nts with Ps, the rate of antibody development with Humira monotherapy was 8%. However, due to the limitation of the assay conditions, antibodies to adalimumab could be detected only when serum adalimumab levels were < 2 ug/ml. Among the patients whose serum adalimumab levels were < 2 ug/ml (approximately 40% of total patients studied), the immunogenicity rate was 20.7%. In Ps patients who were on Humira monotherapy and subsequently withdrawn from the treatment, the rate of antibodies to adalimumab after retreatment was similar to the rate observed prior to withdrawal.
The data reflect the percentage of patients whose test results were considered positive for antibodies to adalimumab in an ELISA assay, and are highly dependent on the sensitivity and specificity of the assay. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to adalimumab with the incidence of antibodies to other products may be misleading.
Other Adverse Reactions
Rheumatoid Arthritis Clinical Studies
The data described below reflect exposure to Humira in 2468 patients, including 2073 exposed for 6 months, 1497 exposed for greater than one year and 1380 in adequate and well-controlled studies (Studies RA-I, RA-II, RA-III, and RA-IV). Humira was studied primarily in placebo-controlled trials and in long-term follow up studies for up to 36 months duration. The population had a mean age of 54 years, 77% were female, 91% were Caucasian and had moderately to severely active rheumatoid arthritis. Most patients received 40 mg Humira every other week.
Table 1 summarizes reactions reported at a rate of at least 5% in patients treated with Humira 40 mg every other week compared to placebo and with an incidence higher than placebo. In Study RA-III, the types and frequencies of adverse reactions in the second year open-label extension were similar to those observed in the one-year double-blind portion.
Table 1. Adverse Reactions Reported by ≥5% of Patients Treated with Humira During Placebo-Controlled Period of Pooled RA Studies (Studies RA-I, RA-II, RA-III, and RA-IV)
Humira
40 mg subcutaneous
Every Other Week Placebo
(N=705) (N=690)
Adverse Reaction (Preferred Term)
Respiratory
Upper respiratory infection 17% 13%
Sinusitis 11% 9%
Flu syndrome 7% 6%
Gastrointestinal
Nausea 9% 8%
Abdominal pain 7% 4%
Laboratory Tests*
Laboratory test abnormal 8% 7%
Hypercholesterolemia 6% 4%
Hyperlipidemia 7% 5%
Hematuria 5% 4%
Alkaline phosphatase increased 5% 3%
Other
Headache 12% 8%
Rash 12% 6%
Accidental injury 10% 8%
Injection site reaction ** 8% 1%
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