Safety Concerns Raised With Higher Dose of Tofacitinib in Post-Marketing Study

Pfizer has announced that the company intends to transition patients with rheumatoid arthritis (RA) who were receiving tofacitinib 10 mg twice daily to receive tofacitinib 5 mg twice daily in its post-marketing study required by the US Food and Drug Administration (FDA). Tofacitinib is currently the only a Janus kinase inhibitor approved by the FDA to treat adults with RA, psoriatic arthritis, and ulcerative colitis.

The company noted that the modification is being taken as a result of a notification from the Rheumatology Data Safety Monitoring Board about a safety concern in the tofacitinib 10 mg twice daily treatment group. The 5 mg twice daily dose has been approved by the FDA for adult patients with moderate to severe RA.

The post-marketing requirement study A3921133 (ClinicalTrials.gov Identifier: NCT02092467)  is an ongoing, open-label study designed to examine the safety of tofacitinib 5 mg and 10 mg compared with a control group receiving tumor necrosis factor inhibitors (TNFi). Patients enrolled in this study were aged ≥50 years, had ≥1 cardiovascular risk factor, and were receiving stable doses of methotrexate at baseline.

Data from a recent analysis of study A3921133 showed that the tofacitinib 10 mg twice daily group had a statistically significant difference in the occurrence of pulmonary embolism compared with the TNFi control group. Data also showed increased mortality in the tofacitinib 10 mg twice daily group compared with the 5 mg twice daily and TNFi control groups.

The Rheumatology Data Safety Monitoring Board has stated that other ongoing studies of tofacitinib in patients with RA, juvenile idiopathic arthritis, psoriatic arthritis, and ankylosing spondylitis should continue unchanged.

Reference

Pfizer announces modification to ongoing tofacitinib FDA post-marketing requirement study in patients with rheumatoid arthritis [press release]. New York, NY: Pfizer, Inc.; February 19, 2019. https://investors.pfizer.com/investor-news/press-release-details/2019/Pfizer-Announces-Modification-to-Ongoing-Tofacitnib-FDA-Post-Marketing-Requirement-Study-in-Patients-with-Rheumatoid-Arthritis/default.aspx. Accessed February 21, 2019.