An updated systematic review and meta-analysis of randomised controlled trials on the effects of urate-lowering therapy init.pdf

Seminars in Arthritis and Rheumatism 65 (2024) 152367 Contents lists available at ScienceDirect Seminars in Arthritis...

Seminars in Arthritis and Rheumatism 65 (2024) 152367 Contents lists available at ScienceDirect Seminars in Arthritis and Rheumatism journal homepage: www.elsevier.com/locate/semarthrit An updated systematic review and meta-analysis of randomised controlled trials on the effects of urate-lowering therapy initiation during a gout flare Vicky Tai a, *, Peter Gow b, Sarah Stewart a, c, Panchalee Satpanich d, Changgui Li e, f, Abhishek Abhishek g, Nicola Dalbeth a a Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand b Counties Manukau Health, Middlemore Hospital, Auckland, New Zealand c School of Clinical Sciences, Auckland University of Technology, Auckland, New Zealand d Rheumatology Division, Department of Internal Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand e Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, Qingdao 266003, China f Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao 266003, China g Academic Rheumatology, School of Medicine, University of Nottingham, Nottingham, United Kingdom A R T I C L E I N F O A B S T R A C T Keywords: Background: There is uncertainty about the optimal time to start urate-lowering therapy (ULT) in the setting of a Gout gout flare. The aim was to perform a systematic review and meta-analysis of randomised controlled trials (RCTs) Urate-lowering therapy assessing the effects of ULT initiation during a gout flare. Systematic review Methods: This systematic review was conducted in accordance with PRISMA methodology. MEDLINE, EMBASE Meta-analysis and The Cochrane Library were searched for studies published between database inception to 1 March 2023. RCTs published in English that examined ULT initiation during a gout flare in adults ≥18 years were included. The quality of included studies was assessed using the revised Cochrane Risk of Bias tool 2.0. Data were extracted for the following outcomes: patient-rated pain score, duration of gout flare, recurrent gout flares, time to achieve target serum urate, adherence to ULT, patient satisfaction with treatment and adverse events. Meta-analyses were performed using Review Manager v5.4. This study is registered on PROSPERO, number CRD42023404680. Results: A total of 972 studies were identified and of these, six RCTs met the criteria for inclusion in the analysis. Three studies were assessed as having high risk of bias, one study as having some concerns, and two studies as having low risk of bias. In total, there were 445 pooled participants; 226 participants randomised to early initiation of ULT and 219 to placebo or delayed initiation of ULT. Allopurinol was used in three studies, febuxostat in two studies and probenecid in one study. Few participants (n = 62, 13.9 %) had tophaceous gout. Participants with renal impairment were excluded from most studies. There were no differences in patient-rated pain scores at baseline, days 3–4, days 7–8, day 10 or days 14–15 (p ≥ 0.42). Additionally, there was no sig­ nificant difference in time to resolution of gout flare (standardised mean difference 0.77 days; 95 % CI -0.26 to 1.79; p = 0.14) or the risk of recurrent gout flare in the subsequent 28 to 30 days (RR 1.06; 95 % CI 0.59 to 1.92; p = 0.84). Adverse events were similar between groups. The included studies did not report time to achieve target serum urate, long-term adherence to ULT, or patient satisfaction with treatment. Conclusion: There appears to be no evidence for harm or for benefit to initiating ULT during a gout flare. These findings have limited applicability to patients with tophaceous gout, or those with renal impairment. Introduction geographical locations, and with rising global incidence and prevalence. Effective long-term treatment of gout requires urate-lowering Gout is a common inflammatory condition caused by the deposition therapy (ULT) to reduce the serum urate level to 7.0 mg/dL. Participants had a mean of 3 ULT to delayed initiation of ULT [12–14,17], whilst two studies to 4 previous gout flares and a mean disease duration of 3 to 5 years. Few compared early initiation of ULT to placebo [15,16]. Background participants (n = 62, 13.9 %) had tophaceous gout. anti-inflammatory prophylaxis was used in all studies and this included non-steroidal anti-inflammatories and colchicine. Of the six studies, five excluded participants with renal impairment – two studies excluded Severity of gout flare participants with eGFR