Multiple Sclerosis Hub

NASHVILLE—Treatment with cladribine tablets 3.5 mg/kg reduces MRI markers of disease activity in patients with highly active relapsing-remitting multiple sclerosis (MS), according to research described at the 2018 CMSC Annual Meeting. Results of a post hoc analysis of the CLARITY study indicated that in patients with relapsing MS who were selected for further study based on high disease activity, treatment with cladribine tablets 3.5 mg/kg showed efficacy in reducing MRI markers of disease activity comparable with the overall CLARITY study population.

In the CLARITY study, treatment with cladribine tablets versus placebo showed strong efficacy in a large cohort of patients with relapsing MS over two years. Because patients with high disease activity have a high risk of relapses and disability, Gavin Giovannoni, MBBCh, PhD, and his CLARITY collaborators conducted a post hoc analysis to compare the effects of cladribine tablets 3.5 mg/kg versus placebo on outcomes assessed by MRI in subgroups of CLARITY patients with evidence of high disease activity at study entry. Professor Giovannoni is Chair of Neurology at the Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry at Queen Mary University of London.

—Erica Tricarico

Suggested Reading

Giovannoni G, Soelberg Sorensen P, Cook S, et al. Efficacy of cladribine tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY Study. Mult Scler. 2018 April 1 [Epub ahead of print].

NASHVILLE—Treatment with cladribine tablets 3.5 mg/kg reduces MRI markers of disease activity in patients with highly active relapsing-remitting multiple sclerosis (MS), according to research described at the 2018 CMSC Annual Meeting. Results of a post hoc analysis of the CLARITY study indicated that in patients with relapsing MS who were selected for further study based on high disease activity, treatment with cladribine tablets 3.5 mg/kg showed efficacy in reducing MRI markers of disease activity comparable with the overall CLARITY study population.

In the CLARITY study, treatment with cladribine tablets versus placebo showed strong efficacy in a large cohort of patients with relapsing MS over two years. Because patients with high disease activity have a high risk of relapses and disability, Gavin Giovannoni, MBBCh, PhD, and his CLARITY collaborators conducted a post hoc analysis to compare the effects of cladribine tablets 3.5 mg/kg versus placebo on outcomes assessed by MRI in subgroups of CLARITY patients with evidence of high disease activity at study entry. Professor Giovannoni is Chair of Neurology at the Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry at Queen Mary University of London.

—Erica Tricarico

Suggested Reading

Giovannoni G, Soelberg Sorensen P, Cook S, et al. Efficacy of cladribine tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY Study. Mult Scler. 2018 April 1 [Epub ahead of print].

NASHVILLE—Treatment with cladribine tablets 3.5 mg/kg reduces MRI markers of disease activity in patients with highly active relapsing-remitting multiple sclerosis (MS), according to research described at the 2018 CMSC Annual Meeting. Results of a post hoc analysis of the CLARITY study indicated that in patients with relapsing MS who were selected for further study based on high disease activity, treatment with cladribine tablets 3.5 mg/kg showed efficacy in reducing MRI markers of disease activity comparable with the overall CLARITY study population.

In the CLARITY study, treatment with cladribine tablets versus placebo showed strong efficacy in a large cohort of patients with relapsing MS over two years. Because patients with high disease activity have a high risk of relapses and disability, Gavin Giovannoni, MBBCh, PhD, and his CLARITY collaborators conducted a post hoc analysis to compare the effects of cladribine tablets 3.5 mg/kg versus placebo on outcomes assessed by MRI in subgroups of CLARITY patients with evidence of high disease activity at study entry. Professor Giovannoni is Chair of Neurology at the Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry at Queen Mary University of London.

—Erica Tricarico

Suggested Reading

Giovannoni G, Soelberg Sorensen P, Cook S, et al. Efficacy of cladribine tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY Study. Mult Scler. 2018 April 1 [Epub ahead of print].

NASHVILLE—In patients with pediatric-onset multiple sclerosis (MS), fingolimod significantly reduces MRI activity and slows brain volume loss for as long as two years, compared with interferon beta-1a, according to data described at the 2018 CMSC Annual Meeting.

Analyzing the PARADIGMS Data

PARADIGMS was a double-blind, double-dummy, active-controlled, parallel-group, multicenter study in which patients participated for as long as two years. The investigators randomized patients with pediatric-onset MS (ages 10 through 17) to oral fingolimod or interferon beta-1a. The dose of fingolimod was adjusted for body weight. MRI was performed at baseline and every six months thereafter until the end of the study core phase. A central reading center analyzed the MRI results. The key MRI outcomes were the number of new or newly enlarged T2 lesions and gadolinium-enhancing T1 lesions, annual rate of brain volume change, number of new T1 hypointense lesions, change in total T2 hyperintense lesion volume, and number of combined unique active lesions.

The researchers randomized 107 participants to oral fingolimod and 108 to interferon beta-1a. At baseline, mean age was about 15. Most patients were female. Mean disease duration was one to two years. The average number of relapses in the year before screening was approximately 1.5. Participants had 2.6 to 3.1 gadolinium-enhancing T1 lesions.

Data Support Fingolimod’s Efficacy in Pediatric MS

At the end of the study, fingolimod significantly reduced the annualized rate of new or newly enlarged T2 lesions by 52.6% and the number of gadolinium-enhancing T1 lesions per scan by 66.0%, compared with interferon beta-1a. The odds ratio of freedom from new or newly enlarged T2 lesions was 4.51 in the fingolimod arm, compared with the interferon beta-1a arm. The odds ratio of freedom from gadolinium-enhancing lesions was 3.0 in the fingolimod arm, compared with the interferon beta-1a arm.

Compared with interferon beta-1a, treatment with fingolimod for as long as two years significantly reduced the annualized rate of brain volume change (least squares mean: −0.48 vs −0.80). Fingolimod reduced the annualized rate of new T1 hypointense lesions by 62.8% and the number of combined unique active lesions per scan by 60.7%, compared with interferon beta-1a. Fingolimod also reduced T2 hyperintense lesion volume, compared with interferon beta-1a (percentage change from baseline: 18.4% vs 32.4%).

“The rate of T2-related atrophy [in pediatric MS] is concerning, and I am particularly interested in looking at the extension study data as they come out, and we’ll see if there is a decrease during longer-term treatment,” said Dr. Chitnis.

“These results, overall, along with the efficacy demonstrated on the clinical relapse rate, support the overall benefit of fingolimod in pediatric patients with MS,” she concluded.

—Erik Greb

NASHVILLE—In patients with pediatric-onset multiple sclerosis (MS), fingolimod significantly reduces MRI activity and slows brain volume loss for as long as two years, compared with interferon beta-1a, according to data described at the 2018 CMSC Annual Meeting.

Analyzing the PARADIGMS Data

PARADIGMS was a double-blind, double-dummy, active-controlled, parallel-group, multicenter study in which patients participated for as long as two years. The investigators randomized patients with pediatric-onset MS (ages 10 through 17) to oral fingolimod or interferon beta-1a. The dose of fingolimod was adjusted for body weight. MRI was performed at baseline and every six months thereafter until the end of the study core phase. A central reading center analyzed the MRI results. The key MRI outcomes were the number of new or newly enlarged T2 lesions and gadolinium-enhancing T1 lesions, annual rate of brain volume change, number of new T1 hypointense lesions, change in total T2 hyperintense lesion volume, and number of combined unique active lesions.

The researchers randomized 107 participants to oral fingolimod and 108 to interferon beta-1a. At baseline, mean age was about 15. Most patients were female. Mean disease duration was one to two years. The average number of relapses in the year before screening was approximately 1.5. Participants had 2.6 to 3.1 gadolinium-enhancing T1 lesions.

