Association Between Smoking Status and the Efficacy and Safety of Tofacitinib in Patients with Ulcerative Colitis.

ABSTRACT

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). This analysis assessed the impact of cigarette smoking on tofacitinib efficacy and safety in the UC clinical program. Methods: Efficacy endpoints and adverse events (AEs) were evaluated by smoking status (ever smokers [current and ex-smokers] and never smokers) in the phase (P)2 induction study (baseline demographics and safety only), P3 studies (OCTAVE Induction 1&2, OCTAVE Sustain, OCTAVE Open), and P3/4b RIVETING study. Results: This post hoc analysis included 1156 patients (ever smokers, n = 416 [36.0%; current smokers, n = 59 (5.1%); ex-smokers, n = 357 (30.9%)]; never smokers, n = 740 [64.0%]; median [range] treatment duration 654 [1-2712] and 615.5 [1-2850] days, respectively). Similar proportions of ever smokers and never smokers achieved efficacy endpoints. AEs were reported in 88.7% of ever smokers and 83.8% of never smokers. Overall, 60.6% of ever smokers had an infection (serious infections, 5.5%; herpes zoster [nonserious and serious], 10.8%; Clostridioides difficile infection, 12.0%; lower respiratory tract infection, 19.5% corresponding values among never smokers were 53.1%, 3.9%, 6.8%, 8.5%, and 11.4%). Major adverse cardiovascular events were reported in 1.0% of ever smokers and 0.7% of never smokers and thromboembolism events (venous and arterial) in 1.0% of ever smokers and 0.9% never smokers. Deaths, malignancies (excluding non-melanoma skin cancer [NMSC]), and NMSC occurred infrequently in ever smokers (0.5%, 2.5%, and 3.7%, respectively) and never smokers (0.1%, 1.5%, and 1.0%, respectively). Colorectal cancer was reported in 0.6% of never smokers; no cases occurred in ever smokers. Conclusions: Efficacy and safety of tofacitinib were generally similar in ever smokers and never smokers. Overall, serious AEs and, as expected, infections were more frequent in ever smokers versus never smokers. This may inform treatment selection and monitoring strategies. ClinicalTrialsgov NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304.