Background/Purpose: Gout is a common form of inflammatory arthritis caused by the crystallisation of uric acid. Sustained reduction of SU below 6mg/dl is critical for successful management of gout. Allopurinol is the most commonly used urate lowering therapy. The creatinine clearance (CrCL) based allopurinol dosing recommendations were based on a proposed relationship between allopurinol dose and allopurinol hypersensitivity syndrome. We have previously reported that target SU can be achieved at year one by titrating allopurinol dose above the CRCL based dose. The aim of this study was to determine if allopurinol was continued and if the reduction in SU was sustained during the subsequent two years.

Methods:

Patients with gout receiving the CrCL based dose of allopurinol with SU >6mg/dl were recruited. The dose of allopurinol was increased until target SU (< 6mg/dl) was achieved. Patients were seen monthly for 12 months and then annually for a further 2 years. Between the annual visits, the patient’s general practitioner (GP) was advised to monitor SU three monthly to ensure target SU was maintained.  

Where patients were lost to follow-up after year 1 available data was collected until the 3 year time point from public and private laboratory databases and hospital records.

Results: Forty five patients were enrolled in the dose escalation study. The mean age was 59.5 years (range 27-83), 93.3% were male, and 80% were of European ancestry. Thirty-five patients completed year 1, 29 patients year 2, and 26 patients year 3. Four patients were lost to follow up, 2 experienced rashes resulting in allopurinol discontinuation, 2 were deemed too unwell to continue and 1 patient died from liver cancer. All patients who completed year 1 and 2 and 25/26 patients at year 3 were receiving allopurinol. The mean dose of allopurinol was 355.71 mg/d (150-600mg/d) at year 1, 353.5 mg/d (150-600mg/d) at year 2 and 358 mg/d (200-600mg/d) at year 3. 31/35 (88.8%) patients that completed year 1 achieved the target SU, mean 5.4mg/dl (3.9-11.3mg/dl). 24/29 (82.8%) patients that completed year 2 achieved target SU, mean 4.9mg/dl (3.2 – 7.2mg/dl). 23/26 (88.5%) patients that completed year 3 achieved target SU, mean 5.4mg/dl (3.9-10.8mg/dl). During year 2, 7/35 (20%) patients had ≥ 4 biochemistry tests including SU. At year 3, 4/35 (11.4%) patients had ≥ 4 biochemistry tests including SU.  The majority of patients had been able to discontinue regular NSAIDs, colchicine or prednisone by year 3. 

Conclusion: In those patients who remain compliant with allopurinol therapy, target SU can be maintained out to three years. Clinicians need to be mindful that rashes can occur even after receiving allopurinol for a prolonged period. There is poor monitoring of SU in the community. Further study is required on how frequently SU should be monitored once target is achieved and attacks have resolved.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/allopurinol-dose-above-creatinine-clearance-based-dose-is-safe-and-effective-in-gout-compliance-efficacy-and-safety-at-2-and-3-years/