Data Support Fingolimod’s Efficacy in Pediatric MS

At the end of the study, fingolimod significantly reduced the annualized rate of new or newly enlarged T2 lesions by 52.6% and the number of gadolinium-enhancing T1 lesions per scan by 66.0%, compared with interferon beta-1a. The odds ratio of freedom from new or newly enlarged T2 lesions was 4.51 in the fingolimod arm, compared with the interferon beta-1a arm. The odds ratio of freedom from gadolinium-enhancing lesions was 3.0 in the fingolimod arm, compared with the interferon beta-1a arm.

Compared with interferon beta-1a, treatment with fingolimod for as long as two years significantly reduced the annualized rate of brain volume change (least squares mean: −0.48 vs −0.80). Fingolimod reduced the annualized rate of new T1 hypointense lesions by 62.8% and the number of combined unique active lesions per scan by 60.7%, compared with interferon beta-1a. Fingolimod also reduced T2 hyperintense lesion volume, compared with interferon beta-1a (percentage change from baseline: 18.4% vs 32.4%).

“The rate of T2-related atrophy [in pediatric MS] is concerning, and I am particularly interested in looking at the extension study data as they come out, and we’ll see if there is a decrease during longer-term treatment,” said Dr. Chitnis.

“These results, overall, along with the efficacy demonstrated on the clinical relapse rate, support the overall benefit of fingolimod in pediatric patients with MS,” she concluded.

—Erik Greb

NASHVILLE—In patients with pediatric-onset multiple sclerosis (MS), fingolimod significantly reduces MRI activity and slows brain volume loss for as long as two years, compared with interferon beta-1a, according to data described at the 2018 CMSC Annual Meeting.

Analyzing the PARADIGMS Data

PARADIGMS was a double-blind, double-dummy, active-controlled, parallel-group, multicenter study in which patients participated for as long as two years. The investigators randomized patients with pediatric-onset MS (ages 10 through 17) to oral fingolimod or interferon beta-1a. The dose of fingolimod was adjusted for body weight. MRI was performed at baseline and every six months thereafter until the end of the study core phase. A central reading center analyzed the MRI results. The key MRI outcomes were the number of new or newly enlarged T2 lesions and gadolinium-enhancing T1 lesions, annual rate of brain volume change, number of new T1 hypointense lesions, change in total T2 hyperintense lesion volume, and number of combined unique active lesions.

The researchers randomized 107 participants to oral fingolimod and 108 to interferon beta-1a. At baseline, mean age was about 15. Most patients were female. Mean disease duration was one to two years. The average number of relapses in the year before screening was approximately 1.5. Participants had 2.6 to 3.1 gadolinium-enhancing T1 lesions.

Data Support Fingolimod’s Efficacy in Pediatric MS

At the end of the study, fingolimod significantly reduced the annualized rate of new or newly enlarged T2 lesions by 52.6% and the number of gadolinium-enhancing T1 lesions per scan by 66.0%, compared with interferon beta-1a. The odds ratio of freedom from new or newly enlarged T2 lesions was 4.51 in the fingolimod arm, compared with the interferon beta-1a arm. The odds ratio of freedom from gadolinium-enhancing lesions was 3.0 in the fingolimod arm, compared with the interferon beta-1a arm.

Compared with interferon beta-1a, treatment with fingolimod for as long as two years significantly reduced the annualized rate of brain volume change (least squares mean: −0.48 vs −0.80). Fingolimod reduced the annualized rate of new T1 hypointense lesions by 62.8% and the number of combined unique active lesions per scan by 60.7%, compared with interferon beta-1a. Fingolimod also reduced T2 hyperintense lesion volume, compared with interferon beta-1a (percentage change from baseline: 18.4% vs 32.4%).

“The rate of T2-related atrophy [in pediatric MS] is concerning, and I am particularly interested in looking at the extension study data as they come out, and we’ll see if there is a decrease during longer-term treatment,” said Dr. Chitnis.

“These results, overall, along with the efficacy demonstrated on the clinical relapse rate, support the overall benefit of fingolimod in pediatric patients with MS,” she concluded.

—Erik Greb

NASHVILLE—Moderate-to-vigorous physical activity is positively associated with retinal nerve fiber layer thickness in children with multiple sclerosis (MS), according to research presented at the 2018 CMSC Annual Meeting. This finding may help to support an intervention targeting moderate-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS.

More than one-third of pediatric patients with MS experience optic neuritis, and most experience visual pathway abnormalities, including reductions in the retinal nerve fiber layer and ganglion cell inner-plexiform layer. Previous studies in adults have shown a positive association between moderate-to-vigorous physical activity and the retinal nerve fiber layer; however, this association has not been evaluated in pediatric patients with MS.

To investigate the associations between mild-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer in pediatric patients with MS, Alexander L. Pearson, a medical student at the University of Ottawa in Ontario, and colleagues conducted a cross-sectional study.

The researchers recruited participants from the Pediatric MS and Demyelinating Disorders Center at the Hospital for Sick Children in Toronto. Eligible participants had a diagnosis of MS (according to the International Pediatric MS Study Group consensus definitions) and were younger than 18. Patients with neuroinflammatory abnormalities associated with underlying systemic or neurologic disorders, recurrent neuroinflammatory disorders other than MS, coexisting ocular pathologies, visual acuity ±6 diopters or worse, were excluded.

Participants received standardized visual evaluations, including ocular coherence tomography. Investigators performed evaluations more than 90 days after an optic neuritis episode using a spectral-domain ocular coherence tomography Cirrus scanner. Participants also completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ) more than 30 days after a relapse. This questionnaire was used to calculate the health contribution score.

Generalized linear models were used to assess the associations between moderate-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer when controlling for sex, number of optic neuritis episodes, disease duration at time of ocular coherence tomography, and within-subject correlation between eyes. Bonferroni correction was used to adjust for multiple comparisons.

Thirty patients participated in this study; 23 were female. Ocular coherence tomography was performed at a mean age of 15.7 (range, 10.6–18.0) and a median of 1.9 years from disease onset. The median retinal nerve fiber layer was 90 μm, and the median ganglion cell inner-plexiform layer was 73.5 μm. The median amount of moderate-to-vigorous physical activity was 26.5 metabolic equivalents per week.

The research team found that moderate-to-vigorous physical activity was positively associated with retinal nerve fiber layer thickness. Although the retinal nerve fiber layer and ganglion cell inner-plexiform layer were moderately correlated, moderate-to-vigorous physical activity was not associated with the ganglion cell inner-plexiform layer, said the authors.

“Next steps include a trial using mild-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS,” the researchers concluded.

NASHVILLE—Moderate-to-vigorous physical activity is positively associated with retinal nerve fiber layer thickness in children with multiple sclerosis (MS), according to research presented at the 2018 CMSC Annual Meeting. This finding may help to support an intervention targeting moderate-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS.

More than one-third of pediatric patients with MS experience optic neuritis, and most experience visual pathway abnormalities, including reductions in the retinal nerve fiber layer and ganglion cell inner-plexiform layer. Previous studies in adults have shown a positive association between moderate-to-vigorous physical activity and the retinal nerve fiber layer; however, this association has not been evaluated in pediatric patients with MS.

To investigate the associations between mild-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer in pediatric patients with MS, Alexander L. Pearson, a medical student at the University of Ottawa in Ontario, and colleagues conducted a cross-sectional study.

The researchers recruited participants from the Pediatric MS and Demyelinating Disorders Center at the Hospital for Sick Children in Toronto. Eligible participants had a diagnosis of MS (according to the International Pediatric MS Study Group consensus definitions) and were younger than 18. Patients with neuroinflammatory abnormalities associated with underlying systemic or neurologic disorders, recurrent neuroinflammatory disorders other than MS, coexisting ocular pathologies, visual acuity ±6 diopters or worse, were excluded.

