Chronic gout that is refractory to conventional therapy occurs in patients whose serum uric acid levels have failed to normalize 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. Xanthine oxidase inhibitors that are often prescribed for the treatment of gout include Zyloprim (allopurinol) and Uloric (febuxostat).
The efficacy and safety of Krystexxa were studied in patients with chronic gout refractory to conventional therapy in 2 replicate, multicenter, randomized, double-blind, placebo-controlled clinical studies of 6 months' duration. Patients were randomly assigned to receive Krystexxa every 2 weeks or every 4 weeks or placebo in a 2:2:1 ratio.
Results of both clinical studies showed that a greater proportion of patients treated with Krystexxa every 2 weeks achieved urate lowering to <6 mg/dL than patients receiving placebo. During the first 6 months of treatment, 47% (P < .001) and 38% (P < .001) of patients in the Krystexxa arms in both studies achieved the primary efficacy end point, compared with 0% of patients in the placebo arm.
Clinical trial results also demonstrated that patients treated with Krystexxa experienced a reduction in deposits of uric acid crystals in joints and soft tissue.
The full prescribing information for Krystexxa contains a boxed warning regarding anaphylaxis and infusion reactions. In clinical trials, 1 of 4 patients experienced severe allergic reactions during Krystexxa infusions. A corticosteroid and an antihistamine should be administered to all patients before a Krystexxa infusion is initiated to minimize the risk of such a reaction.
Other adverse reactions that occurred during the clinical trials include gout flare, nausea, injection-site bruising, irritation of the nasal passages, constipation, chest pain, and vomiting.
Physicians are also being warned to use caution about administering Krystexxa to patients with congestive heart failure because the drug was not studied in this patient population.
Savient plans to conduct a post-approval observational safety study of 500 patients treated for 1 year to further evaluate the frequency and severity of infusion reactions, anaphylaxis, and immune complex-related adverse events, and to identify serious adverse events associated with Krystexxa therapy.
The recommended dose and regimen of Krystexxa is 8 mg given as an IV infusion every 2 weeks. Krystexxa should not be administered by IV push or bolus. The drug should only be administered in a health care setting and by health care providers prepared to manage anaphylaxis
