Adalimumab

Adalimumab is a fully human IgG1 monoclonal antibody that binds with high specificity and affinity to tumour necrosis factor-alpha (TNF-α), neutralising its biological function. TNF-α is a pleiotropic cytokine that drives the chronic inflammatory cascade across diseases ranging from rheumatoid arthritis to inflammatory bowel disease, psoriasis, and hidradenitis suppurativa. Adalimumab does not bind lymphotoxin (TNF-β).

Mechanism of Action

• TNF-α neutralisation: adalimumab binds both soluble TNF-α and transmembrane TNF-α with picomolar affinity, preventing engagement of the p55 (TNFR1) and p75 (TNFR2) cell-surface receptors and thereby blocking downstream NF-κB and MAPK activation.
• Cytolytic effect on TNF-bearing cells: in vitro, in the presence of complement, adalimumab can lyse cells expressing transmembrane TNF-α — relevant to its effect in inflammatory bowel disease, where membrane-bound TNF on lamina propria immune cells is a key driver.
• Downstream biomarker effects: in treated patients, levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), and matrix metalloproteinases (MMP-1, MMP-3) decline; expression of leukocyte adhesion molecules (ELAM-1, VCAM-1, ICAM-1) is reduced (IC50 1–2 × 10⁻¹⁰ M).
• Tissue effects: in psoriasis plaques, adalimumab reduces epidermal thickness and dermal inflammatory cell infiltration; in rheumatoid arthritis, it slows or halts radiographic progression of joint damage.

Pharmacokinetics

• Absorption: subcutaneous bioavailability approximately 64%; peak serum concentration of 4.7 ± 1.6 µg/mL approximately 131 hours (~5.5 days) after a single 40 mg SC dose in healthy adults.
• Distribution: volume of distribution at steady state 4.7–6.0 L (largely vascular compartment for an IgG).
• Metabolism: catabolised to peptides and amino acids by the reticuloendothelial system; no CYP- or transporter-mediated clearance.
• Half-life: mean terminal half-life approximately 2 weeks (range 10–20 days).
• Clearance: systemic clearance approximately 12 mL/h; clearance increases in patients who develop anti-drug antibodies (ADA) and is reduced by methotrexate co-medication.
• Immunogenicity: anti-adalimumab antibody formation is well documented, with rates lower in patients on concomitant methotrexate — the rationale for combination therapy in rheumatoid arthritis.

Approved indications, with regional variation, include:

• Rheumatoid arthritis (RA) — moderately to severely active, as monotherapy or with methotrexate or other non-biologic DMARDs.
• Juvenile idiopathic arthritis (JIA) — polyarticular, in patients ≥2 years.
• Psoriatic arthritis (PsA) in adults.
• Ankylosing spondylitis (AS) in adults.
• Crohn’s disease — moderately to severely active, in adults and paediatric patients ≥6 years.
• Ulcerative colitis (UC) — moderately to severely active, in adults.
• Plaque psoriasis — moderate-to-severe in adult candidates for systemic therapy or phototherapy.
• Hidradenitis suppurativa (HS) — moderate-to-severe in adults and adolescents from age 12.
• Non-infectious intermediate, posterior, and panuveitis in adults and paediatric patients ≥2 years.

Off-label uses: pyoderma gangrenosum, sarcoidosis, Behçet’s disease, and selected refractory inflammatory conditions.

• Hypersensitivity to adalimumab or any of the excipients.
• Active tuberculosis or other severe active infection (including sepsis and opportunistic infections).
• Moderate to severe heart failure (NYHA class III/IV).

Very common (≥1/10): injection site reactions (pain, erythema, pruritus, swelling), upper respiratory tract infections, headache.

Common (≥1/100 to <1/10): lower respiratory infections (including bronchitis, pneumonia), urinary tract infection, herpes simplex, herpes zoster, leukopenia, anaemia, hypersensitivity reactions, mood disturbance, abdominal pain, nausea, transaminase elevations, rash, pruritus, hair loss, musculoskeletal pain, fatigue.

Uncommon (≥1/1,000 to <1/100): opportunistic infections (tuberculosis reactivation, invasive fungal infections, listeriosis, legionellosis), demyelinating CNS disease (multiple sclerosis-like syndromes, optic neuritis), lupus-like syndrome, psoriasis (paradoxical induction), hepatitis B reactivation.

Rare to very rare: lymphoma (especially hepatosplenic T-cell lymphoma in young males with IBD on combined TNF + thiopurine therapy), other malignancies, severe heart failure, Stevens-Johnson syndrome, anaphylaxis, pancytopenia, vasculitis.

Boxed warnings (FDA): serious infections (including TB, bacterial sepsis, invasive fungal, opportunistic infections) and malignancy (including lymphoma in children and adolescents).

