Risk Factors for MACE and Malignancies Among Patients Treated With Tofacitinib vs TNF Inhibitors

Patients aged at least 65 years with a history of smoking may be at greater risk for major adverse cardiovascular events (MACE) and malignancies when receiving treatment with tofacitinib vs tumor necrosis factor (TNF) inhibitors, according to results of a post hoc analysis published in Annals of the Rheumatic Disease.

The investigators conducted a post hoc analysis of the phase 3b/4 randomized, open-label, noninferiority, safety endpoint ORAL Surveillance study (ClinicalTrials.gov Identifier: NCT02092467). The parent study risk stratified patients with rheumatoid arthritis (RA) and additional cardiovascular risk factors treated with tofacitinib vs TNF inhibitors. The results revealed higher incidence of MACE and malignancies among patients treated with tofacitinib vs TNF inhibitors.

The current analysis aimed to identify subpopulations of patients with RA, psoriatic arthritis (PsA), or ulcerative colitis (UC) and their relative risks for malignancies, MACE, fatal and nonfatal myocardial infarction (MI), venous thromboembolism (VTE), and all-cause mortality when treated with tofacitinib vs TNF inhibitors.

A total of 4362 patients were included in the parent ORAL Surveillance study. Patients were randomly assigned to treatment with tofacitinib 5 mg twice a day (n=1455), tofacitinib 10 mg twice a day (n=1456), or TNF inhibitors (n=1451). The current analysis also included data from completed development studies, which involved 9904 patients exposed to tofacitinib. Of these, 7964 patients had RA, 783 had PsA, and 1157 had UC.

Based on the ORAL Surveillance study data, age greater than 65 years and a history of smoking were both found to be independent risk factors for several health outcomes when comparing treatment with tofacitinib vs TNF inhibtors. These outcomes included malignancies, MACE, MI, VTE, and all-cause death (hazard ratios (HRs), 1.41–5.19). Though less significant, an increased risk compared with TNF inhibitors was also observed among patients aged less than 65 years and those with no history of smoking, for certain outcomes.

A total of 34.1% (1016/2911) of patients treated with tofacitinib were aged less than 65 years and had no history of smoking. These patients had low absolute risk and no noticeable increase in risk was identified when treated with tofacitinib vs TNF inhibitors. This effect was observed for up to 6 years of follow-up.

The absolute risk remained low and was consistent across patients with RA, PsA, and UC. These findings were observed for up to 10 years of follow-up.

This study was limited by its post hoc nature. Additionally, average follow-up durations differed significantly among the study groups included in the analysis.

The study authors concluded, “These findings can guide individualised benefit/risk assessment and clinical decision-making on treatment with tofacitinib.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.