The National Institute for Clinical Excellence is examining leukapheresis for inflammatory bowel disease and will publish guidance on its safety and efficacy to the NHS in England, Wales and Scotland. The Institute's Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisors, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about leukapheresis for inflammatory bowel 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 preliminary recommendation
• the identification of factual inaccuracies
• additional relevant evidence.

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

The process that the Institute 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• The Advisory Committee will then prepare draft guidance which will be the basis for the Institute's guidance on the use of the procedure in the NHS in England, Wales and Scotland.

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

Closing date for comments: 22 February 2005
Target date for publication of guidance: May 2005

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

Current evidence suggests that there are no major safety concerns for the use of leukapheresis for inflammatory bowel disease, and that it may be beneficial in carefully selected patients with ulcerative colitis. However, the evidence of efficacy is not yet adequate to support the use of this procedure without special arrangements for consent and for audit or research.

There is inadequate evidence to draw any conclusions about the efficacy of leukapheresis in patients with Crohn's disease and it should only be used in accordance with the recommendations in 1.3 (below).

Clinicians wishing to undertake leukapheresis for inflammatory bowel disease should take the following action.

• Inform the clinical governance leads in their Trusts.
• Ensure that patients understand the uncertainty about the procedure's efficacy and provide them with clear written information. Use of the Institute's Information for the Public is recommended.
• Audit and review clinical outcomes of all patients having leukapheresis

Ulcerative colitis and Crohn's disease are the most common forms of inflammatory bowel disease. Ulcerative colitis causes inflammation and ulceration of the rectum and sometimes the colon. Symptoms include bloody diarrhoea and rectal bleeding. Crohn's disease usually causes inflammation and ulceration of the small and large intestines, but it can affect any part of the digestive tract. The main symptoms are abdominal pain, diarrhoea and weight loss. Both ulcerative colitis and Crohn's disease are chronic conditions characterised by periods of clinical relapse and remission.

Conservative treatments include dietary measures, and medication to control inflammation. Immunosuppressants may be used if other medical therapies are ineffective at maintaining remission. Patients with ulcerative colitis that does not respond to medical therapy may be treated with surgery to remove the colon. Although surgery may also be used for patients with Crohn's disease, it may not be curative and the disease often recurs in a different part of the digestive tract.

Leukapheresis involves extracorporeal removal of leukocytes from the blood, either by centrifugation or through an adsorptive system. In each system, venous blood is removed in a continuous flow, anticoagulated, processed to deplete the leukocytes, and returned to the circulation.

In one randomised controlled trial of patients with ulcerative colitis, 74% (29/39) of patients treated with leukapheresis had an "excellent" or "moderate" improvement, compared with 38% (14/37) of patients treated with high-dose steroids (p = 0.005).

In four case series, 54% (24/44) to 82% (32/39) of patients with ulcerative colitis had an initial remission of disease after treatment. In one study, the proportion of patients in clinical remission dropped from 82% (32/39) at 12 weeks to 67% (26/39) at 12 months after the final treatment. In two further studies, 30% (10/33) and 39% (13/33) of patients relapsed during maintenance therapy after initial complete remission.

Most studies reported only mild adverse events such as dizziness, light headedness, headache and flushing. In three case series, the proportion of patients experiencing at least one non-severe adverse event ranged from 9% (5/53) to 18% (7/39).

In a randomised controlled trial, the incidence of adverse events was significantly lower in the group treated with leukapheresis than in the group treated with high-dose steroids (24% versus 47%, p < 0.001). In the same trial, adverse events were described as moderate or severe in 12% (5/42) of patients treated with leukapheresis: 2 patients had a headache, 1 patient had toxic shock, 1 patient had chest pain and 1 patient had anaemia. For more details, refer to the sources of evidence.

The Committee noted that leukapheresis is an established technique in other conditions.

The Committee also noted that there are different techniques for leukapheresis, and these may have different risk and benefit profiles.

The following document, which summarises the evidence, was considered by the Interventional Procedures Advisory Committee when making its provisional recommendations.

Interventional procedure overview of leukapheresis for inflammatory bowel disease, August 2004

Available from: www.nice.org.uk/ip_250overview