Monoclonal antibodies and anti-TNF therapies

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Adalimumab Humira, biosimilars (Amgevita, Hyrimoz)

Pharmacological Group: Recombinant fully human anti-TNF-alpha monoclonal antibody.

Mechanism of Action: It specifically binds to soluble and membrane TNF-alpha, preventing its interaction with the surface receptors p55 (TNFR1) and p75 (TNFR2). By blocking the TNF-alpha cascade, it suppresses the expression of leukocyte adhesion molecules (ELAM-1, VCAM-1, ICAM-1), decreases inflammatory cell migration and attenuates the secretion of metalloproteinases and proinflammatory cytokines (IL-1, IL-6).

Mandatory Tuberculosis Screening and Contraindications

Risk of Opportunistic Infections: TNF-alpha is essential for the maintenance and containment of granulomas that encapsulate Mycobacterium tuberculosis. Its inhibition causes disintegration of the granuloma and hematogenous dissemination of the pathogen.
Protocol: Before starting adalimumab, extensive screening with tuberculin test (PPD) and/or interferon gamma release assay (IGRA) is mandatory, along with chest x-ray. If there is evidence of latent tuberculosis, at least 1 month of prophylaxis with isoniazid should be completed before starting the first biological dose.
Contraindications: Severe congestive heart failure (NYHA class III/IV, where anti-TNFs increase mortality); serious active infections.

Usual indicative dosage

Rheumatoid Arthritis / Psoriatic Arthritis / Spondylitis: 40 mg SC every two weeks. It can be associated with methotrexate to reduce the rate of development of anti-drug antibodies (ADA).
Inflammatory Bowel Disease: Induction with 160 mg SC on day 1 (or divided over two days), then 80 mg on day 15, followed by maintenance of 40 mg SC every two weeks starting in week 4.

Pregnancy: Avoid unless strictly necessary. Actively crosses placenta in the third trimester Breastfeeding: Considered compatible (low excretion in breast milk) Infliximab Remicade, biosimilars (Remsima, Inflectra)

Pharmacological Group: Chimeric monoclonal antibody (mouse/human) anti-TNF-alpha.

Mechanism of Action: Identical to adalimumab in terms of its pharmacological target (binding to soluble and membrane TNF-alpha with high affinity). However, as it has a variable region of murine origin (~25%), it more frequently induces immediate and delayed hypersensitivity responses, as well as a higher rate of production of neutralizing antibodies.

Pearl of Clinical Management: Infusion Reactions and Immunogenicity

To mitigate immediate infusion reactions mediated by chimeric antibodies, premedication with antihistamines, paracetamol and, in high-risk patients, intravenous corticosteroids is recommended. The concomitant use of a basic immunosuppressant (methotrexate in arthritis, or azathioprine in inflammatory bowel disease) drastically reduces the development of monoclonal antichimeric antibodies (HACA), stabilizing serum levels of the drug.

Induction and Maintenance Dosing

Standard Schedule: 5 mg/kg IV infusion over 2 hours in weeks 0, 2 and 6 (induction phase). Subsequently, continue with maintenance doses of 5 mg/kg IV every 8 weeks. In case of incomplete response in Crohn's disease, the dose can be increased to 10 mg/kg IV or the dosing interval can be shortened to every 4 or 6 weeks under strict monitoring of trough serum levels.

Pregnancy: Crosses the placental barrier from week 22; suspend in the third trimester if feasible to reduce immunosuppression of the neonate Breastfeeding: Compatible Etanercept Enbrel

Pharmacological Group: Soluble TNF receptor fusion protein.

Mechanism of Action: It is a dimer composed of the extracellular ligand-binding portion of the human TNF receptor p75 linked to the Fc fraction of human IgG1. It acts as a soluble "decoy receptor" that competitively binds and neutralizes both TNF-alpha and TNF-beta (lymphotoxin alpha), preventing these cytokines from interacting with cell surface receptors.

Dosage Guideline

Adults: 50 mg SC once a week (given as a single injection) or 25 mg SC twice a week (with an interval of 3 or 4 days between doses).
Pediatrics (>2 years): 0.8 mg/kg SC once a week (maximum 50 mg/dose).
Organic Adjustment: No dose adjustment is required in renal or hepatic insufficiency given its catabolic cellular polypeptide degradation.

Pregnancy: Classified in Category B. Avoid in the third trimester for neonatal safety Breastfeeding: Compatible