Adalimumab (Humira®) is a recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor alpha (TNF-a). Adalimumab (Humira®) was created using phage display technology resulting in an antibody with human derived heavy and light chain variable regions and human IgG1:k constant regions. Adalimumab (Humira®) is produced by recombinant DNA technology in a mammalian cell expression system and is purified by a process that includes specific viral inactivation and removal steps. It consists of 1330 amino acids and has a molecular weight of approximately 148 kilodaltons.Adalimumab (Humira®) binds specifically to (TNF-a) and blocks its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab (Humira®) also lyses surface TNF expressing cells in vitro in the presence of complement. Adalimumab (Humira®) does not bind or inactivate lymphotoxin (TNF-beta). TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF are found in the synovial fluid of rheumatoid arthritis, including juvenile idiopathic arthritis, psoriatic arthritis, and ankylosing spondylitis patients and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases. Increased levels of TNF are also found in psoriasis (Ps) plaques.After treatment with adalimumab (Humira®), a decrease in levels of acute phase reactants of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and serum cytokines (IL-6) was observed compared to baseline in patients with rheumatoid arthritis. A decrease in CRP levels was also observed in patients with Crohn’s disease. Serum levels of matrix metalloproteinases (MMP-1 and MMP-3) that produce tissue remodeling responsible for cartilage destruction were also decreased after adalimumab (Humira®) administration.According to the prospectus, the maximum serum concentration (Cmax) and the time to reach the maximum concentration (Tmax) were 4.7 ± 1.6 µg/mL and 131 ± 56 hours respectively, following a single 40 mg subcutaneous administration of Aadalimumab (Humira®) to healthy adult subjects. The average absolute bioavailability of adalimumab (Humira®) estimated from three studies following a single 40 mg subcutaneous dose was 64%. The pharmacokinetics of adalimumab were linear over the dose range of 0.5 to 10.0 mg/kg following a single intravenous dose. The single dose pharmacokinetics of adalimumab in rheumatoid arthritis (RA) patients were determined in several studies with intravenous doses ranging from 0.25 to 10 mg/kg. The distribution volume (Vss) ranged from 4.7 to 6.0 L. The systemic clearance of adalimumab is approximately 12 mL/hr. The mean terminal half-life was approximately 2 weeks, ranging from 10 to 20 days across studies. Adalimumab concentrations in the synovial fluid from five rheumatoid arthritis patients ranged from 31 to 96% of those in serum. In RA patients receiving 40 mg adalimumab (Humira®) every other week, adalimumab mean steady-state trough concentrations of approximately 5 µg/mL and 8 to 9 µg/mL, were observed without and with 3 methotrexate (MTX), respectively. In patients with RA, MTX reduced adalimumab apparent clearance after single and multiple dosing by 29% and 44% respectively. Mean serum adalimumab trough levels at steady state increased approximately proportionally with dose following 20, 40, and 80 mg every other week and every week subcutaneous dosing. In long-term studies with dosing more than two years, there was no evidence of changes in clearance over time. Adalimumab mean steadystate trough concentrations were slightly higher in psoriatic arthritis patients treated with 40 mg adalimumab (Humira®) every other week (6 to 10 µg/mL and 8.5 to 12 µg/mL, without and with MTX, respectively) compared to the concentrations in RA patients treated with the same dose. 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 adalimumab (Humira®) on week 0 followed by 80 mg adalimumab (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 adalimumab (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 antiadalimumab 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 reported to be not likely to be clinically important 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 adalimumab (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 adalimumab (Humira®) subcutaneously every other week as monotherapy or with concomitant methotrexate were 6.6 µg/mL and 8.1 µg/mL, respectively.It was reported that doses up to 10 mg/kg have been administered to patients in clinical trials without evidence of dose limiting toxicities. However, in case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately.However, no pharmacokinetic data are available in patients with hepatic or renal impairment. Serum concentration of adalimumab (Humira®) might be related to predict some clinical outcome during maintenance therapy. It was also possible that the surveillance of circulating adalimumab (Humira®) concentration during maintenance therapy represents a direct and/or indirect factor for some other side effects. In this context, identification of biomarkers for (non-)response and risk factors for adverse drug reactions that might be related to serum concentrations and maintaining the effective minimum concentration of adalimumab (Humira®) in order to potentially avoid some side effects with a reliable method might be beneficial.