Treatment of Crohns Desease

• Welcome
• Gastro-Intestinal Tract
• Inflammation and Immunity
  • Inflammation
  • Organization
  • Defense Structure
  • Cells involved
  • Cytokines
  • Functional Components
  • Role of TNF- a
• Crohn's Disease and Ulcerative Colitis
• Inflammatory Bowel Disease
  • Causes
  • First line drugs
  • TNF-alpha targeting therapies
  • Herbal Alternative SedaCrohn
  • Surgical Intervention
• Challenges in the Management

TNF-alpha targeting therapies

This category of drugs comprises of those agents that are developed in the laboratory through a biological process involving one or more biological systems,unlike the conventional drugs which are developed through a chemical process.Typically,such "biological" include substances referred to as "monoclonal antibodies" and "recombinant" molecules.Recently wormwood (Artemisia absinthium - Sada Crohn) has been shown to inhibit TNF-alpha in CD patients.

Infliximab

Infliximab is a chimeric (75% human and 25% mouse) IgG1 type of antibody. For induction, it is used intravenously (infusion) in a dose of 5 mg/kg administered at 0, 2, 6 weeks.For maintenance,it is administered as an infusion every 8 weeks.

As with any biological, severe reactions are known to occur (hypotension,shortness of breath, rigors, chest discomfort). Antibodies against infliximab are known to develop in 10% cases.This can limit the therapeutic effect as well as enhance the side-effects.If Infliximab is used with immunomodulating agents such as AZA or 6-MERCAPTOPURINE or methotrexate, the chances of developing antibodies are significantly reduced or may not develop at all.

Adalimumab

Adalimumab is a completely human type IgG1 type of antibody. For induction, it is used subcutaneously in a dose of 160mg at week 0 and 80mg at week 2.For maintenance,40mg is administered subcutaneously every 1-2 weeks.

Side-effects are relatively rare due to the subcutaneous route of administration.Most common side-effects are site-reactions.

Cetrolizumab

Cetrolizumab is also a chimeric (95% human and 5% mouse)antibody but is only a part of the antibody molecule.For induction, 400 mg is administered subcutaneously at 0,2,4 weeks. For maintenance,400mg is administered subcutaneously every 4 weeks.Side-effects are relatively rare due to the subcutaneous route of administration.Most common side-effects are site-reactions.

Common side-effects of Infliximab, Adalimumab and Cetrolizumab

The following side-effects are known to occur though the incidence is low or rare:

1. Serious infections such as sepsis, pneumonia and abscesses can occur IN 2-5% patients though this might also be attributable to the concomitant administration of steroids.
2. Increased chances of bacterial infections and mycoses can result.
3. Reactivation of Hepatitis B
4. Reactivation of tuberculosis (patients should be checked with PPD)
5. Drug-induced lupus
6. Acute Hepatic Failure
7. Increased risk of malignancy
8. Rare cases of optic neuritis and demyelinating diseases
9. Worsening of heart failure

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