JAK inhibitor treatment did not result in an increased risk for MACE compared with TNF inhibitors in patients with RA and a comparable cardiovascular risk.
The post-authorization safety trial ORAL Surveillance (NCT02092467) found an increased risk for major adverse cardiovascular events (MACE) and venous thromboembolism with tofacitinib versus tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) and at least one additional cardiovascular risk factor. It led to issued warnings from both European and US authorities, which raised concern about the safety of Janus kinase (JAK) inhibitor treatment.
The objective of the “JAK-pot” study, presented by statistician Romain Aymon at EULAR 2023, held May 31-June 2, in Italy, was to assess the incidence of MACE in RA patients treated with JAK inhibitors, compared with other biologic agents in a large, multicountry, real-world population. The data were derived from 14 registries from an international collaboration. Patients starting JAK inhibitors, TNF inhibitors, or biological disease-modifying antirheumatic drugs (DMARDs) with other modes of action (OMA, namely abatacept, rituximab, sarilumab, or tocilizumab) were included. A subanalysis was performed on patients at least 50 years old and with one or more cardiovascular risk factors, mimicking the ORAL Surveillance inclusion criteria. Exposure period was from treatment initiation until the first 3 months after discontinuation, the start of a new treatment, the end of participation in the register, or the end of the study period.
Over the 50,325 treatment initiations considered, 182 incident MACE were reported. The study did not find a significantly higher risk for MACE in RA patients treated with JAKi compared with TNFi. “The crude incidence rates for JAKi were lower than for TNF,” Aymon said. However, the adjusted regression analysis demonstrated no significant difference in the incidence of MACE between JAKi versus TNFi (incidence rate ratio (IRR), 0.87; 95% CI, 0.56-1.35) and OMA versus TNFi (IRR, 1.05; 95% CI, 0.74-1.49).
The ORAL Surveillance duplicate cohort accounted for 38.4% of treatment courses and had a higher incidence of MACE in each treatment group. But, similarly to the overall population, there was no significant difference in the incidence rates of MACE observed between JAKi versus TNFi (IRR, 0.78; 95% CI, 0.44-1.38) and OMA versus TNFi (IRR, 0.84; 95% CI, 0.53-1.32). “There were no differences in any outcomes, only maybe a small venous thromboembolic event signal in the ORAL Surveillance duplicate cohort,” Aymon concluded.
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