Long-Term Safety of Teriflunomide in Multiple Sclerosis Patients: Results of Prospective Comparative Studies in Three European Countries.

Background and objectives: Teriflunomide is a disease-modifying therapy (DMT) for multiple sclerosis (MS). This post authorisation safety study assessed risks of adverse events of special interest (AESI) associated with teriflunomide use.

Methods: Secondary use of individual data from the Danish MS Registry (DMSR), the French National Health Data System (SNDS), the Belgian national database of health care claims (AIM-IMA) and the Belgian Treatments in MS Registry (Beltrims). We included patients treated with a DMT at the date of teriflunomide reimbursement or initiating another DMT. Adjusted hazard rates (aHR) and 95% confidence intervals were derived from Cox models with time-dependent exposure comparing teriflunomide treatment with another DMT.

Results: Of 81 620 patients (72% women) included in the cohort, 22 324 (27%) were treated with teriflunomide. After a median follow-up of 4 years, teriflunomide use compared to other DMT was not associated with a risk of all-cause mortality, severe infection, pneumoniae, herpes zoster reactivation, pancreatitis, cardiovascular condition and cancers. For opportunistic infections, aHR for teriflunomide versus other DMT was 2.4 (1.2-4.8) in SNDS, which was not bound to a particular opportunistic agent. The aHR was 2.0 (1.1-3.7) for renal failures in the SNDS, but no association was found in other data sources. A total of 187 SNDS patients had a history of renal failure prior to cohort entry. None of these patients (0%) had a renal failure recurrence when treated with teriflunomide for 19 (13%) recurrences reported for patients on another DMT.

Discussion: We found no evidence that teriflunomide use would be associated with an increased risk of AESI. Trial Registration EUPAS register: EU PAS 19610.