Multiple Sclerosis Express Report

Based on Data Presented at the 15^th Meeting of the European Neurological Society, June 18–22, 2005, Vienna, Austria

Publication date: 2005-06-30

Multiple Sclerosis—Efficacy and Tolerability of Therapy

This report was reviewed for medical and scientific accuracy by Andrew R. Pachner, MD, Professor of Neurology and Neurosciences, University of Medicine & Dentistry of New Jersey—New Jersey Medical School, Newark, New Jersey.

Introduction

Information as to the comparable efficacy and tolerability of the currently available interferon beta agents can guide neurologists in making treatment-related choices for their patients with multiple sclerosis. Several presentations at the 15^th Meeting of the European Neurological Society (ENS) showed comparability among the interferon beta agents, with differences in side effect profiles that could potentially affect long-term adherence to treatment. In the multicenter Prospective and Retrospective Observational Study of Avonex and Rebif (PROOF), intramuscular interferon beta-1a (Avonex) and Rebif demonstrated a similar ability to prevent relapses and disability, although treatment with Avonex was associated with significantly fewer injection-site reactions.¹ Updates from the global QUASIMS trial, as well, upheld previous findings from this study that patients derive similar therapeutic benefit from all the interferon beta agents.^2-4 Looking to future treatment options for multiple sclerosis, investigators reported very promising data for several oral pharma-cologic agents in early clinical trials, including FTY720,⁵ BG00012,⁶ and temsirolimus.⁷ While currently available treatment options for multiple sclerosis offer comparable efficacy, they do require intramuscular or subcutaneous administration. Future oral agents being investigated may prove equally efficacious, as well as offer an alternative to parenteral administration.

PROOF—Comparability between Avonex and Rebif

The relative efficacy and tolerability of Avonex and Rebif has been the subject of debate and were the focus of the open-label, observational PROOF study.¹ The efficacy and tolerability of Avonex and Rebif were assessed in patients with relapsing multiple sclerosis who were receiving either Avonex or Rebif for 12 to 24 consecutive months prior to study enrollment, at baseline, and at 6 months post-enrollment, thus yielding 18 to 30 months of prospective and retrospective observation.

Of 136 patients at baseline, 69 patients (51%) had received intramuscular Avonex 30 mcg once weekly and 67 patients (49%) had received subcutaneous Rebif 44 mcg 3 times weekly for 12 to 24 months prior to enrollment. The patient demographics and disease characteristics at baseline were well balanced between the treatment arms, with the exception of the mean baseline Expanded Disability Status Scale (EDSS) score, which was 0.4 points higher in the Rebif treatment arm (1.8 for Avonex vs 2.2 for Rebif). The mean pre-enrollment duration of therapy at baseline was 19 months in the Avonex treatment arm and 17 months in the Rebif treatment arm.

After 18 to 30 months of therapy, Avonex and Rebif were comparable with respect to the efficacy end points (relapse rate, disability progression, brain atrophy, and T2 lesion volume, T1 lesion volume, and gadolinium-enhancing lesions on magnetic resonance imaging [MRI] scans). The two treatments differed in tolerability, however, as injection-site reactions were significantly more likely to occur with Rebif than Avonex, according to T. J. Murray, MD, Queen Elizabeth II Health Sciences Center, Halifax, Canada.¹

From treatment initiation to study enrollment, 94% of Rebif-treated patients reported injection-site reactions compared to 55.1% with Avonex. From study enrollment to Month 6, moderate-to-severe reactions were reported by 7.5% and 4.3% of Rebif- and Avonex-treated patients, respectively.

On the issue of injection-site reactions, co-investigator Hamid Assar, MD, of Linz, Austria, commented, “These were significant differences. To keep patients on treatment long term, it is important to have an agent with a good side effect profile.”

Due to the difference in mean E