Abstract

Abstract Background Ankylosing spondylitis (AS) is a chronic, inflammatory condition that predominantly manifests as arthritis in the axial skeleton. AS related fatigue remains under-researched despite evidence that it is an important contributor to the quality of life in these patients. The impact of biologic therapy on fatigue in patients with AS is not fully understood. Furthermore, it is not clear whether any of the licensed biologic drugs are more effective in treating fatigue in AS than others. The aim of this review is to critically appraise the evidence regarding the effectiveness of biologic agents in treating AS associated fatigue to help guide clinical practice. Methods Pre-defined search terms were entered into PubMed and Embase to identify papers studying the effectiveness of etanercept, adalimumab, infliximab, golimumab, certolizumab pegol and secukinumab in AS associated fatigue. Results were restricted to those published in English from 1990 onwards. 64 papers were initially identified and screened using predefined exclusion criteria; of these, 13 were selected for final inclusion. Results No head-to-head studies analysing fatigue were identified and all studies included analysed fatigue as a secondary outcome measure. Most studies utilised a single question fatigue measurement such as the BASDAI fatigue score. Variation in methodology precluded a meta-analysis. There is evidence that all six biologics improve fatigue in AS to varying degrees. For etanercept, three out of four studies found significant improvement compared to placebo at week 12 and week 54. However, one study that utilised a more robust form of fatigue assessment found no significant differences between etanercept and placebo at week 12. For Adalimumab, two studies were identified, both of which were robust and suggested strong efficacy in treating AS associated fatigue at week 12. For infliximab, two out of three studies were open label trials which showed significant improvement in fatigue at week 6. The third study was a post-hoc analysis of a randomised placebo-controlled trial and showed improvement in fatigue scores at week 24. Two studies were identified for Golimumab, both of which showed significant improvement in fatigue scores at week 24 and week 104 respectively. One placebo-controlled trial of certolizumab pegol showed significant improvement in fatigue at week 24. For secukinumab, one study was identified: a post-hoc analysis of a randomised, placebo-controlled trial. This showed a significant improvement in fatigue at week 16; however, this improvement was not sustained at week 104. Conclusion Although none of the studies analysed fatigue as a primary outcome measure, it appears that biologic treatment overall is successful to varying degrees in the treatment of AS associated fatigue. Future studies would benefit from utilising robust fatigue assessments, comparing biologics, and evaluating long-term effectiveness. In addition, vigilance in recognising fatigue and subsequent considered holistic management is paramount. Disclosures R. Amarnani None. A. Soni Grants/research support; Oxford-UCB Prize Fellowship.

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