P119 The effectiveness of drug-induced immunosuppression using biologics and Janus-kinase inhibitors in improving fatigue in adults with rheumatoid arthritis: a systematic review of randomised controlled trials
Authors: Ghadanfari Hawraa J , Humphreys Jenny H , Druce Katie L 
Published: April 2024

Abstract

Background/Aims
Fatigue is a prominent and debilitating symptom. Many clinicians indicate that they may not assess fatigue frequently because there are no guidelines for fatigue treatment; thus, they feel unskilled to appropriately manage it. Previous evidence from a 2016 Cochrane review supported the use of biologics for fatigue among people with rheumatoid arthritis (RA). As of yet, this evidence has not been incorporated into management guidelines. Further, it is outdated and lacks data on newer drugs such as biosimilars and Janus-Kinase inhibitors (JAKis). We aimed to update the evidence on the effectiveness of biologics and JAKis for RA-fatigue, with a view to informing future guidelines.

Methods
Five electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL and PubMed) were systematically searched, from 2014 to present, for randomised controlled trials (RCTs) evaluating pharmacological interventions in adults with RA. Two reviewers contributed to the screening and analysis of the included papers, and any dispute was resolved through a comprehensive discussion. One reviewer then extracted the data and assessed methodological quality using the Cochrane Risk of Bias Tool. The effectiveness of treatments was determined by extracting change from baseline (CFB) data and/or the proportion achieving the minimal clinically important difference (MCID) in fatigue. Where only CFB data were provided, reviewers compared absolute change values against the relevant MCID to evaluate intervention superiority. Owing to data heterogeneity, a narrative synthesis approach was undertaken.

Results
A total of 43 RCTs and post hoc analyses were included. No eligible studies were found regarding biosimilars. Drug classes investigated included JAKis (n = 27), interleukin-6 inhibitors (n = 9), anti-CD-20 monoclonal antibody (n = 1), selective so-stimulation modulators (n = 2) and TNF inhibitors (n = 4). Of these studies, four were inactive placebo comparator studies, 33 were active placebo comparator studies (i.e. csDMARDs), and six were head-to-head comparator studies. Studies had a low to unclear risk of bias, perhaps due to the high number of post hoc analyses (n = 28, 65%). In total, 37 studies (86%) determined an advantage to using biologics/JAKis; five (12%) determined that treatment with biologics/JAKis was not superior to csDMARDs. The final study showed no meaningful improvement in fatigue from treatment or control.

Conclusion
Most studies showed that biologics/JAKis hold the potential for fatigue management. However, fatigue reporting was poor, and few studies focussed on fatigue as a primary outcome in post hoc analyses. Therefore, it is not clear whether these treatments may, in fact, be more effective in certain subgroups of patients, for example, those for whom fatigue is a significant problem. Accordingly, the development of treatment guidelines involving these therapies is currently unlikely. We propose that future clinical trials designating fatigue as a primary endpoint will be crucial to improving the establishment of guidelines to support fatigue management.

Disclosure
H.J. Ghadanfari: None. J.H. Humphreys: None. K.L. Druce: None.