Article Text
Abstract
Objective Clinical trials have not consistently demonstrated differences between tumour necrosis factor inhibitor (TNFi) plus methotrexate and triple therapy (methotrexate plus hydroxychloroquine plus sulfasalazine) in rheumatoid arthritis (RA). The study objective was to estimate the efficacy, radiographic benefits, safety and patient-reported outcomes of TNFi–methotrexate versus triple therapy in patients with RA.
Methods A systematic review and network meta-analysis (NMA) of randomised controlled trials of TNFi–methotrexate or triple therapy as one of the treatment arms in patients with an inadequate response to or who were naive to methotrexate was conducted. American College of Rheumatology 70% response criteria (ACR70) at 6 months was the prespecified primary endpoint to evaluate depth of response. Data from direct and indirect comparisons between TNFi–methotrexate and triple therapy were pooled and quantitatively analysed using fixed-effects and random-effects Bayesian models.
Results We analysed 33 studies in patients with inadequate response to methotrexate and 19 in patients naive to methotrexate. In inadequate responders, triple therapy was associated with lower odds of achieving ACR70 at 6 months compared with TNFi–methotrexate (OR 0.35, 95% credible interval (CrI) 0.19 to 0.64). Most secondary endpoints tended to favour TNFi–methotrexate in terms of OR direction; however, no clear increased likelihood of achieving these endpoints was observed for either therapy. The odds of infection were lower with triple therapy than with TNFi−methotrexate (OR 0.08, 95% CrI 0.00 to 0.57). There were no differences observed between the two regimens in patients naive to methotrexate.
Conclusions In this NMA, triple therapy was associated with 65% lower odds of achieving ACR70 at 6 months compared with TNFi–methotrexate in patients with inadequate response to methotrexate. Although secondary endpoints numerically favoured TNFi–methotrexate, no clear differences were observed. The odds of infection were greater with TNFi–methotrexate. No differences were observed for patients naive to methotrexate. These results may help inform care of patients who fail methotrexate first-line therapy.
- Rheumatoid Arthritis
- DMARDs (synthetic)
- DMARDs (biologic)
- Methotrexate
- TNF-alpha
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Footnotes
Contributors All authors meet the criteria for authorship, participated in the writing and/or critical revision of the manuscript, and have seen and approved the submitted version. JC, DC, RF, KN, JP, DHT, VT, RvV and GW contributed to the conception, design or planning of the study. KN, VT, SU and RvV were involved in data acquisition. JC, DC, RF, KN, JP, VT, SU and RvV analysed the data. JC, DC, RF and JP drafted the manuscript. All authors interpreted the results and critically revised the manuscript.
Funding Amgen Inc.
Competing interests RF has received grants and non-financial support from Amgen. VT, SU and KN are employees of ICON plc, which received grants and consulting fees from Amgen. RvV has received grants from Abbvie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche and Union Chimique Belge, and personal fees from Abbvie, Amgen, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Roche, Union Chimique Belge and Vertex. DHT, JC and DC are employees and stockholders of Amgen. JP received grants from Amgen and received consulting fees from Abbvie, Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche and Union Chimique Belge. GW had nothing to disclose.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.