Multiple Sclerosis

BOSTON - Treatment with interferon beta-1a or glatiramer acetate, if used long term, has the potential to be cost effective and to alter the natural history of relapsing-remitting multiple sclerosis, according to findings from a 6-year observational study.

In 4,137 patients with relapsing-remitting MS who were followed for a median of 6 years, the observed increase in the Expanded Disability Status Scale (EDSS) scores was lower than the increase seen in a natural history cohort that served as a comparator group (relative rates, 0.76 using a continuous Markov model and 0.61 using a multilevel model). The observed progression for utility – a quality of life measure derived from the EDSS scores, and the primary outcome of the study – was consistent with this finding (relative rates of 0.58 and 0.56 according to the two models, respectively), Dr. Jacqueline Palace reported at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

The outcome – essentially a reduction of about 42% on the primary outcome measure, compared with the natural history cohort – was better than the 38% reduction that was predicted, said Dr. Palace, leader of the multiple sclerosis and neuromyelitis group at Oxford University Hospitals Trust in England.

A range of sensitivity analyses that examined the potential for various biases consistently demonstrated better outcomes in the treated patients, compared with the natural history cohort, Dr. Palace noted.

If sustained over 20 years, the magnitude of the treatment effect observed in this study would be consistent with a predefined cost-effectiveness target of about $58,400 per quality-adjusted life-year, she said.

Patients included in this study were adults with a mean age of 38 years and a mean age at disease onset of 31 years. Most (76%) were women. Disease duration was a mean of 7.7 years at baseline, and the patients had a mean of three relapses over the prior 2 years. Baseline EDSS score was 3.06.

“In 2002, the National Institute of Clinical Excellence [NICE], which is the U.K. body that sets the guidelines that decide what should be available under the National Health Service, concluded that beta-interferon and glatiramer acetate were not cost effective during the short-term, and thus it recommended that it couldn’t be available under the NHS at that stage,” Dr. Palace explained.

The NICE did notice, however, that if the drug effect was maintained over the long term it might be cost effective and invited the Department of Health to “try and find a way to make the drugs available in a cost-effective manner,” she said.

“This was the birth of the Risk-Sharing Scheme, and it is a way of providing disease-modifying therapies to patients cost effectively,” she said.

At the start of the scheme, the drug prices were reduced in line with a cost-effective requirement using the NICE model, which equated to about $58,400/quality-adjusted life-year..

“We were allowed to reach this target over a 20-year lifespan, and the idea was to monitor a clinical cohort of patients, measuring their EDSS scores,” she said.

The natural history dataset was used as a “virtual placebo,” and a price adjustment would be required if the outcomes of the treated patients were less than predicted to be on target for cost effectiveness.

The findings of this study – the largest observational study to measure the effect and cost-effectiveness of interferon beta-1a and glatiramer acetate – provide evidence that the treatment alters the natural history of relapsing-remitting MS in the real life setting, she concluded.

Dr. Palace reported receiving support for scientific meetings and honorariums for advisory work from Teva, which makes glatiramer acetate, and Bayer Schering, which makes interferon beta-1a, as well as other companies that market drugs for MS. She’s also received unrestricted grants from Bayer Schering and other companies that market drugs for MS.

BOSTON - Treatment with interferon beta-1a or glatiramer acetate, if used long term, has the potential to be cost effective and to alter the natural history of relapsing-remitting multiple sclerosis, according to findings from a 6-year observational study.

In 4,137 patients with relapsing-remitting MS who were followed for a median of 6 years, the observed increase in the Expanded Disability Status Scale (EDSS) scores was lower than the increase seen in a natural history cohort that served as a comparator group (relative rates, 0.76 using a continuous Markov model and 0.61 using a multilevel model). The observed progression for utility – a quality of life measure derived from the EDSS scores, and the primary outcome of the study – was consistent with this finding (relative rates of 0.58 and 0.56 according to the two models, respectively), Dr. Jacqueline Palace reported at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

The outcome – essentially a reduction of about 42% on the primary outcome measure, compared with the natural history cohort – was better than the 38% reduction that was predicted, said Dr. Palace, leader of the multiple sclerosis and neuromyelitis group at Oxford University Hospitals Trust in England.

A range of sensitivity analyses that examined the potential for various biases consistently demonstrated better outcomes in the treated patients, compared with the natural history cohort, Dr. Palace noted.

If sustained over 20 years, the magnitude of the treatment effect observed in this study would be consistent with a predefined cost-effectiveness target of about $58,400 per quality-adjusted life-year, she said.

Patients included in this study were adults with a mean age of 38 years and a mean age at disease onset of 31 years. Most (76%) were women. Disease duration was a mean of 7.7 years at baseline, and the patients had a mean of three relapses over the prior 2 years. Baseline EDSS score was 3.06.

“In 2002, the National Institute of Clinical Excellence [NICE], which is the U.K. body that sets the guidelines that decide what should be available under the National Health Service, concluded that beta-interferon and glatiramer acetate were not cost effective during the short-term, and thus it recommended that it couldn’t be available under the NHS at that stage,” Dr. Palace explained.

The NICE did notice, however, that if the drug effect was maintained over the long term it might be cost effective and invited the Department of Health to “try and find a way to make the drugs available in a cost-effective manner,” she said.

“This was the birth of the Risk-Sharing Scheme, and it is a way of providing disease-modifying therapies to patients cost effectively,” she said.

At the start of the scheme, the drug prices were reduced in line with a cost-effective requirement using the NICE model, which equated to about $58,400/quality-adjusted life-year..

“We were allowed to reach this target over a 20-year lifespan, and the idea was to monitor a clinical cohort of patients, measuring their EDSS scores,” she said.

The natural history dataset was used as a “virtual placebo,” and a price adjustment would be required if the outcomes of the treated patients were less than predicted to be on target for cost effectiveness.

The findings of this study – the largest observational study to measure the effect and cost-effectiveness of interferon beta-1a and glatiramer acetate – provide evidence that the treatment alters the natural history of relapsing-remitting MS in the real life setting, she concluded.

Dr. Palace reported receiving support for scientific meetings and honorariums for advisory work from Teva, which makes glatiramer acetate, and Bayer Schering, which makes interferon beta-1a, as well as other companies that market drugs for MS. She’s also received unrestricted grants from Bayer Schering and other companies that market drugs for MS.

BOSTON - Treatment with interferon beta-1a or glatiramer acetate, if used long term, has the potential to be cost effective and to alter the natural history of relapsing-remitting multiple sclerosis, according to findings from a 6-year observational study.

In 4,137 patients with relapsing-remitting MS who were followed for a median of 6 years, the observed increase in the Expanded Disability Status Scale (EDSS) scores was lower than the increase seen in a natural history cohort that served as a comparator group (relative rates, 0.76 using a continuous Markov model and 0.61 using a multilevel model). The observed progression for utility – a quality of life measure derived from the EDSS scores, and the primary outcome of the study – was consistent with this finding (relative rates of 0.58 and 0.56 according to the two models, respectively), Dr. Jacqueline Palace reported at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

The outcome – essentially a reduction of about 42% on the primary outcome measure, compared with the natural history cohort – was better than the 38% reduction that was predicted, said Dr. Palace, leader of the multiple sclerosis and neuromyelitis group at Oxford University Hospitals Trust in England.

A range of sensitivity analyses that examined the potential for various biases consistently demonstrated better outcomes in the treated patients, compared with the natural history cohort, Dr. Palace noted.

If sustained over 20 years, the magnitude of the treatment effect observed in this study would be consistent with a predefined cost-effectiveness target of about $58,400 per quality-adjusted life-year, she said.

