Potential Adverse Effects of Tofacitinib

Biologic therapies such as tumor necrosis factor (TNF) inhibitors and Janus kinase (JAK) inhibitors usually are prescribed by subspecialists, but generalists should be aware of their potential adverse effects. In this industry-sponsored randomized trial, researchers focused on adverse effects of the JAK inhibitor tofacitinib (Xeljanz), which is U.S. FDA-approved to treat rheumatoid and psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis.

About 4400 patients (age, ≥50) with active rheumatoid arthritis received tofacitinib (either 5 or 10 mg twice daily) or a TNF inhibitor. During average follow-up of 4 years, these findings were noted:

• Risk for major adverse cardiovascular events was greater with the combined tofacitinib doses than with TNF inhibitors (3.4% vs. 2.5%); noninferiority of tofacitinib was not demonstrated statistically, indicating concern that tofacitinib might confer greater risk than TNF inhibitors.
• Risk for cancer was 4.2% versus 2.9% for tofacitinib and TNF inhibitors, respectively — with the same conclusion about noninferiority.
• Compared with TNF inhibitors, both tofacitinib doses were associated with higher risk for herpes zoster; the 10-mg dose was associated with higher risk for venous thromboembolism and higher all-cause mortality.
• Tofacitinib and the TNF inhibitors reduced rheumatoid arthritis disease activity similarly.