ged 40 to >75 years.
Minor increases in apparent clearance were also predicted in RA patients receiving doses lower than the recommended dose and in RA patients with high rheumatoid factor or CRP concentrations. These increases are not likely to be clinically important.
No gender-related pharmacokinetic differences were observed after correction for a patient’s body weight. Healthy volunteers and patients with rheumatoid arthritis displayed similar adalimumab pharmacokinetics.
No pharmacokinetic data are available in patients with hepatic or renal impairment.
In subjects with JIA (4 to 17 years of age), the mean steady-state trough serum adalimumab concentrations for subjects weighing <30 kg receiving 20 mg Humira subcutaneously every other week as monotherapy or with concomitant methotrexate were 6.8 µg/mL and 10.9 µg/mL, respectively. The mean steady-state trough serum adalimumab concentrations for subjects weighing ≥30 kg receiving 40 mg Humira subcutaneously every other week as monotherapy or with concomitant methotrexate were 6.6 µg/mL and 8.1 µg/mL, respectively.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies of Humira have not been conducted to eva luate the carcinogenic potential or its effect on fertility. No clastogenic or mutagenic effects of Humira were observed in the in vivo mouse micronucleus test or the Salmonella-Escherichia coli (Ames) assay, respectively.
Clinical Studies
Rheumatoid Arthritis
The efficacy and safety of Humira were assessed in five randomized, double-blind studies in patients ≥18 years of age with active rheumatoid arthritis (RA) diagnosed according to American College of Rheumatology (ACR) criteria. Patients had at least 6 swollen and 9 tender joints. Humira was administered subcutaneously in combination with methotrexate (MTX) (12.5 to 25 mg, Studies RA-I, RA-III and RA-V) or as monotherapy (Studies RA-II and RA-V) or with other disease-modifying anti-rheumatic drugs (DMARDs) (Study RA-IV).
Study RA-I eva luated 271 patients who had failed therapy with at least one but no more than four DMARDs and had inadequate response to MTX. Doses of 20, 40 or 80 mg of Humira or placebo were given every other week for 24 weeks.
Study RA-II eva luated 544 patients who had failed therapy with at least one DMARD. Doses of placebo, 20 or 40 mg of Humira were given as monotherapy every other week or weekly for 26 weeks.
Study RA-III eva luated 619 patients who had an inadequate response to MTX. Patients received placebo, 40 mg of Humira every other week with placebo injections on alternate weeks, or 20 mg of Humira weekly for up to 52 weeks. Study RA-III had an additional primary endpoint at 52 weeks of inhibition of disease progression (as detected by X-ray results). Upon completion of the first 52 weeks, 457 patients enrolled in an open-label extension phase in which 40 mg of Humira was administered every other week for up to 5 years.
Study RA-IV assessed safety in 636 patients who were either DMARD-naive or were permitted to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a minimum of 28 days. Patients were randomized to 40 mg of Humira or placebo every other week for 24 weeks.
Study RA-V eva luated 799 patients with moderately to severely active RA of less than 3 years duration who were ≥18 years old and MTX naïve. Patients were randomized to receive either MTX (opti |
