Quantifying and predicting the effect of anti-TNF therapy on axSpA-related fatigue: results from the BSRBR-AS registry and meta-analysis

Abstract

Objectives: Effective management of axial spondyloarthritis (axSpA)-related fatigue is a major unmet clinical need. Anti-TNF therapy may reduce fatigue levels, although any effect has yet to be definitively quantified and predictors of any such improvements are unknown.

Methods: The British Society of Rheumatology Register in Axial Spondyloarthritis (BSRBR-AS) prospectively recruited axSpA patients across the UK. Changes in fatigue levels (measured using the Chalder Fatigue Scale) >1 year were compared between those starting anti-TNF therapy at the time of recruitment and those not. Differences between treatment groups were adjusted using propensity score matching. Results were meta-analysed with the extant literature to calculate pooled estimates. Then, among those BSRBR-AS anti-TNF commencers with clinically relevant fatigue, baseline predictors of response were investigated.

Results: Of the 998 BSRBR-AS recruits with complete fatigue data, 310 were anti-TNF commencers. At 1-year follow-up, the former group reported a mean fatigue change of -2.6 (95% CI -4.1, -1.9) points while the latter reported a mean worsening of fatigue by 0.2 points. Following propensity score adjustment, those commencing anti-TNF therapy reduced fatigue by 3.0 points compared with those not. Of those with significant fatigue and commencing anti-TNF, poor sleep quality at baseline predicted fatigue improvement. In the meta-analysis, including 1109 subjects, treatment with anti-TNF therapy resulted in a significant improvement in fatigue [Standardized mean difference (SMD) = 0.36, 95% CI 0.15, 1.56].

Conclusion: Anti-TNF therapy results in a significant but modest reduction in fatigue amongst axSpA patients, with those reporting poor sleep quality most likely to report improvement. Effective management will likely require additional approaches.

Keywords: anti-tumour necrosis factor; axial spondylarthritis; fatigue; meta-analysis; registry; sleep.