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Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients: A systematic review and meta-analysis of randomised trials

Tarp, Simon, Jørgensen, Tanja S., Furst, Daniel E., Dossing, Anna, Taylor, Peter C., Choy, Ernest H., Suarez-Almazor, Maria E., Lyddiatt, Anne, Kristensen, Lars E., Bliddal, Henning and Christensen, Robin 2019. Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients: A systematic review and meta-analysis of randomised trials. Seminars in Arthritis and Rheumatism 48 (6) , pp. 958-966. 10.1016/j.semarthrit.2018.10.002

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Abstract

Objectives To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA). Methods MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals and the GRADE approach was used to assess confidence in the estimates. Results The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32% better when MTX was given concomitantly with biological agents (1.32 [1.20–1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7–16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20% increased (1.21 [0.97–1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0–3 more); Moderate Quality Evidence. Conclusions Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7–16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 0049-0172
Date of First Compliant Deposit: 28 November 2018
Date of Acceptance: 1 October 2018
Last Modified: 18 Oct 2019 22:09
URI: http://orca.cf.ac.uk/id/eprint/117158

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