Interventional procedures consultation document - extracorporeal photopheresis for Crohn's disease

NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE

 

Interventional Procedure Consultation Document

Extracorporeal photopheresis for Crohn's disease

Crohn's disease is a chronic inflammatory disease that affects the gastrointestinal tract. It is sometimes associated with other complications such as skin rashes and arthritis. In extracorporeal photopheresis blood is removed from the patient, then the white blood cells are separated from the whole blood, treated with ultraviolet light and re-infused into the patient.

 

The National Institute for Health and Clinical Excellence (NICE) is examining extracorporeal photopheresis for Crohn's disease and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE's Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about extracorporeal photopheresis for Crohn's disease.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

  • comments on the provisional recommendations
  • the identification of factual inaccuracies
  • additional relevant evidence.

Note that this document is not NICE's formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that NICE will follow after the consultation period ends is as follows.

  • The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
  • The Advisory Committee will then prepare draft guidance which will be the basis for NICE's guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from our website (www.nice.org.uk/ipprogrammemanual).

NICE is committed to promoting through its guidance race and disability equality and equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our guidance on interventional procedures. In particular, we aim to encourage people and organisations from groups in the population who might not normally comment on our guidance to do so. We also ask consultees to highlight any ways in which draft guidance fails to promote equality or tackle discrimination and give suggestions for how it might be improved.

Closing date for comments: 25 November 2008

Target date for publication of guidance: February 2009

 

Note that this document is not the Institute's guidance on this procedure. The recommendations are provisional and may change after consultation.
1 Provisional recommendations
1.1 Current evidence on extracorporeal photopheresis (ECP) for Crohn's disease is based on reports that include a very small number of patients. These reports describe no major safety issues but they provide no good evidence of efficacy. Therefore, this procedure should not be used outside the context of research.
2 The procedure
2.1 Indications and current treatments
2.1.1 Crohn's disease is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract from the mouth to the anus, but most commonly affects the ileum and the colon. It may cause the intestine to develop fistulae to the bowel or skin, or strictures causing narrowing of the bowel. Symptoms of Crohn's disease include diarrhoea, weight loss, rectal bleeding and fever. Complications may include rectal abscesses and joint disease. Some people with Crohn's disease have long periods of symptom-free remission.   
2.1.2 Disease severity is assessed using the Crohn's Disease Activity Index (CDAI), which ranges from 0 to 600 (lower than 150 indicates inactive disease; above 450 represents severe, active disease).
2.1.3 Conservative treatment includes dietary measures and drug therapy. Corticosteroids and immunosuppressive agents are used with the aim of controlling inflammation and other symptoms, and reducing relapse. Surgical removal of the affected bowel is sometimes necessary but this is not curative as the disease can recur in other sites.
2.2 Outline of the procedure
2.2.1 Extracorporeal photopheresis involves drawing blood from the patient via a peripheral line. The red blood cells are separated from the leukocyte-containing buffy coat cells, which include mononuclear cells (one subgroup of which is the T-cells that are thought to be involved in Crohn's disease) and platelets. The red blood cells and the remaining plasma are then returned to the patient via the same indwelling catheter
2.2.2 A photosensitive drug (8-methoxypsoralen) and an anticoagulant are added to the buffy coat cells, which are then passed through a sterile chamber and irradiated with ultraviolet light to activate the drug. The activated drug binds to the DNA in the buffy coat cells, arresting cell proliferation and initiating changes that lead to cell death.
2.2.3 The buffy coat cells are then returned to the patient. These re-infused dying cells produce a generalised immune response against the pathogenic T-cell clones that are involved in the pathogenesis of inflammation in Crohn's disease.
2.2.4 ECP is usually carried out over 2 consecutive days at intervals of 2–4 weeks for about 20 treatment sessions. One ECP session takes about 3–4 hours.
Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview, available at www.nice.org.uk/IP368overview.
2.3 Efficacy
2.3.1 In a case series of 10 patients, a response (defined as a 50% reduction in steroid use) was seen in eight patients (median follow-up of 10 weeks), with remission in four (defined by a CDAI score lower than 150 at median follow‑up of 20 weeks). Three of the four patients remained in remission at the end of the follow-up period (mean 16.5 weeks, range 4–20 weeks).
2.3.2 The Specialist Advisers stated that key efficacy outcomes for this procedure included improved quality of life, reduction of bowel motion frequency and abdominal cramps, reduced steroid use and reduction in inflammatory markers such as faecal calprotectin.
2.4 Safety
2.4.1 Across all three studies (total 14 patients), seven adverse events were reported following the procedure, including two instances of asymptomatic hypotension, one of mild headache and one of a small haematoma at the infusion site. One patient developed monoclonal gammopathy. Worsening of anaemia following the procedure was reported in three patients.
2.4.2 The Specialist Advisers stated that published and anecdotal adverse events following this procedure included vasovagal episodes such as hypotension and fits, light sensitivity or allergy to the photoactivating agent, anaemia and central venous line infection. Theoretical adverse events included haemorrhage caused by heparin use and malignancy from light exposure.
3 Further information
3.1 NICE has produced interventional procedures guidance on leukapheresis for inflammatory bowel disease (www.nice.org.uk/IPG126) and technology appraisals guidance on infliximab for Crohn's disease (www.nice.org.uk/guidance/TA40).   

Bruce Campbell

Chairman, Interventional Procedures Advisory Committee

September 2008

This page was last updated: 30 March 2010

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Copyright 2014 National Institute for Health and Care Excellence. All rights reserved.