Withdrawal of allopurinol in patients with gout.

Abstract

The xanthine oxidase inhibitor allopurinol effectively lowers the plasma level of uric acid and the drug has become widely used in the treatment of gout, especially in patients with renal failure, uric acid calculi, or intolerance to uricosuric agents (Scott, Hall, and Grahame, 1966). Various theoretical complications of treatment have been considered from time to time, such as possible incorporation of ribonucleotide into genetic material or the effects of crystals of allopurinol in voluntary muscle, as discussed below. For these reasons it was thought reasonable a few years ago to determine the effect of discontinuing allopurinol therapy in gouty patients who were not over-producers of uric acid and whose renal function was not impaired.Plan of study Medication was discontinued in 33 patients with gout (32 men and one woman), with a mean age of 58 years (range 33-75 yrs). In five of them the drug would have had to be discontinued in any case because of a skin rash or malaise probably attributable to the drug; in 28 the drug was stopped in the absence of side effects after full discussion with individual patients. None of these latter patients had impairment of renal function (as estimated by blood urea) and none were over-producers of uric acid as indicated by a 24-hour urinary uric acid excretion of less than 600 mg on a low-purine diet.The mean length of history of gout before starting treatment had been 15 years (range 05-42 yrs), with an average of 4-5 attacks per year before starting therapy. The mean duration of allopurinol treatment before the drug was discontinued was 93 weeks (range 19-236 wks), and the mean duration off allopurinol at the time this analysis was made was 86 weeks (range 14-210 wks).

Using serum urate levels to determine the period free of gouty symptoms after withdrawal of long‐term urate‐lowering therapy: A prospective study

“…Although the risk of developing gout appears to be a function of the magnitude and duration of hyperuricemia, other still unknown, predisposing factors are likely because not every patient with sustained hyperuricemia develops gout (16). Prolonged ULT for patients with gout has been supported by several reports demonstrating that gout symptoms frequently recur after ULT withdrawal (11)(12)(13). However, the conclusions of these reports do not entirely agree: 2 reports conclude that ULT should be taken indefinitely (11,13), but another suggests that long-term control of urate levels may induce complete depletion of urate deposits and put patients into an asymptomatic hyperuricemic state for a prolonged period (12).…”

“…First, only a limited number of patients were studied: 64 patients overall in the 3 reports. Second, only 2 of the studies were prospective (11,12), so that one-third of the entire study group was potentially subject to retrospective review bias. Third, the diagnosis of gout was confirmed by crystal identification in only 1 of the reports (12).…”

“…The major criterion for inclusion was that patients were asymptomatic and willing to withdraw from ULT. In one study (11), some patients stopped allopurinol due to adverse events: at least 50% of the previously reported patients had tophaceous gout, and duration of ULT ranged from 1 to 19 years in patients with tophi (12,13). In one series, serum urate levels while receiving ULT ranged from 2.6 mg/dl to 9.2 mg/dl (13), so that some patients did not achieve average urate levels under the solubility limit for monosodium urate while receiving ULT.…”

“…Expert opinion suggests that ULT should be continued indefinitely (10), based in part on the observation that gouty symptoms recur after ULT is discontinued (11)(12)(13). The studies reporting recurrence, however, have some shortcomings: they were not prospective or did not document either a definite diagnosis of gout or long-term control of urate levels during ULT.…”

“…The prospect of life-long ULT might be one of the causes. Also, by comparison with other continuous treatment regimens prescribed for disorders that may be asymptomatic for long periods, patients appear to withdraw frequently from ULT once gouty symptoms have resolved (15), even if the duration of ULT has been Ͻ1 year (11). The current study was designed to ascertain the outcome (with regard to gouty symptoms) of ULT withdrawal after long-term, documented control of serum urate levels.…”