Background/Purpose

Allopurinol is the standard drug for urate-lowering management of gout. Allopurinol is safe in most patients. The most frequent side effects are minor cutaneous reactions, which occur in approximately 2-4 % of patients. Severe, life-threatening cutaneous adverse reactions are observed in 0.1%-0.4% of patients. They include toxic epidermal necrolysis, Steven Johnson syndrome and drug rash with eosinophilia and systemic symptoms (DRESS). They are more frequent in patients with a history of minor reaction to allopurinol, precluding re-challenge with the drug. Febuxostat is a non-purine xanthine oxidase inhibitor which is structurally distinct from allopurinol. Febuxostat is an interesting alternative to allopurinol, especially in patients who do not reach the serum urate target, because of renal impairment or intolerance to allopurinol. The potential for cross reactivity between febuxostat and allopurinol is of obvious clinical importance when assessing treatment alternatives to allopurinol. Skin reactions have been reported in 0.5% to 1.6% of patients treated by febuxostat (Ernst 2009) and have been suspected to be more frequent in patients with previous cutaneous intolerance to allopurinol.

Methods CACTUS was a non-interventional cross-sectional multicentre study conducted in France by GP from November 2010 to May 2011, with the aim to describe characteristics of gouty patients according to the achieved urate-level. The study involved 2762 adult gouty patients. Among them 1513 had a history of consecutive treatments with allopurinol and febuxostat and were involved in a post-hoc analysis aiming at answering two questions: 1) Was the risk of adverse reaction to febuxostat increased in patients with prior adverse reactions to allopurinol? 2) If yes what was the magnitude of the risk? History of reaction with allopurinol was cross-tabulated with history of reaction with febuxosat, allowing calculation of the odds ratio as a measure of risk. This post-hoc analysis was initially aimed at assessing skin reaction rates. Details on adverse events were not collected. Assuming that any discontinuation of either allopurinol or febuxostat for adverse event was related to a skin reaction obviously led to overestimate the rate of skin reactions with both treatments, but still gave some insight into the existence of drug cross-reactivity. 

Results Among 92 patients who had a history of adverse event to allopurinol, only one (1.1%) experienced a reaction with febuxostat. Among 1421 patients who had no history of allopurinol adverse event, two (0.1%) experienced a reaction with febuxostat resulting in a non-significant odds ratio of 7.8 [0.7-86.8]. 

Conclusion In a post-hoc analysis of the CACTUS study, patients with a history of adverse reaction to allopurinol did not carry significantly higher risk of adverse reaction to febuxostat. Most patients intolerant to allopurinol tolerated febuxostat. Absence of cross-reactivity between allopurinol and febuxostat need to be confirmed by other studies.

---

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/gouty-patients-with-history-of-adverse-reaction-to-allopurinol-are-not-at-higher-risk-of-reaction-to-febuxostat/