Patients included in this study were adults with a mean age of 38 years and a mean age at disease onset of 31 years. Most (76%) were women. Disease duration was a mean of 7.7 years at baseline, and the patients had a mean of three relapses over the prior 2 years. Baseline EDSS score was 3.06.

“In 2002, the National Institute of Clinical Excellence [NICE], which is the U.K. body that sets the guidelines that decide what should be available under the National Health Service, concluded that beta-interferon and glatiramer acetate were not cost effective during the short-term, and thus it recommended that it couldn’t be available under the NHS at that stage,” Dr. Palace explained.

The NICE did notice, however, that if the drug effect was maintained over the long term it might be cost effective and invited the Department of Health to “try and find a way to make the drugs available in a cost-effective manner,” she said.

“This was the birth of the Risk-Sharing Scheme, and it is a way of providing disease-modifying therapies to patients cost effectively,” she said.

At the start of the scheme, the drug prices were reduced in line with a cost-effective requirement using the NICE model, which equated to about $58,400/quality-adjusted life-year..

“We were allowed to reach this target over a 20-year lifespan, and the idea was to monitor a clinical cohort of patients, measuring their EDSS scores,” she said.

The natural history dataset was used as a “virtual placebo,” and a price adjustment would be required if the outcomes of the treated patients were less than predicted to be on target for cost effectiveness.

The findings of this study – the largest observational study to measure the effect and cost-effectiveness of interferon beta-1a and glatiramer acetate – provide evidence that the treatment alters the natural history of relapsing-remitting MS in the real life setting, she concluded.

Dr. Palace reported receiving support for scientific meetings and honorariums for advisory work from Teva, which makes glatiramer acetate, and Bayer Schering, which makes interferon beta-1a, as well as other companies that market drugs for MS. She’s also received unrestricted grants from Bayer Schering and other companies that market drugs for MS.

BOSTON – The novel oral sphingosine 1-phosphate 1 receptor modulator RPC1063 safely and effectively reduced the cumulative number of total gadolinium-enhancing lesions in relapsing multiple sclerosis patients in phase II of the randomized, double-blind, placebo-controlled RADIANCE study.

At weeks 12-24 after treatment initiation, 87 patients who received 0.5 mg of RPC1063 and 83 patients who received a 1-mg dose experienced a highly significant 86% reduction in the number of gadolinium-enhancing (GdE) lesions on brain MRI, compared with 88 patients who received placebo (cumulative number of total lesions, 1.5 for both RPC1063 doses vs. 11.1 with placebo), Dr. Amit Bar-Or of the Montreal Neurological Institute and Hospital at McGill University reported at the joint meeting of the European and Americas committees on Treatment and Research in Multiple Sclerosis.

RPC1063 patients also fared significantly better on all secondary endpoints. For example, the mean number of GdE lesions at week 24 was reduced by 91% and 94% in patients who received 0.5 and 1 mg of RPC1063, respectively, compared with the number of lesions in those who received placebo (mean of 0.3 and 0.2 lesions, respectively, vs. 3.2 lesions). In addition, the cumulative number of new or enlarging T2 lesions from weeks 12-24 was reduced by 84% and 91% in the groups, respectively (suggesting a dose response), compared with the number in those who received placebo (cumulative number, 0.8 and 0.5 vs. 9.0).

The annualized relapse rate was 0.35 and 0.24 in the 0.5- and 1-mg dose groups, compared with 0.5 in the placebo group, representing 31% and 53% decreases, respectively. Although the study was not powered to detect an effect on the annualized relapse rate, this finding also hinted at a dose-response.

Immunomodulation through the sphingosine 1-phosphate receptor family is a validated therapeutic approach for the treatment of relapsing MS – the approved oral drug fingolimod (Gilenya) is a sphingosine 1-phosphate receptor modulator with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5 – but RPC1063 has been tested previously only in healthy volunteers. The phase II results of the combined phase II/III RADIANCE trial suggest it is safe and effective in patients with MS, Dr. Bar-Or said.

Study subjects were adults aged 18-55 years (mean of 39 years) with MS as diagnosed by the revised McDonald criteria who exhibited a relapsing clinical course consistent with relapsing disease. The patients had a history of brain MRI lesions consistent with MS, a baseline Expanded Disability Status Scale (EDSS) score between 0 and 5.0 points, and either one documented relapse within the last year, or at least one documented relapse in the past 2 years plus at least one GdE lesion.

All patients underwent a 30-day screening period prior to randomization, followed by a 7-day titration period to either 0.5 mg or 1 mg of active treatment or placebo for 24 weeks. During a blinded safety extension phase, all those who received placebo were randomized to receive 0.5 or 1 mg of RPC1036.

The completion rate was similarly high across all three groups (97.7%, 98.8%, and 96.6%, respectively).

Patients in the 0.5-mg and 1-mg groups experienced approximately 50% and 60% reductions in absolute lymphocyte count at week 24, compared with placebo.

Treatment-emergent adverse events (TEAEs) during the first 24 weeks of the study occurred in 64%, 57%, and 59% of patients in the 0.5-mg, 1-mg, and placebo groups, respectively. The most common TEAEs were nasopharyngitis, headache, and urinary tract infection. Only three serious TEAEs occurred: optic neuritis, somatoform autonomic dysfunction, and uterine cervical squamous metaplasia. All were in the 0.5-mg treatment group but were deemed unrelated to RPC1063.

“There were no notable cardiac, pulmonary, ophthalmologic, infectious, or malignancy-related TEAEs. Three TEAEs of liver enzyme abnormalities greater than or equal to three times the upper limit of normal were documented, but all of these occurred with no signs or symptoms associated,” said Dr. Bar-Or, noting that two occurred in the 0.5-mg group, one occurred in the 1-mg treatment group, and all resolved with continued treatment.

The exclusion criteria of the trial nearly matched those of the label contraindications for fingolimod without “any overt attempt of extending the exclusion,” Dr. Bar-Or said during a press conference. He noted that the RADIANCE trial’s week-long titration process also helped to mitigate any potential adverse events.

Both doses of RPC1063 demonstrated large, significant, and consistent reductions of all MRI measures of MS disease activity, with good overall tolerability and safety – including with respect to cardiac and hepatic safety results. The findings suggest a favorable risk-benefit profile in patients with relapsing MS, and they support the ongoing phase III portion of the RADIANCE trial, as well as a second phase III trial – SUNBEAM – which will compare RPC1063 and interferon beta-1a in relapsing MS, he concluded.

The trial was funded by Receptos. Dr. Bar-Or reported receiving financial support from Biogen Idec, DioGenix, Genentech, GlaxoSmithKline, Guthy-Jackson Charitable Foundation, MedImmune, Merck Serono, Novartis, Ono Pharmaceuticals, Receptos, Roche, Sanofi-Aventis, and Teva Neuroscience.

BOSTON – The novel oral sphingosine 1-phosphate 1 receptor modulator RPC1063 safely and effectively reduced the cumulative number of total gadolinium-enhancing lesions in relapsing multiple sclerosis patients in phase II of the randomized, double-blind, placebo-controlled RADIANCE study.

At weeks 12-24 after treatment initiation, 87 patients who received 0.5 mg of RPC1063 and 83 patients who received a 1-mg dose experienced a highly significant 86% reduction in the number of gadolinium-enhancing (GdE) lesions on brain MRI, compared with 88 patients who received placebo (cumulative number of total lesions, 1.5 for both RPC1063 doses vs. 11.1 with placebo), Dr. Amit Bar-Or of the Montreal Neurological Institute and Hospital at McGill University reported at the joint meeting of the European and Americas committees on Treatment and Research in Multiple Sclerosis.

