The long-term effects of disease modifying therapies on disability in people living with multiple sclerosis: A systematic review and meta-analysis

Background Disease modifying therapies (DMT) are a common medication class for treating people living with MS. However, although treatment with DMT can extend over more than a decade, little is known about their long-term effects. Here, we systematically review long-term (≥4 years) studies on the effect of DMT on disability progression and relapse in people living with MS. Methods We searched the EMBASE and Medline databases in January 2018, using search terms that included DMT and relevant outcome measures. Two authors screened all resulting studies and evaluated the risk of bias of included studies using the ROBINS-I tool for non-randomized studies. Where there was sufficient data, we performed meta-analyses using RevMan 5. Studies that could not be included in a meta-analysis were included in data synthesis. Results Our search returned 7,766 unique articles for review. After screening, 18 articles were included. Follow-up in these studies ranged from a mean of 3.9 years to a median of 17.8 years. Fifteen (83.3%) of the included studies had a moderate risk of bias and three (16.7%) had a serious risk of bias. Meta-analysis showed that DMT significantly reduced the risk of EDSS 6.0 and SPMS compared to no treatment. Conclusion There is some evidence that long-term treatment with interferon beta reduces the risk of EDSS 6.0 and SPMS compared to no treatment or placebo. More work is needed on the effect of second generation DMT and the relative effect of DMT on health outcomes.