(195) Systematic emulation trials to evaluate the real-world effectiveness of multiple sclerosis treatments

Background: The convergence of big real-world data and the emulation trial framework is increasingly used for evaluating the effectiveness of treatments. We apply methods of systematic emulation trial to multiple sclerosis (MS), a chronic neurological condition that presents a diverse therapeutic landscape aimed at mitigating disease activity and reducing relapse frequency.

Objectives: To assess the real-world effectiveness of seven MS treatments on the risk of relapses using a systematic emulation trial framework.

Methods: A cohort of patients with MS was followed in the French health care database (SNDS), which covers 99% of the population (>66 million) from January 1st, 2010 to December 31st, 2020. MS relapses were identified using an algorithm combining hospitalizations, encounters with specialists, and dispensings of high-dose corticosteroids. For each MS treatment (interferon beta, glatiramer acetate, natalizumab, fingolimod, teriflunomide, ocrelizumab, dimethyl fumarate) new users were identified and followed until discontinuation. Each new user was matched to non-users (1:4) based on a high-dimensional propensity score, age (±1 year), calendar date (±2 years), previous relapses and exposure to other MS treatment in the previous 90 days. Time-dependent conditional Poisson models were used to evaluate the association between each MS treatment and the occurrence of relapses, adjusting for individual comorbidities and exposure to corticosteroids.

Results: A total of 115,761 patients with MS were identified and followed for a mean of 8.73 years. During the follow-up, 76,612 relapses were identified among 45,391 patients. Compared to non-users, the aRR and 95% CI for MS treatments were: 0.70, 95%CI: [0.66 – 0.74] for interferon beta (n=15,475), 0.86 [0.80-0.91] for glatiramer acetate (n=12,218), 0.79 [0.73 – 0.86] for natalizumab (n=4,985), 0.71 [0.67 – 0.75] for fingolimod (n=10,580), 0.84 [0.80 – 0.89] for teriflunomide (n=18,273), 0.64 [0.54 – 0.75] for ocrelizumab (n=4,946) and 0.65 [0.62 – 0.69] for dimethyl fumarate (n=18,139).

Conclusions: The effectiveness of each of the MS treatments was confirmed in a very large database representative of the entire population of France. The method of systematic emulated trials yielded effect sizes that are very close to those found in clinical trials.