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Reduction of biologics in rheumatoid arthritis: a systematic review and meta-analysis

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The effects of dose reduction or spacing of all types of biologics in rheumatoid arthritis has not been consistently assessed in systematic reviews. We aimed to assess the effects of biologics reduction compared with dose maintenance in patients with rheumatoid arthritis in low disease activity or remission. We performed a systematic review with meta-analysis according to a previously registered protocol (PROSPERO registration: CRD42017069080); and searched MEDLINE, Embase, Scopus, Cochrane Library and trial registers up to July, 2020. Two researchers selected, extracted and assessed the risk of bias of controlled trials that randomized patients to reduction/spacing or dose maintenance of biologics. Low disease activity, disability and other clinically important outcomes were summarized in random effect meta-analyses. We rated the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation approach. We included ten studies (n = 1331 patients), which assessed reduction or spacing of abatacept, adalimumab, certolizumab pegol, etanercept, or tocilizumab. Risk of bias was high in over half of trials, mainly due to lack of blinding. No statistically significant difference was found in low disease activity (RR = 0.90; 95% CI 0.78–1.04; I2 = 60%, very low certainty), and other outcomes. Subgroup analysis of blinded studies led to homogeneous results, which remained heterogeneous in open-label studies. Reduction or spacing biologics did not affect disease activity and other important outcome. Changes in the doses regimen should consider patient preferences, considering the low certainty of evidence.

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Data transparency

The datasets generated and/or analysed in the current study are available at



Biologic disease modifying antirheumatic drugs


Confidence interval


Disease activity score of 28 joints


Grading of Recommendations Assessment, Development, and Evaluation


Health assessment questionnaire-disability index


Tumour necrosis factor inhibitors


Patient global assessment


Relative risk


Standardized mean difference


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The authors thank Jessica Quintão Pereira for the contribution data extraction and risk of bias assessment, the authors of included manuscripts Rene Westhovens, Alfons den Broeder, Tatsuya Koike, and Yasser el Miedany for providing extra data from upon our requested, and Espaço da Escrita, Pró-Reitoria de Pesquisa, Unicamp for the language revision service.


Leticia Breda e Vasconcelos received an undergraduate scholarship from the program of scientific initiation fellowships of University of Campinas, funded by the National Council of Scientific and Technological Development (CNPq).

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Correspondence to Tais F. Galvao.

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Vasconcelos, L.B., Silva, M.T. & Galvao, T.F. Reduction of biologics in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatol Int 40, 1949–1959 (2020).

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