RPC1063 patients also fared significantly better on all secondary endpoints. For example, the mean number of GdE lesions at week 24 was reduced by 91% and 94% in patients who received 0.5 and 1 mg of RPC1063, respectively, compared with the number of lesions in those who received placebo (mean of 0.3 and 0.2 lesions, respectively, vs. 3.2 lesions). In addition, the cumulative number of new or enlarging T2 lesions from weeks 12-24 was reduced by 84% and 91% in the groups, respectively (suggesting a dose response), compared with the number in those who received placebo (cumulative number, 0.8 and 0.5 vs. 9.0).

The annualized relapse rate was 0.35 and 0.24 in the 0.5- and 1-mg dose groups, compared with 0.5 in the placebo group, representing 31% and 53% decreases, respectively. Although the study was not powered to detect an effect on the annualized relapse rate, this finding also hinted at a dose-response.

Immunomodulation through the sphingosine 1-phosphate receptor family is a validated therapeutic approach for the treatment of relapsing MS – the approved oral drug fingolimod (Gilenya) is a sphingosine 1-phosphate receptor modulator with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5 – but RPC1063 has been tested previously only in healthy volunteers. The phase II results of the combined phase II/III RADIANCE trial suggest it is safe and effective in patients with MS, Dr. Bar-Or said.

Study subjects were adults aged 18-55 years (mean of 39 years) with MS as diagnosed by the revised McDonald criteria who exhibited a relapsing clinical course consistent with relapsing disease. The patients had a history of brain MRI lesions consistent with MS, a baseline Expanded Disability Status Scale (EDSS) score between 0 and 5.0 points, and either one documented relapse within the last year, or at least one documented relapse in the past 2 years plus at least one GdE lesion.

All patients underwent a 30-day screening period prior to randomization, followed by a 7-day titration period to either 0.5 mg or 1 mg of active treatment or placebo for 24 weeks. During a blinded safety extension phase, all those who received placebo were randomized to receive 0.5 or 1 mg of RPC1036.

The completion rate was similarly high across all three groups (97.7%, 98.8%, and 96.6%, respectively).

Patients in the 0.5-mg and 1-mg groups experienced approximately 50% and 60% reductions in absolute lymphocyte count at week 24, compared with placebo.

Treatment-emergent adverse events (TEAEs) during the first 24 weeks of the study occurred in 64%, 57%, and 59% of patients in the 0.5-mg, 1-mg, and placebo groups, respectively. The most common TEAEs were nasopharyngitis, headache, and urinary tract infection. Only three serious TEAEs occurred: optic neuritis, somatoform autonomic dysfunction, and uterine cervical squamous metaplasia. All were in the 0.5-mg treatment group but were deemed unrelated to RPC1063.

“There were no notable cardiac, pulmonary, ophthalmologic, infectious, or malignancy-related TEAEs. Three TEAEs of liver enzyme abnormalities greater than or equal to three times the upper limit of normal were documented, but all of these occurred with no signs or symptoms associated,” said Dr. Bar-Or, noting that two occurred in the 0.5-mg group, one occurred in the 1-mg treatment group, and all resolved with continued treatment.

The exclusion criteria of the trial nearly matched those of the label contraindications for fingolimod without “any overt attempt of extending the exclusion,” Dr. Bar-Or said during a press conference. He noted that the RADIANCE trial’s week-long titration process also helped to mitigate any potential adverse events.

Both doses of RPC1063 demonstrated large, significant, and consistent reductions of all MRI measures of MS disease activity, with good overall tolerability and safety – including with respect to cardiac and hepatic safety results. The findings suggest a favorable risk-benefit profile in patients with relapsing MS, and they support the ongoing phase III portion of the RADIANCE trial, as well as a second phase III trial – SUNBEAM – which will compare RPC1063 and interferon beta-1a in relapsing MS, he concluded.

The trial was funded by Receptos. Dr. Bar-Or reported receiving financial support from Biogen Idec, DioGenix, Genentech, GlaxoSmithKline, Guthy-Jackson Charitable Foundation, MedImmune, Merck Serono, Novartis, Ono Pharmaceuticals, Receptos, Roche, Sanofi-Aventis, and Teva Neuroscience.

BOSTON – The novel oral sphingosine 1-phosphate 1 receptor modulator RPC1063 safely and effectively reduced the cumulative number of total gadolinium-enhancing lesions in relapsing multiple sclerosis patients in phase II of the randomized, double-blind, placebo-controlled RADIANCE study.

At weeks 12-24 after treatment initiation, 87 patients who received 0.5 mg of RPC1063 and 83 patients who received a 1-mg dose experienced a highly significant 86% reduction in the number of gadolinium-enhancing (GdE) lesions on brain MRI, compared with 88 patients who received placebo (cumulative number of total lesions, 1.5 for both RPC1063 doses vs. 11.1 with placebo), Dr. Amit Bar-Or of the Montreal Neurological Institute and Hospital at McGill University reported at the joint meeting of the European and Americas committees on Treatment and Research in Multiple Sclerosis.

RPC1063 patients also fared significantly better on all secondary endpoints. For example, the mean number of GdE lesions at week 24 was reduced by 91% and 94% in patients who received 0.5 and 1 mg of RPC1063, respectively, compared with the number of lesions in those who received placebo (mean of 0.3 and 0.2 lesions, respectively, vs. 3.2 lesions). In addition, the cumulative number of new or enlarging T2 lesions from weeks 12-24 was reduced by 84% and 91% in the groups, respectively (suggesting a dose response), compared with the number in those who received placebo (cumulative number, 0.8 and 0.5 vs. 9.0).

The annualized relapse rate was 0.35 and 0.24 in the 0.5- and 1-mg dose groups, compared with 0.5 in the placebo group, representing 31% and 53% decreases, respectively. Although the study was not powered to detect an effect on the annualized relapse rate, this finding also hinted at a dose-response.

Immunomodulation through the sphingosine 1-phosphate receptor family is a validated therapeutic approach for the treatment of relapsing MS – the approved oral drug fingolimod (Gilenya) is a sphingosine 1-phosphate receptor modulator with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5 – but RPC1063 has been tested previously only in healthy volunteers. The phase II results of the combined phase II/III RADIANCE trial suggest it is safe and effective in patients with MS, Dr. Bar-Or said.

Study subjects were adults aged 18-55 years (mean of 39 years) with MS as diagnosed by the revised McDonald criteria who exhibited a relapsing clinical course consistent with relapsing disease. The patients had a history of brain MRI lesions consistent with MS, a baseline Expanded Disability Status Scale (EDSS) score between 0 and 5.0 points, and either one documented relapse within the last year, or at least one documented relapse in the past 2 years plus at least one GdE lesion.

All patients underwent a 30-day screening period prior to randomization, followed by a 7-day titration period to either 0.5 mg or 1 mg of active treatment or placebo for 24 weeks. During a blinded safety extension phase, all those who received placebo were randomized to receive 0.5 or 1 mg of RPC1036.

The completion rate was similarly high across all three groups (97.7%, 98.8%, and 96.6%, respectively).

Patients in the 0.5-mg and 1-mg groups experienced approximately 50% and 60% reductions in absolute lymphocyte count at week 24, compared with placebo.

