Inadequate Response to Allopurinol Dose Escalation Associated With Younger Age, Low Adherence

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A minority of people with gout never reach target serum urate levels when allopurinol dose is increased in a treat-to-target manner.

According to study data published in Rheumatology, partial or inadequate response to allopurinol dose escalation occurs in a minority of patients with gout and is likely related to low adherence.

Study participants were patients with gout and baseline serum urate levels ≥6 mg/dL (n=150). Patients were randomly assigned to either continue their current allopurinol dosing for 12 months and then enter 12 months of dose escalation, or to immediately begin the dose escalation period. During dose escalation, allopurinol was increased monthly until serum urate levels reached <6 mg/dL. Patients were classified as having complete response if they reached target serum urate levels at 9 and 12 months of the dose escalation phase, or if the dose was escalated at 9 months and the serum urate target was reached at 12 months. Patients who achieved partial response reached target levels at some stage but did not fulfill complete response criteria, and patients with inadequate response did not achieve target response at any time during the 12-month dose escalation period. Plasma oxypurinol levels were also captured as a measure of allopurinol adherence.

Of the total study cohort, 82 (54.7%) participants achieved complete response, 55 (36.6%) had partial response, and 13 (8.7%) had inadequate response. Mean serum urate levels following 12 months of dose escalation were 7.6 mg/dL for the inadequate response group, 5.97 mg/dL for the partial response group, and 5.01 mg/dL for the complete response group (P <.001). The percent change in serum urate levels from baseline to 12 months was -21.7%, -6.38%, and -13.09%, for those in the complete, partial, and inadequate response groups, respectively (P =.001).

Patients with inadequate response were younger (P =.04) and had higher baseline serum urate levels (P <.001) than those with partial or complete response. Specifically, those with baseline serum urate levels ≥8 mg/dL had an odds ratio for inadequate response of 11.7 (95% CI, 3.3-41.2). Per univariate analyses, complete responders were older, received a lower mean allopurinol dose, and were more often of New Zealand European ethnicity compared with inadequate or partial responders. However, these results were no longer statistically significant in the multivariate model. Plasma oxypurinol levels were similar in those with inadequate and complete response across the study period, despite significantly higher mean allopurinol doses in patients with inadequate response. This finding may suggest intermittent or partial adherence in inadequate responders.

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These data identify key predictors for allopurinol response in patients with gout and may be useful for clinicians in titrating pharmacologic treatment. Because inadequate response occurred in a minority of patients, these study results support the efficacy of allopurinol dose escalation for treatment of gout.

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Stamp LK, Chapman PT, Barclay M, et al. Can we predict inadequate response to allopurinol dose escalation? Analysis of a randomized controlled trial [published online August 9, 2018]. Rheumatology. doi:10.1093/rheumatology/key237