Mechanism of Action of Infliximab (Remicade)

Introduction

Infliximab is a chimeric (murine-human) IgG1 monoclonal antibody that targets tumor necrosis factor‑α (TNF‑α). It is used to treat a range of autoimmune and inflammatory disorders, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn’s disease, ulcerative colitis, and plaque psoriasis.

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Step-by-Step Mechanism of Action

1. Binding to TNF‑α
   Infliximab binds with high affinity to both soluble and transmembrane forms of TNF‑α.
2. Neutralization of TNF‑α
   This prevents TNF‑α from interacting with TNF receptors (TNFR1 and TNFR2) on target cells.
3. Inhibition of downstream signaling
   Blocking TNF‑α suppresses activation of NF‑κB and MAPK signaling pathways, reducing inflammatory responses.
4. Fc-mediated effects
   Infliximab can induce antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against TNF‑α–expressing cells.
5. Suppression of immune activation
   Results in lowered production of pro-inflammatory cytokines (IL‑1, IL‑6), reduced recruitment of inflammatory cells, and reversal of disease activity.

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Pharmacokinetic Parameters

Parameter	Value
Route	Intravenous infusion
Half-life	~8–10 days
Distribution	~4–6 L
Metabolism	Proteolytic degradation
Excretion	Catabolized to peptides and amino acids

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Clinical Uses

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn’s disease
• Ulcerative colitis
• Plaque psoriasis

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Adverse Effects

• Risk of serious infections (e.g., reactivation of latent tuberculosis)
• Infusion reactions (e.g., fever, chills, hypotension)
• Development of anti-drug antibodies, reducing efficacy
• Lupus-like syndrome, demyelinating disease (rare)
• Increased risk of certain malignancies, e.g., lymphoma

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Comparative Analysis

Agent	Type	TNF Target	Key Differences
Infliximab	Chimeric mAb	TNF‑α	IV infusion; potential immunogenicity
Adalimumab	Fully human mAb	TNF‑α	Subcutaneous injection; lower immunogenicity
Etanercept	Soluble receptor fusion	TNF‑α/β	Receptor decoy; limited to TNF neutralization

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MCQs

1. Infliximab is classified as a:
   a) Fully human antibody b) Chimeric antibody c) Poorest choice d) Receptor antagonist
   Answer: b) Chimeric antibody
2. It primarily neutralizes:
   a) IL‑6 b) TNF‑α c) IL‑1 d) IFN‑γ
   Answer: b) TNF‑α
3. Fc-mediated functions of infliximab include:
   a) Inhibition of proteases b) ADCC and CDC c) CYP450 induction d) Renin release
   Answer: b) ADCC and CDC
4. Its half-life is approximately:
   a) 1–2 days b) 8–10 days c) 20–30 days d) 12 hours
   Answer: b) 8–10 days
5. A safety concern before initiation includes screening for:
   a) Diabetes b) Tuberculosis c) Hyperlipidemia d) Hypothyroidism
   Answer: b) Tuberculosis
6. Compared to adalimumab, infliximab is:
   a) Fully human b) Chimeric c) Oral tablet d) Fusion protein
   Answer: b) Chimeric
7. Infliximab may trigger production of:
   a) Anti-drug antibodies b) Insulin c) IL‑10 d) Vitamin D
   Answer: a) Anti-drug antibodies
8. Infusion reactions are characterized by:
   a) Hypoglycemia b) Fever and hypotension c) Hypertension d) Diarrhea
   Answer: b) Fever and hypotension
9. The main downstream signaling pathways include NF‑κB and:
   a) JAK‑STAT b) MAPK c) cAMP d) PI3K
   Answer: b) MAPK
10. Compared to etanercept, infliximab:
    a) Is given orally b) Induces less ADCC c) Has higher immunogenicity d) Only targets TNF‑β
    Answer: c) Has higher immunogenicity

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FAQs

1. Why is TB screening essential before starting infliximab?
Because TNF‑α inhibition can reactivate latent tuberculosis.

2. What is the route of administration?
Administered via intravenous infusion, typically every 6–8 weeks after induction dosing.

3. Can patients develop resistance?
Yes—formation of anti-drug antibodies can reduce drug effectiveness and cause infusion reactions.

4. Are vaccines safe during therapy?
Live vaccines are contraindicated during treatment with infliximab.

5. How long are the effects sustained?
Due to its long half-life, effects can last several weeks between doses.

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References

• FDA Label: Infliximab (Remicade)
• DrugBank: Infliximab summary
• StatPearls: Infliximab clinical uses and pharmacology
• PubMed: Antibody-mediated cytotoxicity of infliximab
• PMC: Mechanism of action in autoimmune disease