Treatment-emergent adverse events (TEAEs) during the first 24 weeks of the study occurred in 64%, 57%, and 59% of patients in the 0.5-mg, 1-mg, and placebo groups, respectively. The most common TEAEs were nasopharyngitis, headache, and urinary tract infection. Only three serious TEAEs occurred: optic neuritis, somatoform autonomic dysfunction, and uterine cervical squamous metaplasia. All were in the 0.5-mg treatment group but were deemed unrelated to RPC1063.

“There were no notable cardiac, pulmonary, ophthalmologic, infectious, or malignancy-related TEAEs. Three TEAEs of liver enzyme abnormalities greater than or equal to three times the upper limit of normal were documented, but all of these occurred with no signs or symptoms associated,” said Dr. Bar-Or, noting that two occurred in the 0.5-mg group, one occurred in the 1-mg treatment group, and all resolved with continued treatment.

The exclusion criteria of the trial nearly matched those of the label contraindications for fingolimod without “any overt attempt of extending the exclusion,” Dr. Bar-Or said during a press conference. He noted that the RADIANCE trial’s week-long titration process also helped to mitigate any potential adverse events.

Both doses of RPC1063 demonstrated large, significant, and consistent reductions of all MRI measures of MS disease activity, with good overall tolerability and safety – including with respect to cardiac and hepatic safety results. The findings suggest a favorable risk-benefit profile in patients with relapsing MS, and they support the ongoing phase III portion of the RADIANCE trial, as well as a second phase III trial – SUNBEAM – which will compare RPC1063 and interferon beta-1a in relapsing MS, he concluded.

The trial was funded by Receptos. Dr. Bar-Or reported receiving financial support from Biogen Idec, DioGenix, Genentech, GlaxoSmithKline, Guthy-Jackson Charitable Foundation, MedImmune, Merck Serono, Novartis, Ono Pharmaceuticals, Receptos, Roche, Sanofi-Aventis, and Teva Neuroscience.

BOSTON—An electronic version of the Expanded Disability Status Scale (EDSS), the eEDSS, an algorithm-based, tablet-driven tool, is superior to the standard paper version in providing consistent assessments, according to the results of a validation study presented at the 2014 Joint ACTRIMS–ECTRIMS Meeting.

“By reducing noise, the eEDSS should have a positive impact on the accuracy of individual assessments and statistical power in clinical trials,” said Marcus D’Souza, MD, from the Department of Neurology, University Hospital, Basel, Switzerland, and colleagues.

The EDSS is the most widely used disability rating scale in multiple sclerosis (MS), but has been criticized for its low reliability. To improve reliability, a standardized version of the EDSS (Neurostatus) was established during the last two decades and is used in most major clinical studies, including many of the pivotal trials for regulatory approval of MS drugs.

To further improve EDSS reliability, Dr. D’Souza and colleagues developed the electronic capturing and real-time feedback EDSS (eEDSS), an algorithm-based evaluation performed with a tablet computer (iPad). The eEDSS provides immediate feedback, based on the Neurostatus definitions, indicating inconsistencies in the scoring of parts of the neurologic examination, functional systems, ambulation score, and EDSS. The final decision on the correct scores remains with the physician, who can overrule the algorithm. To validate their tool, the researchers compared results obtained with the standardized EDSS paper version (pEDSS) and the eEDSS.

Three certified EDSS raters who received training in the use of the eEDSS examined 100 patients with MS with varying degrees of neurologic deficits. Each patient was assessed twice. The first rater began by using the pEDSS and then switched to the eEDSS after seeing a third of the study population.

In parallel, the second EDSS rater assessed the same patients on the same day using the eEDSS and switched accordingly. pEDSS and eEDSS were compared for the frequency of inconsistencies in the assignment of the functional systems, ambulation score, and EDSS using generalized mixed-effects models and the exact McNemar test. Calculation of functional system scores based on Neurostatus Subscores were then checked by a third EDSS rater who was blinded for type of assessment, EDSS examiner, and patient.

For all examined end points, errors were more likely when using the pEDSS, compared with using the eEDSS. Examiners were three times as likely to make an error of any type when using the pEDSS, compared with using eEDSS (odds ratio, 2.93). Functional systems errors were more likely when pEDSS was used, compared with eEDSS (odds ratio, 2.54).

Errors were much more likely to occur for patients with low EDSS scores (3.5 or lower) than for those with high EDSS scores (3.5 or higher), with an odds ratio of 5.32. Errors in calculation of functional systems after exclusion of the cerebral functional system were much more likely when pEDSS was used, compared with eEDSS (odds ratio, 3.107). Ambulation score errors and EDSS errors were rare, and the differences between the pEDSS and eEDSS in the rates of these errors were not statistically significant.

—Glenn S. Williams

BOSTON—An electronic version of the Expanded Disability Status Scale (EDSS), the eEDSS, an algorithm-based, tablet-driven tool, is superior to the standard paper version in providing consistent assessments, according to the results of a validation study presented at the 2014 Joint ACTRIMS–ECTRIMS Meeting.

“By reducing noise, the eEDSS should have a positive impact on the accuracy of individual assessments and statistical power in clinical trials,” said Marcus D’Souza, MD, from the Department of Neurology, University Hospital, Basel, Switzerland, and colleagues.

The EDSS is the most widely used disability rating scale in multiple sclerosis (MS), but has been criticized for its low reliability. To improve reliability, a standardized version of the EDSS (Neurostatus) was established during the last two decades and is used in most major clinical studies, including many of the pivotal trials for regulatory approval of MS drugs.

To further improve EDSS reliability, Dr. D’Souza and colleagues developed the electronic capturing and real-time feedback EDSS (eEDSS), an algorithm-based evaluation performed with a tablet computer (iPad). The eEDSS provides immediate feedback, based on the Neurostatus definitions, indicating inconsistencies in the scoring of parts of the neurologic examination, functional systems, ambulation score, and EDSS. The final decision on the correct scores remains with the physician, who can overrule the algorithm. To validate their tool, the researchers compared results obtained with the standardized EDSS paper version (pEDSS) and the eEDSS.

Three certified EDSS raters who received training in the use of the eEDSS examined 100 patients with MS with varying degrees of neurologic deficits. Each patient was assessed twice. The first rater began by using the pEDSS and then switched to the eEDSS after seeing a third of the study population.

In parallel, the second EDSS rater assessed the same patients on the same day using the eEDSS and switched accordingly. pEDSS and eEDSS were compared for the frequency of inconsistencies in the assignment of the functional systems, ambulation score, and EDSS using generalized mixed-effects models and the exact McNemar test. Calculation of functional system scores based on Neurostatus Subscores were then checked by a third EDSS rater who was blinded for type of assessment, EDSS examiner, and patient.

For all examined end points, errors were more likely when using the pEDSS, compared with using the eEDSS. Examiners were three times as likely to make an error of any type when using the pEDSS, compared with using eEDSS (odds ratio, 2.93). Functional systems errors were more likely when pEDSS was used, compared with eEDSS (odds ratio, 2.54).

Errors were much more likely to occur for patients with low EDSS scores (3.5 or lower) than for those with high EDSS scores (3.5 or higher), with an odds ratio of 5.32. Errors in calculation of functional systems after exclusion of the cerebral functional system were much more likely when pEDSS was used, compared with eEDSS (odds ratio, 3.107). Ambulation score errors and EDSS errors were rare, and the differences between the pEDSS and eEDSS in the rates of these errors were not statistically significant.

—Glenn S. Williams

BOSTON—An electronic version of the Expanded Disability Status Scale (EDSS), the eEDSS, an algorithm-based, tablet-driven tool, is superior to the standard paper version in providing consistent assessments, according to the results of a validation study presented at the 2014 Joint ACTRIMS–ECTRIMS Meeting.

