ACR Convergence 2021

The ORAL Surveillance study is a phase 4, open-label, safety trial designed to assess whether adverse effects of the Janus kinase (JAK) inhibitor tofacitinib were comparable (ie, non-inferior) to TNF inhibitors with regard to major adverse cardiovascular events (MACE) and malignancies in high-risk patients with rheumatoid arthritis. Patients with moderate-to-severe rheumatoid arthritis unresponsive to methotrexate, aged 50 years or older, with one or more additional cardiovascular risk factors were randomly assigned (1:1:1) to receive tofacitinib 5 mg (n=1455) or 10 mg (n=1456) twice daily, or a TNF inhibitor (n=1451; adalimumab 40 mg every other week in North America or etanercept 50 mg every week elsewhere); all patients continued taking methotrexate. The primary results of ORAL Surveillance were presented by Roy Fleischmann (University of Texas Southwestern Medical Center, Dallas, TX, USA). Tofacitinib failed to show non-inferiority compared to TNF inhibitors for both MACE and malignancies (excluding non-melanoma skin cancer), with the upper limit of the 95% CI exceeding the non-inferiority margin of 1·8 for both outcomes (hazard ratio [HR] 1·33 [95% CI 0·91–1·94] for MACE and 1·48 [1·04–2·09] for malignancies). A post-hoc analysis of the risk factors for MACE in ORAL Surveillance was presented by Christina Charles-Schoeman (University of California Los Angeles, Los Angeles, CA, USA). Baseline factors including current smoking (HR 2·18 [95% CI 1·50–3·16]), aspirin use (2·11 [1·40–3·19]), age 65 years or older (1·81 [1·27–2·59]), and male sex (1·81 [1·25–2·61]) were identified as independent risk factors for MACE, irrespective of treatment assignment. In a post-hoc analysis presented by Jeffrey Curtis (University of Alabama at Birmingham, Birmingham, AL, USA), age 65 years or older (HR 2·04 [1·49–2·78]), current smoking (2·61 [1·79–3·81]), and past smoking (2·58 [1·72–3·73]) were identified as independent risk factors for malignancies.