he immunogenicity of KRYSTEXXA, patients receiving re-treatment may be at increased risk of anaphylaxis and infusion reactions. Therefore, patients receiving re-treatment after a drug-free interval should be monitored carefully. [see Adverse Reactions ( 6.2 )]
6 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 8Â mg every 2Â weeks, compared to none with placebo; infusion reactions, which occurred at a frequency of 26% in patients treated with KRYSTEXXA 8Â mg every 2Â weeks, compared to 5% treated with placebo; and gout flares, which were more common during the first 3Â 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 7Â days as gout flare prophylaxis before beginning KRYSTEXXA treatment. [see Boxed Warning , Warnings and Precautions ( 5.1 , 5.2 , 5.3 )]
6.1 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: 85Â patients were treated with KRYSTEXXA 8Â mg every 2Â weeks; 84Â patients were treated with KRYSTEXXA 8Â mg every 4Â weeks; and 43Â patients were treated with placebo. These patients were between the ages of 23 and 89Â years (average 55Â years); 173Â patients were male and 39Â were female; and 143Â 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 273Â total patients studied in the clinical program of IV KRYSTEXXA. The frequency was 6.5% for the every 2-week dosing regimen (8 of 123Â 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 2Â hours after treatment. This occurred with patients being pre-treated with an oral antihistamine, intravenous corticosteroid, and acetaminophen. [see Boxed Warning , Warnings and Precautions |