“By reducing noise, the eEDSS should have a positive impact on the accuracy of individual assessments and statistical power in clinical trials,” said Marcus D’Souza, MD, from the Department of Neurology, University Hospital, Basel, Switzerland, and colleagues.

The EDSS is the most widely used disability rating scale in multiple sclerosis (MS), but has been criticized for its low reliability. To improve reliability, a standardized version of the EDSS (Neurostatus) was established during the last two decades and is used in most major clinical studies, including many of the pivotal trials for regulatory approval of MS drugs.

To further improve EDSS reliability, Dr. D’Souza and colleagues developed the electronic capturing and real-time feedback EDSS (eEDSS), an algorithm-based evaluation performed with a tablet computer (iPad). The eEDSS provides immediate feedback, based on the Neurostatus definitions, indicating inconsistencies in the scoring of parts of the neurologic examination, functional systems, ambulation score, and EDSS. The final decision on the correct scores remains with the physician, who can overrule the algorithm. To validate their tool, the researchers compared results obtained with the standardized EDSS paper version (pEDSS) and the eEDSS.

Three certified EDSS raters who received training in the use of the eEDSS examined 100 patients with MS with varying degrees of neurologic deficits. Each patient was assessed twice. The first rater began by using the pEDSS and then switched to the eEDSS after seeing a third of the study population.

In parallel, the second EDSS rater assessed the same patients on the same day using the eEDSS and switched accordingly. pEDSS and eEDSS were compared for the frequency of inconsistencies in the assignment of the functional systems, ambulation score, and EDSS using generalized mixed-effects models and the exact McNemar test. Calculation of functional system scores based on Neurostatus Subscores were then checked by a third EDSS rater who was blinded for type of assessment, EDSS examiner, and patient.

For all examined end points, errors were more likely when using the pEDSS, compared with using the eEDSS. Examiners were three times as likely to make an error of any type when using the pEDSS, compared with using eEDSS (odds ratio, 2.93). Functional systems errors were more likely when pEDSS was used, compared with eEDSS (odds ratio, 2.54).

Errors were much more likely to occur for patients with low EDSS scores (3.5 or lower) than for those with high EDSS scores (3.5 or higher), with an odds ratio of 5.32. Errors in calculation of functional systems after exclusion of the cerebral functional system were much more likely when pEDSS was used, compared with eEDSS (odds ratio, 3.107). Ambulation score errors and EDSS errors were rare, and the differences between the pEDSS and eEDSS in the rates of these errors were not statistically significant.

—Glenn S. Williams

BOSTON – Age and any exposure to disease-modifying therapy were among the factors identified as independent predictors of the likelihood of conversion from clinically isolated syndrome to clinically definite multiple sclerosis in patients in a large prospective cohort study.

The findings could have important implications for treatment initiation in patients at higher risk of conversion, Dr. Tim Spelman said at a joint meeting of the Americas and European committees for Treatment and Research in Multiple Sclerosis. The logical extension of these findings would be to develop a risk calculator that considers the values for the predictors identified in this study, and that helps in the identification of patients who may benefit from closer monitoring and early treatment intervention.

Of 3,296 patients with clinically isolated syndrome who were enrolled in the MSBase Incident Study (MSBASIS) subset of the MSBase global registry, 1,953 (59%) experienced a second attack, marking the conversion to clinically definite disease. Age was one factor found to be significantly associated with conversion; for every additional 5 years of age at the time of clinically isolated syndrome (CIS), the likelihood of relapse was reduced by 10% (hazard ratio, 0.90), Dr. Spelman said.

Relapse risk was also lower in patients with any exposure to disease-modifying therapy compared with those with no such exposure (hazard ratio, 0.57), and in those with increasing proportion of follow-up time on disease-modifying therapy (hazard ratio, 0.35), said Dr. Spelman of the University of Melbourne, Parkville, Australia.

Having at least 1 T1 gadolinium enhancing lesion on cerebral magnetic resonance imaging was associated with an increased risk of relapse, compared with having no such lesions (hazard ratio, 1.25), and having at least 1 infratentorial and at least 1 juxtacortical lesion on cerebral MRI were also associated with an increased risk of relapse, compared with having no such lesions (hazard ratios of 1.23 and 1.21, respectively).

Finally, the presence of oligoclonal bands on baseline cerebrospinal fluid examination was also associated with an increased risk of relapse (hazard ratio, 1.52). Baseline spinal MRI lesion frequency was co-linear with oligoclonal banding in the CSF, Dr. Spelman said.

Patients in the study were recruited from 50 clinics in 22 different countries, contributing a total of 5,379 patient years of data with more than 30,000 observation points.

Dr. Spelman reported receiving honoraria for consultancy and funding for travel from Biogen Idec.

BOSTON – Age and any exposure to disease-modifying therapy were among the factors identified as independent predictors of the likelihood of conversion from clinically isolated syndrome to clinically definite multiple sclerosis in patients in a large prospective cohort study.

The findings could have important implications for treatment initiation in patients at higher risk of conversion, Dr. Tim Spelman said at a joint meeting of the Americas and European committees for Treatment and Research in Multiple Sclerosis. The logical extension of these findings would be to develop a risk calculator that considers the values for the predictors identified in this study, and that helps in the identification of patients who may benefit from closer monitoring and early treatment intervention.

Of 3,296 patients with clinically isolated syndrome who were enrolled in the MSBase Incident Study (MSBASIS) subset of the MSBase global registry, 1,953 (59%) experienced a second attack, marking the conversion to clinically definite disease. Age was one factor found to be significantly associated with conversion; for every additional 5 years of age at the time of clinically isolated syndrome (CIS), the likelihood of relapse was reduced by 10% (hazard ratio, 0.90), Dr. Spelman said.

Relapse risk was also lower in patients with any exposure to disease-modifying therapy compared with those with no such exposure (hazard ratio, 0.57), and in those with increasing proportion of follow-up time on disease-modifying therapy (hazard ratio, 0.35), said Dr. Spelman of the University of Melbourne, Parkville, Australia.

Having at least 1 T1 gadolinium enhancing lesion on cerebral magnetic resonance imaging was associated with an increased risk of relapse, compared with having no such lesions (hazard ratio, 1.25), and having at least 1 infratentorial and at least 1 juxtacortical lesion on cerebral MRI were also associated with an increased risk of relapse, compared with having no such lesions (hazard ratios of 1.23 and 1.21, respectively).

Finally, the presence of oligoclonal bands on baseline cerebrospinal fluid examination was also associated with an increased risk of relapse (hazard ratio, 1.52). Baseline spinal MRI lesion frequency was co-linear with oligoclonal banding in the CSF, Dr. Spelman said.

Patients in the study were recruited from 50 clinics in 22 different countries, contributing a total of 5,379 patient years of data with more than 30,000 observation points.

Dr. Spelman reported receiving honoraria for consultancy and funding for travel from Biogen Idec.

BOSTON – Age and any exposure to disease-modifying therapy were among the factors identified as independent predictors of the likelihood of conversion from clinically isolated syndrome to clinically definite multiple sclerosis in patients in a large prospective cohort study.

The findings could have important implications for treatment initiation in patients at higher risk of conversion, Dr. Tim Spelman said at a joint meeting of the Americas and European committees for Treatment and Research in Multiple Sclerosis. The logical extension of these findings would be to develop a risk calculator that considers the values for the predictors identified in this study, and that helps in the identification of patients who may benefit from closer monitoring and early treatment intervention.