Participants received standardized visual evaluations, including ocular coherence tomography. Investigators performed evaluations more than 90 days after an optic neuritis episode using a spectral-domain ocular coherence tomography Cirrus scanner. Participants also completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ) more than 30 days after a relapse. This questionnaire was used to calculate the health contribution score.

Generalized linear models were used to assess the associations between moderate-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer when controlling for sex, number of optic neuritis episodes, disease duration at time of ocular coherence tomography, and within-subject correlation between eyes. Bonferroni correction was used to adjust for multiple comparisons.

Thirty patients participated in this study; 23 were female. Ocular coherence tomography was performed at a mean age of 15.7 (range, 10.6–18.0) and a median of 1.9 years from disease onset. The median retinal nerve fiber layer was 90 μm, and the median ganglion cell inner-plexiform layer was 73.5 μm. The median amount of moderate-to-vigorous physical activity was 26.5 metabolic equivalents per week.

The research team found that moderate-to-vigorous physical activity was positively associated with retinal nerve fiber layer thickness. Although the retinal nerve fiber layer and ganglion cell inner-plexiform layer were moderately correlated, moderate-to-vigorous physical activity was not associated with the ganglion cell inner-plexiform layer, said the authors.

“Next steps include a trial using mild-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS,” the researchers concluded.

NASHVILLE—Moderate-to-vigorous physical activity is positively associated with retinal nerve fiber layer thickness in children with multiple sclerosis (MS), according to research presented at the 2018 CMSC Annual Meeting. This finding may help to support an intervention targeting moderate-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS.

More than one-third of pediatric patients with MS experience optic neuritis, and most experience visual pathway abnormalities, including reductions in the retinal nerve fiber layer and ganglion cell inner-plexiform layer. Previous studies in adults have shown a positive association between moderate-to-vigorous physical activity and the retinal nerve fiber layer; however, this association has not been evaluated in pediatric patients with MS.

To investigate the associations between mild-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer in pediatric patients with MS, Alexander L. Pearson, a medical student at the University of Ottawa in Ontario, and colleagues conducted a cross-sectional study.

The researchers recruited participants from the Pediatric MS and Demyelinating Disorders Center at the Hospital for Sick Children in Toronto. Eligible participants had a diagnosis of MS (according to the International Pediatric MS Study Group consensus definitions) and were younger than 18. Patients with neuroinflammatory abnormalities associated with underlying systemic or neurologic disorders, recurrent neuroinflammatory disorders other than MS, coexisting ocular pathologies, visual acuity ±6 diopters or worse, were excluded.

Participants received standardized visual evaluations, including ocular coherence tomography. Investigators performed evaluations more than 90 days after an optic neuritis episode using a spectral-domain ocular coherence tomography Cirrus scanner. Participants also completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ) more than 30 days after a relapse. This questionnaire was used to calculate the health contribution score.

Generalized linear models were used to assess the associations between moderate-to-vigorous physical activity, the retinal nerve fiber layer, and the ganglion cell inner-plexiform layer when controlling for sex, number of optic neuritis episodes, disease duration at time of ocular coherence tomography, and within-subject correlation between eyes. Bonferroni correction was used to adjust for multiple comparisons.

Thirty patients participated in this study; 23 were female. Ocular coherence tomography was performed at a mean age of 15.7 (range, 10.6–18.0) and a median of 1.9 years from disease onset. The median retinal nerve fiber layer was 90 μm, and the median ganglion cell inner-plexiform layer was 73.5 μm. The median amount of moderate-to-vigorous physical activity was 26.5 metabolic equivalents per week.

The research team found that moderate-to-vigorous physical activity was positively associated with retinal nerve fiber layer thickness. Although the retinal nerve fiber layer and ganglion cell inner-plexiform layer were moderately correlated, moderate-to-vigorous physical activity was not associated with the ganglion cell inner-plexiform layer, said the authors.

“Next steps include a trial using mild-to-vigorous physical activity to improve anterior visual pathway integrity in children with MS,” the researchers concluded.

NASHVILLE—Patients with multiple sclerosis (MS) with breakthrough disease may benefit from intramuscular interferon beta 1-a treatment twice per week, according to research described at the 2018 CMSC Annual Meeting. “Advantages to using an intramuscular interferon beta 1-a preparation include no skin reactions and a lower incidence of interferon neutralizing antibodies,” said Robert W. Baumhefner, MD, a neurologist at the Veteran Affairs West Los Angeles Medical Center.

Previous clinical trials have suggested a dose-response effect for interferon beta in MS. The European Interferon Beta-1a Dose Comparison Study, however, found no change in efficacy with just doubling the standard dose of intramuscular interferon beta-1a once per week. This may not be the same as increasing the frequency of intramuscular interferon administration, said Baumhefner. In addition, none of the previous studies have information on patients with breakthrough disease on standard-dose intramuscular interferon beta-1a switched to twice-weekly dosing.

Dr. Baumhefner conducted a retrospective observational study of patients MS with breakthrough disease receiving intramuscular interferon beta 1-a once per week who were switched to intramuscular interferon beta 1-a twice per week.

A total of 107 patients with MS were started on intramuscular interferon beta 1-a from 1995 to 2015 at the MS clinic of the VA West Los Angeles Medical Center. Of these, 59 patients with breakthrough disease were switched to twice-weekly intramuscular interferon beta-1a. There was adequate follow-up for at least two years for 52 of these patients. In addition, participants were followed up an average of every four months.

At each visit, an interval history of any relapse; scores on the Incapacity Status Scale, Functional Systems Scale, and Expanded Disability Status Scale (EDSS); and a proprietary graded neurologic examination were obtained. Annual MRI of the brain using a contrast-enhanced MS protocol was obtained in most patients. Baumhefner defined breakthrough disease as continued clinical relapses, new T2 or enhanced lesions on MRI, or worsening of EDSS or neurologic examination.

Of the 52 patients with adequate follow-up, 26 had no further breakthrough disease for 14 months or longer (range, 14-192 months). Five patients did not tolerate the increase in frequency of administration. Interferon beta neutralizing antibody testing was performed on 25 patients while they were receiving twice-weekly dosing. One patient who failed twice-weekly interferon beta had consistently elevated titers on two determinations (4%). African American patients, those with a higher EDSS score when switching, and patients with a longer duration of stability on weekly dosed treatment may be less likely to respond, the researcher concluded.

NASHVILLE—Patients with multiple sclerosis (MS) with breakthrough disease may benefit from intramuscular interferon beta 1-a treatment twice per week, according to research described at the 2018 CMSC Annual Meeting. “Advantages to using an intramuscular interferon beta 1-a preparation include no skin reactions and a lower incidence of interferon neutralizing antibodies,” said Robert W. Baumhefner, MD, a neurologist at the Veteran Affairs West Los Angeles Medical Center.

Previous clinical trials have suggested a dose-response effect for interferon beta in MS. The European Interferon Beta-1a Dose Comparison Study, however, found no change in efficacy with just doubling the standard dose of intramuscular interferon beta-1a once per week. This may not be the same as increasing the frequency of intramuscular interferon administration, said Baumhefner. In addition, none of the previous studies have information on patients with breakthrough disease on standard-dose intramuscular interferon beta-1a switched to twice-weekly dosing.

Dr. Baumhefner conducted a retrospective observational study of patients MS with breakthrough disease receiving intramuscular interferon beta 1-a once per week who were switched to intramuscular interferon beta 1-a twice per week.

A total of 107 patients with MS were started on intramuscular interferon beta 1-a from 1995 to 2015 at the MS clinic of the VA West Los Angeles Medical Center. Of these, 59 patients with breakthrough disease were switched to twice-weekly intramuscular interferon beta-1a. There was adequate follow-up for at least two years for 52 of these patients. In addition, participants were followed up an average of every four months.

