Interferons in the treatment of multiple sclerosis: do they prevent the progression of the disease?

Abstract

HERE IS little doubt that t reatment o f multiple sclerosis (MS) with type 1 interferons reduces the frequency of clinical exacerbations. This observation has been corroborated repeatedly. Treatment of 124 patients with recombinant interferon beta-1b (IFN-b-1b) reduced the frequency of attacks by 33.8%. 1 This reduction was sustained for 5 years but both statistical significance and power were weakened in the later years of the trial, as progressively fewer patients remained in the study. The reduction in the frequency of attacks was associated with a reduction in the severity of attacks, the number of interventions with steroids, and the frequency of hospitalizations. The r eduction i n t he f requency of attacks was modest in comparison with the reduction in activity shown on magnetic resonance imaging (MRI) scans (median, 80% reduction in the number of active scans identified on sequential T2-weighted MRI scans). There was a negligible increase in the burden of disease in patients treated with IFN-b-1b for more than 4 years. 2 The findings from the MRI scans correlated, albeit modestly, with the change in disability scores. 3 Most investigators believed that this clinical and MRI efficacy would have translated into a reduction in the progression of the disease. At the end of 3 years, 20% of patients treated with IFN-b-1b met the definition of confirmed disability (a 3month sustained 1-point increase in score on the Kurtzke Expanded Disability Status Scale) compared with 28% of patients treated with placebo. 1 This difference did not reach statistical significance (P = .16). Several reasons were offered to explain this shortfall in disability outcome. First, the study was neither designed nor powered statistically to identify a moderate effect on disease progression. This would have required more patients and a longer follow-up period. Second, the dosage of IFN-b-1b used in the pivotal study might have been too low. A clear-cut dose response had been associated with the effect of IFNb-1b on attacks in patients with MS. Third, we entertained the possibility that prevention of attacks might be irrelevant to the factors required for slowing the progression of the disease. Even though the indications were favorable, it was conceded that IFNs might not prevent the development of disability in patients with MS. Indeed, in 12 pilot studies in which type 1 IFNs were studied in patients with progressive MS, improvement was identified in patients from only 2, both of which were open-label in design. In 5 studies, patients treated with IFN were thought to worsen, and in another 5 studies, no benefit was identi