Adalimab

• Rheumatoid Arthritis (RA): Moderate to severe active RA in adults; used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDs).
• Juvenile Idiopathic Arthritis (JIA): Moderately to severely active polyarticular JIA in patients aged 2 years and older.
• Psoriatic Arthritis (PsA): Active PsA in adults; helps reduce signs and symptoms and inhibits progression of structural joint damage.
• Ankylosing Spondylitis (AS): Active AS in adults.
• Crohn’s Disease (CD): Moderate to severe active CD in adults and pediatric patients aged 6 years and older who have had an inadequate response to conventional therapy.
• Ulcerative Colitis (UC): Moderate to severe active UC in adults and pediatric patients aged 5 years and older who have not responded adequately to immunosuppressants.
• Plaque Psoriasis (PsO): Moderate to severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
• Hidradenitis Suppurativa (HS): Moderate to severe HS in adults and adolescents aged 12 years and older.
• Non-Infectious Uveitis: Non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients aged 2 years and older.

Important Off-Label (Clinically Accepted) Uses:

• Behçet’s Disease: For refractory cases, particularly with severe ocular involvement.
• Pyoderma Gangrenosum: Used in treatment-resistant cases.
• Refractory Sarcoidosis: Occasionally used for refractory cutaneous or ocular sarcoidosis.

Route: Subcutaneous injection only. Rotate injection sites; avoid injecting into areas that are tender, bruised, red, or hardened.

Adults:

• RA, PsA, AS: 40 mg every other week; may increase to 40 mg weekly if there is an inadequate response.
• Plaque Psoriasis: Initial dose of 80 mg, then 40 mg every other week starting one week after initial dose.
• HS: Initial dose 160 mg (may be split over two consecutive days), then 80 mg at week 2, followed by 40 mg every week starting at week 4.
• CD: Initial dose 160 mg (may be split), then 80 mg at week 2, then 40 mg every other week thereafter.
• UC: Initial dose 160 mg (split), then 80 mg at week 2, then 40 mg every other week.
• Non-Infectious Uveitis: Initial dose 80 mg, then 40 mg every other week starting one week later.

Pediatrics:

• JIA:
• 10–15 kg: 10 mg every other week
• 15–30 kg: 20 mg every other week
• ≥30 kg: 40 mg every other week
• CD (≥6 years):
• 17–39 kg: 80 mg at week 0, 40 mg at week 2, then 20 mg every other week
• ≥40 kg: same as adult dosing
• UC (≥5 years):
• <40 kg: 80 mg at week 0, 40 mg at week 2, then 40 mg every other week
• ≥40 kg: same as adult dosing
• Uveitis (≥2 years): Same as JIA weight-based dosing.

Elderly: No dose adjustment required.

Renal/Hepatic Impairment: No specific adjustment guidelines; use caution and monitor closely.

Adalimumab is a fully human monoclonal IgG1 antibody that specifically binds to tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine involved in systemic inflammation. By binding to both soluble and membrane-bound TNF-α, adalimumab prevents its interaction with the p55 and p75 TNF receptors on cell surfaces. This inhibition blocks downstream inflammatory signaling pathways, reduces recruitment of inflammatory cells, and suppresses the production of other pro-inflammatory mediators, ultimately decreasing tissue inflammation and halting disease progression in autoimmune disorders.

Absorption:
Subcutaneous bioavailability is approximately 64%. Peak plasma concentrations are typically reached about 5 days after administration.

Distribution:
Apparent volume of distribution is about 5 to 6 liters, indicating distribution mainly within the vascular and interstitial spaces.

Metabolism:
Like other monoclonal antibodies, adalimumab is metabolized by proteolytic catabolism into small peptides and amino acids. It is not metabolized by cytochrome P450 enzymes.

Excretion:
Terminal half-life averages 10 to 20 days (mean ~14 days). Clearance occurs primarily via reticuloendothelial pathways with negligible renal excretion.

Pregnancy:
No longer assigned an FDA pregnancy letter category. Human data do not indicate an increased risk of major birth defects, but TNF-α inhibitors cross the placenta, particularly during the third trimester. Use only if clearly needed; live vaccines should be avoided in infants exposed in utero during the third trimester for up to 6 months.

Lactation:
Low levels detected in breast milk. Absorption by the nursing infant is minimal due to protein digestion in the infant’s gastrointestinal tract. Generally considered acceptable to use with caution. Monitor the infant for infections.

• Primary Class: Tumor Necrosis Factor (TNF) Inhibitor
• Subclass: Fully human IgG1 monoclonal antibody

• Known hypersensitivity to adalimumab or any component of the formulation
• Active severe infections, including sepsis or opportunistic infections
• Moderate to severe heart failure (relative contraindication — may worsen condition)

• Serious Infections: Increased risk of tuberculosis (TB), invasive fungal infections, and opportunistic infections; screen for latent TB before starting treatment.
• Malignancy: Rare risk of lymphoma and other malignancies, especially in pediatric and adolescent patients.
• Neurological Events: Rare cases of demyelinating disease reported; discontinue if new-onset demyelinating disease occurs.
• Heart Failure: May worsen or induce new-onset congestive heart failure.
• Hematologic Reactions: Rare reports of pancytopenia and aplastic anemia.
• Hepatitis B Reactivation: Reactivation may occur; screen at-risk patients.
• Monitoring Required: CBC, liver function tests, TB screening before and during treatment.
• Early Signs to Report: Persistent fever, unexplained weight loss, night sweats, or other signs of serious infection.

Common:

• Injection Site: Pain, swelling, itching, redness.
• Infections: Upper respiratory tract infections, sinusitis, bronchitis.
• GI: Nausea, abdominal pain.
• Skin: Rash, pruritus.
• Musculoskeletal: Back pain, arthralgia.

Serious/Rare:

• Serious infections including TB, sepsis, invasive fungal infections
• Lymphoma and other malignancies
• Demyelinating diseases (e.g., multiple sclerosis-like syndrome)
• Anaphylaxis and severe hypersensitivity reactions
• Worsening or new-onset heart failure
• Pancytopenia or other significant cytopenias

Severity, timing, and frequency may depend on dose, duration of use, and comorbid conditions.

• Live Vaccines: Contraindicated during treatment due to immunosuppression.
• Other Biologics: Avoid combination with other TNF inhibitors or biologic immunosuppressants to reduce risk of severe infections.
• Anakinra or Abatacept: Not recommended in combination due to increased risk of serious infections.
• Immunosuppressants: May be used with methotrexate intentionally for RA; increases infection risk.
• CYP450 Enzymes: TNF-α inhibition may normalize CYP450 activity, potentially lowering levels of CYP-metabolized drugs (e.g., warfarin, cyclosporine). Monitor when starting or stopping adalimumab.

• FDA & EMA: Emphasize rigorous TB screening and monitoring for invasive fungal infections.
• NICE: Expanded pediatric use approved for UC and uveitis.
• WHO & Other Guidelines: Reinforce baseline TB screening and continuing vigilance for severe infections.
• Biosimilars: Increasingly recommended as cost-effective alternatives with comparable safety and efficacy.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Do not freeze.
• Protect from light by keeping in the original carton until use.
• If needed, may be stored at room temperature up to 25°C (77°F) for a single period of up to 14 days; do not return to refrigerator once stored at room temperature.
• Do not use if solution is cloudy, discolored, or contains particles.