Objective: The relationship between relapses and long-term disability in multiple sclerosis (MS) remains to be fully elucidated. Current literature is conflicting and focused on early relapses. We investigated the effects of relapses at different stages on disability progression.

Methods: We conducted a retrospective review of 2,477 patients with definite relapsing-onset MS followed until July 2003 in British Columbia, Canada. Time-dependent Cox proportional hazards models examined the effect of relapses at different time periods (0-5; >5-10; >10 years postonset) on time to cane (Expanded Disability Status Scale [EDSS]) and secondary progressive MS (SPMS). Findings were derived from hazard ratios with 95% confidence intervals (CIs), adjusted for sex, onset age, and symptoms.

Results: Mean follow-up was 20.6 years; 11,722 postonset relapses were recorded. An early relapse (within 5 years postonset) was associated with an increased hazard in disease progression over the short term, by 48%; 95% CI 37%-60% for EDSS 6 and 29%; 95% CI 20%-38% for SPMS. However, this substantially lessened to 10%; 95% CI 4%-16% (EDSS 6) and 2%; 95% CI -2%-7% (SPMS) after 10 years postonset. The impact of later relapses (>5-10 years postonset) also lessened over time. Effects were modulated by age, impact being greatest in younger (<25 years at onset) and least in older (35 years) patients where relapses beyond 5-years postonset typically failed to reach significance. Relapses during SPMS had no measurable impact on time to EDSS 6 from SPMS.

Conclusion: Relapses within the first 5 years of disease impacted on disease progression over the short term. However, the long-term impact was minimal, either for early or later relapses. Long-term disease progression was least affected by relapses in patients with an extended disease duration (>10 years) or already in the secondary progressive phase.