Menu Search Donate
clinical guideline banner

Infliximab

This document is only valid for the day on which it is accessed. Please read our disclaimer.

Background

Infliximab is one of a group of anti-inflammatory agents that work by blocking the action of the pro-inflammatory cytokine, Tumour Necrosis Factor-alpha (TNF-α). TNF-α is a signalling protein that increases the activity of cells involved in inflammation. Infliximab stops TNF-α from binding to cells, thereby reducing inflammation.

Gastroenterology

Indications

Infliximab is used for treatment of patients with moderately to severely active Crohn's disease and patients with fistulising Crohn's disease, who have had an inadequate response to conventional therapy. It is also increasingly used in patients with severe ulcerative colitis, most commonly as "rescue therapy" in acute severe colitis to avoid or defer the need for colectomy.

Staging of the disease by endoscopy and/or small bowel/pelvic imaging must be carried out within 3 months prior to starting infliximab to confirm severe disease.

Regime

Induction therapy
The induction regime consists of infusions at 0, 2 and 6 weeks.

Maintenance therapy

Clinical review should be carried out 4-6 weeks after the third induction dose in order to determine:

  • Clinical response to treatment (including clinician assessment, height, weight, repeat PCDAI/PUCAI)
  • Whether maintenance therapy is appropriate

8 weekly maintenance infusions should be continued if appropriate.

When there is loss of effect after a clear initial response to infliximab, several strategies have been employed, including increasing the dose to 10mg/kg, decreasing the dosing interval and switching to other biologic therapy. These decisions need to be taken on an individual patient basis.

Review and follow-up

Patients on maintenance infliximab therapy should be reviewed a minimum of every 6 months by consultant paediatric gastroenterologist.

Exit strategy documented by gastroenterology team in medical notes at each review.

Co-immunosuppression with a thiopurine or Methotrexate should normally be given in conjunction with infliximab.

In accordance with expert guidelines and consensus on good practice, patients on infliximab should have disease reassessment at least annually to inform decisions about the need for ongoing treatment.

Rheumatology

Indications

Infliximab is used in the treatment of a number of rheumatological conditions, including Juvenile Idiopathic Arthritis (JIA)and Uveitis. In patients with active disease, TNF-α level is elevated. In arthritis patients, a persistently high TNF-α level contributes to tissue damage. Infliximab is used in patients who do not respond to standard treatments.

Regime

The treatment regime usually consists of intravenous infusions at 0, 2 and 6 weeks. Subsequent infusions are given 4, 6 or 8 weekly thereafter, depending on clinical response. Another regime is monthly infusions.

Review and follow-up

  • Rheumatology review at each infusion visit with documentation of Core Set Variables.
  • Clinic review at minimum of 6 monthly intervals.
  • When there is loss of effect after a clear initial response to infliximab, several strategies have been employed, including increasing the dose to 10mg/kg, decreasing the dosing interval and switching to other biologic therapy. These decisions need to be taken on an individual patient basis.

Contra-indications

Absolute contra-indications:

  • Untreated chronic infection, such as tuberculosis
  • Presence of undrained abscesses (including perianal)
  • Patients with moderate to severe congestive heart failure
  • Known hypersensitivity to murine proteins or any other component of the product

Relative contraindications/cautions:

  • Intercurrent febrile illness (see below)
  • Chronic hepatitis B carriage
  • History of Guillain-Barré Syndrome, optic neuritis or Multiple Sclerosis
  • Pregnancy
  • Stricturing disease

Pre Treatment

Once the decision has been made that a patient requires infliximab,

  • A written patient information leaflet should be provided and the patient and/or carer given the opportunity to discuss the treatment with the medical team.
  • This must be fully discussed with the patient and/or carer.
  • Responsible consultant to document discussion regarding risks/benefits of treatment (including serious risks) in full, either in patient case notes or on consent form.
  • Responsible consultant to obtain written consent before first dose.

