were treated with KRYSTEXXA 8mg every 4weeks; and 43patients were treated with placebo. These patients were between the ages of 23 and 89years (average 55years); 173patients were male and 39were female; and 143patients 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 273total patients studied in the clinical program of IV KRYSTEXXA. The frequency was 6.5% for the every 2-week dosing regimen (8 of 123patients), 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 2hours after treatment. This occurred with patients being pre-treated with an oral antihistamine, intravenous corticosteroid, and acetaminophen. [seeBoxed Warning, Warnings and Precautions (5.1, 5.2)]
Infusion Reactions:
Infusion reactions occurred in 26% of patients in the 2week dosing regimen group and 41% of patients in the 4week 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 pruritus (frequency of 9.5%). These manifestations overlap with the symptoms of anaphylaxis, but in a given patient did not occur together to satisfy the clinical criteria for diagnosing anaphylaxis. Infusion reactions are thought to result from release of various mediators, such as cytokines. Infusion reactions occurred at any time during a course of treatment with approximately 3% occurring with the first infusion, and approximately 91% occurred during the time of infusion. Some infusion reaction manifestations were reduced with slowing the rate of infusion, or stopping the infusion and restarting the infusion at a slower rate. These infusion reactions occurred with all patients being pre-treated with an oral antihistamine, intravenous corticosteroid and acetaminophen. [seeBoxed Warning, Warnings and Precautions (5.1, 5.2)]
Gout Flares:
Gout flares were common in the study patients before randomization to treatment, with patients experiencing an average of 10flares in the preceding 18months prior to study entry. During the controlled treatment period with KRYSTEXXA or placebo, the frequencies of gout flares were high in all treatment groups, but more so with KRYSTEXXA treatment during the first 3months of treatment, which seemed to decrease in the subsequent 3mo |