Of 3,296 patients with clinically isolated syndrome who were enrolled in the MSBase Incident Study (MSBASIS) subset of the MSBase global registry, 1,953 (59%) experienced a second attack, marking the conversion to clinically definite disease. Age was one factor found to be significantly associated with conversion; for every additional 5 years of age at the time of clinically isolated syndrome (CIS), the likelihood of relapse was reduced by 10% (hazard ratio, 0.90), Dr. Spelman said.

Relapse risk was also lower in patients with any exposure to disease-modifying therapy compared with those with no such exposure (hazard ratio, 0.57), and in those with increasing proportion of follow-up time on disease-modifying therapy (hazard ratio, 0.35), said Dr. Spelman of the University of Melbourne, Parkville, Australia.

Having at least 1 T1 gadolinium enhancing lesion on cerebral magnetic resonance imaging was associated with an increased risk of relapse, compared with having no such lesions (hazard ratio, 1.25), and having at least 1 infratentorial and at least 1 juxtacortical lesion on cerebral MRI were also associated with an increased risk of relapse, compared with having no such lesions (hazard ratios of 1.23 and 1.21, respectively).

Finally, the presence of oligoclonal bands on baseline cerebrospinal fluid examination was also associated with an increased risk of relapse (hazard ratio, 1.52). Baseline spinal MRI lesion frequency was co-linear with oligoclonal banding in the CSF, Dr. Spelman said.

Patients in the study were recruited from 50 clinics in 22 different countries, contributing a total of 5,379 patient years of data with more than 30,000 observation points.

Dr. Spelman reported receiving honoraria for consultancy and funding for travel from Biogen Idec.

BOSTON – The efficacy of alemtuzumab was maintained at 4-year follow-up in patients who had active relapsing-remitting multiple sclerosis and relapsed on prior therapy, according to findings from the extension phase of the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS II) study.

Response was maintained even though most of the 393 patients in the extension study had not received either alemtuzumab or any other disease modifying therapy during the 3 years after they received two courses of alemtuzumab as part of the core CARE-MS II study – a phase 3, randomized comparison of alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a), Dr. Hans-Peter Hartung of Heinrich-Heine University, Dusseldorf, Germany and his colleagues reported in a poster at the joint Americas and European committees on Treatment and Research in MS conference.

In the core CARE-MS II trial, annual treatment with alemtuzumab – a humanized anti-CD52 monoclonal antibody – reduced the annualized relapse rate by 49% (from 0.52 to 0.26), and reduced the rate of sustained accumulation of disability by 42%, compared with SC IFNB-1a (Rebif) at 2 years. Alemtuzumab is not approved in the United States for MS, although it is approved for MS in more than 30 other countries. Alemtuzumab was withdrawn from the market by Genzyme in the form of brand name Campath, indicated for a type of leukemia, when it was being developed for MS.

In 393 patients who were in the alemtuzumab 12-mg arm of the core study and enrolled in the extension study (93% of the population), the annualized relapse rate was 0.22 at 3 years, and 0.23 at 4 years (mean of 0.24 for years 0-4). Disability, as assessed by change in the Expanded Disability Status Scale score, remained stable or improved from baseline; 69%, 66%, and 67% of patients improved or remained stable from years 0-3, 0-4, and 3-4, respectively, the researchers reported.
“At year 4, 71% and 76% of alemtuzumab-treated patients were sustained accumulation of disability-free by 3- and 6-month sustained disability criteria, respectively,” they wrote.

Over the 4 years of the extension study, 68% of the patients received only the initial two annual courses of alemtuzumab; 24% received one additional course, 7% received two additional courses, and 5% received another disease-modifying therapy.

In 146 patients who were in the SC IFNB-1a 44 mcg arm of the core study and enrolled in the extension study (83%), 143 crossed over to alemtuzumab, and 131 of them received 2 courses. The annualized relapse rate in those who received alemtuzumab decreased by 71% at 4 years (from 0.52 to 0.15), and the Expanded Disability Status Scale scores at 2 years either remained stable or improved in 69% of patients.

“Two years after switching to alemtuzumab, the proportion of patients experiencing 3-month sustained accumulation of disability or 6-month sustained accumulation of disability were 15% and 11%, respectively, compared with 23% and 21% during the 2 years of SC IFNB-1a in CARE-MS II,” the researchers reported.

No unexpected adverse events occurred in either group during the extension study, and the safety profile among those who switched from SC IFNB-1a was similar to that in patients who received alemtuzumab for all 4 years.

“These findings augment previously reported data in support of the durable efficacy and positive benefit-risk profile for alemtuzumab in relapsing-remitting multiple sclerosis patients who relapsed on prior therapy,” the investigators concluded.

BOSTON – The efficacy of alemtuzumab was maintained at 4-year follow-up in patients who had active relapsing-remitting multiple sclerosis and relapsed on prior therapy, according to findings from the extension phase of the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS II) study.

Response was maintained even though most of the 393 patients in the extension study had not received either alemtuzumab or any other disease modifying therapy during the 3 years after they received two courses of alemtuzumab as part of the core CARE-MS II study – a phase 3, randomized comparison of alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a), Dr. Hans-Peter Hartung of Heinrich-Heine University, Dusseldorf, Germany and his colleagues reported in a poster at the joint Americas and European committees on Treatment and Research in MS conference.

In the core CARE-MS II trial, annual treatment with alemtuzumab – a humanized anti-CD52 monoclonal antibody – reduced the annualized relapse rate by 49% (from 0.52 to 0.26), and reduced the rate of sustained accumulation of disability by 42%, compared with SC IFNB-1a (Rebif) at 2 years. Alemtuzumab is not approved in the United States for MS, although it is approved for MS in more than 30 other countries. Alemtuzumab was withdrawn from the market by Genzyme in the form of brand name Campath, indicated for a type of leukemia, when it was being developed for MS.

In 393 patients who were in the alemtuzumab 12-mg arm of the core study and enrolled in the extension study (93% of the population), the annualized relapse rate was 0.22 at 3 years, and 0.23 at 4 years (mean of 0.24 for years 0-4). Disability, as assessed by change in the Expanded Disability Status Scale score, remained stable or improved from baseline; 69%, 66%, and 67% of patients improved or remained stable from years 0-3, 0-4, and 3-4, respectively, the researchers reported.
“At year 4, 71% and 76% of alemtuzumab-treated patients were sustained accumulation of disability-free by 3- and 6-month sustained disability criteria, respectively,” they wrote.

Over the 4 years of the extension study, 68% of the patients received only the initial two annual courses of alemtuzumab; 24% received one additional course, 7% received two additional courses, and 5% received another disease-modifying therapy.

In 146 patients who were in the SC IFNB-1a 44 mcg arm of the core study and enrolled in the extension study (83%), 143 crossed over to alemtuzumab, and 131 of them received 2 courses. The annualized relapse rate in those who received alemtuzumab decreased by 71% at 4 years (from 0.52 to 0.15), and the Expanded Disability Status Scale scores at 2 years either remained stable or improved in 69% of patients.

“Two years after switching to alemtuzumab, the proportion of patients experiencing 3-month sustained accumulation of disability or 6-month sustained accumulation of disability were 15% and 11%, respectively, compared with 23% and 21% during the 2 years of SC IFNB-1a in CARE-MS II,” the researchers reported.

No unexpected adverse events occurred in either group during the extension study, and the safety profile among those who switched from SC IFNB-1a was similar to that in patients who received alemtuzumab for all 4 years.

“These findings augment previously reported data in support of the durable efficacy and positive benefit-risk profile for alemtuzumab in relapsing-remitting multiple sclerosis patients who relapsed on prior therapy,” the investigators concluded.

