s were eligible to enroll in a 2-year open label extension study.
Entry criteria for patients to be eligible for the trials were: baseline serum uric acid (SUA) of at least 8Â mg/dL; had symptomatic gout with at least 3Â gout flares in the previous 18Â months or at least 1Â gout tophus or gouty arthritis; and had a self-reported medical contraindication to allopurinol or medical history of failure to normalize uric acid (to less than 6Â mg/dL) with at least 3Â months of allopurinol treatment at the maximum medically appropriate dose.
The mean age of study subjects was 55Â years (23-89); 82% were male, mean body mass index (BMI) was 33Â kg/m, mean duration of gout was 15Â years, and mean baseline SUA was 10Â mg/dL.
To assess the efficacy of KRYSTEXXA in lowering uric acid, the primary endpoint in both trials was the proportion of patients who achieved plasma uric acid (PUA) less than 6 mg/dL for at least 80% of the time during Month 3 and Month 6. As shown in Table 2, a greater proportion of patients treated with KRYSTEXXA every 2 weeks achieved urate lowering to below 6 mg/dL than patients receiving placebo. Although the 4 week regimen also demonstrated efficacy for the primary endpoint, this regimen was associated with increased frequency of anaphylaxis and infusion reactions and less efficacy with respect to tophi.
The effect of treatment on tophi was a secondary efficacy endpoint and was assessed using standardized digital photography, image analysis, and a Central Reader blinded to treatment assignment. Approximately 70% of patients had tophi at baseline. A pooled analysis of data from Trial 1 and Trial 2 was performed as pre-specified in the protocols. At Month 6, the percentage of patients who achieved a complete response (defined as 100% resolution of at least one target tophus, no new tophi appear and no single tophus showing progression) was 45%, 26%, and 8%, with KRYSTEXXA 8 mg every 2 weeks, KRYSTEXXA 8 mg every 4 weeks, and placebo, respectively. The difference between KRYSTEXXA and placebo was statistically significant for the every 2 week dosing regimen, but not for the every 4 week dosing regimen.
Table 2 Plasma Uric Acid < 6 mg/dL for at Least 80% of the Time During Months 3 and 6 Treatment Group N Number (%) of Subjects Who Met Response Criteria 95% Confidence Interval1 P-Value2
1 95% confidence interval for differences in responder rate between pegloticase group vs. placebo
2 P-value using Fisher's exact test to compare pegloticase group vs. placebo
Note: Based on post-hoc analyses of the clinical trial data, if KRYSTEXXA had been stopped when a patient's uric acid level rose to greater than 6Â mg/dL on a single occasion, the incidence of infusion reactions would have been reduced by approximately 67%, but the success rates for the primary efficacy endpoint would have been reduced by approximately 20%. If KRYSTEXXA had been stopped after 2Â consecutive uric acid levels greater than 6Â mg/dL, the incidence of infusion reactions would have been half, and there would have been little change in the efficacy outcome.
Trial 1
   Pegloticase 8 mg every 2 weeks 43 20 (47%) [32%, 61%] <0.001
   Pegloticase 8& |
