MS Treatment: What Predicts Fewer Relapses Over Time?

Published in Journal of neurology by et al.. Reproduced from the PubMed record.

Cladribine is regarded highly efficacious in relapsing-remitting multiple sclerosis (RRMS). However, prediction of treatment response and optimal management remain elusive, particularly during long-term. We screened the Danish Multiple Sclerosis Registry for patients with RRMS who received ≥2 5-day treatment cycles of cladribine and were followed for >90 days. Annualised relapse rates (ARR) and activity parameters (relapses or MRI activity) were analysed from 90 days after the first dose (index) to year 3 (short-term) together with time-to-first 24-week confirmed disability worsening (CDW), CDW independent of relapses (PIRA), and activity/CDW (loss of "no evidence of disease activity", NEDA-3). Kaplan-Meier log-rank tests were validated in a subgroup who completed ≥4 five-day cladribine cycles before year 3 and contributed with >3 years follow-up (3YFS). Predicting covariables included age (< /≥ 45 years), pre-baseline activity, and short-term NEDA-3 status regarding 3YFS outcomes beyond year 3 (long-term). ARR declined significantly from ~0.55 in the year pre-baseline to ~0.23-0.25 from index to year 3. Younger age and pre-baseline activity predicted more frequent short-term activity. Pre-baseline activity additionally predicted short-term NEDA-3 loss. Short-term findings were consistent in 3YFS patients. CDW and PIRA were rare during short-term (~ 10%) and long-term (~ 20%), even in older patients. However, during long-term, NEDA-3 loss resumed steadily and this was largely unpredictable. While cladribine showed sustained short-term efficacy, treatment response appeared more favourable in older patients and patients without pre-baseline activity. Rare CDW and PIRA events warrant more research in cladribine for disability prevention. Optimal long-term management following cladribine treatment requires more research.