Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data.

Tofacitinib is a Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ulcerative colitis, and has been investigated in psoriasis (PsO). Routine pharmacovigilance of an ongoing, open-label, blinded-endpoint, tofacitinib RA trial (Study A3921133; NCT02092467) in patients aged ≥50 years and with ≥1 cardiovascular risk factor identified a higher frequency of pulmonary embolism (PE) and all-cause mortality for patients receiving tofacitinib 10 mg twice daily versus those receiving tumour necrosis factor inhibitors and resulted in identification of a safety signal for tofacitinib. Here, we report the incidence of deep vein thrombosis (DVT), PE, venous thromboembolism (VTE; DVT or PE) and arterial thromboembolism (ATE) from the tofacitinib RA (excluding Study A3921133), PsA and PsO development programmes and observational studies. Data from an ad hoc safety analysis of Study A3921133 are reported separately within. This post-hoc analysis used data from separate tofacitinib RA, PsO and PsA programmes. Incidence rates (IRs; patients with events per 100 patient-years' exposure) were calculated for DVT, PE, VTE and ATE, including for populations stratified by defined baseline cardiovascular or VTE risk factors. Observational data from the US Corrona registries (including cardiovascular risk factor stratification), IBM MarketScan research database and the US FDA Adverse Event Reporting System (FAERS) database were analysed. 12 410 tofacitinib-treated patients from the development programmes (RA: n=7964; PsO: n=3663; PsA: n=783) were included. IRs (95% CI) of thromboembolic events among the DVT, PE and ATE IRs in the tofacitinib RA, PsO and PsA programmes were similar across tofacitinib doses, and generally consistent with observational data and published IRs of other treatments. As expected, IRs of thromboembolic events were elevated in patients with versus without baseline cardiovascular or VTE risk factors, and were broadly consistent with those observed in the Study A3921133 ad hoc safety analysis data, although the IR (95% CI) for PE was greater in patients treated with tofacitinib 10 mg twice daily in Study A3921133 (0.54 (0.32-0.87)), versus patients with baseline cardiovascular risk factors treated with tofacitinib 10 mg twice daily in the RA programme (0.24 (0.13-0.41)).

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Competing interests: PM has received research grants and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, Sun and UCB; and has participated in speakers’ bureaus for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer Inc and UCB. CC-S has received research grants from AbbVie, Bristol-Myers Squibb and Pfizer Inc; and consulting fees from AbbVie, Amgen, Gilead, Pfizer Inc and Regeneron-Sanofi. SC has received consulting fees and other remuneration from AbbVie, Amgen, Boehringer Ingelheim, Gilead, Merck and Pfizer Inc. HY has received research grants from Bristol-Myers Squibb and Pfizer Inc. JK is an employee and shareholder of Corrona LLC; and has received research grants and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Genentech, Novartis, Pfizer Inc, Regeneron and Sanofi. JG is an employee and shareholder of Corrona LLC. WM and AO are employees of Corrona LLC; Corrona has been supported through contracted subscriptions in the last 2 years by AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Gilead, Janssen, Merck, Novartis, Ortho Dermatologics, Pfizer Inc, Regeneron and Sun. JRC has received research grants and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Corrona LLC, Crescendo Bio, Eli Lilly, Janssen, Myriad, Pfizer Inc, Roche and UCB. MH is an employee of Pfizer Inc and owns stock/stock options in Pfizer Inc and in other pharmaceutical companies that may manufacture and/or market drugs mentioned in this article or from the same pharmacological/therapeutic class. LF, JW, KSK, DG, CW, CC, HV, EH, AM and TVJ are employees and shareholders of Pfizer Inc.