Direct questioning is required regarding:

  • Recent/current infections
  • Personal/family history and/or risk factors for TB
  • Personal/family history of Guillain-Barré Syndrome, optic neuritis or Multiple Sclerosis
  • Possibility of pregnancy and advice re use of contraception during treatment

Before commencing infliximab, it is important to exclude the possibility of TB.

Children under 5 years should undergo:

  • CXR
  • Mantoux

Discuss with Infectious Diseases if Mantoux is positive.

Children over 5 years should undergo:

  • CXR
  • Quantiferon Gold test

Pre-treatment bloods:

  • ESR or CRP
  • FBC, U&E, LFT, albumin
  • ANA, dsDNA (if not performed within 3 months)
  • Varicella Zoster serology (if not already documented)
  • Measles serology (if not already documented)
  • Hep B serology (HBsAg, AntiHBcAb, Anti-HBsAb)
  • Hep A serology (consider immunisation if non-immune)
  • Hep C serology
  • Urinalysis
  • Consider pregnancy testing in females of childbearing age

Disease activity scores at baseline

  • PCDAI (Crohn's patients) - see below
  • PUCAI (Ulcerative colitis patients) - see below
  • Core set variables (JIA)

On admission and PRIOR to infusion

  • Prior to each infusion, interval symptoms should be enquired about.
  • Ask about recent infections (colds, URTIs, temps etc). If these are present and severe, discuss with consultant prior to commencing infusion. It may be prudent to defer the infusion for a week to allow recovery from the infection.
  • Nurse to take baseline TPR, BP and facilitate IV access.
  • Obtain bloods for ESR, CRP, FBC, electrolytes, urea and creatinine, LFT's, albumin. Consider yearly ANA. Consider repeating screening for TB e.g. TB quantiferon gold if new risk factors.
  • Medical review, particularly if patient febrile
  • Disease activity score (PCDAI/PUCAI/Core set variables) as per specific indication 

Dosage and Administration

Regime

See under specialty notes above.

Premedication - please chart

  1. Loratadine (Claratyne) or cetirizine - dose 0.5mg/kg PO (max 25mg) 30-60 minutes prior to the infusion. Loratadine comes as 5 and 10 mg tablets. Give dose to the nearest 5mg.
  2. Hydrocortisone - 4mg/kg IV (max 200mgs) 15-30 minutes prior to infusion.
  3. Paracetamol - 15mg/kg PO (max dose 1gm) 15-30 minutes prior to infusion.

Anaphylaxis medication - please chart adrenaline (see Anaphylaxis Guideline for dose)

Infusion

  • The Infliximab dose is usually 5mg/kg iv (dose range 3-10mg/kg). Any variation from standard dosage should be under advice from the responsible Consultant

Standard Infusion Protocol

  • All patients should receive Infliximab as per standard infusion protocol for the first four doses
  • Dilute infliximab in 250ml of 0.9% normal saline. (For children <35kg, consider dilution in 125ml 0.9% normal saline, especially if concerns about fluid overload)
  • Infuse using intravenous giving set with an in-line low protein-binding filter pore (1.2 microns or less)
  • When reconstituting medicine DO NOT SHAKE THE VIAL. A swirling action can be used.
  • Infuse over 2 hours unless otherwise stated and documented by medical staff
  • Flush line with 0.9% sodium chloride to complete infusion

Patient Monitoring

Temperature, Pulse, Respiratory rate and BP as follows:

  • At baseline
  • ¼ hourly for 1 hour
  • ½ hourly thereafter until one hour post-infusion

Observe for signs of adverse drug reaction

The patient must remain on the ward for 2 hours post infusion as delayed reactions to the drug can occur.

Rapid Infusion Protocol

  • If each each of the first four infusions have been uncomplicated and free of adverse events, a more rapid infusion rate may be considered (under direction of responsible consultant). Caution is required when considering rapid infusion in any child under 25kg
  • Dilute infliximab in 250ml of 0.9% normal saline. (For children <35kg, consider dilution in 125ml 0.9% normal saline, especially if concerns about fluid overload)

  • Infuse using intravenous giving set with an in-line low protein-binding filter pore (1.2 microns or less)

  • When reconstituting medicine DO NOT SHAKE THE VIAL. A swirling action can be used.