BOSTON – The efficacy of alemtuzumab was maintained at 4-year follow-up in patients who had active relapsing-remitting multiple sclerosis and relapsed on prior therapy, according to findings from the extension phase of the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS II) study.

Response was maintained even though most of the 393 patients in the extension study had not received either alemtuzumab or any other disease modifying therapy during the 3 years after they received two courses of alemtuzumab as part of the core CARE-MS II study – a phase 3, randomized comparison of alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a), Dr. Hans-Peter Hartung of Heinrich-Heine University, Dusseldorf, Germany and his colleagues reported in a poster at the joint Americas and European committees on Treatment and Research in MS conference.

In the core CARE-MS II trial, annual treatment with alemtuzumab – a humanized anti-CD52 monoclonal antibody – reduced the annualized relapse rate by 49% (from 0.52 to 0.26), and reduced the rate of sustained accumulation of disability by 42%, compared with SC IFNB-1a (Rebif) at 2 years. Alemtuzumab is not approved in the United States for MS, although it is approved for MS in more than 30 other countries. Alemtuzumab was withdrawn from the market by Genzyme in the form of brand name Campath, indicated for a type of leukemia, when it was being developed for MS.

In 393 patients who were in the alemtuzumab 12-mg arm of the core study and enrolled in the extension study (93% of the population), the annualized relapse rate was 0.22 at 3 years, and 0.23 at 4 years (mean of 0.24 for years 0-4). Disability, as assessed by change in the Expanded Disability Status Scale score, remained stable or improved from baseline; 69%, 66%, and 67% of patients improved or remained stable from years 0-3, 0-4, and 3-4, respectively, the researchers reported.
“At year 4, 71% and 76% of alemtuzumab-treated patients were sustained accumulation of disability-free by 3- and 6-month sustained disability criteria, respectively,” they wrote.

Over the 4 years of the extension study, 68% of the patients received only the initial two annual courses of alemtuzumab; 24% received one additional course, 7% received two additional courses, and 5% received another disease-modifying therapy.

In 146 patients who were in the SC IFNB-1a 44 mcg arm of the core study and enrolled in the extension study (83%), 143 crossed over to alemtuzumab, and 131 of them received 2 courses. The annualized relapse rate in those who received alemtuzumab decreased by 71% at 4 years (from 0.52 to 0.15), and the Expanded Disability Status Scale scores at 2 years either remained stable or improved in 69% of patients.

“Two years after switching to alemtuzumab, the proportion of patients experiencing 3-month sustained accumulation of disability or 6-month sustained accumulation of disability were 15% and 11%, respectively, compared with 23% and 21% during the 2 years of SC IFNB-1a in CARE-MS II,” the researchers reported.

No unexpected adverse events occurred in either group during the extension study, and the safety profile among those who switched from SC IFNB-1a was similar to that in patients who received alemtuzumab for all 4 years.

“These findings augment previously reported data in support of the durable efficacy and positive benefit-risk profile for alemtuzumab in relapsing-remitting multiple sclerosis patients who relapsed on prior therapy,” the investigators concluded.

BOSTON – When trying to predict how quickly high-risk patients with clinically isolated syndrome may convert to clinically definite multiple sclerosis, consider age at onset, disease-modifying drug use, MRI lesion load, and the presence of cerebrospinal fluid oligoclonal bands, according to Dr. Tim Spelman.
 
Dr. Spelman and his colleagues analyzed the MSBase Incident Study subset of high-risk patients from the MSBase Registry to conduct the largest longitudinal, prospective study of patients followed from onset of clinically isolated syndrome (CIS).

Older age at CIS was protective for conversion to clinically definite MS. The basis for how older age at onset lowers risk “is still somewhat of a mystery because the variable itself doesn’t correlate with other known predictors like oligoclonal bands, MRI, EDSS [Expanded Disease Status Scale],” Dr. Spelman said in a video interview at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis. Spinal lesions on MRI also tended to capture about the same amount of risk at baseline as did oligoclonal bands, he noted. Treatment with disease-modifying drugs (DMDs) extended the median time to conversion from 11 months without treatment to 4 years with treatment, regardless of the DMD type or duration.

With all of these predictors assembled, the next phase is to develop a risk calculator, said Dr. Spelman of the Melbourne Brain Centre at the Royal Melbourne Hospital in Parkville, Australia.

jevans@frontlinemedcom.com

BOSTON – When trying to predict how quickly high-risk patients with clinically isolated syndrome may convert to clinically definite multiple sclerosis, consider age at onset, disease-modifying drug use, MRI lesion load, and the presence of cerebrospinal fluid oligoclonal bands, according to Dr. Tim Spelman.
 
Dr. Spelman and his colleagues analyzed the MSBase Incident Study subset of high-risk patients from the MSBase Registry to conduct the largest longitudinal, prospective study of patients followed from onset of clinically isolated syndrome (CIS).

Older age at CIS was protective for conversion to clinically definite MS. The basis for how older age at onset lowers risk “is still somewhat of a mystery because the variable itself doesn’t correlate with other known predictors like oligoclonal bands, MRI, EDSS [Expanded Disease Status Scale],” Dr. Spelman said in a video interview at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis. Spinal lesions on MRI also tended to capture about the same amount of risk at baseline as did oligoclonal bands, he noted. Treatment with disease-modifying drugs (DMDs) extended the median time to conversion from 11 months without treatment to 4 years with treatment, regardless of the DMD type or duration.

With all of these predictors assembled, the next phase is to develop a risk calculator, said Dr. Spelman of the Melbourne Brain Centre at the Royal Melbourne Hospital in Parkville, Australia.

jevans@frontlinemedcom.com

BOSTON – When trying to predict how quickly high-risk patients with clinically isolated syndrome may convert to clinically definite multiple sclerosis, consider age at onset, disease-modifying drug use, MRI lesion load, and the presence of cerebrospinal fluid oligoclonal bands, according to Dr. Tim Spelman.
 
Dr. Spelman and his colleagues analyzed the MSBase Incident Study subset of high-risk patients from the MSBase Registry to conduct the largest longitudinal, prospective study of patients followed from onset of clinically isolated syndrome (CIS).

Older age at CIS was protective for conversion to clinically definite MS. The basis for how older age at onset lowers risk “is still somewhat of a mystery because the variable itself doesn’t correlate with other known predictors like oligoclonal bands, MRI, EDSS [Expanded Disease Status Scale],” Dr. Spelman said in a video interview at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis. Spinal lesions on MRI also tended to capture about the same amount of risk at baseline as did oligoclonal bands, he noted. Treatment with disease-modifying drugs (DMDs) extended the median time to conversion from 11 months without treatment to 4 years with treatment, regardless of the DMD type or duration.

With all of these predictors assembled, the next phase is to develop a risk calculator, said Dr. Spelman of the Melbourne Brain Centre at the Royal Melbourne Hospital in Parkville, Australia.

jevans@frontlinemedcom.com

BOSTON – The International Progressive MS Alliance has announced the first round of grants to fund groundbreaking research on progressive forms of multiple sclerosis.

A panel of more than 40 experts in multiple sclerosis (MS) reviewed 195 research proposals received from 22 countries. The panel chose to make 22 “challenge” grants to researchers in nine countries. The grants will fund 1- to 2-year pilot studies that represent the first steps in a program that will cumulatively invest nearly $30 million over a 5-year period.

“This is the first time we’ve had a truly global, international initiative,” said Dr. Alan Thompson, chair of the alliance’s scientific steering committee and a neurologist and professor at University College London Faculty on Brain Sciences. “It’s much more about being a catalyst to bring together the best institutions worldwide.”

