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

Abstract

ObjectivesTo 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).MethodsSLR 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.ResultsFifty-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.ConclusionThe 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.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update

“…The results of the SLRs will not be presented here in detail but are presented in respective parallel publications 14–16. However, if pertinent for the explanation of the results, parts of these data will be mentioned.…”

“…Information on pragmatic strategy trials was also included in the efficacy and GC SLRs. The SLR results, whose details are published separately, [14][15][16] were presented to the steering committee in full detail and to the whole task force in an abbreviated fashion focusing on the most important findings. The steering committee thoroughly discussed the SLR results and formulated suggestions for an update of the recommendations which were then presented to the whole task force and discussed in greater detail.…”

“…However, no such drug was discussed this time. Aside from the data presented in the safety SLR, 15 physicians should always also gain information from the summary of product characteristics or label to be fully informed about risks and other safety aspects, which are not discussed in this paper.…”

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

“…The steering committee included a main convenor (KLH) and a co-convenor (JG), one methodologist (EN), a co-methodologist (DSC) and a main fellow (GEF). Two co-fellows (MD and SSZ) supported the undertaking of the systematic literature review (SLR),8 especially during validation steps (see below). TF members were selected based on their experience in the field of infections in the setting of AIIRD, considering also gender and regional equity.…”

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

“…To address this stream of constantly evolving evidence, the European Alliance of Associations for Rheumatology (EULAR) management recommendations for pharmacological treatment of RA were updated in 2022 3. Three systematic literature reviews (SLRs) were conducted covering the areas of (1) efficacy, (2) safety of DMARD treatment and (3) utilisation of glucocorticoids in RA and are published separately 4 5…”