Infliximab

Infliximab is a chimeric IgG1κ monoclonal antibody (75% human, 25% murine) that binds soluble and transmembrane TNF-α with high affinity, disrupting the pro-inflammatory signalling cascade central to the pathogenesis of many chronic immune-mediated diseases.

Mechanism of Action

• TNF-α neutralisation: infliximab binds the trimeric soluble form and the membrane-bound precursor of TNF-α, preventing engagement with the p55 and p75 cell-surface receptors. It does not bind lymphotoxin (TNF-β).
• Downstream effects: blocked TNF-α signalling reduces production of secondary pro-inflammatory cytokines (IL-1, IL-6), decreases lymphocyte and leukocyte migration to inflammation sites, lowers expression of endothelial adhesion molecules (E-selectin, ICAM-1, VCAM-1) and chemoattractants (IL-8, MCP-1), and reduces matrix metalloproteinase (MMP-1, MMP-3) activity responsible for tissue destruction.
• Cytolysis of TNF-bearing cells: by binding to transmembrane TNF-α expressing cells (notably activated lamina propria mononuclear cells in IBD), infliximab can induce apoptosis through reverse signalling and antibody-dependent cellular cytotoxicity — a property that may explain superior efficacy in mucosal inflammatory diseases versus pure soluble-TNF blockade.
• Joint and bowel protection: in mouse models of TNF-driven polyarthritis, infliximab decreases synovitis and joint erosions and permits eroded joints to heal. In Crohn’s disease, it promotes mucosal healing and fistula closure.

Pharmacokinetics

• Distribution: predominantly intravascular; apparent steady-state volume of distribution 65–80 mL/kg in Crohn’s disease and 3–4 L in rheumatoid arthritis.
• Absorption (SC formulation): bioavailability approximately 80% relative to IV.
• Metabolism: catabolised by the reticuloendothelial system to peptides and amino acids; no CYP or transporter involvement.
• Half-life: median terminal half-life 7.7–9.5 days (single dose); steady-state pharmacokinetics depend on dosing interval and immunogenicity status.
• Clearance: 11–18 mL/h in adults; markedly increased in patients who develop anti-drug antibodies, in obesity, and in heavy proteinuria (e.g., severe Crohn’s with protein-losing enteropathy).
• Immunogenicity: anti-infliximab antibodies (ATIs) are a known and clinically meaningful concern, more frequent than with humanised or fully human anti-TNFs due to the murine variable regions. ATIs accelerate clearance, reduce efficacy, and increase infusion reactions. Co-medication with methotrexate or azathioprine substantially reduces ATI formation.

Approved indications, with regional variation, include:

• Rheumatoid arthritis (RA) — moderately to severely active, in combination with methotrexate.
• Crohn’s disease — moderately to severely active, in adults and paediatric patients ≥6 years; including fistulising Crohn’s disease.
• Ulcerative colitis (UC) — moderately to severely active, in adults and paediatric patients ≥6 years.
• Ankylosing spondylitis (AS) — severe, active, in adults inadequately responsive to conventional therapy.
• Psoriatic arthritis (PsA) — active and progressive in adults with inadequate response to DMARDs.
• Plaque psoriasis — moderate-to-severe in adult candidates for systemic therapy.

The subcutaneous formulation (Zymfentra / Remsima SC) is approved as maintenance therapy after IV induction in Crohn’s disease, ulcerative colitis, and rheumatoid arthritis, with extending indications in some regions to PsA, AS, plaque psoriasis, and spondyloarthritis.

• Hypersensitivity to infliximab, other murine proteins, or any of the excipients.
• Active tuberculosis or other severe active infections (sepsis, abscess, opportunistic infections).
• Moderate to severe heart failure (NYHA class III/IV) — high-dose infliximab (10 mg/kg) is specifically contraindicated; lower doses used with caution.

Very common (≥1/10): viral infections (notably upper respiratory), infusion reactions, abdominal pain, nausea.

Common (≥1/100 to <1/10): serious infections (bacterial, mycobacterial including tuberculosis reactivation, fungal, viral), neutropenia, lymphopenia, anaemia, lymphadenopathy, allergic reactions, depression, insomnia, headache, dizziness, vasculitis, dyspnoea, sinusitis, vomiting, diarrhoea, dyspepsia, transaminase elevations, urticaria, rash, pruritus, increased sweating, dry skin, alopecia, arthralgia, myalgia, back pain, urinary tract infection, chills, fatigue, chest pain, fever.

Uncommon to rare: serious infusion reactions including anaphylaxis, demyelinating disease (multiple sclerosis-like syndromes, optic neuritis, Guillain-Barré), drug-induced lupus, hepatic injury including autoimmune hepatitis, severe cytopenia, hepatitis B reactivation, opportunistic infections (histoplasmosis, coccidioidomycosis, listeriosis, pneumocystis pneumonia), worsening or new-onset heart failure, paradoxical psoriasis, vasculitis, sarcoid-like granulomatosis, malignancies including lymphoma (notably hepatosplenic T-cell lymphoma in young males with IBD on combined infliximab + thiopurine therapy), Stevens-Johnson syndrome, toxic epidermal necrolysis.

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

• Other biologic DMARDs and JAK inhibitors (anakinra, abatacept, rituximab, tocilizumab, JAK inhibitors): contraindicated or strongly discouraged — additive immunosuppression and serious infection risk.
• Live vaccines: contraindicated during therapy; complete live vaccinations (MMR, varicella, yellow fever, BCG, oral polio) before initiation where possible. In infants exposed in utero, defer live vaccines for at least 6 months after birth or until infant infliximab levels are undetectable.
• Methotrexate, azathioprine, 6-mercaptopurine: reduce immunogenicity (ATI formation) and increase efficacy — standard companion therapy in RA and IBD; balance against the elevated risk of hepatosplenic T-cell lymphoma in young males on combination therapy for IBD.
• No clinically meaningful small-molecule CYP interactions, though TNF-α suppression may transiently normalise CYP expression suppressed by chronic inflammation, with theoretical effects on warfarin, ciclosporin, and theophylline.