At each visit, an interval history of any relapse; scores on the Incapacity Status Scale, Functional Systems Scale, and Expanded Disability Status Scale (EDSS); and a proprietary graded neurologic examination were obtained. Annual MRI of the brain using a contrast-enhanced MS protocol was obtained in most patients. Baumhefner defined breakthrough disease as continued clinical relapses, new T2 or enhanced lesions on MRI, or worsening of EDSS or neurologic examination.

Of the 52 patients with adequate follow-up, 26 had no further breakthrough disease for 14 months or longer (range, 14-192 months). Five patients did not tolerate the increase in frequency of administration. Interferon beta neutralizing antibody testing was performed on 25 patients while they were receiving twice-weekly dosing. One patient who failed twice-weekly interferon beta had consistently elevated titers on two determinations (4%). African American patients, those with a higher EDSS score when switching, and patients with a longer duration of stability on weekly dosed treatment may be less likely to respond, the researcher concluded.

NASHVILLE—Patients with multiple sclerosis (MS) with breakthrough disease may benefit from intramuscular interferon beta 1-a treatment twice per week, according to research described at the 2018 CMSC Annual Meeting. “Advantages to using an intramuscular interferon beta 1-a preparation include no skin reactions and a lower incidence of interferon neutralizing antibodies,” said Robert W. Baumhefner, MD, a neurologist at the Veteran Affairs West Los Angeles Medical Center.

Previous clinical trials have suggested a dose-response effect for interferon beta in MS. The European Interferon Beta-1a Dose Comparison Study, however, found no change in efficacy with just doubling the standard dose of intramuscular interferon beta-1a once per week. This may not be the same as increasing the frequency of intramuscular interferon administration, said Baumhefner. In addition, none of the previous studies have information on patients with breakthrough disease on standard-dose intramuscular interferon beta-1a switched to twice-weekly dosing.

Dr. Baumhefner conducted a retrospective observational study of patients MS with breakthrough disease receiving intramuscular interferon beta 1-a once per week who were switched to intramuscular interferon beta 1-a twice per week.

A total of 107 patients with MS were started on intramuscular interferon beta 1-a from 1995 to 2015 at the MS clinic of the VA West Los Angeles Medical Center. Of these, 59 patients with breakthrough disease were switched to twice-weekly intramuscular interferon beta-1a. There was adequate follow-up for at least two years for 52 of these patients. In addition, participants were followed up an average of every four months.

At each visit, an interval history of any relapse; scores on the Incapacity Status Scale, Functional Systems Scale, and Expanded Disability Status Scale (EDSS); and a proprietary graded neurologic examination were obtained. Annual MRI of the brain using a contrast-enhanced MS protocol was obtained in most patients. Baumhefner defined breakthrough disease as continued clinical relapses, new T2 or enhanced lesions on MRI, or worsening of EDSS or neurologic examination.

Of the 52 patients with adequate follow-up, 26 had no further breakthrough disease for 14 months or longer (range, 14-192 months). Five patients did not tolerate the increase in frequency of administration. Interferon beta neutralizing antibody testing was performed on 25 patients while they were receiving twice-weekly dosing. One patient who failed twice-weekly interferon beta had consistently elevated titers on two determinations (4%). African American patients, those with a higher EDSS score when switching, and patients with a longer duration of stability on weekly dosed treatment may be less likely to respond, the researcher concluded.

NASHVILLE—The benefits of ocrelizumab on 24-week confirmed disability improvement, which were demonstrated in two-year, double-blind, controlled trials, were maintained for two years in an open-label extension study in patients with relapsing-remitting multiple sclerosis (MS), according to data described at the 2018 CMSC Annual Meeting.

The 96-week, double-blind, controlled periods of the OPERA I and II trials demonstrated the efficacy and safety of ocrelizumab in relapsing-remitting MS. Upon completion of the controlled treatment periods, all patients were eligible to enter an open-label extension phase during which they would receive ocrelizumab. Robert T. Naismith, MD, Associate Professor of Neurology at Washington University School of Medicine in St. Louis, and colleagues reviewed data from this extension phase to assess the effect of switching to ocrelizumab or maintaining ocrelizumab therapy on the proportion of patients experiencing disability improvement.

Difference Between Groups Endured

During the controlled treatment period, patients received IV ocrelizumab (600 mg) every 24 weeks or subcutaneous interferon beta-1a (44 μg) three times weekly for 96 weeks. At the start of the open-label extension period, patients continued ocrelizumab or were switched from interferon beta-1a to ocrelizumab. Disability improvement compared with baseline was defined as a reduction in Expanded Disability Status Scale (EDSS) score of 1.0 or more points for patients with a baseline EDSS score from 2.0 to 5.5, or a reduction of 0.5 or more points for patients with a baseline EDSS score greater than 5.5. Time to onset of 24-week confirmed disability improvement was analyzed in patients with a baseline EDSS score of 2.0 or greater.

More than 89% of patients who entered the open-label extension period completed two years of the open-label extension. The group that started and continued ocrelizumab (n = 454), compared with the group that switched from interferon beta-1a to ocrelizumab (n = 419), had a higher proportion of patients with 24-week confirmed disability improvement in the year before the switch (16.8% vs 13.3%). At year 1 of the extension, the group that started and continued ocrelizumab included 399 participants, and 20.6% had 24-week confirmed disability improvement, compared with 16.6% of the group that switched from interferon beta-1a to ocrelizumab, which included 366 participants. At year 2, the former group included 363 patients, and 23.7% had 24-week confirmed disability improvement. The latter group included 339 participants, and 18.9% of them achieved this outcome.

Analyzing Four Years of Treatment

When the investigators examined data for four years of treatment (ie, the double-blind and extension phases), they observed that between 20% and 25% of patients with an EDSS score of 2 or more who received ocrelizumab had improvement in EDSS score. When they examined patients with EDSS scores lower than 2, the results were similar. “This [finding] parallels some of the effects that we see in clinical efficacy, based upon a reduction in MRI parameters such as T1 and T2 lesions,” said Dr. Naismith.

“What we are seeing, especially with some of our high-efficacy therapies, is that patients come back and report that they are feeling better in subsequent visits. I admit, I never tell patients that this is an expectation they should have…. But it is always nice to hear from a patient that they are doing better in some tangible way in their lives,” Dr. Naismith concluded.

—Erik Greb

NASHVILLE—The benefits of ocrelizumab on 24-week confirmed disability improvement, which were demonstrated in two-year, double-blind, controlled trials, were maintained for two years in an open-label extension study in patients with relapsing-remitting multiple sclerosis (MS), according to data described at the 2018 CMSC Annual Meeting.

The 96-week, double-blind, controlled periods of the OPERA I and II trials demonstrated the efficacy and safety of ocrelizumab in relapsing-remitting MS. Upon completion of the controlled treatment periods, all patients were eligible to enter an open-label extension phase during which they would receive ocrelizumab. Robert T. Naismith, MD, Associate Professor of Neurology at Washington University School of Medicine in St. Louis, and colleagues reviewed data from this extension phase to assess the effect of switching to ocrelizumab or maintaining ocrelizumab therapy on the proportion of patients experiencing disability improvement.

Difference Between Groups Endured

During the controlled treatment period, patients received IV ocrelizumab (600 mg) every 24 weeks or subcutaneous interferon beta-1a (44 μg) three times weekly for 96 weeks. At the start of the open-label extension period, patients continued ocrelizumab or were switched from interferon beta-1a to ocrelizumab. Disability improvement compared with baseline was defined as a reduction in Expanded Disability Status Scale (EDSS) score of 1.0 or more points for patients with a baseline EDSS score from 2.0 to 5.5, or a reduction of 0.5 or more points for patients with a baseline EDSS score greater than 5.5. Time to onset of 24-week confirmed disability improvement was analyzed in patients with a baseline EDSS score of 2.0 or greater.

