Safety of synthetic and biological DMARDs: A systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

Alexandre Sepriano, Andreas Kerschbaumer, Sytske Anne Bergstra, Josef S. Smolen, Désirée Van Der Heijde, Roberto Caporali, Christopher J. Edwards, Patrick Verschueren, Savia De Souza, Janet Pope, Tsutomu Takeuchi, Kimme Hyrich, Kevin L. Winthrop, Daniel Aletaha, Tanja Stamm, Jan W. Schoones, Robert B.M. Landewé

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Objectives To perform a systematic literature review (SLR) concerning the safety of synthetic(s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) to inform the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis (RA). Methods SLR of observational studies comparing safety outcomes of any DMARD with another intervention in RA. A comparator group was required for inclusion. For treatments yet without, or limited, registry data, randomised controlled trials (RCTs) were used. Results Fifty-nine observational studies addressed the safety of DMARDs. Two studies (unclear risk of bias (RoB)) showed an increased risk of serious infections with bDMARDs compared with conventional synthetic (cs)DMARDs. Herpes zoster infections occurred more with JAKi than csDMARDs (adjusted HR (aHR): 3.66) and bDMARDs (aHR: 1.9-2.3) (four studies, two low RoB). The risk of malignancies was similar across bDMARDs (five studies) and with tofacitinib compared with bDMARDs (one study, low RoB). The risk of major adverse cardiovascular events (MACE) was similar with bDMARDs and tofacitinib (two studies, one low RoB). Thirty studies reported safety from RCTs, with one, designed to evaluate safety, showing that malignancies (HR (95% CI): 1.48 (1.04 to 2.09)) and MACE (HR (95% CI): 1.33 (0.91 to 1.94)) occurred numerically more frequently with tofacitinib (5 mg and 10 mg doses combined) than with TNFi in patients with cardiovascular risk factors. In this study, the risk of venous thromboembolism (VTE) was higher with tofacitinib 10 mg than with TNFi. Conclusion The safety profile of bDMARDs was further demonstrated. Whether the difference in incidence of malignancies, MACE and VTE between tofacitinib and TNFi applies to other JAKi needs further evaluation.

Original languageEnglish (US)
Pages (from-to)107-118
Number of pages12
JournalAnnals of the rheumatic diseases
Volume82
Issue number1
DOIs
StatePublished - Nov 14 2022

Keywords

  • DMARDs (biologic)
  • DMARDs (synthetic)
  • Outcomes research
  • Rheumatoid Arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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