Risk for Gout Flares With Initiation of Urate-Lowering Therapy Varies by Drug/Dose
Risk for Gout Flares With Initiation of Urate-Lowering Therapy Varies by Drug/Dose
The introduction of urate-lowering therapy (ULT) can affect the risk for gout flares, with fewer flares observed when less intensive treatment and flare prophylaxis were used. These study findings were published in Arthritis Care & Research.Researchers conducted a systematic review and meta-analysis to examine the comparative gout flare risks after initiating or escalating different ULTs with or without concomitant flare prophylaxis, as well as rates of adverse events (AEs) associated with flare prophylaxis and the optimal duration of use.Data were sourced from 5 databases, with studies including adult patients with gout initiating or escalating ULT used for analysis. Random-effects network meta-analysis models were used to estimate risk ratios (RR) with confidence intervals for flares, and AEs were calculated for each pairwise comparison. The primary study outcomes were rates of flares and AEs related to prophylaxis. A total of 29 publications were included in the analysis, of which 27 were randomized controlled trials; 19 trials focused on ULT randomization, 7 on prophylaxis, and 1 on both. Among these, 3 trials enhanced existing ULT through dose escalation or by adding lesinurad. Fixed ULT dosing was employed in 17 trials, while 8 trials adopted a gradual up-titration of ULT doses; 2 trials did not specify the ULT dose. The geographic scope of these trials mainly covered North America and China. Participants were predominantly men (over 90%) with a mean age around 50 years. Thirteen trials with 7816 participants were included within 2 ULT-based flare network analyses, focusing on ULT-initiation trials. Flare rates varied, with the RR for flares associated with febuxostat 40 mg plus any prophylaxis being 1.08 (95% CI, 0.87-1.33) compared with 2.65 (95% CI, 1.58-4.45) for febuxostat 80 mg plus lesinurad 400 mg and any prophylaxis. In contrast, results from another ULT-based sub-network analysis revealed that the RR for flares was significantly lower with febuxostat up-titration plus any prophylaxis (RR, 0.27; 95% CI, 0.12-0.58) and allopurinol up-titration plus any prophylaxis (RR, 0.40; 95% CI, 0.31-0.51), compared with allopurinol up-titration without prophylaxis,. The prophylaxis-based flare network analysis included 5 trials with 758 participants. Results demonstrated that ULT plus prophylaxis reduced flare rates when compared with ULT alone, with RRs ranging from 0.35 (95% CI, 0.25-0.50) for rilonacept 160 mg to 0.50 (95% CI, 0.35-0.72) for colchicine. The prophylaxis-based AE network analysis included 7 trials that indicated no statistically significant differences in AEs between the different prophylactic drugs. However, rilonacept at doses of 160 mg (RR, 2.99; 95% CI, 1.40-6.38) and 80 mg (RR, 2.29; 95% CI, 1.19-4.43) was associated with a higher risk for treatment-related AEs when compared against ULT without prophylaxis. Four trials reported flare rates after prophylaxis cessation, noting an increased number of flares were observed after stopping prophylaxis in some cases but not significantly in others. One trial suggested the optimal prophylaxis duration might be between 7 and 9 months for efficacy and cost-effectiveness, despite lower flare rates associated with 10 to 12 months of treatment. Significant heterogeneity in treatment-related AEs was found within the prophylaxis-based network analysis, though, no significant inconsistency was noted. Treatment rankings based on P-scores and an absence of publication bias were reported, but the study lacked sufficient data for planned sub-group analyses. Study limitations included a high risk for bias in most publications, limited data and comparisons due to trial reporting, and the exclusion of some available therapies. Study authors concluded, “The optimal duration and efficacy of nonsteroidal anti-inflammatory drugs and corticosteroids as flare prophylaxis is unclear.”
References
Risk for Gout Flares With Initiation of Urate-Lowering Therapy Varies by Drug/Dose