• Other biologic DMARDs and JAK inhibitors (anakinra, abatacept, rituximab, tocilizumab, sarilumab, JAKi): combination is contraindicated or strongly discouraged due to additive immunosuppression and infection risk.
• Live vaccines: contraindicated during adalimumab therapy; complete live vaccinations (MMR, yellow fever, varicella, BCG, oral polio) before initiating where possible.
• Methotrexate: pharmacokinetic — methotrexate reduces adalimumab clearance and immunogenicity; clinical pairing is the standard of care for RA.
• Anakinra and abatacept: increased risk of serious infection — avoid.
• Newborns of mothers on adalimumab: avoid live vaccines for at least 5 months after birth due to placental transfer of IgG.
• No clinically meaningful small-molecule CYP interactions, though TNF-α suppression can theoretically normalise CYP enzyme expression that is suppressed by chronic inflammation, transiently affecting narrow-therapeutic-index substrates (warfarin, ciclosporin, theophylline).

Adalimumab is administered subcutaneously into the abdomen or anterior thigh. Rotate injection sites; avoid skin that is tender, bruised, red, or hard.

Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis

• Adults: 40 mg every other week. In RA without methotrexate, some patients may benefit from 40 mg weekly.

Juvenile Idiopathic Arthritis (Polyarticular)

• Weight-based dosing every other week:
  • 10–14 kg: 10 mg
  • 15–29 kg: 20 mg
  • ≥30 kg: 40 mg

Crohn’s Disease and Ulcerative Colitis (Adults)

• Induction: 160 mg on day 1 (as four 40 mg injections in one day, or two injections per day on two consecutive days), then 80 mg on day 15.
• Maintenance (starting day 29): 40 mg every other week; some patients require 40 mg weekly.

Paediatric Crohn’s Disease (≥6 Years)

• 17 to <40 kg: induction 80 mg day 1, then 40 mg day 15; maintenance 20 mg every other week.
• ≥40 kg: induction 160 mg day 1, then 80 mg day 15; maintenance 40 mg every other week.

Plaque Psoriasis

• Adults: initial 80 mg, then 40 mg every other week starting one week after the initial dose.

Hidradenitis Suppurativa

• Adults: 160 mg day 1, 80 mg day 15, then 40 mg every week (or 80 mg every other week) starting day 29.
• Adolescents 12–17 years and ≥30 kg: weight-band dosing per current labelling.

Uveitis

• Adults: 80 mg loading, then 40 mg every other week starting one week later.
• Paediatric ≥2 years: weight-band dosing.

Renal/Hepatic Impairment

No specific dose adjustment; not studied formally in severe organ impairment.

Missed Dose

Administer as soon as remembered, then resume the regular schedule from the next planned dose (not from the rescheduled dose).

Tuberculosis and Hepatitis B Screening

Screen for latent tuberculosis (IGRA or tuberculin skin test plus chest radiography) and hepatitis B (HBsAg, anti-HBc) before initiation. Treat latent TB before or concurrently with adalimumab. Monitor HBV carriers throughout therapy and for several months after discontinuation.

Infection Surveillance

Withhold adalimumab during serious active infections. Counsel patients to report fever, malaise, weight loss, persistent cough, or unusual symptoms. Increased vigilance in patients from areas endemic for tuberculosis, histoplasmosis, coccidioidomycosis, or strongyloidiasis.

Malignancy

Risk of lymphoma and other malignancies, particularly in IBD patients on concomitant thiopurines (hepatosplenic T-cell lymphoma in young males) and in patients with prolonged PUVA-treated psoriasis. Periodic skin examinations recommended.

Heart Failure

Avoid in NYHA class III/IV heart failure; use cautiously in milder forms with close monitoring.

Neurological Events

Discontinue if demyelinating disease or new neurological signs develop.

Pregnancy and Lactation

• Pregnancy: adalimumab crosses the placenta in the third trimester. Use when clearly needed; consider stopping in late pregnancy where disease activity permits. Newborns exposed in utero should avoid live vaccines for at least 5 months.
• Breastfeeding: small amounts excreted in milk; minimal infant absorption (degraded in the gut). Generally considered compatible.

Immunogenicity and Concomitant Methotrexate

ADA development reduces efficacy and increases injection-site reaction frequency. In RA, co-administration of methotrexate reduces ADA incidence and is the standard of care.

Self-Injection Training

Train patients or caregivers using both pre-filled syringe and pen formats. Verify proper technique at follow-up visits.

Effect on Driving

Adalimumab has no or negligible influence on the ability to drive or use machines.

Store in a refrigerator (2–8°C) in the original carton to protect from light. Do not freeze. A single pre-filled syringe or pen may be stored at temperatures up to 25°C for a single period of up to 14 days, protected from light, and discarded if not used within 14 days or exposed to higher temperatures.

Typically 24–30 months from manufacture. After-opening rules vary by formulation; do not re-refrigerate after removal.

Prescription required (Rx). Cold-chain logistics required for distribution. Specialty pharmacy channels are common given price, biosimilar/originator interchangeability rules that vary by country, patient assistance programmes, and pharmacovigilance reporting.