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 Adverse Reaction
(Preferred Term) KRYSTEXXA
8 mg every 2 weeks
(N=85)
Na (%) Placebo
(N=43)
N (%)
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).
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%)
6.2 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. High anti-pegloticase antibody titer was associated with a failure to maintain pegloticase-induced normalization of uric acid. The impact of anti-PEG antibodies on patients' responses to other PEG-containing therapeutics is unknown.
There was a higher incidence of infusion reactions in patients with high anti-pegloticase antibody titer: 53% (16 of 30) in the KRYSTEXXA every 2 weeks group compared to 6% in patients who had undetectable or low antibody titers.
As with all therapeutic proteins, there is a potential for immunogenicity. The observed incidence of antibody positivity in an assay is highly dependent on several factors including assay sensitivity and specificity and assay methodology, sam |