More than 89% of patients who entered the open-label extension period completed two years of the open-label extension. The group that started and continued ocrelizumab (n = 454), compared with the group that switched from interferon beta-1a to ocrelizumab (n = 419), had a higher proportion of patients with 24-week confirmed disability improvement in the year before the switch (16.8% vs 13.3%). At year 1 of the extension, the group that started and continued ocrelizumab included 399 participants, and 20.6% had 24-week confirmed disability improvement, compared with 16.6% of the group that switched from interferon beta-1a to ocrelizumab, which included 366 participants. At year 2, the former group included 363 patients, and 23.7% had 24-week confirmed disability improvement. The latter group included 339 participants, and 18.9% of them achieved this outcome.

Analyzing Four Years of Treatment

When the investigators examined data for four years of treatment (ie, the double-blind and extension phases), they observed that between 20% and 25% of patients with an EDSS score of 2 or more who received ocrelizumab had improvement in EDSS score. When they examined patients with EDSS scores lower than 2, the results were similar. “This [finding] parallels some of the effects that we see in clinical efficacy, based upon a reduction in MRI parameters such as T1 and T2 lesions,” said Dr. Naismith.

“What we are seeing, especially with some of our high-efficacy therapies, is that patients come back and report that they are feeling better in subsequent visits. I admit, I never tell patients that this is an expectation they should have…. But it is always nice to hear from a patient that they are doing better in some tangible way in their lives,” Dr. Naismith concluded.

—Erik Greb

NASHVILLE—The benefits of ocrelizumab on 24-week confirmed disability improvement, which were demonstrated in two-year, double-blind, controlled trials, were maintained for two years in an open-label extension study in patients with relapsing-remitting multiple sclerosis (MS), according to data described at the 2018 CMSC Annual Meeting.

The 96-week, double-blind, controlled periods of the OPERA I and II trials demonstrated the efficacy and safety of ocrelizumab in relapsing-remitting MS. Upon completion of the controlled treatment periods, all patients were eligible to enter an open-label extension phase during which they would receive ocrelizumab. Robert T. Naismith, MD, Associate Professor of Neurology at Washington University School of Medicine in St. Louis, and colleagues reviewed data from this extension phase to assess the effect of switching to ocrelizumab or maintaining ocrelizumab therapy on the proportion of patients experiencing disability improvement.

Difference Between Groups Endured

During the controlled treatment period, patients received IV ocrelizumab (600 mg) every 24 weeks or subcutaneous interferon beta-1a (44 μg) three times weekly for 96 weeks. At the start of the open-label extension period, patients continued ocrelizumab or were switched from interferon beta-1a to ocrelizumab. Disability improvement compared with baseline was defined as a reduction in Expanded Disability Status Scale (EDSS) score of 1.0 or more points for patients with a baseline EDSS score from 2.0 to 5.5, or a reduction of 0.5 or more points for patients with a baseline EDSS score greater than 5.5. Time to onset of 24-week confirmed disability improvement was analyzed in patients with a baseline EDSS score of 2.0 or greater.

More than 89% of patients who entered the open-label extension period completed two years of the open-label extension. The group that started and continued ocrelizumab (n = 454), compared with the group that switched from interferon beta-1a to ocrelizumab (n = 419), had a higher proportion of patients with 24-week confirmed disability improvement in the year before the switch (16.8% vs 13.3%). At year 1 of the extension, the group that started and continued ocrelizumab included 399 participants, and 20.6% had 24-week confirmed disability improvement, compared with 16.6% of the group that switched from interferon beta-1a to ocrelizumab, which included 366 participants. At year 2, the former group included 363 patients, and 23.7% had 24-week confirmed disability improvement. The latter group included 339 participants, and 18.9% of them achieved this outcome.

Analyzing Four Years of Treatment

When the investigators examined data for four years of treatment (ie, the double-blind and extension phases), they observed that between 20% and 25% of patients with an EDSS score of 2 or more who received ocrelizumab had improvement in EDSS score. When they examined patients with EDSS scores lower than 2, the results were similar. “This [finding] parallels some of the effects that we see in clinical efficacy, based upon a reduction in MRI parameters such as T1 and T2 lesions,” said Dr. Naismith.

“What we are seeing, especially with some of our high-efficacy therapies, is that patients come back and report that they are feeling better in subsequent visits. I admit, I never tell patients that this is an expectation they should have…. But it is always nice to hear from a patient that they are doing better in some tangible way in their lives,” Dr. Naismith concluded.

—Erik Greb

NASHVILLE, Tenn. – Recent epidemiologic studies of multiple sclerosis from around the globe paint a confusing picture, with incidence up in some countries and down in others, latitudinal associations strong in some regions and waning in others, and an overall lack of well-managed databases to bring order to these findings.

Alberto Ascherio, MD, who moderated a global epidemiology session during the annual meeting of the Consortium of Multiple Sclerosis Centers, said it’s tough to draw firm conclusions from the vastly varied studies assessing epidemiologic patterns of MS around the world. Most researchers are trying to extrapolate population data from smaller groups – a process always fraught with the potential for misinterpretation.

Global data, however, converge on some of the most well-established risk factors for the disease, he said. “There seems to be no doubt that vitamin D deficiency, teenager obesity, Epstein-Barr virus infection, and smoking remain strong risk factors for MS in every database in every country that has examined this,” said Dr. Ascherio, a professor of epidemiology and nutrition at Harvard University, Boston.

He sat down for a video interview to pick apart some of the findings from studies in Australia, New Zealand, Western Europe, Canada, and the United States.

Dr. Ascherio had no financial disclosures.

[email protected]

NASHVILLE, Tenn. – Recent epidemiologic studies of multiple sclerosis from around the globe paint a confusing picture, with incidence up in some countries and down in others, latitudinal associations strong in some regions and waning in others, and an overall lack of well-managed databases to bring order to these findings.

Alberto Ascherio, MD, who moderated a global epidemiology session during the annual meeting of the Consortium of Multiple Sclerosis Centers, said it’s tough to draw firm conclusions from the vastly varied studies assessing epidemiologic patterns of MS around the world. Most researchers are trying to extrapolate population data from smaller groups – a process always fraught with the potential for misinterpretation.

Global data, however, converge on some of the most well-established risk factors for the disease, he said. “There seems to be no doubt that vitamin D deficiency, teenager obesity, Epstein-Barr virus infection, and smoking remain strong risk factors for MS in every database in every country that has examined this,” said Dr. Ascherio, a professor of epidemiology and nutrition at Harvard University, Boston.

He sat down for a video interview to pick apart some of the findings from studies in Australia, New Zealand, Western Europe, Canada, and the United States.

Dr. Ascherio had no financial disclosures.

[email protected]

NASHVILLE, Tenn. – Recent epidemiologic studies of multiple sclerosis from around the globe paint a confusing picture, with incidence up in some countries and down in others, latitudinal associations strong in some regions and waning in others, and an overall lack of well-managed databases to bring order to these findings.

Alberto Ascherio, MD, who moderated a global epidemiology session during the annual meeting of the Consortium of Multiple Sclerosis Centers, said it’s tough to draw firm conclusions from the vastly varied studies assessing epidemiologic patterns of MS around the world. Most researchers are trying to extrapolate population data from smaller groups – a process always fraught with the potential for misinterpretation.

Global data, however, converge on some of the most well-established risk factors for the disease, he said. “There seems to be no doubt that vitamin D deficiency, teenager obesity, Epstein-Barr virus infection, and smoking remain strong risk factors for MS in every database in every country that has examined this,” said Dr. Ascherio, a professor of epidemiology and nutrition at Harvard University, Boston.

