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Randomized Controlled Trial
. 2024 Oct;76(10):1552-1559.
doi: 10.1002/art.42927. Epub 2024 Jul 15.

Comparison of Gout Flares With the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-Hoc Analysis of a Randomized Multicenter Trial

Austin Barry  1 , Lindsay N Helget  1 , Maria Androsenko  2 , Hongsheng Wu  3 , Bridget Kramer  1 , Jeff A Newcomb  1 , Mary T Brophy  4 , Anne Davis-Karim  5 , Bryant R England  1 , Ryan Ferguson  6 , Michael H Pillinger  7 , Tuhina Neogi  8 , Paul M Palevsky  9 , Tony R Merriman  10 , James R O'Dell  1 , Ted R Mikuls  1
Affiliations
Randomized Controlled Trial

Comparison of Gout Flares With the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-Hoc Analysis of a Randomized Multicenter Trial

Austin Barry et al. Arthritis Rheumatol. 2024 Oct.

Abstract

Objective: Initiating urate-lowering therapy (ULT) in gout can precipitate arthritis flares. There have been limited comparisons of flare risk during the initiation and escalation of allopurinol and febuxostat, administered as a treat-to-target strategy with optimal anti-inflammatory prophylaxis.

Methods: This was a post-hoc analysis of a 72-week randomized, double-blind, placebo-controlled, noninferiority trial comparing the efficacy of allopurinol and febuxostat. For this analysis, the occurrence of flares was examined during weeks 0 to 24 when ULT was initiated and titrated to a serum urate (sUA) goal of less than 6 mg/dl (<5 mg/dl if tophi). Flares were assessed at regular intervals through structured participant interviews. Predictors of flare, including treatment assignment, were examined using multivariable Cox proportional hazards regression.

Results: Study participants (n = 940) were predominantly male (98.4%) and had a mean age of 62.1 years with approximately equal proportions receiving allopurinol or febuxostat. Mean baseline sUA was 8.5 mg/dl and all participants received anti-inflammatory prophylaxis (90% colchicine). In a multivariable model, there were no significant associations of ULT treatment (hazard ratio [HR] 1.17; febuxostat vs allopurinol), ULT-dose escalation (HR 1.18 vs no escalation), prophylaxis type, or individual comorbidity with flare and no evidence of ULT-dose escalation interaction. Factors independently associated with flare risk during ULT initiation/escalation included younger age, higher baseline sUA, and absence of tophi.

Conclusion: These results demonstrate that gout flare risk during the initiation and titration of allopurinol is similar to febuxostat when these agents are administered according to a treat-to-target strategy using gradual ULT-dose titration and best practice gout flare prophylaxis.

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Conflict of interest statement

TRM has served as a consultant for Horizon Therapeutics, Olatech Therapeutics, Pfizer, UCB, and Sanofi and receives research support from Horizon. BRE has received consulting fees and research support from Boehringer-Ingelheim. MHP has served as a consultant for Horizon Therapeutics, Sobi, Federation Bio, Fortress Bioscience and Scilex, and receives research support from Hikma Pharmaceuticals. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.

Figures

Figure 1:
Figure 1:
Time to First Flare with Treat-to-Target Urate Lowering Therapy (ULT) Initiation. Participants initiated allopurinol (solid line) or febuxostat (dotted line) with appropriate anti-inflammatory prophylaxis; ULT dose was titrated as part of a treat-to-target strategy over a 24-week period. The Kaplan-Meier curve depicts flare-free survival for participants.
Figure 2:
Figure 2:
Risk Factors for Gout Flare with Urate Lowering Therapy (ULT). Hazard ratios and 95% confidence intervals shown for univariable (A) and multivariable (B) analyses.
See this image and copyright information in PMC

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