Infliximab

Article Author:
Rawish Fatima
Article Editor:
Muhammad Aziz
Updated:
10/27/2018 12:31:39 PM
PubMed Link:
Infliximab

Indications

Infliximab is a biologic, monoclonal, antibody drug.

The United States Food and Drug Administration has approved Infliximab in the following cases (with doses mentioned):

  • For moderate to severely active Crohn disease in adults and children (six years and above) who have had a non-satisfactory response to conventional therapy, the induction dose is 5 mg/kg, given as intravenous therapy at 0, 2 and 6 weeks, followed by maintenance therapy at the same dosage every 8 weeks. 10 mg/kg is considered in patients who do not benefit from the lower dose.
  • For moderate to severely active ulcerative colitis in adult patients with unsatisfactory response to conventional therapy, the usual dose is 5 mg/kg intravenously (IV) at 0, 2 and 6 months as the initial dose, followed by 5 mg/kg every 8 weeks for maintenance. 
  • For moderate to severely active rheumatoid arthritis, induction therapy at 3 mg/kg is given at 0, 2 and 6 weeks, followed by maintenance therapy every 8 weeks. 
  • With active ankylosing spondylitis, a dose of 5 mg/kg IV is given at 0, 2, and 6 weeks, followed by dosing every 6 weeks.
  • With active psoriatic arthritis, a dose of 5 mg/kg IV is given at 0, 2 and 6 weeks, followed by dosing every 8 weeks.
  • For chronic severe plaque psoriasis in adult patients, a dose of 5 mg/kg IV is given at 0, 2 and 6 weeks, followed by dosing every 8 weeks. 

Although there is little supporting data, studies have shown that infliximab is not effective in very young patients. A study published in 2014 showed a remission rate of 36% in one year in patients younger than 7 years as compared to a remission rate of 88% in older children. The remission achieved in older children is comparable to that achieved in adults.

It is also used off-label (not FDA-approved) to treat the following conditions:

  • Bechet disease
  • Relapsing polychondritis
  • Juvenile idiopathic arthritis 
  • Pyoderma gangrenosum
  • Pustular psoriasis 

This drug is usually given in combination with methotrexate to avoid an immunologic response by the host which would decrease or blunt the effect of the drug. 

Mechanism of Action

Infliximab is a type of biologic therapy/immunotherapy which is designed to stimulate our body's immune system and treat certain diseases. Infliximab is a monoclonal antibody that inhibits tumor necrosis factor alpha (TNF-a). TNF-a is a signaling protein involved in acute phase reaction and systemic inflammation. It is produced by macrophages, CD4+ lymphocytes, NK cells, neutrophils, mast cells, eosinophils, and neurons. This inhibition of TNF-a stops the cascade of inflammatory reaction, leading to improvement of the disease condition (psoriasis, Crohn disease, etc.). Infliximab is a chimeric protein which contains both murine and human components. In adults, it has been shown to have a half-life of 7 to 12 days.

Administration

Infliximab is administered via an intravenous route. It has been shown to cause type I and type III hypersensitivity reaction in the studies conducted.

A variety of strategies are used to prevent infliximab-induced infusion reaction including the following:

  • Administering antihistamine and acetaminophen 90 minutes before the infusion
  • Using a test dose of infliximab
  • In patients with prior history of anaphylaxis reaction to infliximab, administering prednisone, antihistamine, and acetaminophen prior to infusion

Dosage Adjustments

  • In patients with mild heart failure (NYHA class I/II), no dosage adjustment is required but caution and monitoring are needed.
  • In patients with severe heart failure (NYHA Class III/IV), dosage adjustment is required such that the dose is kept less than or equal to 5 mg/kg.
  • In patients with renal or hepatic impairment, no dosage adjustments have been advised.

Adverse Effects

Infliximab is a generally safe and a well-tolerated medication, but as the dose or the age of the patient (greater than 60 years) increases, there are heightened chances of side effects:

  • Infections are more commonly reported in patients taking additional immunosuppressive therapy
  • Infusion-related reactions (fever, pruritis, anaphylaxis, etc.)
  • Headache
  • Nausea
  • Abdominal pain
  • Dyspepsia
  • Diarrhea
  • Constipation
  • Hepatotoxicity - cases severe enough to be fatal and to necessitate a liver transplant have been reported 
  • Heart failure
  • Anemia, leukopenia, neutropenia, thrombocytopenia - patients are advised to seek immediate medical care if they develop symptoms of an infection
  • Demyelination disease
  • Paradoxical reaction
  • Tuberculosis reactivation
  • Malignancy - half of the cases reported are lymphomas
  • Reactivation of Hepatitis B
  • Psoriasis
  • Vitiligo or other autoimmune disorders - antinuclear antibody has been positive in patients taking infliximab with normal baseline levels.
  • Transient vision loss - has been reported within 2 hours of infusion, stopping the drug is advised if serious

Infliximab has been shown to cross the placenta and is found in the serum of babies whose mothers were given infliximab during pregnancy for up to 6 months. Agranulocytosis and reaction to live vaccines have been noticed in these infants. Therefore, a wait of 6 or more months is recommended in exposed infants before administering live vaccines.

Patients have developed antibodies (human anti-chimeric antibodies) against infliximab, which not only lowers the efficacy of the drug but also causes infusion reactions. To reduce this risk, co-administration of other immunosuppressors like methotrexate is considered.

Contraindications

Infliximab can be administered with care in certain conditions, but the following conditions are defined as a contraindication to infliximab administration:

  • Heart failure (NYHA class III/IV) - According to the American Heart Association, TNF inhibitors may cause myocardial toxicity or may exacerbate the underlying myocardial dysfunction.
  • Previous hypersensitivity reaction to infliximab
  • Current severe infection (sepsis, tuberculosis)
  • Active infection

Use infliximab with caution in the following conditions:

  • Preexisting demyelinating disease
  • Mild to moderate heart failure (NYHA classI/II)
  • History of seizures

It is known to cause a cross-reaction with some drugs (eg., abatacept, adalimumab, etanercept), so care is administered when the patient is on another medicine. 

Monitoring

Before administering Infliximab following tests are recommended, patients should be tested for the following:

Tuberculosis: A thorough screening for tuberculosis (TB) should be performed with: 

  • A detailed history of previous exposure/infection AND one of the following
  • Negative purified protein derivative (PPD less than 5 mm) testing
  • Negative interferon-gamma release assay test
  • Positive TB screening but negative chest x-ray with infectious disease consultation
  • At least 4 weeks post-initiation of isoniazid therapy for latent TB
  • Standard drug therapy for active TB with infectious disease consultation

Hepatitis B: A negative hepatitis screen (particularly Hep B surface antigen) is required.

Heart Failure: Careful monitoring is necessary with serial echocardiograms to avoid heart failure exacerbations. Therapy should be immediately discontinued if the patient has frequent or worsening heart failure exacerbations.

Others: Detailed history should be taken to evaluate the patient for any recent or active infection, any recent or upcoming surgery, and recent or upcoming live virus vaccination. Live vaccine administration should be avoided in patients taking infliximab.

Toxicity

As Infliximab is usually administered by healthcare personnel in a medical setting. Toxicity is very rare. Therefore, there is no specific treatment for it. The best treatment if such an event occurs is supportive treatment.