GLENDALE, Wis., Dec. 12, 2014 /PRNewswire/ -- 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.”
About the Study
Access to the complete study publication can be obtained online through the following link:
Infusion-Related Reactions with Pegloticase, a Recombinant Uricase for the Treatment of Chronic Gout Refractory to Conventional Therapy - Baraf HSB, Yood RA, et al. JCR: Journal of Clinical Rheumatology. 2014; 20(8): 427432.
About Krystexxa
Krystexxa is indicated for adults who have tried or cannot take oral gout medications and still have high uric acid levels and signs and symptoms of gout. Krystexxa is not indicated for the treatment of asymptomatic hyperuricemia. Patients who have a genetic condition known as G6PD deficiency should not use Krystexxa.
Warnings and Precautions:
- Anaphylaxis and infusion reactions have been reported to occur during and after administration of Krystexxa. Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. However, delayed-type hypersensitivity reactions have also been reported.
- Krystexxa should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions. Patients should be pre-medicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of Krystexxa.
- In the event of an infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate. If a severe infusion reaction occurs, discontinue infusion and institute treatment as needed.
- The risk of an infusion reaction is higher in patients who have lost therapeutic response.
- Monitor serum uric acid before each infusion and discontinue treatment if levels rise above 6mg/dL, particularly when two consecutive levels above 6 mg/dL are observed.
- Concomitant use of Krystexxa and oral urate-lowering agents may blunt the rise of serum uric acid levels. It is recommended that patients discontinue oral urate-lowering agents and not institute therapy with oral urate-lowering agents while taking Krystexxa.
- An increase in gout flares was seen in some patients treated with Krystexxa. Gout flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1 week before initiation of Krystexxa therapy and lasting at least 6 months, unless medically contraindicated or not tolerated.
- Krystexxa has not been formally studied in patients with congestive heart failure, but some patients in clinical trials experienced exacerbation. Exercise caution when using Krystexxa in patients who have congestive heart failure and monitor patients closely following infusion.
- Patients receiving re-treatment may be at increased risk for anaphylaxis and infusion reactions and should be monitored carefully.
The most commonly reported serious adverse reactions were gout flares, infusion reactions and anaphylaxis. Most common adverse reactions: gout flares (77%), infusion reactions (26%), nausea (12%), contusion or ecchymosis (11%), nasopharyngitis (7%), constipation (6%), chest pain (6%), anaphylaxis (5%), and vomiting (5%). In addition to events occurring in greater than 5%, exacerbation of pre-existing congestive heart failure occurred in 2%.
Please see the Full Prescribing Information, including Boxed Warning and Medication Guide at www.krystexxa.com.
About Chronic Refractory Gout
Symptoms of gout are caused by the body’s response to the presence of high uric acid (urate) levels which can lead to the formation of urate crystals in the joints and surrounding tissue, which form when uric acid levels in the blood are elevated (a condition called hyperuricemia). The longer hyperuricemia persists, the higher the risk of developing gout. Symptoms of gout may include painful flares, pain or swelling in the joints (known as “gouty arthritis”) or deposits of urate crystals under the skin, called “tophi.” Although most cases of gout can be controlled with conventional urate-lowering therapy, uric acid levels may remain high and symptoms persist despite treatment efforts, even at maximum medically appropriate doses of conventional therapies.
Chronic Refractory Gout is a disease that, if left untreated, can lead to chronic pain, tophi-induced joint destruction and disfigurement, and significant mobility restrictions for patients. Chronic Refractory Gout has been granted orphan status by the FDA due to the relatively small patient population afflicted with this debilitating condition.
About Crealta
Crealta is a specialty pharmaceutical company focused on innovative therapeutics designed to improve patient outcomes. The company was formed to acquire, develop, and market specialty pharmaceutical products with a focus on select physician specialties. For more information about Crealta, please visit www.crealtapharma.com, call 1-781-639-1910, or email kaplan@kogspr.com.
To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/to-mitigate-risk-of-infusion-reactions-with-krystexxa-serum-urate-should-be-used-as-a-predictive-marker-300008867.html
SOURCE Crealta Pharmaceuticals LLC
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