many, many times, no one can show that it’s harmful,” she said. For mothers who want to breastfeed, “you can support them in the breastfeeding choice, because they are not going to have more severe disease because of that.”

Whether breastfeeding is exclusive or not has not always been tracked in studies of childbearing women with MS, but when it was captured in the data, exclusive breastfeeding has exerted a protective effect, with about a 50% reduction in risk for postpartum relapse seen in one study (JAMA Neurol. 2015 Oct;72[10]:1132-8).

There is a hormonal rationale for exclusive breastfeeding exerting a protective effect on MS: With exclusive breastfeeding comes more frequent, intense suckling, with more profound elevations in prolactin, and larger drops in follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol. All these hormonal changes work together to produce more prolonged amenorrhea and anovulation, Dr. Langer-Gould said, with potentially beneficial immunologic effects.

When other, more general maternal and infant health benefits of breastfeeding also are taken into account, there’s strong evidence for the benefits of breastfeeding for women with MS whose medication profile allows them to breastfeed, she said.

However, the “treatment” effect of exclusive breastfeeding is only effective until the infant starts taking regular supplemental feedings, including the introduction of table food at around 6 months of age. “Once regular supplemental feedings are introduced, relapses return,” Dr. Langer-Gould said.

There is some suggestion that, in women without MS, prolonged breastfeeding may be associated with reduced risk of MS. In the MS Sunshine study, breastfeeding for 15 months or longer decreased the risk of later MS by 23%-53% (Nutrients. 2018 Feb 27;10[3]:268). The investigators, led by Dr. Langer-Gould, summed the total months of breastfeeding across all children, so that the 15-month threshold could be reached by breastfeeding one child for 15 months, or three children for 5 months each. “It’s a single study; I wouldn’t make too much out of it,” Dr. Langer-Gould said.

Open questions still remain, she said: “So far, no one has been able to demonstrate a clear beneficial effect in reducing the risk of postpartum relapse if they resume their DMT early in the postpartum period.” Dr. Langer-Gould noted that the literature in this area is hampered by heterogeneity and by the fact that newer, more highly active DMTs have not been well studied.

Also, the link between postpartum relapses and long-term prognosis is not completely delineated. Indirect evidence, she said, points to a postpartum relapse as being “overall, a low-impact event.”

Dr. Langer-Gould reported that she has been the site principal investigator for clinical trials sponsored by Roche and Biogen.

[email protected]

SOURCE: Langer-Gould A. ECTRIMS 2018, Abstract 5.

BERLIN – In the changing multiple sclerosis landscape, more women are having babies, and more are asking questions. With these women, what’s the best way to address the complicated interplay among pregnancy, relapse risk, breastfeeding, and medication resumption? A starting point is to recognize that “women with MS are very different today than they were 25 years ago,” said Annette Langer-Gould, MD, PhD. Not only have diagnostic criteria changed but also highly effective treatments now exist that were not available when the first pregnancy cohorts were studied, she pointed out, speaking at the annual congress of the European Committee on Treatment and Research in Multiple Sclerosis.

SelectStock/Getty Images

The existing literature, said Dr. Langer-Gould, has addressed one controversy: “Most women with MS can have normal pregnancies – and breastfeed – without incurring harm,” though it’s true that severe rebound relapses are possible if natalizumab (Tysabri) or fingolimod (Gilenya) are stopped before pregnancy. In any case, new small-molecule MS medications need to be stopped during pregnancy and breastfeeding, she pointed out. “We didn’t have to worry about that too much when we only had injectables and monoclonal antibodies because they were larger and didn’t cross the placenta.”

Since the 1980s, the conversation about pregnancy and MS has moved from asking “Is pregnancy bad for women with MS?” to the current MS landscape, in which sicker women are able to become pregnant, Dr. Langer-Gould said, adding that how women with MS fare through pregnancy and in the postpartum period is changing over time as well. She and her colleagues’ experience with pregnancy in a cohort of women with MS in the Kaiser Permanente care system, where she is a clinical neurologist and regional research lead, revealed a relapse rate of 8.4%. “So it was pretty rare for a woman to have a relapse during pregnancy,” Dr. Langer-Gould said.

