Incomplete Relapse Recovery and Sustained Disability Progression In MS

Background: Patients with relapsing-remitting multiple sclerosis (RRMS) may experience relapses from which they do not fully recover, resulting in disease progression. However, patients may also have disease progression without relapses.

Objectives: Determine the frequency with which disability progression occurred in the absence of clinical relapses in placebo-treated patients with RRMS in 2 therapeutic trials.

Methods: Data from 2 prospective clinical trials, Multiple Sclerosis Collaborative Research Group (MSCRG) and Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM), were retrospectively analyzed to determine the frequency of placebo-treated patients with RRMS developing progressive MS characterized by disease progression without relapse, defined as a change in Expanded Disability Status Scale (EDSS) score of ≥1 point sustained for ≥6 months without evidence of relapse over the 180 days prior to the start of ≥6-month sustained progression. Relapsing disease leading to progression was defined as a change of EDSS score of ≥1 point sustained for ≥6 months with evidence of relapse during the 180 days before the start of ≥6-month sustained progression as a cause of progression. Relapse was defined as the appearance of a new symptom or the reappearance of old symptoms lasting >24 hours.

Results: Data for 87 placebo patients from MSCRG (mean disease duration, 6.1 years) and 315 placebo patients from AFFIRM (mean disease duration, 7.7 years) were analyzed. In both studies, more patients receiving placebo had sustained progression due to incomplete recovery from relapse than sustained progression without relapse. In MSCRG, 29 of 87 placebo patients (33.3%) had sustained EDSS progression; of these 29 patients, 20 (69.0%) had sustained progression due to incomplete recovery from relapse and 9 (31.0%) had sustained progression without relapse (P=0.04). In AFFIRM, 84 of 315 placebo patients (26.7%) had sustained EDSS progression; of these 84 patients, 48 (57.1%) had sustained progression due to incomplete recovery from relapse and 36 (42.9%) had sustained progression without relapse (P=0.19). Combined data showed a similar trend; more patients had sustained progression due to incomplete recovery from relapse than sustained progression without relapse (P=0.05).

Conclusions: MS progression associated with relapse was more common than progression without relapse. Further evaluation of this phenomenon is recommended.