Fast track — ArticlesComparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial
Introduction
Multiple sclerosis (MS) is a chronic disorder that is characterised by pathological (immune-mediated CNS demyelination and axonal injury)1, 2 and clinical (exacerbations, disability progression) dissemination in time and space.3 At present, six treatments are approved for patients with MS, including three interferon beta preparations, glatiramer acetate, mitoxantrone, and natalizumab. This study focuses on the safety, tolerability, and efficacy of 44 μg subcutaneous interferon beta-1a three times per week and 20 mg subcutaneous glatiramer acetate once per day.
The landmark trial of interferon beta-1a in patients with relapsing-remitting MS (RRMS), the Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis (PRISMS), showed that 44 μg subcutaneous interferon beta-1a three times per week gave significant benefit compared with placebo by reducing relapse rate, time to first relapse, disability progression, gadolinium-enhancing lesions, and T2 lesion load.4 Glatiramer acetate was superior to placebo only for reducing the relapse rate.5 Although MRI findings were not an outcome in the glatiramer acetate trial, a short-term, placebo-controlled study of an active cohort that required patients to have gadolinium-enhancing lesions at screening did show a significant, albeit less robust, treatment effect of glatiramer acetate on MRI: gadolinium-enhancing and new T2 lesions were reduced.6 The results of large, randomised, head-to-head studies have shown differences among interferon beta formulations and regimens.7, 8 Here, we present a comparative trial between interferon beta and glatiramer acetate in patients with RRMS.
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Patients
Between February and December, 2004, 764 patients with RRMS aged between 18 and 60 years who were interferon beta and glatiramer acetate naive were recruited from 81 centres in 14 countries (Argentina, Austria, Brazil, Canada, France, Germany, Ireland, Italy, Netherlands, Russia, Spain, Switzerland, UK, and USA). RRMS was diagnosed with the McDonald criteria,9 and patients had to have an expanded disability status scale (EDSS) score of 0–5·5. Inclusion criteria were that patients had at least
Results
Of 803 patients who gave consent and were screened, 766 passed screening and were enrolled. 764 patients (the intention-to-treat population) were randomised: 386 to interferon beta-1a and 378 to glatiramer acetate. Figure 1 shows the trial profile. 758 patients received at least one injection of either treatment and 756 of these had safety follow-up data (safety population). Of the 758 patients who received one of the treatments, 625 (301 [79%] in the interferon beta-1a group and 324 [86%] in
Discussion
In this randomised, assessor-blinded study to compare glatiramer acetate and high-dose, high-frequency interferon beta-1a, no difference was seen in the primary outcome measure—time to first relapse. There was also no difference between treatment groups in the other clinical endpoints, the proportion of patients who were free from relapse, relapse rate, and disability progression.
Baseline demographics were similar between the treatment groups, with the exception that more patients in the
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