He sat down for a video interview to pick apart some of the findings from studies in Australia, New Zealand, Western Europe, Canada, and the United States.

Dr. Ascherio had no financial disclosures.

[email protected]

NASHVILLE, TENN. – Some patients use multiple sclerosis as an excuse to make poor health choices, but Allen C. Bowling, MD, PhD, of the Colorado Neurological Institute has seen another kind of story unfold. Fifteen to 20 years ago, Dr. Bowling said, he treated patients who took the development of MS in their 20s as a sign they needed to take better care of themselves. “They said MS was the best thing that happened to them ‘because it motivated me to make these healthy lifestyle changes I wouldn’t have made otherwise.’ ”

These patients have maintained their lifestyle changes, he said, lowering their risk of comorbidities and – perhaps – changing the course of their MS for the better.

“It’s all one machine, and sometimes we lose sight of that in our sub-sub-specialized world of treating MS ... You’re caring for a whole person. If you start thinking about that, it does make you think differently about how you treat the person, how you try to prevent disease in terms of certain pathways,” Dr. Bowling said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers, where he spoke to colleagues about the importance of helping patients to adopt lifestyle changes.

According to Dr. Bowling, there’s evidence linking lifestyle-related comorbidities, poorer food quality, and tobacco use to higher levels of overall MS risk, relapses, disability, and symptoms.

Researchers have also linked other life factors to higher MS risks: obesity (linked to overall MS risk, disability, symptoms); lack of physical activity (linked to relapses, disability, symptoms); emotional factors (relapses, symptoms); and alcohol overuse (linked to overall risk, disability, symptoms).

“Data is mild to moderate to strong in all those areas for lifestyle approaches like diet, physical activity, emotional health, alcohol in moderation or less, and no tobacco smoking,” Dr. Bowling said.

NASHVILLE, TENN. – Some patients use multiple sclerosis as an excuse to make poor health choices, but Allen C. Bowling, MD, PhD, of the Colorado Neurological Institute has seen another kind of story unfold. Fifteen to 20 years ago, Dr. Bowling said, he treated patients who took the development of MS in their 20s as a sign they needed to take better care of themselves. “They said MS was the best thing that happened to them ‘because it motivated me to make these healthy lifestyle changes I wouldn’t have made otherwise.’ ”

These patients have maintained their lifestyle changes, he said, lowering their risk of comorbidities and – perhaps – changing the course of their MS for the better.

“It’s all one machine, and sometimes we lose sight of that in our sub-sub-specialized world of treating MS ... You’re caring for a whole person. If you start thinking about that, it does make you think differently about how you treat the person, how you try to prevent disease in terms of certain pathways,” Dr. Bowling said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers, where he spoke to colleagues about the importance of helping patients to adopt lifestyle changes.

According to Dr. Bowling, there’s evidence linking lifestyle-related comorbidities, poorer food quality, and tobacco use to higher levels of overall MS risk, relapses, disability, and symptoms.

Researchers have also linked other life factors to higher MS risks: obesity (linked to overall MS risk, disability, symptoms); lack of physical activity (linked to relapses, disability, symptoms); emotional factors (relapses, symptoms); and alcohol overuse (linked to overall risk, disability, symptoms).

“Data is mild to moderate to strong in all those areas for lifestyle approaches like diet, physical activity, emotional health, alcohol in moderation or less, and no tobacco smoking,” Dr. Bowling said.

NASHVILLE, TENN. – Some patients use multiple sclerosis as an excuse to make poor health choices, but Allen C. Bowling, MD, PhD, of the Colorado Neurological Institute has seen another kind of story unfold. Fifteen to 20 years ago, Dr. Bowling said, he treated patients who took the development of MS in their 20s as a sign they needed to take better care of themselves. “They said MS was the best thing that happened to them ‘because it motivated me to make these healthy lifestyle changes I wouldn’t have made otherwise.’ ”

These patients have maintained their lifestyle changes, he said, lowering their risk of comorbidities and – perhaps – changing the course of their MS for the better.

“It’s all one machine, and sometimes we lose sight of that in our sub-sub-specialized world of treating MS ... You’re caring for a whole person. If you start thinking about that, it does make you think differently about how you treat the person, how you try to prevent disease in terms of certain pathways,” Dr. Bowling said in an interview at the annual meeting of the Consortium of Multiple Sclerosis Centers, where he spoke to colleagues about the importance of helping patients to adopt lifestyle changes.

According to Dr. Bowling, there’s evidence linking lifestyle-related comorbidities, poorer food quality, and tobacco use to higher levels of overall MS risk, relapses, disability, and symptoms.

Researchers have also linked other life factors to higher MS risks: obesity (linked to overall MS risk, disability, symptoms); lack of physical activity (linked to relapses, disability, symptoms); emotional factors (relapses, symptoms); and alcohol overuse (linked to overall risk, disability, symptoms).

“Data is mild to moderate to strong in all those areas for lifestyle approaches like diet, physical activity, emotional health, alcohol in moderation or less, and no tobacco smoking,” Dr. Bowling said.

NASHVILLE, Tenn. – Gadolinium-based contrast agents (GBCAs) are necessary for the accurate initial diagnosis of patients experiencing a first clinical attack of symptoms consistent with multiple sclerosis and for following patients with highly active disease or sudden, unexpected declines.

But according to new guidelines issued by the Consortium of Multiple Sclerosis Centers, GBCAs are optional – although helpful – in many other clinical scenarios, especially when noncontrast MRI can provide answers.

“The key is that there is an optional role for gadolinium,” David Li, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. Although a GBCA is still “essential” for some clinical scenarios in clinically isolated syndrome and MS, the new guidelines suggest that standard, high-quality MRI without contrast can adequately identify the majority of new MS lesions over time.

“But I would like to remind you that if you need to know about ongoing, current activity,” in settings of acute change, then gadolinium is still necessary, Dr. Li of the University of British Columbia, Vancouver, said in a video interview.

The guideline is an update of CMSC’s 2015 document, which endorsed a more liberal use of GBCAs. This more conservative stance reflects new research on the agents and an update in 2017 from the Food and Drug Administration that required a class-wide warning about gadolinium retention.

The agency began investigating gadolinium in 2015. In May 2017, it issued a statement confirming that gadolinium accumulates in neural tissue and can be retained for an extended period. However, in reviewing the evidence, FDA found no concerning safety signals. Despite the presumed lack of toxicity, the agency issued the warning and recommended limiting the contrast agent’s use – a move reflected in CMSC’s new MRI protocol guidelines.

“While there is no known CNS toxicity, these agents should be used judiciously, recognizing that gadolinium continues to play an invaluable role in specific circumstances related to the diagnosis and follow-up of individuals with MS,” the document notes.

[email protected]

NASHVILLE, Tenn. – Gadolinium-based contrast agents (GBCAs) are necessary for the accurate initial diagnosis of patients experiencing a first clinical attack of symptoms consistent with multiple sclerosis and for following patients with highly active disease or sudden, unexpected declines.

But according to new guidelines issued by the Consortium of Multiple Sclerosis Centers, GBCAs are optional – although helpful – in many other clinical scenarios, especially when noncontrast MRI can provide answers.

“The key is that there is an optional role for gadolinium,” David Li, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. Although a GBCA is still “essential” for some clinical scenarios in clinically isolated syndrome and MS, the new guidelines suggest that standard, high-quality MRI without contrast can adequately identify the majority of new MS lesions over time.

“But I would like to remind you that if you need to know about ongoing, current activity,” in settings of acute change, then gadolinium is still necessary, Dr. Li of the University of British Columbia, Vancouver, said in a video interview.

