Session Type: ACR Late-breaking Abstract Session
Session Time: 9:00AM-11:00AM
Background/Purpose: Tofacitinib is an oral Janus kinase(JAK) inhibitor that preferentially inhibits signaling by JAK3 and JAK1, with functionalselectivity over JAK2. Potential increased risk of venous thromboembolic events(VTE) in patients (pts) with rheumatoid arthritis (RA) has been reported for a JAK1/2 inhibitor.1 To assess VTE risk with tofacitinib, data werereviewed from the tofacitinib development program in RA, psoriasis (PsO),psoriatic arthritis (PsA), and ulcerative colitis (UC).
Methods: Data from Phase (P) 2 (RA, PsO, UC) and P3 (RA, PsO, PsA, UC) randomized clinical studies oftofacitinib as monotherapy or in combination with conventional synthetic(cs)DMARDs were included. Two cohorts were defined; 1) the placebo (PBO)-controlledcohort: pts randomized to tofacitinib 5 or 10 mg BID, or PBO up to Month (M) 3 inRA, PsO, and PsA studies, and pts randomized to tofacitinib 10 mg BID or PBOfor the 9-week induction period in UC studies; 2) the dose-comparison cohort: ptsrandomized to tofacitinib 5 or 10 mg BID, adalimumab (ADA) 40 mg SC Q2W (RA andPSA only) or methotrexate (MTX) 20 mg QW (RA only) throughout the P2/3 studies forRA (up to M24), PsO (up to M12), and PsA (up to M12), and for the 12-month P3UC maintenance study. First deep vein thrombosis (DVT) and pulmonary embolism(PE) events were identified using the MedDRA embolic and thrombotic SMQ preferredterms restricted to the respiratory, thoracic, mediastinal, and vasculardisorder System Organ Classes; incidence rates (IRs; pts with events/100 pt-years)were based on single events occurring during treatment or ≤28 days afterthe last dose or up to the cohort cut-off date. IRs for PE in pts with RA werecompared with Corrona Registry data.
Results: Up to M3 in the PBO-controlled cohort, DVT and PEwere both independently reported in 1 pt with RA and 1 with UC, who bothreceived PBO; no pts receiving tofacitinib had DVT or PE events (Table).In the dose-comparison cohort there were 2 DVT events in tofacitinib-treated ptswith RA (5 mg BID, n=1; 10 mg BID n=1) and 1 DVT event in a pt with PsA(tofacitinib 10 mg BID) (Table). IRs were 0.1 (95% CI: 0.0, 0.3) for bothtofacitinib doses in RA, and 0.5 (95% CI: 0.0, 2.8) for tofacitinib 10 mg BIDin PsA. Five PE events occurred in the dose‑comparison cohort, all in RA(5 mg BID, n=2; 10 mg BID, n=3). IRs were 0.1 (95% CI: 0.0, 0.4) fortofacitinib 5 mg BID and 0.2 (95% CI: 0.0, 0.4) for 10 mg BID. IRs for PE with tofacitinib in RA weresimilar to those reported by the Corrona Registry in pts with RA treated withtofacitinib (0.1 [95% CI: 0.0, 0.4]), biologic DMARDs (0.2 [95% CI: 0.1, 0.3]), and csDMARDs (0.2 [95% CI: 0.0, 0.5]). DVT were reported twice with MTX, and nonewith ADA.
Conclusion: Analysis of DVT and PE across randomized clinical studiesfor RA, PsO, PsA, and UC showed no evidence of an increased risk of events withtofacitinib.
1. Kremer K, et al.EULAR 2017 Abstract, FRI0090.
To cite this abstract in AMA style:Mease PJ, Kremer J, Cohen S, Curtis JR, Charles-Schoeman C, Loftus EV, Greenberg JD, Palmetto N, Kanik KS, Graham D, Wang C, Biswas P, Chan G, DeMasi R, Valdez H, Hendrikx T, Jones TV. Incidence of Thromboembolic Events in the Tofacitinib Rheumatoid Arthritis, Psoriasis, Psoriatic Arthritis and Ulcerative Colitis Development Programs [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/incidence-of-thromboembolic-events-in-the-tofacitinib-rheumatoid-arthritis-psoriasis-psoriatic-arthritis-and-ulcerative-colitis-development-programs/. Accessed November 18, 2017.
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ACR Meeting Abstracts - http://acrabstracts.org/abstract/incidence-of-thromboembolic-events-in-the-tofacitinib-rheumatoid-arthritis-psoriasis-psoriatic-arthritis-and-ulcerative-colitis-development-programs/