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. [see Boxed 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 10 flares in the preceding 18 months 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 3 months of treatment, which seemed to decrease in the subsequent 3 months of treatment. The percentages of patients with any flare for the first 3 months were 74%, 81%, and 51%, for Krystexxa 8 mg every 2 weeks, Krystexxa 8 mg every 4 weeks, and placebo, respectively. The percentages of patients with any flare for the subsequent 3 months were 41%, 57%, and 67%, for Krystexxa 8 mg every 2 weeks, Krystexxa 8 mg every 4 weeks, and placebo, respectively. Patients received gout flare prophylaxis with colchicine and/or nonsteroidal anti-inflammatory drugs (NSAIDs) starting at least one week before receiving Krystexxa. [see Warnings and Precautions (5.3)]
Congestive Heart Failure:
Two cases of congestive heart failure exacerbation occurred during the trials in patients receiving treatment with Krystexxa 8 mg every 2 weeks. No cases were reported in placebo-treated patients. Four subjects had exacerbations of pre-existing congestive heart failure while receiving Krystexxa 8 mg every 2 weeks during the open-label extension study. [see Warnings and Precautions (5.4)].
Other Adverse Reactions:
The most commonly reported adverse reactions that occurred in greater than or equal to 5% of patients treated with Krystexxa 8 mg every 2 weeks are provided in Table 1.
Table 1. Adverse Reactions Occurring in 5% or More of Patients Treated with Krystexxa Compared to Placebo a If the same subject in a given group had more than one occurrence in the same preferred term event category, the subject was counted only once.
b Most did not occur on the day of infusion and could be related to other factors (e.g. concomitant medications relevant to contusion or ecchymosis, insulin dependent diabetes mellitus).
Adverse Reaction
(Preferred Term) Krystexxa
8 mg every 2 weeks
(N=85)
Na (%) Placebo
(N=43)
N (%)
Gout flare 65 (77%) 35 (81%)
Infusion reaction 22 (26%) 2 (5%)
Nausea 10 (12%) 1 (2%)
Contusionb or Ecchymosisb 9 (11%) 2 (5%)
Nasopharyngitis 6 (7%) 1 (2%)
Constipation 5 (6%) 2 (5%)
Chest Pain 5 (6%) 1 (2%)
Anaphylaxis 4 (5%) 0 (0%)
Vomiting 4 (5%) 1 (2%)
Immunogenicity
Anti-pegloticase antibodies developed in 92% of patients treated with Krystexxa every 2 weeks, and 28% for placebo. Anti-PEG antibodies were also detected in 42% of patients treated with Krystexxa |
