ADVERSE REACTIONS
The most serious adverse reactions occurring in clinical studies with Xolair are malignancies and anaphylaxis (see WARNINGS). The observed incidence of malignancy among Xolair-treated patients (0.5%) was numerically higher than among patients in control groups (0.2%). Anaphylactic reactions were rare but temporally associated with Xolair administration.
The adverse reactions most commonly observed among patients treated with Xolair included injection site reaction (45%), viral infections (23%), upper respiratory tract infection (20%), sinusitis (16%), headache (15%), and pharyngitis (11%). These events were observed at similar rates in Xolair-treated patients and control patients. These were also the most frequently reported adverse reactions resulting in clinical intervention (e.g., discontinuation of Xolair, or the need for concomitant medication to treat an adverse reaction).
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in medical practice.
The data described above reflect Xolair exposure for 2076 adult and adolescent patients ages 12 and older, including 1687 patients exposed for six months and 555 exposed for one year or more, in either placebo-controlled or other controlled asthma studies. The mean age of patients receiving Xolair was 42 years, with 134 patients 65 years of age or older; 60% were women, and 85% Caucasian. Patients received Xolair 150 to 375 mg every 2 or 4 weeks or, for patients assigned to control groups, standard therapy with or without a placebo.
Table 4 shows adverse events that occurred >/= 1% more frequently in patients receiving Xolair than in those receiving placebo in the placebo-controlled asthma studies. Adverse events were classified using preferred terms from the International Medical Nomenclature (IMN) dictionary. Injection site reactions were recorded separately from the reporting of other adverse events and are described following Table 4.
Table 4
Adverse Events >/=1% More Frequent in Xolair-Treated
Patients
Adverse event
|
Xolair
n=738
(%)
|
Placebo
n=717
(%)
|
Body as a whole
|
|
|
Pain
|
7
|
5
|
Fatigue
|
3
|
2
|
Musculoskeletal system
|
|
|
Arthralgia
|
8
|
6
|
Fracture
|
2
|
1
|
Leg pain
|
4
|
2
|
Arm pain
|
2
|
1
|
Nervous system
|
|
|
Dizziness
|
3
|
2
|
Skin and appendages
|
|
|
Pruritus
|
2
|
1
|
Dermatitis
|
2
|
1
|
Special senses
|
|
|
Earache
|
2
|
1
|
|
Age (among patients under age 65), race, and gender did not appear to affect the between group differences in the rates of adverse events.
INJECTION SITE REACTIONS
Injection site reactions of any severity occurred at a rate of 45% in Xolair-treated patients compared with 43% in placebo-treated patients. The types of injection site reactions included: bruising, redness, warmth, burning, stinging, itching, hive formation, pain, indurations, mass, and inflammation.
Severe injection-site reactions occurred more frequently in Xolair-treated patients compared with patients in the placebo group (12% versus 9%).
The majority of injection site reactions occurred within 1 hour-post injection, lasted less than 8 days, and generally decreased in frequency at subsequent dosing visits.
IMMUNOGENICITY
Low titers of antibodies to Xolair were detected in approximately 1 / 1723 (<0.1%) of patients treated with Xolair. The data reflect the percentage of patients whose test results were considered positive for antibodies to Xolair in an ELISA assay and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in the assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease. Therefore, comparison of the incidence of antibodies to Xolair with the incidence of antibodies to other products may be misleading.
Allergic symptoms, including urticaria, dermatitis, and pruritus were observed in patients treated with Xolair. There were also 3 cases of anaphylaxis observed within 2 hours of Xolair administration in which there were no other identifiable allergic triggers (see WARNINGS: Anaphylaxis).
|