ma 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.
Table 2 Plasma Uric Acid < 6 mg/dL for at Least 80% of the Time During Months 3 and 6 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 6 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 2 consecutive uric acid levels greater than 6 mg/dL, the incidence of infusion reactions would have been half, and there would have been little change in the efficacy outcome.
Treatment Group N Number (%) of Subjects Who Met Response Criteria 95% Confidence Interval1 P-Value2
Trial 1
Pegloticase 8 mg every 2 weeks 43 20 (47%) [32%, 61%] <0.001
Pegloticase 8 mg every 4 weeks 41 8 (20%) [7%, 32%] 0.044
Placebo 20 0 (0%)
Trial 2
Pegloticase 8 mg every 2 weeks 42 16 (38%) [23%, 53%] <0.001
Pegloticase 8 mg every 4 weeks 43 21 (49%) [34%, 64%] <0.001
Placebo 23 0 (0%)
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.
How Supplied/Storage and Handling
How Supplied
Krystexxa is supplied as a clear, colorless, sterile solution in phosphate buffered saline intended for intravenous infusion after dilution. Krystexxa is supplied in a single-use 2 mL glass vial with a Teflon® coated (latex-free) rubber injection stopper to deliver Krystexxa as 8 mg of uricase protein in 1 mL volume.
Storage and Handling
Before the preparation for use, Krystexxa must be stored in the carton and maintained at all times under refrigeration between 2° to 8°C (36° to 46°F). Protect from light. Do not shake or freeze.
Do not use beyond the expiration date stamped.
NDC# 54396-801-01
Patient Counseling Information
See Medication Guide
General Information
Provide and instruct patients to read the accompanying Medication Guide before starting |