The guideline is an update of CMSC’s 2015 document, which endorsed a more liberal use of GBCAs. This more conservative stance reflects new research on the agents and an update in 2017 from the Food and Drug Administration that required a class-wide warning about gadolinium retention.

The agency began investigating gadolinium in 2015. In May 2017, it issued a statement confirming that gadolinium accumulates in neural tissue and can be retained for an extended period. However, in reviewing the evidence, FDA found no concerning safety signals. Despite the presumed lack of toxicity, the agency issued the warning and recommended limiting the contrast agent’s use – a move reflected in CMSC’s new MRI protocol guidelines.

“While there is no known CNS toxicity, these agents should be used judiciously, recognizing that gadolinium continues to play an invaluable role in specific circumstances related to the diagnosis and follow-up of individuals with MS,” the document notes.

[email protected]

NASHVILLE, Tenn. – Gadolinium-based contrast agents (GBCAs) are necessary for the accurate initial diagnosis of patients experiencing a first clinical attack of symptoms consistent with multiple sclerosis and for following patients with highly active disease or sudden, unexpected declines.

But according to new guidelines issued by the Consortium of Multiple Sclerosis Centers, GBCAs are optional – although helpful – in many other clinical scenarios, especially when noncontrast MRI can provide answers.

“The key is that there is an optional role for gadolinium,” David Li, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. Although a GBCA is still “essential” for some clinical scenarios in clinically isolated syndrome and MS, the new guidelines suggest that standard, high-quality MRI without contrast can adequately identify the majority of new MS lesions over time.

“But I would like to remind you that if you need to know about ongoing, current activity,” in settings of acute change, then gadolinium is still necessary, Dr. Li of the University of British Columbia, Vancouver, said in a video interview.

The guideline is an update of CMSC’s 2015 document, which endorsed a more liberal use of GBCAs. This more conservative stance reflects new research on the agents and an update in 2017 from the Food and Drug Administration that required a class-wide warning about gadolinium retention.

The agency began investigating gadolinium in 2015. In May 2017, it issued a statement confirming that gadolinium accumulates in neural tissue and can be retained for an extended period. However, in reviewing the evidence, FDA found no concerning safety signals. Despite the presumed lack of toxicity, the agency issued the warning and recommended limiting the contrast agent’s use – a move reflected in CMSC’s new MRI protocol guidelines.

“While there is no known CNS toxicity, these agents should be used judiciously, recognizing that gadolinium continues to play an invaluable role in specific circumstances related to the diagnosis and follow-up of individuals with MS,” the document notes.

[email protected]

NASHVILLE, TENN. – Armed with new statistics, neurologist Joseph R. Berger, MD, has a message for colleagues about the widely feared risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis: It’s not as inevitable as you might think.

“You can actually prevent this disease from occurring because we have risk-limiting strategies in many circumstances,” said Dr. Berger of the University of Pennsylvania, Philadelphia, in a presentation on PML at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Unlike other conditions such as HIV, MS itself is not linked to a higher risk of PML, said Dr. Berger, a leading PML researcher. Instead, it’s the medications that spark the condition, he said, with at least three and possibly four drugs posing a risk to patients.

Natalizumab (Tysabri) is especially risky. “We know that the risk with natalizumab is incredibly high in the context of JC [John Cunningham] virus antibody positivity and prolonged therapy,” Dr. Berger said in an interview after his presentation.

Still, “you can safely give natalizumab for a short period of time when treating patients with aggressive MS,” he said. “I will frequently employ that strategy even in the context of JC virus antibody positivity.”

According to Dr. Berger, there’s no risk of PML when natalizumab is used for under 8 months (Mult Scler Relat Disord. 2017 Feb;12:59-63).

However, “if you leave people on the drug indefinitely, there is a substantial risk of developing PML,” he said. “Individuals who have been left on the drug for 2 years, who’ve seen prior immunosuppressant therapy, who are JC virus antibody positive – that group of individuals develops PML at rates of 1 in 50 to 1 in 100.”

NASHVILLE, TENN. – Armed with new statistics, neurologist Joseph R. Berger, MD, has a message for colleagues about the widely feared risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis: It’s not as inevitable as you might think.

“You can actually prevent this disease from occurring because we have risk-limiting strategies in many circumstances,” said Dr. Berger of the University of Pennsylvania, Philadelphia, in a presentation on PML at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Unlike other conditions such as HIV, MS itself is not linked to a higher risk of PML, said Dr. Berger, a leading PML researcher. Instead, it’s the medications that spark the condition, he said, with at least three and possibly four drugs posing a risk to patients.

Natalizumab (Tysabri) is especially risky. “We know that the risk with natalizumab is incredibly high in the context of JC [John Cunningham] virus antibody positivity and prolonged therapy,” Dr. Berger said in an interview after his presentation.

Still, “you can safely give natalizumab for a short period of time when treating patients with aggressive MS,” he said. “I will frequently employ that strategy even in the context of JC virus antibody positivity.”

According to Dr. Berger, there’s no risk of PML when natalizumab is used for under 8 months (Mult Scler Relat Disord. 2017 Feb;12:59-63).

However, “if you leave people on the drug indefinitely, there is a substantial risk of developing PML,” he said. “Individuals who have been left on the drug for 2 years, who’ve seen prior immunosuppressant therapy, who are JC virus antibody positive – that group of individuals develops PML at rates of 1 in 50 to 1 in 100.”

NASHVILLE, TENN. – Armed with new statistics, neurologist Joseph R. Berger, MD, has a message for colleagues about the widely feared risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis: It’s not as inevitable as you might think.

“You can actually prevent this disease from occurring because we have risk-limiting strategies in many circumstances,” said Dr. Berger of the University of Pennsylvania, Philadelphia, in a presentation on PML at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Unlike other conditions such as HIV, MS itself is not linked to a higher risk of PML, said Dr. Berger, a leading PML researcher. Instead, it’s the medications that spark the condition, he said, with at least three and possibly four drugs posing a risk to patients.

Natalizumab (Tysabri) is especially risky. “We know that the risk with natalizumab is incredibly high in the context of JC [John Cunningham] virus antibody positivity and prolonged therapy,” Dr. Berger said in an interview after his presentation.

Still, “you can safely give natalizumab for a short period of time when treating patients with aggressive MS,” he said. “I will frequently employ that strategy even in the context of JC virus antibody positivity.”

According to Dr. Berger, there’s no risk of PML when natalizumab is used for under 8 months (Mult Scler Relat Disord. 2017 Feb;12:59-63).

However, “if you leave people on the drug indefinitely, there is a substantial risk of developing PML,” he said. “Individuals who have been left on the drug for 2 years, who’ve seen prior immunosuppressant therapy, who are JC virus antibody positive – that group of individuals develops PML at rates of 1 in 50 to 1 in 100.”

NASHVILLE—Demographic characteristics, comorbidities, and previous treatments can predict intentional and unintentional nonadherence to disease-modifying therapy (DMT) for multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting. Neurologists should consider risk factors for nonadherence to treatment when selecting an appropriate therapy, said the researchers.

Approximately 33% of patients with MS do not adhere to their DMT regimens. Nonadherence results in suboptimal therapeutic efficacy and increased disability and costs. Unintentional nonadherence may result from cognitive impairment or circumstances that the patient does not control directly. Intentional nonadherence, on the other hand, involves a deliberate decision not to take prescribed medication as directed. Factors that predict patient nonadherence to treatment, whether intentional or unintentional, could affect the choice of DMT.

An Observational Study

Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues sought to explore factors associated with intentional and unintentional nonadherence to DMT in patients with MS. They conducted an observational, cross-sectional study of patient-reported outcomes (PROs) obtained at a single MS center in the United States during routine clinical care. The assessments included standardized, validated, computerized cognitive testing (NeuroTrax); Expanded Disability Status Scale (EDSS) score; and PROs (ie, Beck Depression Inventory [BDI], Modified Fatigue Impact Scale [MFIS], and Morisky Medication Adherence Scale [MMAS-8]). The investigators also obtained demographic data such as age, gender, marital status, employment, driving capability, and prior DMTs. Patients receiving an infused DMT were excluded from the study.

