Bermel et al. Predictors of long-term outcome in multiple sclerosis patients treated with interferon beta.Ann Neurol. 2013 Jan;73(1):95-103. doi: 10.1002/ana.23758
OBJECTIVE: To identify early predictors of long-term outcomes in MSers with relapsing-remitting multiple sclerosis (RRMS) treated with intramuscular (IM) interferon beta-1a (IFNβ-1a).
METHODS: A multicenter, observational, 15-year follow-up study of MSers who completed ≥2 years in the pivotal trial of IM IFNβ-1a for RRMS was conducted. One hundred thirty-six MSers participated in the 15-year follow-up (69 originally randomized to IM IFNβ-1a and 67 to placebo). After the 2-year clinical trial, treatment was not regulated by study protocol. Disease activity during the 2-year trial was defined as: ≥2 gadolinium-enhancing lesions (cumulative) on year 1 and/or year 2 magnetic resonance imaging (MRI); ≥3 new T2 lesions on year 2 MRI compared to baseline; and ≥2 relapses over 2 years. Odds ratios were calculated for early disease activity predicting severe Expanded Disability Status Scale (EDSS) worsening (worst quartile of change, ≥4.5 EDSS points) during the 15-year interval.
RESULTS: The proportion of MSers experiencing early disease activity was lower in patients on IM IFNβ-1a than placebo for all disease activity markers (range, 23.5-29.0% vs 41.0-45.5%). In the IM IFNβ-1a group, persistent disease activity predicted severe EDSS worsening: gadolinium-enhancing lesions (odds ratio [OR], 8.96; p < 0.001); relapses (OR, 4.44; p = 0.010); and new T2 lesions (OR, 2.90; p = 0.080). In placebo-treated MSers, early disease activity was not as strongly associated with long-term outcomes (OR range, 1.53-2.62; p = 0.069-0.408).
INTERPRETATION: Disease activity despite treatment with IFNβ is associated with unfavorable long-term outcomes. Particular attention should be paid to gadolinium-enhancing lesions on IFNβ therapy, as their presence strongly correlates with severe disability 15 years later. The results provide rationale for monitoring IFNβ-treated MSers with MRI, and for changing therapy in patients with active disease.
|MS disease activity is like an iceberg; most of the activity you can’t see clinically until it is too late and you enter the progressive phase of the disease. Inflammation is not a good thing, which is why we treat-to-target.|
“The results of this study are consistent with several data sets that are already published; disease activity on a DMT, in this case interferon-beta, is not good for you. Hence the need for regular MRIs to monitor your disease activity.”