Comi G, Filippi M, Barkhof F, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study.
The CHAMPS (Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study) data had previously shown that patients with an initial monosymptomatic demyelinating event, including optic neuritis, had better clinical outcomes and lesser accumulation of MRI lesion burden when managed with intravenous methylprednisolone (ONTT doses) followed by weekly intramuscular interferon beta-1a than with methylprednisolone alone. The European ETOMS (Early Treatment of Multiple Sclerosis) group performed a similar study, albeit with important differences. They enrolled patients with new onset of neurologic symptoms or signs, either unifocal or multifocal, and four white matter lesions on T2-weighted MRI scans (three if one or more was enhancing or infratentorial). Patients were randomized to either Rebif (subcutaneous interferon beta-1a) 22 μg or placebo, injected weekly for 2 years.
Of 308 patients randomized, 241 received management of the full 2 years. The endpoint of converting to clinically definite multiple sclerosis was reached by 34% of patients in the interferon group and 45% in the placebo group (P = 0.047). The number of white matter lesions on MRI per was significantly lower in the interferon group than in the placebo group (2.0 [range 0.5–4.5] versus 3.0 [1.5–6.25];P < 0.001). There were no significant differences between groups in disability scores. As expected, there were significantly higher rates of adverse effects in the interferon group, including inflammation at the injection site (60% versus 12%), fever (28% versus 12%), and chills (11% versus 5%).
These data largely confirm the findings of the CHAMPS study, even though there were several differences in study design. In the current study the patient population had both unifocal and multifocal clinical disease. The dose of interferon used was smaller than in the CHAMPS study, and the delivery route different. Patients were enrolled as long as 3 months after onset of clinical symptoms, as compared with the 2-week limit in CHAMPS. No stratification by type of demyelinating event was done. Nonetheless, it is encouraging that two studies of the same type of interferon both showed significant effects on preventing conversion to multiple sclerosis.