Of 499 patients, 273 (54.7%) met the inclusion criteria. About 76% of participants were female, and the population’s average age was 49. Of the 273 participants, 82 (30.0%) were intentionally nonadherent and 133 (48.7%) were unintentionally nonadherent. Higher depression scores and previous DMTs were associated with a greater risk of intentional nonadherence, as predicted by MMAS-8. Higher MFIS scores were associated with greater risk of unintentional nonadherence.

Increased age was associated with a lower risk of intentional and unintentional nonadherence. EDSS scores, mean NeuroTrax global cognitive summary scores, and MFIS physical subscale scores were not associated with intentional nonadherence. Prior DMT and EDSS scores were not associated with unintentional nonadherence.

How Can Adherence Be Improved?

“Treatment of the underlying cause of nonadherence might be critical to improve quality of life and impact outcomes and adherence,” Dr. Gudesblatt told Neurology Reviews.

“Identifying the risk of nonadherence is critical to the choice of DMT. For example, if self-administered therapy is prescribed to someone who is not adherent, that would be a bad choice,” he added. “If there are multiple risk factors for nonadherence, then the clinician must take this into account in the final discussion of [the] choice … of DMT. This [consideration] will be critical in the long run for preservation of ability and avoiding disability.”

Dr. Gudesblatt and colleagues plan to investigate this topic in longitudinal studies and research the effect of cognition on nonadherence. Neurologists have “so much more to do to better understand patients’ perceptions, improve outcomes, and improve decision making and management,” Dr. Gudesblatt concluded.

—Erik Greb

NASHVILLE—Demographic characteristics, comorbidities, and previous treatments can predict intentional and unintentional nonadherence to disease-modifying therapy (DMT) for multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting. Neurologists should consider risk factors for nonadherence to treatment when selecting an appropriate therapy, said the researchers.

Approximately 33% of patients with MS do not adhere to their DMT regimens. Nonadherence results in suboptimal therapeutic efficacy and increased disability and costs. Unintentional nonadherence may result from cognitive impairment or circumstances that the patient does not control directly. Intentional nonadherence, on the other hand, involves a deliberate decision not to take prescribed medication as directed. Factors that predict patient nonadherence to treatment, whether intentional or unintentional, could affect the choice of DMT.

An Observational Study

Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues sought to explore factors associated with intentional and unintentional nonadherence to DMT in patients with MS. They conducted an observational, cross-sectional study of patient-reported outcomes (PROs) obtained at a single MS center in the United States during routine clinical care. The assessments included standardized, validated, computerized cognitive testing (NeuroTrax); Expanded Disability Status Scale (EDSS) score; and PROs (ie, Beck Depression Inventory [BDI], Modified Fatigue Impact Scale [MFIS], and Morisky Medication Adherence Scale [MMAS-8]). The investigators also obtained demographic data such as age, gender, marital status, employment, driving capability, and prior DMTs. Patients receiving an infused DMT were excluded from the study.

Of 499 patients, 273 (54.7%) met the inclusion criteria. About 76% of participants were female, and the population’s average age was 49. Of the 273 participants, 82 (30.0%) were intentionally nonadherent and 133 (48.7%) were unintentionally nonadherent. Higher depression scores and previous DMTs were associated with a greater risk of intentional nonadherence, as predicted by MMAS-8. Higher MFIS scores were associated with greater risk of unintentional nonadherence.

Increased age was associated with a lower risk of intentional and unintentional nonadherence. EDSS scores, mean NeuroTrax global cognitive summary scores, and MFIS physical subscale scores were not associated with intentional nonadherence. Prior DMT and EDSS scores were not associated with unintentional nonadherence.

How Can Adherence Be Improved?

“Treatment of the underlying cause of nonadherence might be critical to improve quality of life and impact outcomes and adherence,” Dr. Gudesblatt told Neurology Reviews.

“Identifying the risk of nonadherence is critical to the choice of DMT. For example, if self-administered therapy is prescribed to someone who is not adherent, that would be a bad choice,” he added. “If there are multiple risk factors for nonadherence, then the clinician must take this into account in the final discussion of [the] choice … of DMT. This [consideration] will be critical in the long run for preservation of ability and avoiding disability.”

Dr. Gudesblatt and colleagues plan to investigate this topic in longitudinal studies and research the effect of cognition on nonadherence. Neurologists have “so much more to do to better understand patients’ perceptions, improve outcomes, and improve decision making and management,” Dr. Gudesblatt concluded.

—Erik Greb

NASHVILLE—Demographic characteristics, comorbidities, and previous treatments can predict intentional and unintentional nonadherence to disease-modifying therapy (DMT) for multiple sclerosis (MS), according to a study presented at the 2018 CMSC Annual Meeting. Neurologists should consider risk factors for nonadherence to treatment when selecting an appropriate therapy, said the researchers.

Approximately 33% of patients with MS do not adhere to their DMT regimens. Nonadherence results in suboptimal therapeutic efficacy and increased disability and costs. Unintentional nonadherence may result from cognitive impairment or circumstances that the patient does not control directly. Intentional nonadherence, on the other hand, involves a deliberate decision not to take prescribed medication as directed. Factors that predict patient nonadherence to treatment, whether intentional or unintentional, could affect the choice of DMT.

An Observational Study

Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues sought to explore factors associated with intentional and unintentional nonadherence to DMT in patients with MS. They conducted an observational, cross-sectional study of patient-reported outcomes (PROs) obtained at a single MS center in the United States during routine clinical care. The assessments included standardized, validated, computerized cognitive testing (NeuroTrax); Expanded Disability Status Scale (EDSS) score; and PROs (ie, Beck Depression Inventory [BDI], Modified Fatigue Impact Scale [MFIS], and Morisky Medication Adherence Scale [MMAS-8]). The investigators also obtained demographic data such as age, gender, marital status, employment, driving capability, and prior DMTs. Patients receiving an infused DMT were excluded from the study.

Of 499 patients, 273 (54.7%) met the inclusion criteria. About 76% of participants were female, and the population’s average age was 49. Of the 273 participants, 82 (30.0%) were intentionally nonadherent and 133 (48.7%) were unintentionally nonadherent. Higher depression scores and previous DMTs were associated with a greater risk of intentional nonadherence, as predicted by MMAS-8. Higher MFIS scores were associated with greater risk of unintentional nonadherence.

Increased age was associated with a lower risk of intentional and unintentional nonadherence. EDSS scores, mean NeuroTrax global cognitive summary scores, and MFIS physical subscale scores were not associated with intentional nonadherence. Prior DMT and EDSS scores were not associated with unintentional nonadherence.

How Can Adherence Be Improved?

“Treatment of the underlying cause of nonadherence might be critical to improve quality of life and impact outcomes and adherence,” Dr. Gudesblatt told Neurology Reviews.

“Identifying the risk of nonadherence is critical to the choice of DMT. For example, if self-administered therapy is prescribed to someone who is not adherent, that would be a bad choice,” he added. “If there are multiple risk factors for nonadherence, then the clinician must take this into account in the final discussion of [the] choice … of DMT. This [consideration] will be critical in the long run for preservation of ability and avoiding disability.”

Dr. Gudesblatt and colleagues plan to investigate this topic in longitudinal studies and research the effect of cognition on nonadherence. Neurologists have “so much more to do to better understand patients’ perceptions, improve outcomes, and improve decision making and management,” Dr. Gudesblatt concluded.

—Erik Greb