066 Impact of long-term teriflunomide treatment on lymphocyte counts and infections in pooled temso and tower studies

Introduction In TEMSO (NCT00134563) and TOWER (NCT00751881), teriflunomide was associated with early reductions in mean lymphocyte counts, which remained within the normal range. Here, we analyse long-term effects of teriflunomide on lymphocyte counts and infections in pooled TEMSO/TOWER core and extension data (TEMSO extension, NCT00803049). Methods Pooled data from core studies are reported for patients receiving placebo or teriflunomide 14 mg. In the extensions, placebo-treated patients received active treatment; results from pooled core and extension studies are reported for the teriflunomide 14 mg group. Lymphocyte counts were obtained every 2 weeks until Week 24, and every 6 weeks thereafter. Lymphopenia was identified from 2 consecutive lymphocyte counts below LLN and graded by Common Terminology Criteria for Adverse Events. Results In the core studies, placebo/teriflunomide-treated patients rarely experienced Grade 1 (0.7%/2.1%) or 2 (0.5%/1.4%) lymphopenia. Infections were reported in placebo-treated (40.0%/75.0%) and teriflunomide-treated (73.3%/20.0%) patients with Grade 1 or 2 lymphopenia, respectively. No patients with Grade 1 lymphopenia and 1 placebo-treated patient with Grade 2 lymphopenia developed a serious infection. In the combined core and extension studies, teriflunomide-treated patients (n=1354) experienced few Grade 1 (3.0%) or 2 (2.4%) lymphopenias; infections were reported in 25/40 (62.5%) and 19/33 (57.6%) patients, respectively, vs 718/1281 (56.0%) patients without lymphopenia. Serious infections occurred in patients without lymphopenia (47 patients [3.7%]) and in those with Grade 1 (1 [2.5%]) or Grade 2 (3 [9.1%]) lymphopenia. No Grade 3/4 lymphopenias were recorded. Despite the overall low rate of lymphopenia, occurrence and severity of lymphopenia will also be reported in subgroups of Asian and white patients. Conclusion In long-term TEMSO and TOWER trials, low-grade lymphopenia was uncommon, with no reports of high-grade lymphopenia. Infection rates were similar in patients with or without lymphopenia, consistent with an immunomodulatory mechanism of action of teriflunomide with limited impact on protective immunity.