nths of treatment. The percentages of patients with any flare for the first 3months were 74%, 81%, and 51%, for KRYSTEXXA 8mg every 2weeks, KRYSTEXXA 8mg every 4weeks, and placebo, respectively. The percentages of patients with any flare for the subsequent 3months were 41%, 57%, and 67%, for KRYSTEXXA 8mg every 2weeks, KRYSTEXXA 8mg every 4weeks, 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 8mg every 2weeks. No cases were reported in placebo-treated patients. Four subjects had exacerbations of pre-existing congestive heart failure while receiving KRYSTEXXA 8mg every 2weeks 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 8mg every 2weeks are provided in Table1.
Table 1. Adverse Reactions Occurring in 5% or More of Patients Treated with KRYSTEXXA Compared to Placebo Adverse Reaction
(Preferred Term) KRYSTEXXA
8mg every 2weeks
(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 2weeks, 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 2weeks 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, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, the comparison of the incidence of antibodies to pegloticase with the incidence of antibodies to other products may be misleading.
7 DRUG INTERACTIONS
No studies of interactions of KRYSTEXXA with other drugs have been conducted.
Because anti-pegloticase antibodies appear to bind to the PEG portion of the drug, there may be potential for binding with other PEGylated products. The impact of anti-PEG antibodies on pat |
