Optimal Dosing of Interferon in MS
Abstract & Commentary
Source: Durelli L, et al. Lancet. 2002;359:1453-1460.
In this open-label Italian study, 188 patients with relapsing-remitting multiple sclerosis (MS) at 15 centers were randomly assigned to either interferon (IFN) beta-1b (250 mcg, 8 MIU, Betaseron ) SC QOD, vs. IFN beta-1a (30 mcg, 6 MIU, Avonex ) IM Q weekly. The primary clinical outcome measure was the proportion of patients free from relapses during the 24-month study period, with secondary measures of annualized relapses, treated relapses, and sustained progression of disability. All clinical outcomes were assessed in an open-label manner. The primary brain MRI outcome measure from yearly scans, which were analyzed in a blinded manner, was the proportion of patients free from new proton density/T2 hyperintense lesions, with secondary MRI outcomes of gadolinium-enhancing lesions and burden of disease.
The proportion of patients free from relapses at 24 months was 36% for IFN beta-1a vs. 51% for IFN beta-1b (P = 0.03). Patients with sustained and confirmed progression of disability of 1 EDSS point at 24 months was 30% for IFN beta-1a vs. 13% for IFN beta-1b (P < 0.01). The percentage of patients free from new T2 lesions was 26% in the IFN beta-1a group vs. 55% in the IFN beta-1b group. Similarly, the percentage of patients free from enhancing lesions in the IFN beta-1a group was 49% vs. 76% in the IFN beta-1b group (P = 0.001). There was, however, a higher incidence of adverse effects, especially injection site reactions, in the IFN beta-1b group, as was the incidence of neutralizing antibodies approximately 4-fold higher in the IFN beta-1b group (6% vs 22%).
Commentary
Evidence-based medicine can provide helpful comparisons about the relative efficacy of treatments and provide practical information about benefits and risks of therapy. This trial showed better primary and secondary outcome measures for the patients treated with IFN beta-1b every other day, than in patients treated weekly with IFN beta-1a. These effects were more apparent at month 24 than at 12 months. A significant and incontrovertible limitation of these data is the unblinded, open-label study design, not only for the patient, but also for the evaluating clinician. This introduces unavoidable investigator and patient bias which can drive an anticipated result. Further, there were more male patients with longer disease duration and more PD/T2 brain lesions at baseline in the weekly IFN beta-1a group, arguably a more difficult patient group to treat. It remains to be seen to what extent the added therapeutic benefit of more frequent SC IFN beta-1b injections is offset by the higher incidence of neutralizing antibodies. —Brian R. Apatoff, Associate Professor of Neurology, New York Presbyterian Hospital-Cornell Campus, Assistant Editor, Neurology Alert.
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