Crealta Pharmaceuticals LLC ("Crealta"), today announced that the Journal of Clinical Rheumatology published a comprehensive review of a post-hoc safety analysis that was completed for Krystexxa (pegloticase), including data from the two pivotal randomized Phase III trials and one open-label extension trial. The analysis looked at all infusion-related reactions (IRs) that occurred during the clinical trials, and examined the relationship between loss of urate-lowering response to Krystexxa and the risk of infusion reactions that is cited in the product's FDA-approved labeling.
Infusion-related reactions were reported for 22 of 85 (26%) patients treated with the FDA-approved dose of Krystexxa (8 mg bi-weekly) and two of 43 (5%) patients receiving placebo during the Phase III trials. Retrospective analyses showed that most IRs (91%) occurred in patients receiving the FDA-approved dose who lost response to Krystexxa, as determined by a pre-infusion sUA level greater than 6 mg/dL. For patients sustaining a sUA of <6 mg/dL, IRs occurred in fewer than 1 per 100 infusions.
"Krystexxa is a treatment option that may provide clinical improvements in patients who have failed to respond to other urate-lowering therapies," said Herbert S. B. Baraf, M.D., Clinical Professor of Medicine at The George Washington University School of Medicine and lead author of the study. "This analysis increased our understanding of the drug's safety profile and confirmed the treatment guidance we use today in managing patients with chronic refractory gout with Krystexxa."
Based on the post-hoc analysis, treatment guidance related to serum uric acid (sUA) monitoring and discontinuation of therapy were included and highlighted prominently within the product's prescribing information at the time of approval by FDA. The study publication provides an in-depth review of the data that support these recommendations.
"Infusion-related reactions were the second most common adverse event in the clinical trials. We hope these stopping rules are helping physicians mitigate the risk of infusion reactions with Krystexxa in clinical practice," said Kome Okposo, Pharm.D., Crealta's Senior Director of Medical Affairs.
Based on this analysis, the authors reiterated the following recommendations for administering Krystexxa:
- Monitor serum uric acid (sUA) levels prior to each infusion
- Discontinue therapy if sUA exceeds 6 mg/dL, particularly when two consecutive measurements of sUA greater than 6 mg/dL occur
- Pre-medicate patients with antihistamines and corticosteroids and monitor closely for signs and symptoms of IRs and anaphylaxis for an appropriate period of time
Baraf concluded, "The relationship between sUA and increased risk of IRs was not apparent during the clinical trials because investigators and patients were blinded to uric acid levels and the study treatments. This comprehensive review affirms a critical insight into how we can mitigate the risk of IRs in clinical practice. Identifying individuals who are likely to develop an infusion-related reaction is challenging with any infused therapy, so having a predictive and inexpensive marker like sUA that can be easily measured prior to treatment with Krystexxa has been a clinically meaningful finding."
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