The pharmacokinetics of adalimumab in patients with ankylosing spondylitis were similar to those in patients with RA.

In patients with Crohn's disease, the loading dose of 160 mg HUMIRA on Week 0 followed by 80 mg HUMIRA on Week 2 achieves mean serum adalimumab trough levels of approximately 12 µg/mL at Week 2 and Week 4. Mean steady-state trough levels of approximately 7 µg/mL were observed at Week 24 and Week 56 in Crohn's disease patients after receiving a maintenance dose of 40 mg HUMIRA every other week.

In patients with plaque psoriasis, the mean steady-state trough concentration was approximately 5 to 6 µg/mL during adalimumab 40 mg every other week monotherapy treatment.

Population pharmacokinetic analyses in patients with RA revealed that there was a trend toward higher apparent clearance of adalimumab in the presence of anti-adalimumab antibodies, and lower clearance with increasing age in patients aged 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 juvenile idiopathic arthritis ( 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&micro;g/mL and 10.9 &micro;g/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&micro;g/mL and 8.1 &micro;g/mL, 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 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 evaluated 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 evaluated 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 evaluated 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 evaluated 799 patients with moderately to severely active rheumatoid arthritis of less than 3 years duration who were ≥ 18 years old and MTX naïve. Patients were randomized to receive either MTX (optimized to 20 mg/week by week 8), HUMIRA 40 mg every other week or HUMIRA/MTX combination therapy for 104 weeks. Patients were evaluated for signs and symptoms, and for radiographic progression of joint damage. The median disease duration among patients enrolled in the study was 5 months. The median MTX dose achieved was 20 mg.

Clinical Response

The percent of HUMIRA treated patients achieving ACR 20, 50 and 70 responses in Studies RA-II and III are shown in Table 2.

Table 2. ACR Responses in Studies RA-II and RA-III (Percent of Patients)

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