Investigators have found no evidence of an increased risk of venous thromboembolic events (VTE) in patients treated with tofacitinib for rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), or ulcerative colitis (UC).
Philip J. Mease, MD, University of Washington School of Medicine, Seattle, Washington, reported the results in a late-breaking poster session on November 7 at the 2017 Annual Meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP).
Systemic inflammation is a risk factor for VTE, and an increased risk of VTE has been reported in patients with RA, PsO, and UC, compared with the general population, and in patients with PsA receiving disease-modifying antirheumatic drugs (DMARDs).
For the current study, the researchers reviewed safety data from phase 2 and 3 randomised clinical studies of tofacitinib as monotherapy or in combination with conventional synthetic(cs) DMARDs that were completed as of August 2017.
Two analysis cohorts were defined within each clinical programme for RA, PsO, PsA, and UC. One cohort was the placebo-controlled cohort which included patients randomised to tofacitinib 5 or 10 mg BID, or placebo up to month 3 in RA, PsO, and PsA studies and patients randomised to tofacitinib 10 mg BID or placebo for the 9-week induction period in UC studies.
The other cohort was a dose-comparison cohort which included patients randomised to tofacitinib 5 or 10 mg BID, subcutaneous adalimumab 40 mg q2w (RA and PsA only) or methotrexate 20 mg/week (RA only) throughout the phase 2/3 studies for RA (up to month 24), PsO (up to month 12), and PsA (up to month 12), and for the 12-month phase 3 UC maintenance study.
In total, 5,432 patients with RA, 2,773 patients with PsO, 816 patients with PsA, and 1,220 patients with UC were included.
Results showed no imbalance of deep-vein thrombosis (DVT) or pulmonary embolism (PE) events with tofacitinib versus placebo or active comparators, and no dose-response relationship was reported for tofacitinib 5 and 10 mg BID.
The incidence rate of DVT events in tofacitinib-treated patients was similar to that reported in the literature for patients with RA (0.21-0.62) and PsA (0.32-0.38), including untreated patients and patients receiving DMARDs in both populations.
The incidence of PE events reported for tofacitinib in the present analysis was in line with findings from the Corrona Registry.
"Overall, these findings do not support a causal relationship between tofacitinib treatment and DVT or PE events," the authors concluded. "Therefore, it is unlikely that the JAK inhibitor drug class as a whole is associated with increased risk of VTE."
Funding for this study was provided by Pfizer.
[Presentation title: Incidence of Thromboembolic Events in the Tofacitinib Rheumatoid Arthritis, Psoriasis, Psoriatic Arthritis and Ulcerative Colitis Development Programs. Abstract 16L]