Canadian Association of Gastroenterology Clinical Practice Guidelines: The use of infliximab in Crohn s disease

Transcription

1 CLINICAL PRACTICE GUIDELINES Canadian Association of Gastroenterology Clinical Practice Guidelines: The use of infliximab in Crohn s disease PARTICIPANTS* Dr Remo Panaccione (Co-chair) University of Calgary Calgary, Alberta Dr Richard N Fedorak (Chair) University of Alberta Edmonton, Alberta Dr Brian Feagan (Co-chair) The University of Western Ontario London, Ontario Dr Hillary Steinhart (Co-chair) Dr Gary Wild (Co-chair) McGill University Montreal, Quebec Dr David Baron* Dr Charles Bernstein University of Manitoba Winnipeg, Manitoba Dr Alain Bitton McGill University Montreal, Quebec Dr Alan Buckley* University of Victoria Victoria, British Columbia Dr Ken Croitoru McMaster University Hamilton, Ontario Dr Robert Enns University of British Columbia, Vancouver, British Columbia Dr Gordon Greenberg Dr Phil Hassard University of Ottawa Ottawa, Ontario Dr Eric Semlacher* University of Alberta Edmonton, Alberta Dr Lloyd Sutherland University of Calgary Calgary, Alberta Dr Anthony Tavenor* Memorial University Corner Brook, Newfoundland Dr Marc Tourigny* Université Laval Quebec, Quebec Dr Eric Walli* University of Manitoba Winnipeg, Manitoba Dr Noel Williams Dalhousie University Halifax, Nova Scotia *Members of the Canadian Association of Gastroenterology Practice Affairs Committee Correspondence and reprints: Dr Richard Neil Fedorak, Division of Gastroenterology, University of Alberta, 519 Robert Newton Building, Edmonton, Alberta T6G 2C2. Telephone , fax , Richard.Fedorak@ualberta.ca Received for publication February 22, Accepted February 23, 2001 Can J Gastroenterol Vol 15 No 6 June

2 Canadian Association of Gastroenterology RESEARCH OF PUBLISHED EVIDENCE MEDLINE was searched using the key words TNF and Crohn s disease, TNF and ulcerative colitis, TNF and intestinal inflammation, TNF and colitis, anti-tnf therapy and infliximab. In addition, abstracts of the 1998 to 2000 annual meetings of the American Gastroenterological Association (published in Gastroenterology) and the 1998 to 1999 annual United European Federation of Gastroenterological Societies annual meeting (published in Gut) were searched for the key word TNF. Abstracts were only admitted as evidence if the necessary details were given in the abstract to perform the grading for the degree of evidence (as outlined below) or if the studies were known in sufficient detail to the experts through availability of detailed official study reports or other documents to perform such grading. GRADING OF THE EVIDENCE The guidelines were developed following the recommendations outlined by Marshall (1). The following categories were used to grade the statements in the guidelines according to the guidelines of the Agency for Health Care Policy and Research (AHCPR). Ia Evidence obtained from meta-analysis of randomized, controlled trials Ib Evidence obtained through one or more randomized, controlled trials IIa Evidence obtained through a well-designed controlled study without randomization IIb Evidence obtained through another type of well-designed experimental study III Evidence obtained through a well-designed nonexperimental study (eg, descriptive studies including comparative studies, correlation studies and case studies) IV Evidence obtained through expert committees opinions or clinical experience from experts GRADING OF THE GUIDELINES Guidelines deduced from published evidence and/or from expert opinions were graded according to the recommendations of AHCPR The following grading system was used. A Based on at least one randomized, controlled trial (evidence categories Ia or Ib) B Based on clinical studies without randomization (evidence categories IIa, IIb or III) C Based on expert committees, opinions or experiences (evidence category IV) TARGET POPULATION These clinical practice guidelines are directed at specialists who treat adult patients with Crohn s disease. OBJECTIVE OF THE GUIDELINES The objective is to provide rational and optimal guidelines for the use of the anti-tumour necrosis factor (TNF) infliximab in patients with Crohn s disease. VALIDITY OF THE GUIDELINES The present guidelines acknowledge the unique nature of each clinical encounter and practice setting, and allow practitioners and their patients to choose other options when appropriate. An update through a consensus meeting is planned for the second half of It is assumed that the therapeutic use of anti-tnf agents will be influenced by a large number of continuing clinical studies, which will be concluded in 2001 and The present guidelines should be modified at the end of 2002 through formal consensus. GUIDELINES A Indications i. Infliximab is indicated for patients who demonstrate continuing symptoms despite the optimal use of conventional therapies such as 5-acetylsalicylic acid (5-ASA) agents, glucocorticoids and immunosuppressive therapy (level of evidence A) (2). ii. Infliximab is indicated for patients who are unable to tolerate conventional therapy, including 5-ASA, glucocorticoids and immunosuppressive therapy (level of evidence C). Note: infliximab should not be used in patients with Crohn s disease unless the above criteria have been met. i. Infliximab is indicated for patients with symptomatic enterocutaneous and perineal fistulae (level of evidence A) (3), enterovaginal fistulae (level of evidence C) and enterovesical fistulae (level of evidence C) (Appendix 1 [1.1]). B. Initial dosing i. Initial dose is one 5 mg/kg intravenous infusion of infliximab, and the clinical response is assessed (level of evidence A) (2). ii. Patients who have not responded within four weeks may be considered for treatment with a second 5 mg/kg infusion (level of evidence B) (2). iii. Patients who do not respond to two infusions given within eight weeks of each other should no longer receive infliximab for this indication (level of evidence C). 368 Can J Gastroenterol Vol 15 No 6 June 2001

