American College of Rheumatology Annual Meeting
American College of Rheumatology Annual Meeting
December 10, 2018
3 min read

Tofacitinib does not confer meaningful increase in risk for venous thromboembolism

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CHICAGO – Treatment with tofacitinib results in a numerically higher, but not statistically significant, risk for venous thromboembolism versus tumor necrosis factor inhibitors among patients with rheumatoid arthritis, according to findings presented at the ACR/ARHP 2018 Annual Meeting.

“A potentially increased risk [for] venous thromboembolism was noted in pre-marketing trials of baricitinib, which is a JAK1 inhibitor,” the researchers wrote. “This led the FDA to restrict approval of baricitinib [Olumiant, Eli Lilly] to only the low dose (2 mg) for treatment of RA. It remains unknown whether the risk of venous thromboembolism is attributable to JAK inhibition and extends to tofacitinib (Xeljanz, Pfizer), which is increasingly used in RA since its approval in 2012.”

Rishi J . Desai, MS, PhD, instructor of medicine at Harvard Medical School and associate epidemiologist in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, and colleagues performed a new-user cohort study to assess the risk for venous thromboembolism with tofacitinib versus tumor necrosis factor (TNF) inhibitors in patients with RA. The researchers collected administrative claims data from the Truven MarketScan database from 2012 to 2016 and from Medicare Parts A, B and D from 2012 to 2015.

The study identified 34,074 patients with RA from the Truven MarketScan database and 17,086 patients with RA from the Medicare database. All patients were aged 18 years or older; the mean age of patients was 50 years in the Truven MarketScan database and 71 years in the Medicare database. Tofacitinib was started in 5.6% of patients from the Truven MarketScan database and in 5.8% of patients from the Medicare database.

Data was collected during a 180-day baseline period of constant insurance enrollment prior to a cohort entry date denoted by the start of treatment with tofacitinib or a TNF inhibitor, including adalimumab (Humira, AbbVie), certolizumab (Cimzia, UCB), etanercept (Enbrel, Amgen), golimumab (Simponi, Janssen) or infliximab (Remicade, Janssen). Previous treatment with biologics or tofacitinib was not permitted.

The researchers tracked the incidence of venous thromboembolism, defined as a composite outcome of pulmonary embolism or deep vein thrombosis diagnosis on inpatient claims, as patients were treated.

Treatment with three or more non-biologic disease-modifying therapies and glucocorticoids at baseline was more likely among patients starting treatment with tofacitinib, which suggests more active disease or lengthier duration of disease, according to the researchers. They also noted that propensity score adjustment resulted in an “excellent balance” for all 60 covariates.


More patients started treatment with TNF inhibitors in both the Truven MarketScan (n = 32,164) and Medicare (n = 16,091) groups than with tofacitinib (Truven, n = 1,910; Medicare, n = 995). The pooled analysis included 48,255 patients who began treatment with TNF inhibitors and 2,905 patients who began treatment with tofacitinib.

Venous thromboembolism events occurred more often in patients treated with TNF inhibitors in both the Truven MarketScan (n = 98) and Medicare groups (n = 117) compared with patients in both groups who were treated with tofacitinib (Truven, n = 8; Medicare, n = <11). The actual number of venous thromboembolism events among patients in the Medicare database who were treated with tofacitinib was “suppressed as required by [a] data-use agreement with the Centers for Medicare and Medicaid Services for counts below 11,” according to the study results.

The incidence rates per 100 person-years were 0.60 and 0.34 among patients in the Truven MarketScan group and 1.12 and 0.92 among patients in the Medicare group for tofacitinib and TNF inhibitors, respectively.

Propensity-score adjusted hazard ratios demonstrated no substantial changes in the risk for venous thromboembolism between tofacitinib and TNF inhibitors in either database. The pooled HR was 1.33 (95% CI, 0.78-2.24).

Absolute rates of venous thromboembolism are low in routine treatment of RA and similar to the findings observed in premarketing trials of baricitinib and tofacitinib, according to Desai and colleagues.

“Although residual confounding is possible and the precision of estimates was limited due to a small event count, these results are helpful in ruling out the possibility of a large increase in the risk [for] venous thromboembolism with tofacitinib and provide preliminary evidence regarding the safety of this JAK inhibitor agent with respect to venous thromboembolism risk,” the researchers wrote. - by Julia Ernst, MS


Desai RJ, et al. Abstract L09. Presented at: 2018 ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.

Disclosures: Desai reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.