Impaired response or insufficient dosage?—Examining the potential causes of “inadequate response” to allopurinol in the treatment of gout

Abstract

Objectives Gout is one of the most common forms of arthritis. It is well established that urate lowering therapy that aims for a serum urate less than at least 0.36mmol/l (6mg/dL) is required for successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor is the most commonly used urate lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol, these patients can be considered to have “inadequate response” to allopurinol. Herein we examine the potential mechanisms and implications of inadequate response to allopurinol. Methods The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol. Results The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be “partially resistant” to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and or function such that oxypurinol is rendered less effective, and/or drug interactions. Conclusions It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician toward making a therapeutic choice that is more likely to result in achieving the serum urate target.

Pilot study of a multidisciplinary gout patient education and monitoring program

“…Maintaining patients at their SUA goal is effective in preventing attacks, shrinking tophi and preventing joint damage (14,21). Careful up-titration of ULT successfully achieves this goal (3,12,22,23).…”

Pneumocystic Pneumonia in Rheumatic Diseases: Current Issues in Prophylaxis

“…Среди возможных при-чин -низкая приверженность к терапии, использование недостаточной дозы препарата, неэффективность макси-мально допустимой дозы [20]. Основная причина, по которой назначение высоких доз аллопуринола при даже незначительном снижении функции почек считается опасной, -относительно частое развитие тяжелых аллер-гических реакций, прежде всего синдрома лекарствен-ной гиперчувствительности (DRESS-синдром (drug rash with eosinophilia and systemic symptoms)), в случае алло-пуринола -синдрома гиперчувствительности к аллопу-ринолу, наиболее тяжело протекающего именно при назначении данного препарата.…”

Effectiveness of an electronic patient-centred self-management tool for gout sufferers: a cluster randomised controlled trial protocol

“…Rates of achievement of target urate in gout patients, with approximately the same inclusion criteria and offered standard treatment, lie anywhere between 28% and 69%. 45 Based on these studies, we have assumed that 50% of the standard care group will achieve the target urate concentration at Open Access 6 months. We expect that this is an optimistic prediction.…”