Tofacitinib May Increase Risk of Heart-related Problems, Cancer: FDA Alert

Tofacitinib, a drug used to treat arthritis and ulcerative colitis, may increase the risk of heart-related problems and cancer compared to tumor necrosis factor inhibitors (TNFis), according to an alert from the FDA.

The news comes following the results of a safety trial, which was mandated by the FDA, and of which the results were announced last week by Pfizer (Xeljans is Pfizer’s brand name of tofacitinib).

According to the FDA, “preliminary results from a safety clinical trial show an increased risk of serious heart-related problems and cancer with the arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib)” when compared to TNFis. The trial also evaluated the risks of blood clots in the lungs and death, but those results are not yet available.

The primary objective of the post-marketing required safety study, ORAL Surveillance, compared the safety of two doses of tofacitinib (5 mg twice daily and 10 mg twice daily) versus a TNFi in patients with rheumatoid arthritis aged 50 years or older with at least one additional cardiovascular risk factor.

The co-primary endpoints were non-inferiority of tofacitinib versus TNFi in regard to major adverse cardiovascular events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]). According to Pfizer, these endpoints were not met. The primary endpoints also did not differ between the two treatment groups.

A total of 4,362 patients were included in the study (tofacitinib 5 mg, n=1,455; tofacitinib 10 mg, n=10 mg [both groups combined, n=2,911]; and TNFi, n=1,451). In the primary analyses, there were 135 patients with MACE and 164 patients with malignancies (excluding NMSC).

In the combined tofacitinib groups, 3.37% of patients sustained a first MACE event within the risk period (up to 60 days past last dose), compared to 2.55% of patients in the TNFi group. The combined hazard ratio (HR) for tofacitinib versus TNFi was 1.33 (95% confidence interval [CI], 0.91-1.94). The most common MACE among patients taking tofacitinib was myocardial infarction.

In the combined tofacitinib groups, 4.19% of patients sustained a first malignancy event within the risk period, compared to 2.89% of patients in the TNFi group. The combined HR for tofacitinib versus TNFi was 1.48 (95% CI, 1.04-2.09). The most common malignancy (excluding NMSC) was lung cancer.

The FDA said it will share its final conclusions when the full results of the trial are available and does not recommend that patients stop treatment before consulting with their provider.

“Health care professionals should consider the benefits and risks of tofacitinib when deciding whether to prescribe or continue patients on the medicine. Continue to follow the recommendations in the tofacitinib prescribing information,” the FDA noted.