Drug choice, dosing strategy impact gout flare risk when starting urate lowering therapy
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Key takeaways:
- Prophylaxis use and less-intense urate lowering therapy were associated with fewer gout flares.
- More studies are needed on the optimal duration of gout flare prophylaxis.
The risk for gout flare when initiating urate lowering therapy varies based on the drug and dosing strategy used, according to a systematic review and network meta-analysis published in Arthritis Care & Research.
“In recent years, gradual [urate lowering therapy (ULT)] dose escalation strategies without prophylaxis have demonstrated comparable flare rates to standard dose ULT with prophylaxis and may therefore mitigate the need for prophylaxis,” Dorsa Maher, BPharm (Hons), of the University of South Australia, and colleagues wrote in Arthritis Care & Research. “Avoidance of unnecessary therapy is important given the complexity and multi-morbidity often encountered in the gout population, and the well-known toxicities and potential drug-disease and drug-drug interactions of the available prophylactic medications.
“A systematic examination of the comparative flare rates following initiation or escalation of ULT, with and without prophylaxis, at various ULT and/or prophylaxis starting doses and dosing schedules may enable more informed decision-making, particularly for individuals that may be intolerant or have contraindications to prophylactic therapy or for individuals whose only prophylactic option is corticosteroids,” they added.
To help improve this decision-making, Maher and colleagues conducted a systematic review and network meta-analysis of 27 randomized controlled trials reported in 29 publications. They examined the flare risks from initiating and escalating different urate-lowering therapies, with and without gout flare prophylaxis, as well as adverse event rates and the optimal duration of prophylaxis.
Trials published through Nov. 10, 2021, were included from Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Library and the Cochrane Central Register of Controlled Trials. Most publications were assessed as having a high risk for bias, largely due to missing outcome data or selection of the reported results.
According to the researchers, febuxostat (Uloric, Takeda) 40 mg alongside prophylaxis demonstrated a RR for flare of 1.08 (95% CI, 0.87-1.33), compared with placebo plus prophylaxis. At the high end, febuxostat 80 mg alongside lesinurad (Zurampic, Astra Zeneca) 400 mg and prophylaxis demonstrated an RR of 2.65 (95% CI, 1.58-4.45).
Meanwhile, the RRs for gout flare were lower for rilonacept (Arkalyst, Kiniksa) 160 mg plus urate lowering therapy (RR = 0.35; 95% CI, 0.25-0.5), rilonacept 80 mg alongside urate lowering therapy (RR = 0.43; 95% CI, 0.31-0.6), and colchicine plus urate lowering therapy (RR = 0.5; 95% CI, 0.35-0.72), vs. urate-lowering therapy alone.
In addition, the review found “limited evidence” regarding other prophylaxis approaches such as gradual up-titration, NSAIDs and corticosteroids, as well as on potential harms and optimal duration, the researchers wrote.
“High fixed doses of ULT were associated with a greater risk of flares, but since most treatment guidelines have shifted to a gradual ULT up-titration approach, coupled with the reductions in flare risk noted with prophylaxis, there should be a greater emphasis on the need for future studies to compare gradual up-titration approaches against the prophylactic therapies currently used in clinical practice (ie, colchicine, NSAIDs and/or corticosteroids) and to define the optimal duration of prophylaxis,” Maher and colleagues wrote.
“Emphasis should be placed on ensuring more consistent and comprehensive trial reporting of flares as well as pre-specification and thorough reporting of prophylaxis-related AEs in future clinical trials,” they added.
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