POS0201 RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS INITIATING BIOLOGICS/APREMILAST FOR PSORIATIC ARTHRITIS: A NATIONWIDE POPULATION-BASED STUDY USING THE FRENCH HEALTH INSURANCE DATABASE
Authors: L. Pina Vegas, P. Le Corvoisier, L. Penso, M. Paul, E. Sbidian, P. Claudepierre
Journal: Annals of the Rheumatic Diseases (2021)

Background: Psoriatic arthritis (PsA) is associated with other diseases of the spectrum of spondyloarthritis but also appears to be linked to an increased prevalence of numerous comorbidities and more specifically cardiovascular risk factors and events. Several biological disease-modifying anti-rheumatic drugs (bDMARDs) have demonstrated anti-inflammatory effects in PsA. However, their comparative cardiovascular safety profiles remain unknown. Objectives: Our objective was to assess the relative comparative risk of major adverse cardiovascular events (MACEs) of different classes of bDMARDs or apremilast for PsA. Methods: This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme covering approximately 67 million individuals linked to the hospital discharge database. All adults with PsA who were new users of bDMARDs/apremilast (neither in the year before the index date) during 2015-2019 were included. Patients with previous cardiovascular diseases were excluded. End of follow-up was December 31, 2019. The primary end point was an occurrence of MACE (acute myocardial infarction and ischaemic stroke) in a time-to-event analysis with propensity score-weighted Cox and Fine-Gray models (including age, sex, inflammatory diseases associated, cardiovascular risk biomarkers and other comorbidities). To assess the sensitivity of the estimated weighted hazard ratio (HRw) with respect to several possible models, we performed a per-protocol analysis, a conventional multivariate Cox model, an analysis using a larger definition of MACE, an analysis modifying the new-user definition (as those who had not filled a prescription for a bDMARDs or apremilast for 5 years before the index date) and an analysis modifying the treatment discontinuation definition. Results: Between 2015 and 2019, we included 9,510 bDMARD new users (mean age 48.5±12.7 years; 42% men), including 7,289 starting a TNF inhibitor, 1,058 an IL12/23 inhibitor and 1,163 an IL17 inhibitor, with 1,885 apremilast new users (mean age 54.0±12.5 years; 44% men). MACEs occurred in 51 (0.4%) patients (Figure 1). After propensity score weighting, the risk of MACEs was significantly greater with IL12/23 (HRw 2.0, 95%CI 1.3-3.0) and IL17 (HRw 1.9, 95%CI 1.2-3.0) inhibitors than TNF inhibitors, with no significant increased risk with apremilast (HRw 1.3, 95%CI 0.8-2.2). Similar results were observed with the Fine-Gray competing-risks survival model. The sensitivity analyses results were consistent with those of the main analysis. Conclusion: Analysis of a large national database revealed an overall small number of MACEs. Using robust methodology from the causal inference field, the risk of MACEs was greater for PsA new users of IL12/23 and IL17 versus TNF inhibitors. The risk of MACEs did not significantly differ between new users of apremilast and new users of TNF inhibitors. Figure 1. Flowchart for analytic approach Data are n. bDMARD: biological disease-modifying antirheumatic drugs; CVD: cardiovascular disease; TNF: tumor necrosis factor; IL: interleukin; MACE: major adverse cardiac events. Acknowledgements: L Pina Vegas received a Master 2 grant from the French Society of Rheumatology (Bourse Master 2ème Année 2019) Disclosure of Interests: Laura Pina Vegas: None declared, Philippe Le Corvoisier: None declared, Laetitia Penso: None declared, Muriel Paul: None declared, Emilie Sbidian: None declared, Pascal Claudepierre Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Consultant of: Abbvie, Pfizer, Roche-Chugai, Bristol-Myers Squibb, MSD, UCB, Novartis, Janssen, Lilly, Celgene (consulting fees, less than 10,000 $ each)., Employee of: Roche Chugai, Sanofi Aventis, Celgene, Pfizer, MSD, Novartis and BMS (investigator).