Therapy Optimization in Multiple Sclerosis: A cohort study of therapy adherence and risk of relapse

Objectives The objective of the Therapy Optimization in MS (TOP MS) Study was to prospectively assess the relationship between MS disease-modifying therapy (DMT) adherence and MS relapse risk over 2 years. Methods Potential participants were recruited for TOP MS by specialty pharmacies who dispensed glatiramer acetate and beta interferons for MS nationwide. Signed IRB-approved informed consents were returned to the pharmacies. TOP MS used electronic data capture with monthly patient entries. Adherence, measured by medication possession ratio (MPR), was derived from pharmacy shipment records. Logistic regression examined the association between protocol-defined relapses and DMT MPR (<0.5; >0.5-<0.9; >0.9). Results TOP MS enrolled 3151 persons with MS, and 2410 completed the full 2 years. Across all therapies, the mean MPR for the 2-year completer cohort of 2049 who maintained the same DMT was 0.9+0.2 (range: 0.1-1.0), with 63.8% reaching a 2-year MPR >0.9. Evaluated by categories of MPR, the proportion of participants remaining relapse-free for 24 months increased with increasing MPR, and the proportion with >1 relapses declined with increasing levels of MPR (p<0.0008). Regression analysis revealed the odds of relapse for a patient in the MPR >0.9 MPR group was 64% that of a patient in the MPR <0.5 category (p=0.02). Use of >1 DMT prior to the current one was an independent predictor of relapse. Conclusions The study provides class III evidence that improvement in adherence to DMT for MS is associated with improved clinical outcomes as measured by relapse reduction.