Progression in Disability Status in Patients with Relapsing- Remitting MS

The median age at onset of multiple sclerosis (MS) is approximately 30 years. Initially, the disease is often characterized by relapses and remissions, followed by a progressive worsening of neurologic function (secondary progressive MS). In patients with relapsing-remitting multiple sclerosis (RRMS), disability may be due to incomplete recovery from relapses or continuously progressive loss of neurologic function. Due to the variable clinical course of the disease, there is a need for reliable predictors of long-term disability in patients with RRMS. Researchers recently conducted a retrospective analysis to determine the value of Expanded Disability Status Scale (EDSS) worsening sustained for a minimum of 6 months as a predictor for disability status. They also investigated the effects of treatment and number of relapses to evaluate their predictive value relative to the predictive value of disease progression. Analysis results were reported in Archives of Neurology [2010;67(11):1329-1335]. Data were gathered from a 2-year phase 3 RRMS double-blind, placebo-controlled clinical trial from patients who had previously participated in the Multiple Sclerosis Collaborative Research Group study who had received a minimum of 2 years of treatment. Patients received 30 mcg of intramuscular interferon beta-1a (IM IFNβ-1a) or placebo once a week during the 2-year clinical trial. The primary outcome measures of the current analysis were the positive predictive values for a 6-month sustained progression during the 2 years as calculated to determine the ability to predict disability status at 8 years. A multivariate logistic regression model was used to assess the relationship between predictors and EDSS milestones at follow-up. There were 160 patients enrolled in the 8-year follow-up study. In the original trial, 79 of the 160 patients were treated with IM IFNβ-1a and 81 were given placebo. Upon completion of the study, patients in the IM IFNβ-1a group were using disease-modifying therapies 46.4% of the time during the follow-up interval, compared with 55.8% of the patients in the placebo group. At the end of the original study, 28% (n=45) of eligible patients met the criteria for disability progression; of those, 23% (n=18) were in the IM IFNβ-1a group and 33% (n=27) were in the placebo group. With the exception of T2 lesion volume, baseline characteristics of patients who met the criteria for disability progression and those who did not progress were similar (those who experienced disability progression had a significantly greater T2 lesion volume at baseline). Of the total cohort (n=160), 45 patients had sustained disability progression and 115 did not. Those randomized to IM IFNβ-1a were significantly less likely to progress to an EDSS score of ≥4.0 compared with patients who received placebo. Patients with disability progression were more likely to reach all 4 EDSS milestones compared with those who did not progress (P<.001 for each milestone). The positive predictive value of disability progression at 2 years was high for EDSS scores of ≥4.0, ≥5.0, and ≥6.0 at the 8-year follow-up (84%, 73%, and 67%, respectively). Worsening of ≥1 point on EDSS from baseline sustained for 6 months was the strongest predictor of clinically significant disability at 8 years after randomization. Other independent predictors were treatment arm assignment and baseline EDSS score. The researchers concluded by saying that “EDSS remains the gold standard for observing progression in controlled trials. Results from this study suggest that this measure can be used to meaningfully identify disability in an RRMS population and to determine the effect of a disease-modifying therapy on disability progression at this early stage of MS.”