Adalimumab binds specifically to TNF-alpha and blocks its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface TNF expressing cells in vitro in the presence of complement. Adalimumab 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 patients with RA, JIA, PsA, and AS 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 plaques. In Ps, treatment with HUMIRA may reduce the epidermal thickness and infiltration of inflammatory cells. The relationship between these pharmacodynamic activities and the mechanism(s) by which HUMIRA exerts its clinical effects is unknown. Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 with an IC50 of 1-2 X 10-10M).

HUMIRA is a tumor necrosis factor (TNF) blocker indicated for treatment of:
• Rheumatoid Arthritis (RA): Reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients witmoderately to severely active RA.
• Juvenile Idiopathic Arthritis (JIA): Reducing signs and symptoms of moderately to severely active polyarticular JIA in pediatric patients 4 years of age and older.
• Psoriatic Arthritis (PsA): Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active PsA.
• Ankylosing Spondylitis (AS): Reducing signs and symptoms in adult patients with active AS.
• Adult Crohn’s Disease (CD): Reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. Reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.
• Pediatric Crohn’s Disease: Reducing signs and symptoms and inducing and maintaining clinical remission in patients 6 years of age and older with moderately to severely active Crohn’s disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate.
• Ulcerative Colitis (UC): Inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine or 6-mercaptopurine (6-MP). The effectiveness of HUMIRA has not been established in patients who have lost response to or were intolerant to TNF blockers.
• Plaque Psoriasis (Ps): The treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate.
• Lupus-like syndrome: Stop HUMIRA if syndrome develops.

Administered by subcutaneous injection.

Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis:
• 40 mg every other week. 
• Some patients with RA not receiving methotrexate may benefit from increasing the frequency to 40 mg every week.

Juvenile Idiopathic Arthritis:
• 15 kg (33 lbs) to < 30 kg (66 lbs): 20 mg every other week
• ≥ 30 kg (66 lbs): 40 mg every other week

Adult Crohn's Disease and Ulcerative Colitis:
• Initial dose (Day 1): 160 mg (four 40 mg injections in one day or two 40 mg injections per day for two consecutive days)
• Second dose two weeks later (Day 15): 80 mg
• Two weeks later (Day 29): Begin a maintenance dose of 40 mg every other week.
• For patients with Ulcerative Colitis only: Only continue HUMIRA in patients who have shown evidence of clinical remission by eight weeks (Day 57) of therapy.

Pediatric Crohn's Disease
• 17 kg (37 lbs) to < 40 kg (88 lbs):

• Initial dose (Day 1): 80 mg (two 40 mg injections in one day)
• Second dose two weeks later (Day 15): 40 mg
• Two weeks later (Day 29): Begin a maintenance dose of 20 mg every other week.

• ≥ 40 kg (88 lbs):

• Initial dose (Day 1): 160 mg (four 40 mg injections in one day or two 40 mg injections per day for two consecutive days)
• Second dose two weeks later (Day 15):80 mg (two 40 mg injections in one day)
• Two weeks later (Day 29): Begin a maintenance dose of 40 mg every other week.

Plaque Psoriasis
• 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose.

Most common adverse reactions (incidence >10%): infections (e.g. upper respiratory, sinusitis), injection site reactions, headache and rash.

• Serious infections: Do not start HUMIRA during an active infection. If an infection develops, monitor carefully, and stop HUMIRA if infection becomes serious.
• Invasive fungal infections: For patients who develop a systemic illness on HUMIRA, consider empiric antifungal therapy for those who reside or travel to regions where mycoses are endemic.
• Malignancies: Incidence of malignancies was greater in HUMIRA treated patients than in controls.
• Anaphylaxis or serious allergic reactions may occur.
• Hepatitis B virus reactivation: Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop HUMIRA and begin anti-viral therapy.
• Demyelinating disease: Exacerbation or new onset, may occur.
• Cytopenias, pancytopenia: Advise patients to seek immediate medical attention if symptoms develop, and consider stopping HUMIRA.
• Heart failure: Worsening or new onset, may occur.