Intravenous Administration

Infliximab is reconstituted from lyophilised powder (10 mg/mL after addition of 10 mL sterile water for injection) and further diluted in 250 mL of 0.9 % sodium chloride to a final concentration of 0.4–4 mg/mL. The infusion is administered over not less than 2 hours; some patients tolerate accelerated infusions of 1 hour after at least three uneventful standard infusions.

Rheumatoid Arthritis

• Dose: 3 mg/kg at weeks 0, 2, and 6 (induction), then every 8 weeks. Inadequate responders may be increased to up to 10 mg/kg or shortened to every 4 weeks. Always combined with methotrexate.

Crohn’s Disease (including Fistulising)

• Adults and paediatric ≥6 years: 5 mg/kg at weeks 0, 2, 6, then every 8 weeks. Loss of response may be addressed by dose escalation to 10 mg/kg or interval shortening.

Ulcerative Colitis

• Adults and paediatric ≥6 years: 5 mg/kg at weeks 0, 2, 6, then every 8 weeks.

Ankylosing Spondylitis

• Adults: 5 mg/kg at weeks 0, 2, and 6, then every 6–8 weeks.

Psoriatic Arthritis

• Adults: 5 mg/kg at weeks 0, 2, 6, then every 8 weeks; may be combined with methotrexate.

Plaque Psoriasis

• Adults: 5 mg/kg at weeks 0, 2, 6, then every 8 weeks.

Subcutaneous Maintenance (Zymfentra / Remsima SC)

After completion of two IV induction doses (week 0 and week 2 at 5 mg/kg for IBD; comparable dosing for other indications), maintenance is administered subcutaneously: 120 mg every 2 weeks starting at week 10 for IBD; comparable maintenance schedules apply for other indications per current labelling.

Renal/Hepatic Impairment

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

Missed Dose

For IV maintenance, contact the infusion centre to reschedule; resume the every-8-week schedule from the rescheduled date if a single dose is missed by more than 1–2 weeks. For SC dosing, take as soon as remembered if within a few days; if close to the next scheduled dose, skip the missed dose.

Tuberculosis and Hepatitis B Screening

Screen for latent tuberculosis and hepatitis B before initiation. Treat latent TB before or concurrently with infliximab. Monitor HBV carriers throughout therapy and for several months after discontinuation.

Infusion Reactions

Reactions occur in approximately 10–20% of patients, most mild. Pre-medication with antihistamines, acetaminophen, and/or corticosteroids reduces incidence. Severe reactions including anaphylaxis require immediate cessation, supportive care, and consideration of switching to a different biologic. Late-onset hypersensitivity reactions (serum-sickness-like, 3–14 days after infusion) may occur especially after long drug-free intervals.

Infection Surveillance

Withhold infliximab during serious active infections. Counsel patients on signs of infection (fever, malaise, weight loss, persistent cough, draining wounds). Heightened vigilance in regions endemic for tuberculosis, histoplasmosis, coccidioidomycosis, and strongyloidiasis.

Heart Failure

Contraindicated at high dose (10 mg/kg) in NYHA III/IV; standard doses with caution in mild-to-moderate heart failure.

Malignancy

Risk of lymphoma and other malignancies; particular concern for hepatosplenic T-cell lymphoma in young males with IBD on combined TNF + thiopurine. Periodic skin examinations recommended.

Neurological Events

Discontinue if demyelinating or other significant neurological events develop.

Immunogenicity Management

Use combination immunomodulator (methotrexate, azathioprine, mercaptopurine) where indication and patient profile permit. Therapeutic drug monitoring (trough infliximab level and anti-drug antibody titre) is increasingly used to guide dose adjustments, particularly in IBD.

Pregnancy and Lactation

• Pregnancy: infliximab crosses the placenta in the second and third trimesters; consider stopping in late pregnancy when disease activity permits. Newborns exposed in utero should defer live vaccines for at least 6 months.
• Breastfeeding: small amounts excreted in milk with minimal infant absorption — generally compatible.

Switching Between IV and SC

Patients may transition from IV to SC maintenance after IV induction; do not initiate SC formulation as monotherapy without prior IV exposure (label-dependent).

Effect on Driving

Infusion reactions and post-infusion fatigue may transiently impair the ability to drive or operate machines.

Lyophilised IV vial: store in a refrigerator (2–8°C) in the original carton, protected from light. Remicade may be stored at temperatures up to 25°C for a single period of up to 6 months but not exceeding the original expiry date; the new expiry date must be written on the carton, and once removed from refrigerated storage the product must not be returned to it. After reconstitution and dilution, chemical and physical in-use stability has been demonstrated for up to 28 days at 2–8°C and an additional 24 hours at 25°C after removal from refrigeration; from a microbiological point of view, administer immediately.

Subcutaneous formulation (Zymfentra / Remsima SC): refrigerate at 2–8 °C in the original carton; may be kept at room temperature ≤30 °C for up to 30 days as a single excursion, then discard if not used. Do not freeze. Do not shake.

3 years (36 months) for the unopened lyophilised IV vial at 2–8°C; 18–24 months for the subcutaneous formulation (brand-specific). Refer to the product expiry date on the packaging.

Prescription required (Rx). IV product administered in infusion centres or specialist outpatient clinics; SC product distributed via specialty pharmacy with cold-chain logistics.