Abstract
BackgroundFor patients with recurrent flares of gout, tophi, urate crystal arthropathy, and renal stones, urate-lowering therapies (ULTs, including allopurinol and febuxostat) are the first-line treatment. Due to the widespread use of these ULTs (especially in patients with impaired renal function), assessment of the associated renal risk is essential. Accordingly, we performed a disproportionality analysis of reported cases of acute renal failure (ARF) associated with allopurinol and febuxostat.MethodsWe carried out a case/non-case study of the World Health Organization’s VigiBase® pharmacovigilance database between January 1, 2008, and December 31, 2018. The frequency of reports of ARF as a standardized Medical Dictionary for Regulatory Activities query for allopurinol and febuxostat was compared with that of all other reports for the two drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval (CI)]. The results’ stability was assessed in a series of sensitivity analyses (notably after the exclusion of putative competing drugs).ResultsAmong 3509 “suspected drug” notifications for febuxostat and 18,730 for allopurinol, we identified respectively 317 and 1008 cases of ARF. Acute renal failure was reported significantly more frequently for febuxostat and allopurinol than for other drugs (ROR [95%CI] 5.67 [5.05–6.36] and 3.25 [3.05–3.47], respectively). For both drugs, the ROR was higher in women than in men, respectively 11.60 [9.74–13.82] vs. 3.14 [2.69–3.67] for febuxostat and 4.45 [4.04–4.91] vs. 2.29 [2.11–2.50] for allopurinol. The sensitivity analyses confirmed the disproportionality for these two ULTs.ConclusionsAcute renal failure was reported respectively 5.7 and 3.3 times more frequently for febuxostat and for allopurinol than for other drugs. Due to the potential consequences of ARF, physicians should take account of this disproportionality signal when prescribing the ULTs febuxostat and allopurinol.
Highlights
For patients with recurrent flares of gout, tophi, urate crystal arthropathy, and renal stones, uratelowering therapies (ULTs, including allopurinol and febuxostat) are the first-line treatment
Medical Dictionary for Regulatory Activities (MedDRA) includes standardized MedDRA queries (SMQs), which are collections of MedDRA terms consistent with a description of a clinical syndrome associated with Adverse drug reactions (ADRs) and drug exposure
Most of the analyzed cases of acute renal failure (ARF) due to febuxostat or allopurinol had been notified by healthcare professionals (88.6% and 85.6%, respectively)
Summary
For patients with recurrent flares of gout, tophi, urate crystal arthropathy, and renal stones, uratelowering therapies (ULTs, including allopurinol and febuxostat) are the first-line treatment. We performed a disproportionality analysis of reported cases of acute renal failure (ARF) associated with allopurinol and febuxostat. Rey et al Arthritis Research & Therapy (2019) 21:229 tophi, urate crystal arthropathy, and kidney stones, uratelowering therapies (ULTs) are still the recommended firstline treatment. The oldest and most frequently prescribed ULT is allopurinol, which was first marketed in 1966. The second most frequently prescribed ULT is febuxostat, which has been authorized in France since 2008. In both cases, the mechanism of action is based on xanthine oxidase (XO) inhibition [6]. Febuxostat is a potent, selective non-purine inhibitor of XO and does not influence the activity of other enzymes involved in purine or pyrimidine pathways [6]
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