Adalimumab

Mechanism

💊 Common Business Names

Humira, Amgevita, Hyrimoz, Imraldi, Idacio, Hulio.

🔬 Pharmacological Group

Completely human anti-TNF-α IgG1 monoclonal antibody. bDMARD.

Mechanism of Action

Adalimumab exerts a selective and specific immunological blockade of the pro-inflammatory TNF cascade:

• Selective Binding to Tumor Necrosis Factor Alpha (TNF-α): It specifically binds to both the soluble portion of circulating free TNF-α and the portion bound to the cell membrane (mTNF-α), mechanically preventing the interaction of this cytokine with its target surface receptors such as p55 and p75 (TNFR1 and TNFR2). It does not react against TNF-β (lymphotoxin).
• Inhibition of the Cytokine Transcriptional Cascade: Blocks the intracellular signaling of dural NF-κB, which drastically decreases the endothelial synthesis of adhesion molecules (ELAM-1, VCAM-1, ICAM-1) and stops the recruitment of macrophages and lymphocytes.
• Immune-mediated Cell Lysis: By binding to mTNF-α of active inflammatory cells, its Fc portion of human origin can activate the classical complement cascade (complement-mediated cytotoxicity - CDC) or bind to NK effector cells to induce antibody-dependent cellular cytotoxicity (ADCC), inducing apoptosis of pro-inflammatory cell populations.

Pharmacokinetics

Key Pharmacokinetics

Indicators and dose

Dosage and Adjustment

• Adults (Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis):
  • Standard Dose: 40 mg subcutaneously administered every 2 weeks (every other week). It can be prescribed as monotherapy or preferably co-administered with weekly methotrexate.
• Adults (Crohn's Disease and Ulcerative Colitis):
  • Induction Dose: 160 mg subcutaneously on day 1, followed by 80 mg on day 15.
  • Maintenance Dose: 40 mg subcutaneously every 2 weeks starting on day 29.
• Pediatrics: Indicated in polyarticular juvenile idiopathic arthritis in children over 2 years of age with dosages adjusted according to body weight (10-30 kg: 20 mg every two weeks; ≥ 30 kg: 40 mg every two weeks).
• Adjustment in Renal and Hepatic Failure: No specific studies have been carried out. As it is metabolized by non-specific systemic protein proteolytic cellular catabolism, no dose adjustment is required in mild to moderate renal or hepatic insufficiency.

Security

Pathophysiology of the Risk of Reactivation of Latent Tuberculosis

The cytokine TNF-α plays a critical biological role in immunity against intracellular mycobacteria such as Mycobacterium tuberculosis. TNF is the main mediator responsible for the recruitment and maintenance of alveolar macrophages, forming the dural immune granuloma, a structure that keeps mycobacteria confined and in latency. By administering adalimumab and blocking TNF-α, the destructuring of active granulomas occurs, diffusely releasing viable bacilli into the lung parenchyma and lymphatic stream. This induces a massive reactivation of disseminated miliary pulmonary or extrapulmonary tuberculosis with a rapid and potentially fatal clinical course.

Contraindications

• Absolute: Active tuberculosis or other pre-existing severe opportunistic fungal or bacterial infections (pulmonary sepsis); moderate to severe congestive heart failure (NYHA III-IV - TNF inhibition is paradoxically associated with hemodynamic worsening and increased mortality); hypersensitivity to the active ingredient or to the excipients of the biological formulation.
• Relative: Personal history of multiple sclerosis or central demyelinating disorders (associated with worsening or appearance of demyelinating flares); chronic carriers of hepatitis B virus (HBV - risk of acute liver reactivation).

Adverse Effects (ADR)

• Common / Tolerable: Local reactions at the injection site (erythema, pruritus, pain and transient swelling), headache, moderate muscle fatigue, skin rashes, nausea, mild transaminasitis.
• Rare / Serious: Reactivation of Latent Tuberculosis; opportunistic infections (histoplasmosis, aspergillosis, listeriosis); induction of de novo heart failure; development of demyelinating disorders (optic neuropathy, neuritis); appearance of a drug-induced lupus syndrome (positive ANA and anti-DNA autoantibodies reversible after discontinuation).

Drug Interactions

• Live Attenuated Virus Vaccines (Yellow Fever, MMR, BCG): Systemic immunosuppression induced by adalimumab can cause uncontrolled replication of the vaccine pathogen, inducing severe vaccine-induced systemic disease. Contraindicated during treatment and until at least 3-5 months after withdrawal.
• Methotrexate: It presents a favorable analgesic and immunological synergism and decreases the rate of formation of neutralizing anti-drug antibodies (ADA), prolonging the steady state of adalimumab in plasma.
• Other bDMARDs (Abatacept, Anakinra) or tsDMARDs: Significantly increase the risk of serious opportunistic infections without providing additive analgesic benefit. Avoid systematically.

Pregnancy and Breastfeeding

Historically classified in FDA Category B. Adalimumab is an IgG1 and, therefore, actively crosses the placental barrier through transport mediated by the neonatal Fc receptor (FcRn) from the second trimester, increasing massively in the third trimester. Epidemiological studies do not show an increased risk of major congenital malformations. However, to avoid profound immunosuppression of the neonate, it is usually recommended to suspend the drug at 30-32 weeks of gestation if the underlying pathology remains stable. Infants exposed in utero should not receive live vaccines during the first 6-12 months of life. Breastfeeding: Safe choice compatible; It is excreted in negligible quantities in milk and the remaining drug is degraded by acid gastric proteolysis in the infant's tract.

Clinical

Clinical Protocol for Mandatory Screening for Latent Tuberculosis

Prior to starting adalimumab (or any anti-TNF biological drug), it is mandatory to screen for latent tuberculosis by:

1. Mantoux test (PPD - intradermorreaction) or preferably interferon gamma release immunoassay (IGRA - QuantiFERON-TB Gold).
2. Chest x-ray in two projections.

If the PPD test is positive (>5 mm) or the IGRA is positive, without clinical or radiological evidence of active disease, chemoprophylaxis should be prescribed with Isoniazid (300 mg/day orally for a minimum of 6 to 9 months), and the administration of adalimumab can be safely initiated after at least 1 month from the start of treatment. prophylaxis with isoniazid.