ADVERSE REACTIONS
The data described herein reflect exposure to ILARIS in 104 adult and pediatric CAPS patients, (including 20 FCAS, 72 MWS, 10 MWS/NOMID (Neonatal Onset Multisystem Inflammatory Disorder) overlap, 1 non-FCAS non-MWS, and 1 mis-diagnosed in placebo-controlled (35 patients) and uncontrolled trials. Sixty-two patients were exposed to ILARIS for at least 6 months, 56 for at least 1 year and 4 for at least 3 years. A total of 9 serious adverse reactions were reported for CAPS patients. Among these were vertigo (2 patients), infections (3 patients), including intra-abdominal abscess following appendectomy (1 patient). The most commonly reported adverse reactions associated with ILARIS treatment in the CAPS patients were nasopharyngitis, diarrhea, influenza, headache, and nausea. No impact on the type or frequency of adverse drug reactions was seen with longer-term treatment. One patient discontinued treatment due to potential infection.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Clinical Trial Experience
Approximately 833 subjects have been treated with ILARIS in blinded and open-label clinical trials in CAPS and other diseases, and healthy volunteers. A total of 15 patients reported serious adverse reactions during the clinical program.
Study 1 investigated the safety of ILARIS in an 8-week, open-label period (Part 1), followed by a 24-week, randomized withdrawal period (Part 2), followed by a 16-week, open-label period (Part 3). All patients were treated with ILARIS 150 mg subcutaneously or 2 mg/kg if body weight was greater than or equal to 15 kg and less than or equal to 40 kg (see Table 1).
Since all CAPS patients received ILARIS in Part 1, there are no controlled data on adverse events (AEs). Data in Table 1 are for all AEs for all CAPS patients receiving canakinumab. In study 1, no pattern was observed for any type or frequency of adverse events throughout the three study periods.
Table 1 Number (%) of Patients with AEs by Preferred Terms, in > 10% of Patients in Parts 1 to 3 of the Phase 3 Trial for CAPS Patients
Preferred Term |
ILARIS
N=35
n (%) |
| n % of Patients with Adverse Events |
35 (100) |
| Nasopharyngitis |
12 (34) |
| Diarrhea |
7 (20) |
| Influenza |
6 (17) |
| Rhinitis |
6 (17) |
| Nausea |
5 (14) |
| Headache |
5 (14) |
| Bronchitis |
4 (11) |
| Gastroenteritis |
4 (11) |
| Pharyngitis |
4 (11) |
| Weight increased |
4 (11) |
| Musculoskeletal pain |
4(11) |
| Vertigo |
4(11) |
Vertigo
Vertigo has been reported in 9 to 14% of patients in CAPS studies, exclusively in MWS patients, and reported as a serious adverse event in two cases. All events resolved with continued treatment with ILARIS.
Hypersensitivity
Hypersensitivity reactions have been reported with ILARIS therapy. No anaphylactic reactions have been reported. ILARIS should not be administered to any patients with known clinical hypersensitivity to ILARIS [ see Contraindications (4) and Warnings and Precautions (5.3) ].
Injection Site Reactions
In Study 1, subcutaneous injection site reactions were observed in 9% of patients in Part 1 with mild tolerability reactions; in Part 2, one patient each (7%) had a mild or a moderate tolerability reaction and, in Part 3, one patient had a mild local tolerability reaction. No severe injection-site reactions were reported and none led to discontinuation of treatment.
Immunogenicity
A specific biosensor binding assay was used to detect antibodies directed against canakinumab in patients who received ILARIS. None of the 60 CAPS patients who had received ILARIS tested positive for treatment-emergent binding antibodies at the time points tested. Thirty-one of 60 CAPS patients had a duration of exposure to canakinumab >48 weeks. The data obtained in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, underlying disease, and the number of patients tested. For these reasons, comparison of the incidence of antibodies to canakinumab with the incidence of antibodies to other products may be misleading.
Laboratory Findings
Hematology
During clinical trials with ILARIS, mean values decreased for white blood cells, neutrophils and platelets.
Hepatic transaminases
Elevations of transaminases have been observed in patients treated with ILARIS.
Bilirubin
Asymptomatic and mild elevations of serum bilirubin have been observed in patients treated with ILARIS without concomitant elevations of transaminases.
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