What is the use of Infliximab (Chimeric monoclonal antibody against Tumor Necrosis Factor-alpha, TNF-alpha)?

From the Guidelines

Infliximab is a chimeric monoclonal antibody that targets tumor necrosis factor-alpha (TNF-α), used primarily to treat autoimmune inflammatory conditions, and its use is recommended for the treatment of moderate to severe Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis, with an initial induction regimen at weeks 0,2, and 6, followed by maintenance dosing every 8 weeks, at a dose of 5 mg/kg intravenously 1.

Indications and Administration

• Infliximab is FDA-approved for the treatment of rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.
• The recommended dose is 5 mg/kg intravenously, with an initial induction regimen at weeks 0,2, and 6, followed by maintenance dosing every 8 weeks.
• Patients should be screened for tuberculosis, hepatitis B, and other infections before starting treatment, as infliximab can reactivate latent infections and increase infection risk.

Mechanism of Action and Efficacy

• Infliximab works by binding to TNF-α, preventing it from interacting with cell receptors and thereby reducing inflammation.
• The medication has been shown to be effective in inducing and maintaining remission in patients with Crohn's disease, with a clinical response rate of 58% at week 2, and 39% of patients achieving clinical remission at week 30 with maintenance therapy 1.

Safety and Monitoring

• Common side effects include infusion reactions, which can range from mild (headache, nausea) to severe (anaphylaxis).
• Long-term use carries risks of serious infections, malignancies, and demyelinating disorders.
• Patients should receive all appropriate vaccinations before starting therapy, and live vaccines should be avoided during treatment.
• Regular monitoring of complete blood count, liver function, and signs of infection is essential throughout the treatment course.

Combination Therapy

• Combination therapy with azathioprine may be beneficial in patients with Crohn's disease, with higher rates of clinical remission and mucosal healing compared to infliximab monotherapy 1.
• However, the decision to use combination therapy should be individualized, taking into account the patient's disease severity, medical history, and potential risks and benefits.

From the FDA Drug Label

Infliximab products neutralize the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα and inhibit binding of TNFα with its receptors. Elevated concentrations of TNFα have been found in involved tissues and fluids of patients with rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis In rheumatoid arthritis, treatment with infliximab products reduced infiltration of inflammatory cells into inflamed areas of the joint as well as expression of molecules mediating cellular adhesion In Crohn's disease, treatment with infliximab products reduced infiltration of inflammatory cells and TNFα production in inflamed areas of the intestine, and reduced the proportion of mononuclear cells from the lamina propria able to express TNFα and interferon In psoriatic arthritis, treatment with infliximab products resulted in a reduction in the number of T-cells and blood vessels in the synovium and psoriatic skin lesions as well as a reduction of macrophages in the synovium. In plaque psoriasis, treatment with infliximab products may reduce the epidermal thickness and infiltration of inflammatory cells

The primary use of Infliximab is to neutralize the biological activity of TNFα, which is involved in various inflammatory diseases, including:

• Rheumatoid arthritis
• Crohn's disease
• Ulcerative colitis
• Ankylosing spondylitis
• Psoriatic arthritis
• Plaque psoriasis 2 2 2

From the Research

Use of Infliximab

Infliximab is a chimeric monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha) that has shown efficacy in:

• Crohn's disease: effective in treating patients with moderately to severely active Crohn's disease with an inadequate response to other treatment options or those with fistulising disease 3, 4, 5, 6
• Rheumatoid arthritis: effective in reducing signs and symptoms and delaying disease progression in patients with active, methotrexate-refractory rheumatoid arthritis and in those with early disease 3, 4, 5, 6

Administration and Efficacy

• Administered intravenously, generally in a schedule with initial infusions at 0,2, and 6 weeks, followed by administration once every 8 weeks 3, 4
• Effective in achieving a clinical response and remission in patients with Crohn's disease and rheumatoid arthritis 5, 6
• May be cost-effective, especially when long-term clinical outcomes and burden of the diseases are taken into account 3, 4

Safety and Toxicity

• Generally well tolerated, but may be associated with an increased risk of reactivation of tuberculosis in patients with latent disease 3, 4, 5, 7
• May cause severe side effects, including pneumonia, lymphoma, drug-induced lupus, and hepatotoxicity 7
• Concurrent use of other immunosuppressive agents may reduce the incidence of less serious side effects 7