http://www.thelancet.com/journal/vol359/iss9316/abs/llan.359.9316.original_research.20875.1

Lancet 2002; 359: 1453-60
Luca Durelli, Elisabetta Verdun, Pierangelo Barbero, Mauro Bergui, Elisabetta Versino, Angelo Ghezzi, Enrico Montanari, Mauro Zaffaroni, and the Independent Comparison of Interferon (INCOMIN) Trial Study Group
Universita' di Torino, Torino, Italy (Prof L Durelli MD, E Verdun MD, P Barbero MD, M Bergui MD, E Versino MD); Azienda Ospedaliera S Antonio Abate, Gallarate, Italy (A Ghezzi MD, M Zaffaroni MD); Ospedale Civile, Fidenza, Italy (E Montanari MD)

Background

The three interferon beta preparations approved for treatment of relapsing-remitting multiple sclerosis (MS) differ in dose and frequency of administration. Interferon beta-1a 30 µg is administered once a week, interferon beta-1a 22 µg or 44 µg is given three times a week, and interferon beta-1b 250 µg is administered on alternate days. No clinical study directly comparing the different regimens has been published. The INCOMIN study was designed to compare the clinical and magnetic resonance imaging (MRI) benefits of on-alternate-day interferon beta-1b 250 µg with once-weekly interferon beta-1a 30 µg.

Methods

INCOMIN was a 2-year, prospective, randomised, multicentre study. 188 patients with relapsing-remitting MS were assigned to interferon beta-1b (n=96) or interferon beta-1a (n=92). Primary outcome measures were the proportion of patients free from relapses and that of patients free from new proton density/T2 lesions at MRI assessment. Several secondary outcome measures were also assessed. Analysis was by intention to treat.

Findings

Over 2 years, 49 (51%) individuals administered interferon beta-1b remained relapse-free compared with 33 (36%) given interferon beta-1a (relative risk of relapse 0·76; 95% CI 0·59-0·9; p=0·03); and 42 (55%) compared with 19 (26%), respectively, remained free from new T2 lesions at MRI (relative risk of new T2 lesion 0·6; 0·45-0·8; p<0·0003). In both groups, the differences between the two treatments increased during the second year. There were also significant differences in favour of interferon beta-1b in most of the secondary outcome measures, including delay of confirmed disease progression.

Interpretation

High-dose interferon beta-1b administered every other day is more effective than interferon beta-1a given once a week.