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Background Patients with IMID, and notably patients with rheumatoid arthritis (RA), are at increased risk of major adverse cardiovascular event (MACE) compared with the general population [1,2]. It is hence paramount to assess the impact of biological or targeted DMARD (e.g., tofacitinib and TNFi) on the risk of MACE in patients already at-risk, particularly in the context of ORAL Surveillance which showed a higher risk MACE with tofacitinib, in comparison with TNFI, in RA patients [3].
Objectives To assess the impact of tofacitinib and TNFi on the risk of MACE in patients with RA treated in real-world clinical practice.
Methods The RELATION study is a retrospective observational cohort study using the French nationwide healthcare database (SNDS). Patients aged 18 years or older, affiliated to the national health insurance with a diagnosis of RA and initiating tofacitinib after November 1, 2017 or TNFi after January 1, 2010 (including adalimumab, etanercept, or other TNFi, without previous exposure to tofacitinib) were followed from treatment initiation to December 31, 2020. Patients with a previous history of MACE in the 4 years preceding cohort entry were excluded. All MACE excluding cardiovascular (CV) death were defined by the first hospitalization for MACE during follow-up. Comorbidities and traditional CV risk factors were identified using hospitalizations, procedures, or medication dispensing in the 4 years prior cohort entry. The unadjusted incidence rate (IR) of MACE excluding CV death was assessed in patients initiating either tofacitinib or a TNFi (with associated 95% confidence intervals (95% CI)). A 1:3 PS matching was conducted to balance the baseline characteristics of patients initiating tofacitinib and TNFi. Cox proportional hazards regression models were used to compare the risk of MACE with tofacitinib vs TNFi during the follow-up period.
Results Between 2010 and 2020, a total of 39,578 patients with RA were included in the study. Among these, 2,811 initiated tofacitinib and 36,767 initiated a TNFi (adalimumab: 10,621, etanercept: 16,512, other TNFi: 9,634). Patients had a mean age of 53 years at cohort entry, and 72% to 81% were women. Around 61% of the cohort had at least one CV risk factor (66.3%for tofacitinib compared to 60.9% for TNFi). The two major co-medications at treatment initiation in the two groups were methotrexate (60.9%) and corticosteroids (50.8%).
After PS matching, the tofacitinib cohort included 2,628 patients, and the TNFi cohort included 7,884 patients. Over a median follow-up period of 11.21 months (tofacitinib: 8.54 months, TNFi: 12.43 months), 25 incident MACE occurred in the tofacitinib group (IR: 9.86 (6.66–14.60) per 1,000 patient-year (PY)) and 159 occurred in the TNFi group (9.59 (8.21–11.20)). The risk of MACE (overall) was similar with tofacitinib vs TNFi (adjusted HR 1.06 [95% CI 0.68, 1.64]; p=0.8127). Similar results were found for ischemic heart disease (HR 0.71 [95% CI 0.35, 1.44]; p=0.3433) and cerebrovascular disease (HR 1.41 [95% CI 0.73, 2.73]; p=0.3116). For peripheral artery disease, the number of events was too low to perform these analyses.
Conclusion In this large population-based study, tofacitinib was not associated with an increased risk of MACE in comparison with TNFi in patients with RA treated in real-world settings. Studies with longer follow-up durations may be necessary to understand the long-term implications of tofacitinib vs TNFi on the risk of MACE.
References
Acknowledgements This study was sponsored by Pfize.r.
Disclosure of Interests Jacques-Eric Gottenberg Consultant of: AbbVie, Bristol Myers Squibb, Galapagos, Gilead, Lilly, MSD, Novartis, Pfizer, Grant/research support from: Pfizer, Bristol Myers Squibb, Meriem Kessouri Shareholder of: Pfizer, Employee of: Pfizer, Jeremie Rudant Shareholder of: Pfizer, Employee of: Pfizer, Nada Assi Employee of: Heva, Benjamin Grenier Employee of: Heva, Julien Kirchgesner Speakers bureau: Pfizer, Consultant of: Gilead, Pfizer, Roche.
Keywords: Rheumatoid arthritis, Targeted synthetic drugs, Real-world evidence
DOI: 10.1136/annrheumdis-2023-eular.4497