Risk of major adverse cardiovascular events in patients initiating biologics/apremilast for psoriatic arthritis: a nationwide cohort study

Rheumatology (Oxford). 2022 Apr 11;61(4):1589-1599. doi: 10.1093/rheumatology/keab522.


Objective: Several biological DMARDs (bDMARDs) have demonstrated anti-inflammatory effects in PsA. However, their comparative cardiovascular safety profiles remain unknown. We evaluated the risk of major adverse cardiovascular events (MACEs) in PsA patients on therapy with different classes of bDMARDs and apremilast.

Methods: This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme 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 2015-19 were included. Patients with previous cardiovascular diseases were excluded. End of follow-up was 31 December 2019. The primary endpoint was an occurrence of MACEs in a time-to-event analysis with propensity score-weighted Cox and Fine-Gray models.

Results: Between 2015 and 2019, we included 9510 bDMARD new users [mean age 48.5 (s.d. 12.7) years; 42% men], including 7289 starting a TNF inhibitor, 1058 an IL-12/23 inhibitor and 1163 an IL-17 inhibitor, with 1885 apremilast new users [mean age 54.0 (s.d. 12.5) years; 44% men]. MACEs occurred in 51 (0.4%) patients. After propensity score weighting, the risk of MACEs was significantly greater with IL-12/23 (weighted hazard ratio 2.0, 95% CI 1.3, 3.0) and IL-17 (weighted hazard ratio 1.9, 95% CI 1.2, 3.0) inhibitors than TNF inhibitors, with no significant increased risk with apremilast (weighted hazard ratio 1.3, 95% CI 0.8, 2.2). Similar results were observed with the Fine-Gray competing risks survival model.

Conclusion: Analysis of a large database revealed a small overall number of MACEs, and the risk of MACEs was greater for PsA new users of IL-12/23 and IL-17 vs TNF inhibitors.

Keywords: National Health Data System; PsA; apremilast; biologics; major adverse cardiovascular event (MACE).

MeSH terms

  • Adult
  • Antirheumatic Agents* / adverse effects
  • Arthritis, Psoriatic* / epidemiology
  • Biological Factors / therapeutic use
  • Biological Products* / adverse effects
  • Cardiovascular Diseases* / chemically induced
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / epidemiology
  • Cohort Studies
  • Female
  • Humans
  • Interleukin-12
  • Interleukin-17
  • Male
  • Middle Aged
  • Thalidomide / analogs & derivatives
  • Tumor Necrosis Factor Inhibitors


  • Antirheumatic Agents
  • Biological Factors
  • Biological Products
  • Interleukin-17
  • Tumor Necrosis Factor Inhibitors
  • Interleukin-12
  • Thalidomide
  • apremilast