Pfizer announced results from a recently completed postmarketing safety study that compared the risk of cardiovascular (CV) events and malignancies with tofacitinib vs a tumor necrosis factor inhibitor (TNFi) among patients 50 years of age and older with moderate to severe rheumatoid arthritis (RA) and at least 1 additional CV risk factor.

The randomized phase 3b/4 ORAL Surveillance study included 4362 RA patients who were taking methotrexate without adequate control of symptoms. Patients were randomly assigned to receive tofacitinib 5mg or 10mg orally twice daily or TNFi (adalimumab or etanercept). The coprimary end points were the incidence of malignancies, excluding non-melanoma skin cancer, and major adverse cardiovascular events (MACE).

Results showed that the noninferiority criteria was not met for the primary comparison of the combined tofacitinib doses vs TNFi with regard to MACE (hazard ratio [HR] 1.33; 95% CI, 0.91-1.94) and malignancies (HR 1.48; 95% CI, 1.04-2.09), as the upper limit of the 95% CI exceeded the prespecified noninferiority criterion of 1.8. As for secondary comparisons, there was no evidence of a difference in the primary end points between the 2 doses of tofacitinib.

The primary analyses included 135 patients with MACE (98 for combined tofacitinib doses and 37 for TNFi) and 164 patients with malignancies (122 for combined tofacitinib doses and 42 for TNFi), excluding non-melanoma skin cancer. The most frequently reported MACE and malignancy for tofacitinib-treated patients were myocardial infarction and lung cancer, respectively, with a higher occurrence of events seen in patients with a known risk factor.

“Providing information on the safe and effective use of our medicines is imperative,” said Tamas Koncz, MD, PhD, Chief Medical Officer, Inflammation and Immunology, Pfizer. “We believe that extensive additional analyses of these study data, and communicating them as soon as possible, will further clarify the benefit and risk profile of tofacitinib to help inform medical decision making and patient care.”

Tofacitinib, a Janus kinase (JAK) inhibitor, is marketed under the brand names Xeljanz and Xeljanz XR. Xeljanz and Xeljanz XR are both approved for the treatment of moderate to severe active rheumatoid arthritis, active psoriatic arthritis, and moderate to severe active ulcerative colitis.


Pfizer shares co-primary endpoint results from post-marketing required safety study of Xeljanz® (tofacitinib) in subjects with rheumatoid arthritis (RA). [press release]. New York, NY: Pfizer Inc.; January 27, 2021.