  • Infuse over 1 hour 

  • Flush line with 0.9% sodium chloride to complete infusion

Patient Monitoring
Temperature, Pulse, Respiratory rate and BP as follows:

  • At baseline
  • ¼ hourly for 1 hour
  • ½ hourly thereafter until one hour post-infusion

Observe for signs of adverse drug reaction.

After rapid infusion, patient may be discharged 1 hour post-infusion if no adverse events occur.

Adverse Drug Reactions

If any reaction is suspected, stop infusion and obtain medical review.

Mild-moderate allergic reactions
Occur most frequently with first and second infusions
Symptoms include:

  • Flushing
  • Rash
  • Pruritus
  • Urticaria
  • Nausea
  • Fatigue
  • Headache
  • Fever/chills
  • Dizziness

Severe allergic reactions/Anaphylaxis
Signs and symptoms include

Respiratory:

  • Difficulty/noisy breathing
  • Swelling of tongue
  • Swelling/tightness in throat
  • Difficulty talking and/or hoarse voice
  • Wheeze or persistent cough

Cardiovascular:

  • Loss of consciousness
  • Collapse
  • Pallor and floppiness (in young children)
  • Hypotension

Management of allergic reactions

Mild-moderate reaction

  1. Stop infusion
  2. Administer paracetamol 15mg/kg PO, if not received a dose within the previous 4 hours
  3. Administer cetirizine/loratadine dose 0.5mg/kg PO (max 25mg)
  4. Restart infusion after 30 minutes at halved rate if symptoms resolved

Severe allergic reaction/Anaphylaxis

  1. Stop infusion
  2. Call 777 immediately
  3. Lie patient flat
  4. Administer high flow oxygen
  5. Administer resuscitation drugs
    - Adrenaline 1 in 1,000 dilution 0.01ml/kg IM (min dose 0.1ml to max dose of 0.5ml) Adrenaline may be repeated if no effect within 2 minutes.
    - Hydrocortisone 4mg/kg IV
  6. Refer to Starship Anaphylaxis Guideline
  7. Contact on-call consultant responsible for care

PCDAI (Paediatric Crohn's Disease Activity Index)


Link to the PCDAI appendix of the Gastroenterology Clinical Network's guideline on the treatment of inflammatory bowel disease.

Scoring

Disease Activity
<10 - remission
10 - 27.5 - mild
30 - 37.5 - moderate
>40 - severe 

PUCAI (Paediatric Ulcerative Colitis Activity Index)

Link to the PUCAI appendix of the Gastroenterology Clinical Network's guideline on the treatment of inflammatory bowel disease.

Information for Families

Handout on Infliximab medication in IBD from Starship Children's Health

Handout on Infliximab medication for rheumatology patients

Crohn's and Colitis UK information sheet on Infliximab

References

Hyams J, Crandall W, Kugathasan S, Griffiths A, Olson A, Johanns J et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology 2007; 132(3):863-873.

National Institute for Clinical Excellence (UK) TA187 Crohn's disease - infliximab (review) and adalimumab (review of TA40): guidance; 19 May 2010

Turner D, Otley AR, Mack D et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology. 2007 Aug;133(2):423-32.

Hyams JS, Ferry GD, Mandel FS et al. Development and validation of a pediatric Crohn's disease activity index. J Pediatr Gastroenterol Nutr. 1991 May;12(4):439-47.

Remicade Information leaflet (Janssen) http://www.remicade.com/shared/product/remicade/prescribing-information.pdf

Did you find this information helpful?

Document Control

  • Date last published: 22 February 2016
  • Document type: Clinical Guideline
  • Services responsible: Paediatric Gastroenterology/Hepatology, Paediatric Rheumatology
  • Author(s): Jackie Yan, Jon Bishop
  • Editor: Greg Williams
  • Review frequency: 2 years

More From Starship