Most women with MS who become pregnant, whether their care is received in a referral center or is community based, are now doing so while on a disease-modifying therapy (DMT), Dr. Langer-Gould said. On these highly effective treatments, “women who were too sick to get pregnant are now well controlled and having babies.”

As more women with MS become pregnant, more conversations about breastfeeding will inevitably crop up, she said. And the discussion about breastfeeding has now begun to acknowledge the “strong benefits to mom and the baby of not just breastfeeding, but longer breastfeeding,” as well.

“Because of this baby-friendly push in a lot of hospitals in the United States, where they’re trying to encourage all women to breastfeed,” a full 87% of women breastfed their infants at least some of the time, and over a third of women (35%) breastfed exclusively for at least 2 months, Dr. Langer-Gould said.

“There’s no one clear explanation of why the women seem to be healthier and doing better through pregnancy as a group, but it’s probably a combination of having milder disease, breastfeeding more, and they’ve got better controlled disease before pregnancy,” she said.


At least eight studies to date have examined the relationship between postpartum MS relapses and breastfeeding, Dr. Langer-Gould said.

“The thing to take away ... is that, even though we’ve studied this many, many times, no one can show that it’s harmful,” she said. For mothers who want to breastfeed, “you can support them in the breastfeeding choice, because they are not going to have more severe disease because of that.”

Whether breastfeeding is exclusive or not has not always been tracked in studies of childbearing women with MS, but when it was captured in the data, exclusive breastfeeding has exerted a protective effect, with about a 50% reduction in risk for postpartum relapse seen in one study (JAMA Neurol. 2015 Oct;72[10]:1132-8).

There is a hormonal rationale for exclusive breastfeeding exerting a protective effect on MS: With exclusive breastfeeding comes more frequent, intense suckling, with more profound elevations in prolactin, and larger drops in follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol. All these hormonal changes work together to produce more prolonged amenorrhea and anovulation, Dr. Langer-Gould said, with potentially beneficial immunologic effects.

When other, more general maternal and infant health benefits of breastfeeding also are taken into account, there’s strong evidence for the benefits of breastfeeding for women with MS whose medication profile allows them to breastfeed, she said.

However, the “treatment” effect of exclusive breastfeeding is only effective until the infant starts taking regular supplemental feedings, including the introduction of table food at around 6 months of age. “Once regular supplemental feedings are introduced, relapses return,” Dr. Langer-Gould said.

There is some suggestion that, in women without MS, prolonged breastfeeding may be associated with reduced risk of MS. In the MS Sunshine study, breastfeeding for 15 months or longer decreased the risk of later MS by 23%-53% (Nutrients. 2018 Feb 27;10[3]:268). The investigators, led by Dr. Langer-Gould, summed the total months of breastfeeding across all children, so that the 15-month threshold could be reached by breastfeeding one child for 15 months, or three children for 5 months each. “It’s a single study; I wouldn’t make too much out of it,” Dr. Langer-Gould said.

Open questions still remain, she said: “So far, no one has been able to demonstrate a clear beneficial effect in reducing the risk of postpartum relapse if they resume their DMT early in the postpartum period.” Dr. Langer-Gould noted that the literature in this area is hampered by heterogeneity and by the fact that newer, more highly active DMTs have not been well studied.

Also, the link between postpartum relapses and long-term prognosis is not completely delineated. Indirect evidence, she said, points to a postpartum relapse as being “overall, a low-impact event.”

Dr. Langer-Gould reported that she has been the site principal investigator for clinical trials sponsored by Roche and Biogen.

[email protected]

SOURCE: Langer-Gould A. ECTRIMS 2018, Abstract 5.

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.