Improving long-term follow-up studies of immunomodulatory therapies.

Goals in the treatment of multiple sclerosis (MS) focus on reducing symptoms and disease progression. Registry data indicate that the accumulation of significant disability can take decades. Therefore, long-term follow-up (LTFU) studies are needed to understand the impact of disease-modifying therapy (DMT) in MS. Based on analyses of available LTFU study data, recommendations for future LTFU studies can be made. A disability milestone may be considered because exploratory data show that DMT may slow the progression of disability. Achievement of the EDSS steps 4 or 6 may be sufficient milestones because, once reached, MS progresses inevitably. Since a placebo control cannot be ethically used in LTFU studies, a standard-of-care comparator could be considered. The ideal LTFU study should be performed according to the highest possible standards. A high-quality LTFU study would achieve high retention rates, capture complete data at prespecified assessment intervals, and be powered to the key outcome measure. In addition, propensity scoring is an approach used to reduce bias in treatment comparisons in observational studies and might be a suitable approach for analyzing LTFU studies. With careful consideration of LTFU limitations and study design, it is possible to attain a high degree of rigor in future studies.