Venous thromboembolic events in the tofacitinib ulcerative colitis clinical development programme

Abstract

Summary Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Aim To report incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in the tofacitinib UC programme. Methods DVT and PE were evaluated from one phase 2 and two phase 3 induction studies, one phase 3 maintenance study and an ongoing, open‐label, long‐term extension (OLE) study (September 2018 datacut). Data were analysed in induction, maintenance and overall (patients receiving ≥ 1 dose of tofacitinib 5 or 10 mg b.d. in any phase 2, 3 or OLE study) cohorts. Results 1157 patients (2404 patient‐years’ exposure; ≤ 6.1 years’ tofacitinib treatment) were evaluated in the overall cohort. In induction, one placebo‐treated patient had DVT and one had PE; no tofacitinib‐treated patients had DVT/PE. In maintenance, one placebo‐treated patient had DVT and one had PE; no tofacitinib‐treated patients had DVT/PE. In the overall cohort, one patient had DVT (incidence rate [patients with events/100 patient‐years; 95% CI]: 0.04 [0.00‐0.23]); four had PE (0.16 [0.04‐0.41]); all received predominant dose tofacitinib 10 mg b.d.; all had venous thromboembolism risk factors alongside UC. Conclusions In this post hoc analysis of patients with UC, during tofacitinib exposure, one patient had DVT and four had PE, all during the OLE study, on predominant dose 10 mg b.d. (83% of overall cohort patients received predominant dose 10 mg b.d.) with venous thromboembolism risk factors. This analysis is limited by small sample size and limited drug exposure; further studies are needed. ClinicalTrials.gov: NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612.

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

“…In the first half of 2019, the FDA and EMA issued new safety warnings about an increased risk of venous thromboembolic events and related death, following the results of the ORAL Surveillance study in rheumatoid arthritis. In this study, patients aged >50 years with at least one additional cardiovascular risk factor, used tofacitinib 10 mg twice daily as maintenance therapy . In our cohort one‐third of patients at week 24 received 10 mg twice daily while no thromboembolic events were reported.…”

Letter: thromboembolic and cardiovascular events with tofacitinib in ulcerative colitis—two cases in real world clinical practice. Authors’ reply

“…We thank Kotze et al for their interest in our work 1 and their report of adverse events in patients with UC receiving tofacitinib 10 mg twice daily (b.d.) in Brazil.…”

Lessons from tofacitinib in patients with cardiovascular risk factors: increased pulmonary embolism or isolated (thrombotic) pulmonary occlusion rates?

“…Comparison of reported IRs of DVT and PE and the ratio of IR DVT/IR PE Data from Mease et al5 and Sandborn et al24 for the ulcerative colitis programme. Available data from long-term extension studies of baricitinib 5 and the upadacitinib programme23 among patients not enriched for risk factors are shown for comparison.…”