dverse Reactions (6.2)]
Adverse Reactions
The most commonly reported serious adverse reactions from pre-marketing controlled clinical trials were anaphylaxis, which occurred at a frequency of 6.5% in patients treated with Krystexxa 8 mg every 2 weeks, compared to none with placebo; infusion reactions, which occurred at a frequency of 26% in patients treated with Krystexxa 8 mg every 2 weeks, compared to 5% treated with placebo; and gout flares, which were more common during the first 3 months of treatment with Krystexxa compared with placebo. All patients in pre-marketing controlled clinical trials were pre-treated with an oral antihistamine, intravenous corticosteroid and/or acetaminophen to prevent anaphylaxis and infusion reaction. Patients also received non-steroidal anti-inflammatory drugs or colchicine, or both, for at least 7 days as gout flare prophylaxis before beginning Krystexxa treatment. [see Boxed Warning, Warnings and Precautions (5.1, 5.2, 5.3)]
Clinical Trials Experience
The data described below reflect exposure to Krystexxa in patients with chronic gout refractory to conventional therapy in two replicate randomized, placebo-controlled, double-blind 6-month clinical trials: 85 patients were treated with Krystexxa 8 mg every 2 weeks; 84 patients were treated with Krystexxa 8 mg every 4 weeks; and 43 patients were treated with placebo. These patients were between the ages of 23 and 89 years (average 55 years); 173 patients were male and 39 were female; and 143 patients were White/Caucasian, 27 were Black/African American, 24 were Hispanic/Latino and 18 were all other ethnicities. Common co-morbid conditions among the enrolled patients included hypertension (72%), dyslipidemia (49%), chronic kidney disease (28%), diabetes (24%), coronary artery disease (18%), arrhythmia (16%), and cardiac failure/left ventricular dysfunction (12%).
Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug, and may not predict the rates observed in a broader patient population in clinical practice.
Anaphylaxis:
Diagnostic criteria of anaphylaxis were skin or mucosal tissue involvement, and, either airway compromise, and/or reduced blood pressure with or without associated symptoms, and a temporal relationship to Krystexxa or placebo injection with no other identifiable cause. Using these clinical criteria, anaphylaxis was identified in 14 (5.1%) of 273 total patients studied in the clinical program of IV Krystexxa. The frequency was 6.5% for the every 2-week dosing regimen (8 of 123 patients), and 4.8% for the 4-week dosing frequency (6 of 126) of Krystexxa. There were no cases of anaphylaxis in patients receiving placebo. Anaphylaxis generally occurred within 2 hours after treatment. This occurred with patients being pre-treated with an oral antihistamine, intravenous corticosteroid, and acetaminophen. [see Boxed Warning, Warnings and Precautions (5.1, 5.2)]
Infusion Reactions:
Infusion reactions occurred in 26% of patients in the 2 week dosing regimen group and 41% of patients in the 4 week dosing regimen group, compared to 5% of placebo-treated patients. Manifestations of these reactions included urticaria (frequency of 10.6%), dyspnea (frequency of 7.1%), chest discomfort (frequency of 9.5%), chest pain (frequency of 9.5%), erythema (frequency of 9.5%), and |
