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


Therapeutics

Monthly immunoglobulin therapy improved relapsing-remitting multiple sclerosis

ACP J Club. 1997 Jul-Aug;127:11. doi:10.7326/ACPJC-1997-127-1-011


Source Citation

Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B, for the Austrian Immunoglobulin in Multiple Sclerosis Study Group. Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Lancet. 1997 Mar 1;349:589-93.


Abstract

Objective

To evaluate the effectiveness of monthly intravenous immunoglobulin (IVIg) therapy in improving the clinical course of relapsing-remitting multiple sclerosis (MS).

Design

Randomized, double-blind, placebo-controlled trial with 2-year follow-up.

Setting

13 neurologic centers throughout Austria.

Patients

150 patients (mean age 37 y, 75% women) with relapsing-remitting MS, a baseline Kurtzke expanded disability status scale (EDSS) score between 1.0 and 6.0, and a history of ≥ 2 relapses during the previous 2 years. Exclusion criteria were use of immunotherapy in the previous 3 months or corticosteroids in the previous 2 weeks, lack of reliable contraception, a primary or secondary progressive course of MS, or a benign course of MS.

Intervention

75 patients were allocated to IVIg, 0.15 to 0.2 g/kg body weight once per month, and 73 were allocated to saline placebo, both for 2 years.

Main outcome measures

The primary outcome measure was difference in absolute change in clinical disability between treatment groups measured with the EDSS. The secondary outcome measure assessed relapse rates.

Main results

Analysis was by intention to treat. The final EDSS score decreased (improved) from baseline in patients in the IVIg group but increased in the placebo group (mean change - 0.23 [95% CI - 0.43 to - 0.03] vs 0.12 [CI - 0.13 to 0.37], P = 0.008). 23 patients (31%) in the IVIg group improved by ≥ 1.0 grade on the EDSS compared with 10 patients (14%) in the placebo group { P = 0.01}* (Table). Overall, 24% of patients in the IVIg group did better than those who received placebo in terms of improvement (17%) and prevention of deterioration (7%). The number of confirmed relapses in the IVIg group was half that in the placebo group. IVIg was well tolerated.

Conclusion

Monthly intravenous immunoglobulin improved the course of clinical disability and reduced the frequency of relapses in relapsing-remitting multiple sclerosis.

Source of funding: Sero-Merieux, Vienna, Austria.

For article reprint: Dr. F. Fazekas, Department of Neurology, Karl-Franzens University, Auenbruggerplatz 22, A-8036 Graz, Austria. FAX 43-316-325520.

* P value calculated from data in article.


Table. Intravenous immunoglobulin (IVIg) vs placebo†

Outcome at 2 years IVIg EER Placebo CER RBI (95% CI) ABI |EER-CER| NNT (CI)
Improvement of ≥ 1 grade on the EDSS 31% 14% 124% (17 to 337) 17% 6 (3 to 27)

†Abbreviations defined in Glossary; RBI, ABI, NNT, and CI calculated from data in article.


Commentary

To date, the only disease-modifying therapies shown to be effective in relapsing-remitting MS are the β-interferons (1, 2) and copolymer 1 (3). These therapies reduce relapse frequency by about one third and may slow disability progression.

In this interesting Austrian study by Fazekas and colleagues, several comments are in order. Previous attempts at IVIg therapy in MS have yielded mixed results, and most studies have been uncontrolled or unblinded (4, 5). The primary end point in this study was the difference in the absolute change in EDSS score between groups rather than relapse frequency. These changes were very modest, although statistically significant. The authors chose to measure disability level at the end of the study rather than the more conservative sustained disability change, and this would tend to overstate the likelihood of progression in both treatment groups. Finally, magnetic resonance imaging was not done.

Nonetheless, the findings from this work strongly suggest the need for a large multi-center trial of this therapy in relapsing-remitting MS in which change in disability and relapse frequency are the primary end points and magnetic resonance imaging analysis is a secondary outcome measure. From the perspective of cost, convenience, side effects, and safety, IVIg is a potentially attractive treatment for patients with MS.

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


References

1. The IFNB Multiple Sclerosis Study Group. Neurology. 1993;43:655-61.

2. Johnson KP, Brooks BR, Cohen JA, et al., and the Copolymer 1 Multiple Sclerosis Study Group. Neurology. 1995;45:1268-76.

3. Jacobs LD, Cookfair DL, Rudick RA, et al., and The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol. 1996;39:285-94.

4. Yan J, Richert JR, Sirdafsky MD. Lancet. 1990;11:692.

5. Achiron A, Pras E, Gilad R, et al. Arch Neurol. 1992;49:1233-6.