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Meta-Analysis
. 2023 Dec 6;9(4):e003349.
doi: 10.1136/rmdopen-2023-003349.

Efficacy of pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases

Bayram Farisogullari #  1 , Eduardo José Ferreira Santos #  2   3 , Emma Dures  4   5 , Rinie Geenen  6 , Pedro M Machado  7   8   9 ; EULAR taskforce on recommendations for the management of fatigue in people with inflammatory rheumatic diseases; EULAR taskforce on Recommendations for the management of fatigue in people withinflammatory rheumatic diseases
Collaborators, Affiliations
Meta-Analysis

Efficacy of pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases

Bayram Farisogullari et al. RMD Open. .

Abstract

Objective: To identify the best evidence on the efficacy of pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and to summarise their safety in the identified studies to inform European Alliance of Associations for Rheumatology recommendations for the management of fatigue in people with I-RMDs.

Methods: Systematic review of adults with I-RMDs conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Only randomised controlled trials (RCTs) or controlled clinical trials were eligible. Assessment of risk of bias, data extraction and synthesis performed by two reviewers independently and in duplicate. Data pooled in statistical meta-analyses.

Results: From 4151 records, 455 were selected for full-text review, 99 fulfilled the inclusion criteria and 19 RCTs were included in meta-analyses. Adalimumab was superior to placebo in reducing fatigue at 12 and 52 weeks in rheumatoid arthritis (RA) (n=3 and 2 RCTs; mean difference (MD)= -3.03, p<0.001; MD=-2.25, p=0.03, respectively). Golimumab (n=2 RCTs; 24 weeks: MD=-5.27, p<0.001), baricitinib (n=2 RCTs; 24 weeks: MD=-4.06, p<0.001), sarilumab (n=2 RCTs; 24 weeks: MD=-3.15, p<0.001), tocilizumab (n=3 RCTs; 24 weeks: MD=-3.69, p<0.001) and tofacitinib (n=3 RCTs; 12 weeks: MD=-4.44, p<0.001) were also superior to placebo in reducing fatigue in RA. A dose/effect relationship was observed for sarilumab, tocilizumab and tofacitinib. In spondyloarthritis (excluding psoriatic arthritis), secukinumab was superior to placebo in reducing fatigue at 16 weeks (n=2 RCTs; MD=-4.15, p<0.001), with a dose/effect relationship also observed. The narrative results of the RCTs not included in the meta-analysis indicated that several other pharmacological interventions were efficacious in reducing fatigue, with reassuring safety results.

Conclusions: Several pharmacological interventions are efficacious and generally safe for managing fatigue in people with I-RMDs.

Keywords: Arthritis; Autoimmune Diseases; Biological Therapy; Inflammation; Outcome Assessment, Health Care.

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Conflict of interest statement

Competing interests: PMM has received consulting/speaker's fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos,Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, and is supported by the National Institute for Health Research (NIHR), University College London Hospitals (UCLH), Biomedical Research Centre (BRC).

Figures

Figure 1
Figure 1
Flow chart of the study selection and inclusion process.
Figure 2
Figure 2
Risk of bias summary graph for included clinical trials. Review authors’ judgements about each risk of bias item presented as percentages across all included studies using the Cochrane RoB tool.
Figure 3
Figure 3
Meta-analyses summary. The values shown are mean differences in overall fatigue levels and their 95% CIs from the comparison of the identified pharmacological intervention versus placebo. A negative value indicates a reduction in fatigue levels. MD, mean difference; RA, rheumatoid arthritis; SpA, spondyloarthritis.
See this image and copyright information in PMC

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