The announcement was made at a press conference held during the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis, although the press conference was not officially part of the meeting.

Seven of the grants were made to researchers investigating potential new treatments as well as biomarkers and outcome measures that could be used to track disease progression in clinical trials. Another seven funded studies will seek to understand the underlying cause of progressive disease. One grant-winning study aims to discover biomarkers that reflect progression pathophysiology for primary progressive MS.

Three studies will investigate the genetics of progressive subtypes of MS. Two will be used to develop animal models of progressive MS. Two will investigate new rehabilitative methods for patients with progressive disease.

The next step is for the alliance to provide 4 years of funding for a global, collaborative research network of about 10 centers. The next call for research proposals will come at the beginning of November 2014.

In a video interview, we spoke with one of the grant award winners, Francisco Quintana, Ph.D., of Brigham and Women’s Hospital, Boston, about his research proposal and views on the initiative.

jevans@frontlinemedcom.com

BOSTON – The International Progressive MS Alliance has announced the first round of grants to fund groundbreaking research on progressive forms of multiple sclerosis.

A panel of more than 40 experts in multiple sclerosis (MS) reviewed 195 research proposals received from 22 countries. The panel chose to make 22 “challenge” grants to researchers in nine countries. The grants will fund 1- to 2-year pilot studies that represent the first steps in a program that will cumulatively invest nearly $30 million over a 5-year period.

“This is the first time we’ve had a truly global, international initiative,” said Dr. Alan Thompson, chair of the alliance’s scientific steering committee and a neurologist and professor at University College London Faculty on Brain Sciences. “It’s much more about being a catalyst to bring together the best institutions worldwide.”

The announcement was made at a press conference held during the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis, although the press conference was not officially part of the meeting.

Seven of the grants were made to researchers investigating potential new treatments as well as biomarkers and outcome measures that could be used to track disease progression in clinical trials. Another seven funded studies will seek to understand the underlying cause of progressive disease. One grant-winning study aims to discover biomarkers that reflect progression pathophysiology for primary progressive MS.

Three studies will investigate the genetics of progressive subtypes of MS. Two will be used to develop animal models of progressive MS. Two will investigate new rehabilitative methods for patients with progressive disease.

The next step is for the alliance to provide 4 years of funding for a global, collaborative research network of about 10 centers. The next call for research proposals will come at the beginning of November 2014.

In a video interview, we spoke with one of the grant award winners, Francisco Quintana, Ph.D., of Brigham and Women’s Hospital, Boston, about his research proposal and views on the initiative.

jevans@frontlinemedcom.com

BOSTON – The International Progressive MS Alliance has announced the first round of grants to fund groundbreaking research on progressive forms of multiple sclerosis.

A panel of more than 40 experts in multiple sclerosis (MS) reviewed 195 research proposals received from 22 countries. The panel chose to make 22 “challenge” grants to researchers in nine countries. The grants will fund 1- to 2-year pilot studies that represent the first steps in a program that will cumulatively invest nearly $30 million over a 5-year period.

“This is the first time we’ve had a truly global, international initiative,” said Dr. Alan Thompson, chair of the alliance’s scientific steering committee and a neurologist and professor at University College London Faculty on Brain Sciences. “It’s much more about being a catalyst to bring together the best institutions worldwide.”

The announcement was made at a press conference held during the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis, although the press conference was not officially part of the meeting.

Seven of the grants were made to researchers investigating potential new treatments as well as biomarkers and outcome measures that could be used to track disease progression in clinical trials. Another seven funded studies will seek to understand the underlying cause of progressive disease. One grant-winning study aims to discover biomarkers that reflect progression pathophysiology for primary progressive MS.

Three studies will investigate the genetics of progressive subtypes of MS. Two will be used to develop animal models of progressive MS. Two will investigate new rehabilitative methods for patients with progressive disease.

The next step is for the alliance to provide 4 years of funding for a global, collaborative research network of about 10 centers. The next call for research proposals will come at the beginning of November 2014.

In a video interview, we spoke with one of the grant award winners, Francisco Quintana, Ph.D., of Brigham and Women’s Hospital, Boston, about his research proposal and views on the initiative.

jevans@frontlinemedcom.com

BOSTON – 3-Tesla axial MR imaging in patients with multiple sclerosis can reveal important information about the extent of lesions in the cervical spinal cord that differentiates milder forms of disease from progressive subtypes, according to new research presented by Dr. Hugh Kearney at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

While most MRI studies of the cervical spinal cord have used sagittal views to determine the number of lesions, axial views can show the extent of lesions and the involvement of gray matter that goes unseen with sagittal views, Dr. Kearney, a researcher at the University College London Institute of Neurology, said in a video interview.

In a study of 120 patients, Dr. Kearney and his colleagues found that this MRI technique, which used a fine resolution of 0.5-by-0.5 mm², detected extensive focal lesions involving multiple white matter columns significantly more often among patients with progressive subtypes of MS, whereas patients with relapsing remitting disease or clinically isolated syndrome tended to have lesions usually limited to a single spinal cord column. Patients with progressive subtypes also more commonly had involvement of the gray matter and diffuse abnormalities. The presence of lateral column lesions involving gray matter and the number of columns involved was an independent predictor of disability on the Expanded Disability Status Scale.

jevans@frontlinemedcom.com

BOSTON – 3-Tesla axial MR imaging in patients with multiple sclerosis can reveal important information about the extent of lesions in the cervical spinal cord that differentiates milder forms of disease from progressive subtypes, according to new research presented by Dr. Hugh Kearney at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

While most MRI studies of the cervical spinal cord have used sagittal views to determine the number of lesions, axial views can show the extent of lesions and the involvement of gray matter that goes unseen with sagittal views, Dr. Kearney, a researcher at the University College London Institute of Neurology, said in a video interview.

In a study of 120 patients, Dr. Kearney and his colleagues found that this MRI technique, which used a fine resolution of 0.5-by-0.5 mm², detected extensive focal lesions involving multiple white matter columns significantly more often among patients with progressive subtypes of MS, whereas patients with relapsing remitting disease or clinically isolated syndrome tended to have lesions usually limited to a single spinal cord column. Patients with progressive subtypes also more commonly had involvement of the gray matter and diffuse abnormalities. The presence of lateral column lesions involving gray matter and the number of columns involved was an independent predictor of disability on the Expanded Disability Status Scale.

jevans@frontlinemedcom.com

BOSTON – 3-Tesla axial MR imaging in patients with multiple sclerosis can reveal important information about the extent of lesions in the cervical spinal cord that differentiates milder forms of disease from progressive subtypes, according to new research presented by Dr. Hugh Kearney at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

While most MRI studies of the cervical spinal cord have used sagittal views to determine the number of lesions, axial views can show the extent of lesions and the involvement of gray matter that goes unseen with sagittal views, Dr. Kearney, a researcher at the University College London Institute of Neurology, said in a video interview.

In a study of 120 patients, Dr. Kearney and his colleagues found that this MRI technique, which used a fine resolution of 0.5-by-0.5 mm², detected extensive focal lesions involving multiple white matter columns significantly more often among patients with progressive subtypes of MS, whereas patients with relapsing remitting disease or clinically isolated syndrome tended to have lesions usually limited to a single spinal cord column. Patients with progressive subtypes also more commonly had involvement of the gray matter and diffuse abnormalities. The presence of lateral column lesions involving gray matter and the number of columns involved was an independent predictor of disability on the Expanded Disability Status Scale.

jevans@frontlinemedcom.com