Venous thromboembolic events in the tofacitinib ulcerative colitis clinical development programme
Open Access
- 9 October 2019
- journal article
- research article
- Published by Wiley in Alimentary Pharmacology & Therapeutics
- Vol. 50 (10), 1068-1076
- https://doi.org/10.1111/apt.15514
Abstract
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.Funding Information
- Pfizer
This publication has 23 references indexed in Scilit:
- Rheumatoid arthritis increases the risk of deep vein thrombosis and pulmonary thromboembolism: a nationwide cohort studyAnnals Of The Rheumatic Diseases, 2013
- Risk of Venous Thromboembolism in Patients With Rheumatoid ArthritisArthritis Care & Research, 2013
- A population-based case-control study on the association between rheumatoid arthritis and deep vein thrombosisJournal of Vascular Surgery, 2012
- Risk of Venous Thromboembolism in Patients With Rheumatoid Arthritis and Association With Disease Duration and HospitalizationJAMA, 2012
- Tofacitinib, an Oral Janus Kinase Inhibitor, in Active Ulcerative ColitisThe New England Journal of Medicine, 2012
- Noncardiac vascular disease in rheumatoid arthritis: Increase in venous thromboembolic events?Arthritis & Rheumatism, 2011
- Venous thrombotic events are not increased in patients with rheumatoid arthritis treated with anti‑TNF therapy: results from the British Society for Rheumatology Biologics RegisterAnnals Of The Rheumatic Diseases, 2011
- Thromboembolic risk among Danish children and adults with inflammatory bowel diseases: a population-based nationwide studyGut, 2011
- Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage studyBMC Medicine, 2011
- Incidence of noncardiac vascular disease in rheumatoid arthritis and relationship to extraarticular disease manifestationsArthritis & Rheumatism, 2006