Tofacitinib Shows Similar Safety Profile in PsA, RA Post-Marketing Data

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Researchers report on the global real-world safety profile of tofacitinib in psoriatic arthritis.

In patients with psoriatic arthritis (PsA), overall adverse events (AE) with tofacitinib (Xeljanz, Pfizer) were consistent with that found in patients with rheumatoid arthritis (RA). This is according to an analysis of post-marketing surveillance (PMS) data, published in Rheumatology and Therapy, which were aligned with the established safety profile of tofacitinib.1

“While these results should be interpreted in the context of the limitations of PMS studies and spontaneous AE reporting, these data provide insight to the clinician regarding expected real-world safety outcomes in patients with PsA treated with tofacitinib,” noted Gerd R Burmester, MD, professor of medicine at the Charité University Hospital in Berlin, Germany, and colleagues.

The safety of tofacitinib, an oral Janus kinase (JAK) inhibitor approved for the treatment of PsA and RA, has been shown in clinical trials of up to 4 years in PsA and 9.5 years in RA. PMS data using AE reports have been previously published for tofacitinib in RA, but not PsA, and there are limited reports of the real-world safety profile of tofacitinib in PsA.

This retrospective analysis included spontaneous AE reports submitted to Pfizer’s safety database from December 2017 — when 5 mg twice daily (immediate release [IR]) and 11 mg once daily (modified release [MR]) doses of tofacitinib were approved for PsA in the US — to November 2021 for PsA, and from November 2012 — when the 5 mg twice daily IR dose was approved for RA in the US followed by the 11 mg once daily MR dose on in February 2016 — to November 2021 for RA.The endpoints included AEs; serious AEs (SAEs); AEs of special interest (AESIs), comprising serious infections, herpes zoster, cardiovascular events, malignancies and venous thromboembolism; and fatal cases. IQVIA global commercial sales data was used to estimate drug exposure. The number, frequency (number of events/100 patient-years' exposure), and reporting rates (RRs) were summarized by indication and formulation.

A total of 73,525 case reports were reviewed, of which 5394 were for PsA and 68,131 were for RA, with 20,706 and 439,370 patient years of exposure, respectively. Of the case reports, 6.8% for PsA and 6.2% for RA did not report a tofacitinib formulation and were excluded. For both PsA and RA, a higher number of AEs were reported for tofacitinib IR than MR (IR/MR: PsA = 8349/7602; RA = 137,476/82,153). However, the RRs for AEs (IR/MR: PsA = 59.6/113.4; RA = 44.0/64.8) and SAEs (PsA = 8.1/13.6; RA = 8.0/9.5) were higher with MR than IR.

The frequency of SAEs, AESIs and fatalities was largely similar across formulations and indications. The most frequently-reported AE preferred terms for PsA and RA, respectively, included drug ineffective, at 20.0% and 17.8%; pain, at 9.7% and 10.6%; condition aggravated, at 9.9% and 10.5%; and headache, at 8.8% and 7.9%. Off-label use was the second most frequently reported AE for PsA, at 10.5% compared with 3.4% in RA. Investigators explained this might be attributable to use of tofacitinib as monotherapy or at a higher dose.

Limitations of the PMS data analysis include the potential for reporting bias, with higher RRs observed in females and in younger patients, and the exposure estimation from commercial sales data. Additionally, more data were available for RA than for PsA, and for IR than for MR tofacitinib. Further, most patients would have received concomitant medication per regulatory labeling, which may have contributed to the AE risk.

The difference in RRs may relate to “differences in cumulative exposure, regional reporting trends or different patient populations,” investigators noted. “Potential trends in reporting by sex and age require further assessment.”


  1. Burmester GR, Coates LC, Cohen SB, et al. Post-Marketing Safety Surveillance of Tofacitinib over 9 Years in Patients with Psoriatic Arthritis and Rheumatoid Arthritis [published online ahead of print, 2023 Jul 17]. Rheumatol Ther. 2023;10.1007/s40744-023-00576-8. doi:10.1007/s40744-023-00576-8