For patients with relapsing-remitting multiple sclerosis (MS), teriflunomide (TF) is a disease-modifying therapy (DMT). Risks of adverse events of special interest (AESI) were evaluated in this post-approval safety study of TF. Patients’ personal information was obtained secondarily 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). Patients who had never had any kind of therapy before but who began taking a DMT or switched to a different DMT after the date of TF reimbursement were included in the studies. The incidence of AESI in patients treated with TF was compared with the incidence of AESI in patients treated with a platform DMT other than TF, and the hazard ratios (HR) and (95% CI) of AESI were calculated for each data source. Cox models accounting for exposure over time were used to calculate HR for AESI that did not result in cancer. Cox proportional hazards modeling with an ever/never exposure threshold was used to calculate HR for malignant AESI. HR was adjusted for gender, age, new or prevalent user status, major comorbidities, and (when available) the expanded disability status scale (EDSS).  There were a total of 81,620 patients in the research (72% female), with 22,324 (27%) receiving TF. There was no increased risk of death from any cause, serious infection, pneumonia, herpes zoster reactivation, pancreatitis, peripheral neuropathy, cardiovascular disease, or cancer after a median of 3.5 years of TF therapy compared to another platform DMT. There was general agreement amongst the various data sets. No cases of progressive multifocal leukoencephalopathy were found in the TF user population. In the SNDS, the HR for TF compared to other platform DMT for opportunistic infections was 2.4 (1.2-4.8), and this result was independent of the specific opportunistic agent. For renal failure, the SNDS reported an HR of 2.0 (1.1-3.7), although this number was not elevated in any other data sets. Renal failure did not develop in any 187 French patients with a history of renal failure who were treated with TF before entering the cohort. Interstitial lung disease, psoriasis, and peripheral neuropathy had insufficient case numbers to provide meaningful findings. This comprehensive analysis using national registries did not indicate that TF consumption was connected with an increased incidence of AESI. The inconclusiveness of the renal failure data is due to the fact that they are contradictory.


Reference: ECTRIMS 2022