Efficacy 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 update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of rheumatoid arthritis (RA).MethodsThis systematic literature review (SLR) investigated the efficacy of conventional synthetic (cs), biological (b), biosimilar and targeted synthetic (ts)DMARDs in patients with RA. Medline, EMBASE, Cochrane CENTRAL and Web of Science were used to identify all relevant articles published since the previous update in 2019 to 14 January 2022.ResultsOf 8969 search results, 169 articles were selected for detailed review and 47 were finally included. Trials investigated the efficacy of csDMARDs, bDMARDs and tsDMARDs, DMARD switching, tapering and trials investigating different treatment strategies. The compounds investigated were csDMARDs (methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine), bDMARDs (abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, tocilizumab) and tsDMARDs (baricitinib, filgotinib, tofacitinib, upadacitinib). The efficacy of csDMARDs+ short-term glucocorticoids in early RA was confirmed and similar to bDMARD+MTX combination therapy. Interleukin-6 pathway inhibition was effective in trials on olokizumab and levilimab. Janus kinase inhibitor (JAKi) was efficacious in different patient populations. After insufficient response to JAKi, patients could respond to TNFi treatment. Tapering of DMARDs was feasible for a proportion of patients, who were able to taper therapy while remaining in low disease activity or remission.ConclusionThe results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA.

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

“…Inability to discontinue GCs due to persistently active disease suggests that the ongoing DMARD therapy is not sufficiently effective and needs to be amended, in line with the treat-to-target approach that is also strongly recommended by the EULAR Task Force. The SLR on efficacy 16 confirmed the excellent efficacy of a combination of csDMARDs with GC as for instance evidenced in the NORD-STAR trial: non-inferiority was shown for csDMARDs+GC versus certolizumab+MTX and tocili-zumab+MTX while abatacept+MTX was statistically superior, 40 but in this respect it is important to refer to two other trials, namely AMPLE, comparing abatacept with adalimumab 41 and EXXELERATE, comparing certolizumab pegol with adalimumab, 42 with superimposable results in both studies. Thus, also NORD-STAR revealed clinical similarity between csDMARD+GC therapy and any bDMARD+MTX treatment, with high rates of stringent remission by CDAI at 24 weeks (>40%) for all these therapies.…”

“…The results of the SLRs will not be presented here in detail but are presented in respective parallel publications. [14][15][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.…”

Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice: results from the ARTIS programme

“…In practice, the evidence that informs this choice is, even on a population level, limited. [1][2][3] While superior/non-inferior efficacy of one treatment over another can be demonstrated in relatively small studies with limited follow-up, many safety concerns require larger studies and longer follow-up times for differences to become clear, even when the induction time for a given safety event itself is not an issue. This is recognised by the regulatory framework where data from pivotal randomised controlled trials (RCTs) are usually considered sufficient for demonstrating the efficacy and non-toxicity of the drug, but postapproval safety studies (PASS) are required for several years to evaluate drugassociated risks.…”

Greetings from the editor 2023

“…The current issue of ARD focuses on the advances that were brought about by several of EULAR’s international Task Forces. To this end, an update of the EULAR recommendations for the management of RA,6 accompanied by three systematic literature researches,7–9 is now presented. These recommendations account for the most recent developments in the field and do not back away from thoroughly addressing challenges that have occurred in the recent past 10 11.…”