Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Interferon β-1a slowed progression of disability in multiple sclerosis

ACP J Club. 1996 Sept-Oct;125:35. doi:10.7326/ACPJC-1996-125-2-035


Source Citation

Jacobs LD, Cookfair DL, Rudick RA, et al and The Multiple Sclerosis Collaborative Research Group (MSCRG). Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol. 1996 Mar;39:285-94. [PubMed ID: 8602746]


Abstract

Objective

To determine the effectiveness of interferon β-1a (IFN-β-1a) in slowing the progression of irreversible neurologic disability in patients with relapsing multiple sclerosis (MS).

Design

2-year randomized, double-blind, placebo-controlled trial.

Setting

4 clinical centers in the United States.

Patients

301 patients who had relapsing MS and were aged 18 to 55 years (mean age 37 y, 73% women). Inclusion criteria were MS for ≥ 1 year, baseline Expanded Disability Status Score (EDSS) of 1.0 to 3.5, and ≥ 2 exacerbations in the previous 3 years but none in the past 2 months. Exclusion criteria were previous immunosuppression or interferon therapy, corticotropin or corticosteroid treatment 2 months before study entry, pregnancy or potential for pregnancy, lactation, chronic progressive MS, or other serious illness that would affect organ function. 5 patients were lost to follow-up before their primary end point was definitely determined.

Intervention

Patients were allocated to IFN-β-1a, 30 µg/wk by intramuscular injection (n = 158) or placebo (n = 143). Patients received acetaminophen, 650 mg, before and for 24 hours after each injection to decrease interferon-related side effects. All patients received appropriate standard medical care. Patients in exacerbation could receive corticotropin gel or methylprednisone, if deemed necessary by the treating physician.

Main outcome measures

The primary outcome was time to onset of sustained worsening in disability (increase of ≥ 1.0 point on the EDSS for ≥ 6 mo). Secondary outcomes were neurologic exacerbations and the number and volume of magnetic resonance imaging (MRI)-detected discrete gadolinium-enhanced lesions.

Main results

Analysis was by intention to treat. Treatment with IFN-β-1a delayed the progression of disability compared with placebo. Progression of disability at 2 years, estimated from Kaplan-Meier curves, was 21.9% of patients who received IFN-β-1a compared with 34.9% of patients who received placebo (P = 0.02). {This absolute risk reduction of 13% means that 8 patients would need to be treated (NNT) with IFN-β-1a (compared with placebo) to prevent 1 additional patient from developing disability progression.}* Patients who received IFN-β-1a had a lower annual exacerbation rate than did patients who received placebo (0.67 vs 0.82 per patient year, P = 0.04). 93% of patients who received IFN-β-1a completed treatment.

Conclusions

Interferon-β-1a slowed sustained disability progression and decreased the relapse rate in patients with relapsing multiple sclerosis. The drug was well tolerated.

Sources of funding: National Institutes of Health and Biogen, Inc.

For article reprint: Dr. L.D. Jacobs, Department of Neurology, The Buffalo General Hospital, 100 High Street, Buffalo, NY 14203, USA. FAX 716-859-2430.

*Numbers calculated from data in article.


Commentary

This well-designed study provides further evidence that β-interferons are useful in decreasing the exacerbation rate in relapsing MS. In the first major β-interferon trial (1-3), it was shown that subcutaneous injection of 8 MIU of IFN-β-1b every 2 days was associated with a 28% decrease in relapse rate after 3 years. A trend toward a delay in sustained disability progression was also identified, but this did not reach statistical significance even after a subset of patients was followed for 5 years (P = 0.09). The primary end point of that study, however, was relapse rate. In contrast, the primary end point of this study was sustained disability progression, and a delay in disability progression with treatment was seen. The annual relapse rate was also reduced in the treated group. MRI findings in each of the studies supported the conclusion that β-interferons have a beneficial biological effect in relapsing MS.

We now have 2 large, well-designed studies that indicate that β-interferons have a beneficial effect on the clinical relapse rate. IFN-β-1a was well tolerated. The overall suggestion from these data is that IFN-β-1a is at least as clinically effective as 1b, if not slightly more so, in treating relapsing MS. In the near future, neurologists likely will have a choice of 3 medications of comparable effectiveness (IFN-β-1a, IFN-β-1b, and co-polymer 1) for the treatment of relapsing MS (4). The choice of medication will be determined by cost, convenience, side effects, and patient preferences.

Paul O'Connor, MD, MSc
St. Michael's HospitalToronto, Ontario, Canada


References

1. IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology. 1993;43:655-61.

2. Paty DW, Li DK. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology. 1993;43:662-7.

3. The IFNB Multiple Sclerosis Study Group and the British Columbia MS/MRI Analysis Group. Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. Neurology. 1995;45:1277-85.

4. Johnson KP, Brooks BR, Cohen J, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology. 1995;45:1268-76.