'Uncontrolled gout has been increasingly linked to a range of complications, including cardiovascular and renal risks, making it crucially important that we continue to gather more insight on how physicians can best treat this disease,' said
While KRYSTEXXA has been traditionally used as a biologic monotherapy with a clinically demonstrated impact on uncontrolled gout, recent literature suggests that using an immunomodulator such as methotrexate has the potential to increase the durability of response to KRYSTEXXA.1 Reducing the burden of urate is critical to improving overall outcomes and quality of life.
'Multiple studies presented at
New data from the Methotrexate to Increase Response Rates in Patients With Uncontrolled GOut Receiving KRYSTEXXA (MIRROR OL, NCT03635957) open-label trial showed that when treated with oral methotrexate (15 mg/week) prior to and throughout the KRYSTEXXA treatment period, 78.6 percent of patients (11 of 14 patients) achieved a complete response, defined as the proportion of serum uric acid (sUA) responders (sUA < 6 mg/dL) during Month 6. All patients tolerated methotrexate and no new safety concerns were identified. [Pegloticase response improvement by co-treatment with methotrexate: results from the MIRROR open-label clinical trial in patients with uncontrolled gout]
Additional data presented during the
Methotrexate addition to KRYSTEXXA allowed most patients to complete therapy and achieve a full therapeutic response. Based on experience in a community rheumatology practice between 2017 and 2019, this chart review included 10 patients treated with a combination of KRYSTEXXA and methotrexate. Most were treated with subcutaneous methotrexate. All 10 patients experienced a rapid decrease in serum uric acid and 80.0 percent (8 of 10 patients) were complete responders. Two patients discontinued treatment before infusion 12; one due to a mild infusion reaction and one lost to follow-up. A gout flare was reported in one patient and no new safety concerns were identified. [Pegloticase response rate in uncontrolled gout patients co-treated with methotrexate: experience in a community rheumatology practice]
Leflunomide as an immunomodulator showed high response rates with KRYSTEXXA. This in-practice case series shows 70.0 percent (7 of 10 patients) achieved a complete response when co-treated with KRYSTEXXA and leflunomide. Three patients discontinued or were lost to follow-up. The findings indicated that low-to-moderate immunomodulation could minimize or prevent the formation of anti-drug antibodies and increase the number of patients who gain the full benefit of a course of treatment, with no new safety concerns. [Leflunomide co-therapy with pegloticase in uncontrolled gout]
Azathioprine with KRYSTEXXA could increase the frequency of patients experiencing long-term lowering of serum urate. The interim data for this investigator-initiated open-label trial of 12 uncontrolled gout patients showed that at the time of data publication 60.0 percent (6 of 10 patients) achieved a complete response; two patients were still receiving treatment with persistent urate-lowering. No adverse events related to azathioprine were reported and gout flares were noted in six patients. [Companion Immunosuppression with Azathioprine Increases the frequency of Persistent Responsiveness to pegloticase in patients with chronic refractory gout]
In addition to the above, an oral presentation on real-world use of KRYSTEXXA with immunomodulators will be held on
On
About KRYSTEXXA
INDICATIONS AND USAGE
KRYSTEXXA (pegloticase injection) is a PEGylated uric acid specific enzyme indicated for the treatment of chronic gout in adult patients refractory to conventional therapy.
Gout refractory to conventional therapy occurs in patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated.
Important Limitations of Use: KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia.
IMPORTANT SAFETY INFORMATION
WARNING: ANAPHYLAXIS AND INFUSION REACTIONS
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 premedicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA. Serum uric acid levels should be monitored prior to infusions, and healthcare providers should consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.
The risk of anaphylaxis and infusion reactions is higher in patients who have lost therapeutic response.
Concomitant use of KRYSTEXXA and oral urate-lowering agents may blunt the rise of sUA levels. Patients should discontinue oral urate-lowering agents and not institute therapy with oral urate-lowering agents while taking KRYSTEXXA.
In the event of anaphylaxis or infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate.
Patients should be informed of the symptoms and signs of anaphylaxis and instructed to seek immediate medical care should anaphylaxis occur after discharge from the healthcare setting.
CONTRAINDICATIONS: G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA
Patients should be screened for G6PD deficiency prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. KRYSTEXXA should not be administered to these patients.
GOUT FLARES
An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, including treatment with KRYSTEXXA. If a gout flare occurs during treatment, KRYSTEXXA need not be discontinued. 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.
CONGESTIVE HEART FAILURE
KRYSTEXXA has not been studied in patients with congestive heart failure, but some patients in the clinical trials experienced exacerbation. Caution should be exercised when using KRYSTEXXA in patients who have congestive heart failure, and patients should be monitored closely following infusion.
ADVERSE REACTIONS
The most commonly reported adverse reactions in clinical trials with KRYSTEXXA were gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting.
Please see Full Prescribing Information and Medication Guide for more information.
About Horizon
Horizon is focused on researching, developing and commercializing medicines that address critical needs for people impacted by rare and rheumatic diseases. Our pipeline is purposeful: we apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, please visit www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.
Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding the potential benefits of KRYSTEXXA in treating uncontrolled gout and the potential benefits of using immunomodulators with KRYSTEXXA. These forward-looking statements are based on management's expectations and assumptions as of the date of this press release and actual results may differ materially from those in these forward-looking statements as a result of various factors. These factors include, but are not limited to, risks regarding whether results of additional clinical trials will be consistent with results of prior trials or Horizon's expectations, and the risks associated with clinical development. For a further description of these and other risks facing Horizon, please see the risk factors described in Horizon's filings with the
References
Botson J and Peterson J. Ann Rheum Dis. 2019; 78: A1289 and Bessen SY, et al. Semin Arthritis Rheum. 2019;49:56-61.
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