Background In 2021, the European and US-American regulatory agencies EMA and FDA issued warnings about the cardiovascular (CV) safety of the Janus kinase inhibitor (JAKi) tofacitinib and required changes in labelling. These actions were based on results of the post-authorisation safety trial Oral Surveillance⁽¹⁾.

Objectives To analyse major cardiovascular events (MACE) under treatment with JAKi, tumor necrosis factor inhibitors (TNFi) or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs - bionaive) in patients with rheumatoid arthritis (RA) observed in daily rheumatological care.

Methods Data from patients enrolled in the biologics register RABBIT with treatment episodes from 01/2017 - 04/2021 were included. Incidence rates (IR) of MACE per 100 patient-years (PY) with 95% confidence intervals (CI) and adjusted risk ratios (RR) were calculated for all and for high-risk patients (age ≥ 50 years and ≥ 1 CV risk factor). Poisson regression analysis was adjusted for age, sex, smoking, disease activity, prior therapies, glucocorticoids and comorbidities.

Results Starting from 2017, 2030 JAKi, 2338 TNFi and 871 csDMARD initiations were documented. Patients with a JAKi start were slightly older, more often women and had a longer RA disease duration (Table 1). The proportion with positive autoantibodies was higher than in the TNFi and csDMARD group, the physical function was lower, and they had received more previous biologic treatments. Characteristics of high-risk patients are also given in the Table 1.

In total, 28 incident MACE were reported. Patients under treatment with JAKi, TNFi and csDMARD showed comparable IR for MACE between 0.26 and 0.41 events per 100 PY (Figure 1). High-risk patients showed higher IRs. The median time under treatment was 10 months on JAKi and TNFi, and 12 months on csDMARDs. The majority of events were reported in the first year after treatment start. In the adjusted analyses, JAKi (RR 0.94 [95% CI 0.39; 2.28]) and csDMARDs (RR 0.85 [0.25; 2.88]) did not show a significantly increased risk for MACE compared with TNFi in unselected patients, and also not in high-risk patients (JAKi: RR 0.90 [0.37; 2.17]; csDMARDs: RR 0.61 [0.16; 2.28]).

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Figure 1.

Incidence rates of MACE per 100 patient years by treatment group.

Conclusion IR of MACE in patients receiving JAKi in a real-world setting was lower than the IR reported for tofacitinib in the Oral Surveillance study. We found no evidence of an increased risk of MACE with JAKi compared to TNFi, although patients in the JAKi group were older and had longer disease duration.

References [1]Pfizer Press Release (27 Jan 2021): https://www.pfizer.com/news/press-release/press-release-detail/pfizer-shares-co-primary-endpoint-results-post-marketing

Acknowledgements RABBIT is supported by a joint, unconditional grant from AbbVie, Amgen, BMS, Fresenius-Kabi, Galapagos, Hexal, Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, VIATRIS and UCB.

Disclosure of Interests Yvette Meissner Speakers bureau: Pfizer, Katinka Albrecht: None declared, Jörn Kekow: None declared, Silke Zinke Speakers bureau: Biogen, Galapagos, UCB, Lilly, Consultant of: Abbvie, Biogen, Galapagos, Novartis, Hans-Peter Tony Consultant of: AbbVie, Astra-Zeneca, BMS, Chugai, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Martin Schaefer: None declared, Anja Strangfeld Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, Pfizer, Roche, Sanofi, UCB.