Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Oral contraceptives combined with interferon β in multiple sclerosis

Objective: To test the effect of oral contraceptives (OCs) in combination with interferon b (IFN-b) on disease activity in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: One hundred fifty women with RRMS were randomized in a 1:1:1 ratio to receive IFNb-1a subcutaneously (SC) only (group 1), IFN-b-1a SC plus ethinylstradiol 20 mg and desogestrel 150 mg (group 2), or IFN-b-1a SC plus ethinylestradiol 40 mg and desogestrel 125 mg (group 3). The primary endpoint was the cumulative number of combined unique active (CUA) lesions on brain MRI at week 96. Secondary endpoints included MRI and clinical and safety measures. Results: The estimated number of cumulative CUA lesions at week 96 was 0.98 (95% confidence interval [CI] 0.81–1.14) in group 1, 0.84 (95% CI 0.66–1.02) in group 2, and 0.72 (95% CI 0.53–0.91) in group 3, with a decrease of 14.1% (p 5 0.24) and 26.5% (p 5 0.04) when comparing group 1 with groups 2 and 3, respectively. The number of patients with no gadoliniumenhancing lesions was greater in group 3 than in group 1 (p 5 0.03). No significant differences were detected in other secondary endpoints. IFN-b or OC discontinuations were equally distributed across groups. Conclusions: Our results translate the observations derived from experimental models to patients, supporting the anti-inflammatory effects of OCs with high-dose estrogens, and suggest possible directions for future research

Prognostic factors for long-term outcomes in relapsing-remitting multiple sclerosis

Objective: The objective of this article is to investigate potential clinical and MRI predictors of long-term outcomes in multiple sclerosis (MS). Methods: This was a post hoc analysis using data from all 382 patients in the PRISMS long-term follow-up (LTFU) study collected up to eight years after randomisation. An additional analysis was performed including only those patients originally randomised to receive early subcutaneous interferon (IFN) β-1a (n = 259). Baseline/prestudy variables, indicators of early clinical and MRI activity (baseline to month 24), and indicators of IFN β-1a treatment exposure (including medication possession ratio (MPR)) were investigated as candidate prognostic factors for outcomes measured from baseline and from month 24 to LTFU. Explanatory variables identified from univariate regression models (p ≤ 0.15) were selected for inclusion in stepwise multiple regression models. Results: Candidate prognostic factors selected by the univariate analysis (p ≤ 0.15) included age, MS duration, baseline brain volume, EDSS score, and log(T2 burden of disease (BOD)). In most of the multivariate regression models applied, higher baseline brain volume and MPR predicted better long-term clinical outcomes, while higher baseline and greater early increase in EDSS score predicted worse outcomes. Conclusion: Identification of markers that may be prognostic for long-term disability could help identify MS patients at higher risk of disability progression

Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis

Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biologics. Although there is consensus that these therapies reduce the frequency of relapses, their relative benefit in delaying new relapses or disability worsening remains unclear due to the limited number of direct comparison trials

Brain health: time matters in multiple sclerosis

publisher: Elsevier articletitle: Brain health: time matters in multiple sclerosis journaltitle: Multiple Sclerosis and Related Disorders articlelink: http://dx.doi.org/10.1016/j.msard.2016.07.003 content_type: article copyright: © 2016 Oxford PharmaGenesis Ltd. Published by Elsevier B.V

Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as “lack of efficacy” (3.3% vs. 1.7%), “scheduled stop” (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from “real-world” database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry

The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis.

The recently completed European trial of interferon beta-1b (IFNβ-1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T1-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9%, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1%, IFNβ-1b 1.8%, P < 0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFNβ-1b (placebo 2.6%, IFNβ-1b 3.7%; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFNβ. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFNβ-treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced diseas

香港華人多發性硬化症的流行病學研究：問卷調查

OBJECTIVE: To study the epidemiology of multiple sclerosis in Hong Kong Chinese. DESIGN: Cross-sectional questionnaire survey. SETTING: Neurology and paediatric neurology departments in Hong Kong from January through June 1999. PARTICIPANTS: All confirmed multiple sclerosis patients. MAIN OUTCOME MEASURES: Demographic data, investigation results, Kurtzke's Expanded Disability Status Scale during the last follow-up visit, number of relapses between 1997 and 1998, and treatments used/currently in use. RESULTS: Fifty-three Chinese multiple sclerosis patients were identified. The prevalence was thus estimated to be 0.77 per 100,000 population. This low prevalence was also noted in other multiple sclerosis studies from South-East Asia (range, 0.8-4 per 100,000 population). The female to male ratio among the Chinese multiple sclerosis sufferers was 9.6:1, a figure somewhat higher than that reported in the other studies from South-East Asia (range, 3.2-6.6:1). The Chinese multiple sclerosis patients in this study also had a high spinal cord involvement (66%) and a low presence of cerebrospinal fluid oligoclonal banding (40%). These findings were different from those in Caucasian multiple sclerosis patients. CONCLUSION: Multiple sclerosis in Hong Kong Chinese has a low prevalence, a high female to male ratio, and a low cerebrospinal fluid oligoclonal banding presence.published_or_final_versio

Multiple sclerosis, the measurement of disability and access to clinical trial data

Background: Inferences about long-term effects of therapies in multiple sclerosis (MS) have been based on surrogate markers studied in short-term trials. Nevertheless, MS trials have been getting steadily shorter despite the lack of a consensus definition for the most important clinical outcome - unremitting progression of disability. Methods: We have examined widely used surrogate markers of disability progression in MS within a unique database of individual patient data from the placebo arms of 31 randomised clinical trials. Findings: Definitions of treatment failure used in secondary progressive MS trials include much change unrelated to the target of unremitting disability. In relapsing-remitting MS, disability progression by treatment failure definitions was no more likely than similarly defined improvement for these disability surrogates. Existing definitions of disease progression in relapsing-remitting trials encompass random variation, measurement error and remitting relapses and appear not to measure unremitting disability. Interpretation: Clinical surrogates of unremitting disability used in relapsing -remitting trials cannot be validated. Trials have been too short and/or degrees of disability change too small to evaluate unremitting disability outcomes. Important implications for trial design and reinterpretation of existing trial results have emerged long after regulatory approval and widespread use of therapies in MS, highlighting the necessity of having primary trial data in the public domain