ArticlesPlacebo-controlled multicentre randomised trial of interferon β-1b in treatment of secondary progressive multiple sclerosis
Introduction
In 1993, interferon β-1b emerged as a therapeutic option in multiple sclerosis (MS) and has been hailed as a major advance in the management of this disorder.1 Three products containing interferon β are available, and phase III trials for each product have shown a reduction in relapse rate by 18–34% in patients with relapsing-remitting MS.1, 2, 3 This reduction in disease activity was associated with a striking effect on abnormalities detected by magnetic resonance imaging (MRI), particularly on the development of new and contrast enhancing lesions.
A major concern of patients with MS and their physicians, is accrual of disability when the disease has reached the secondary-progressive (SP-MS) phase. In SP-MS, disability becomes the dominant factor and determines the level of support required and costs incurred.4 Three studies1, 2, 3 have given some indication of an effect of interferon β on the accrual of disability but such an effect was difficult to address persuasively: the patient groups studied were in the early stage of the disease with little if any disability, reflected by low Expanded Disability Status Scale (EDSS) scores, and at a time when disability was unlikely to develop over a 2–3 year period. The EDSS measured impairment rather than disability in the group of patients who had scores in the lower part (0–3·0) of the scale.5, 6 The one study2 in which time to sustained change on the EDSS was used as the primary outcome measure, recruited patients with the lowest EDSS scores and was of the shortest duration.
Disability in MS can result from two distinct, though in many cases, overlapping mechanisms: failure to recover from relapse (incomplete remission) and slow insidious progression. These mechanisms may have different underlying pathologies.7 In patients with relapsing-remitting disease, the failure to recover from relapse is the sole cause of disability, while patients with secondary progressive MS accrue disability from both relapses and insidious progression.
To address the effects of interferon β-1b on disease progression in patients with SP-MS, we started a large placebo-controlled multicentre European study in 1994.8 The main clinical findings of a prospectively planned interim analysis are presented here.
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Design
This is a European, multicentre, double-blind, placebo-controlled study of two parallel-treatment groups of outpatients with SP-MS. The study was planned to have a 36-month period of treatment, followed by a drug-free follow-up of 3 months. Regular visits were scheduled for days 1, 3, 5, and 15, months 1–3, and thereafter every 3 months until month 36 (end of treatment) and month 39 (end of drug-free follow-up). Unscheduled visits for assessment and treatment of relapses and other non-MS
Study population
As shown in figure 1, 718 of 768 patients screened in 32 European centres were randomly assigned interferon β-1b (n=360) or placebo (n=358). The mean follow-up time at inerim cut-off was 892 study days in the placebo group and 901 days in the interferon β-1b group, comprising about 85% of EDSS information anticipated over the planned study duration of 3 years. Treatment groups were comparable for all baseline variables (table 2). Of these, 57 patients (31 [8·7%] placebo, 26 [7·2%] interferon
Discussion
This phase III study shows a therapeutic benefit of interferon β-1b in SP-MS. SP-MS is reported to be the most common phase of the disease and the one during which major irreversible disabilities most often appear.17, 18
The cohort studied was representative for this disease group, including patients who progressed with or without superimposed relapses following an initial relapsing-remitting phase.10 Patients were in the early stage of progression beginning about 10 years after initial
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2022, Value in HealthCitation Excerpt :Among the DMTs used in our cohort, only interferon beta-1b was approved in Italy. Nevertheless, based on published trials, interferon beta-1b does not affect disability progression.29-31 The other DMTs used (empirically and with no specific and approved indication) have not shown efficacy in reducing the disability progression in clinical trials too.
Members of the study group are listed at end of paper