3 Infliximab guidelines for Crohn s disease i. Initial dose is three intravenous infusions of infliximab 5 mg/kg at zero, two and six weeks, and the clinical response is assessed (level of evidence A) (3). ii. Patients who have not responded to three infusions should no longer receive infliximab for this indication (level of evidence C) (Appendix 1 [1.2]). C. Maintenance dosing i. Repeat dosing is effective in maintaining clinical remission (level of evidence B) (4). ii. In patients with recurrence of disease following an initial infliximab-induced response/remission, therapy with infliximab 5 mg/kg intravenous every eight weeks and adjusted to clinical response may be effective in re-establishing and maintaining remission (level of evidence C). i. Repeat dosing is effective in maintaining clinical remission (level of evidence B) (3). ii. In patients with recurrence of disease following an initial infliximab-induced response/remission, therapy with infliximab 5 mg/kg intravenous every eight weeks and adjusted to clinical response may be effective in re-establishing and maintaining remission (level of evidence C). D. Concomitant therapy 1. Patients with Crohn s disease who require therapy with infliximab should be considered for concomitant administration with immunosuppressive therapy (ie, 6-mercaptopurine, azathioprine or methotrexate) if no contraindications exist (level of evidence C). 2. For patients on immunosuppressive therapy, the physician should ensure that the dose and mode of administration have been optimized (level of evidence C). 3. Patients receiving corticosteroids should have the corticosteroids tapered and discontinued. For patients who are unable to discontinue corticosteroids, the role of infliximab in the long term management should be reassessed (level of evidence C) (Appendix 1 [1.3]). E. Precautions and safety 1. Infliximab should not be administered in the following patients: i. Patients with known hypersensitivity to any murine proteins or other component of the product (level of evidence C) ii. Patients with known active infection (viral, tuberculosis, other bacterial or atypical) (level of evidence C) iii. Patients who have had a severe life-threatening infection within the past three months (level of evidence C) iv. Patients with serious opportunistic infection within the past two months (level of evidence C) v. Patients with known malignancy or previous malignancy (level of evidence C) vi. Females who are pregnant, lactating or are not willing to use appropriate birth control during infliximab therapy (level of evidence C) 2. Infliximab should be administered with caution to the following patients. i. Patients with fistulizing Crohn s disease should be evaluated carefully for the presence of any underlying abscess. An abscess should be drained and infection controlled before infliximab is started (level of evidence C). ii. Patients with intestinal obstructive symptoms or documented intestinal narrowing should be evaluated carefully (level of evidence C). iii. Patients should be evaluated for inactive ( latent ) tuberculosis and, if suspected, appropriate consultation should be sought before infliximab treatment is started (level of evidence C). ACKNOWLEDGEMENTS: The development of these guidelines and the expert consensus were supported by the Canadian Association of Gastroenterology and by an unrestricted educational grant from Schering Canada Inc. Appendix I Infliximab in fistulizing Crohn s disease 1.1 Infliximab is the only therapy for fistulizing disease that has been found to be effective in a randomized, controlled trial. Clinicians may choose to treat patients with fistulizing Crohn s disease with antibiotics before the use of, or concomitantly with, infliximab. 1.2 Complete closure of fistulae may be seen after one or two infusions; however, it is at the clinical discretion of the treating physician whether the remainder of the infusions are required. 1.3 Concomitant therapy of antibiotics with infliximab may be considered when treating patients with fistulae. This may include ciprofloxacin, metronidazole or both. This is especially true in perianal and/or enterocutaneous fistulae in which abscess formation has occurred. REFERENCES 1. Marshall JK. A critical approach to clinical practice guidelines. Can J Gastroenterol 2000;14: Targan SR, Hanauer SB, Van Deventer SJH, et al. A short-term study of chimeric monoclonal antibody ca2 to tumour necrosis factor α for Crohn s disease. N Engl J Med 1977;337: Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn s disease. N Engl J Med 1999;340: Rutgeerts P, D Haens G, Targan S, et al. Efficacy and safety of retreatment with anti-tumour necrosis factor antibody (infliximab) to maintain remission in Crohn s disease. Gastroenterology 1999;117: Can J Gastroenterol Vol 15 No 6 June

4 Canadian Association of Gastroenterology Canadian Association of Gastroenterology Practice Guideline Disclaimer This clinical practice guideline has been developed by the authors on behalf of the Canadian Association of Gastroenterology (CAG) in order to outline the clinical approach to management problems of training issues. After preparation by the authors, based on a review of the literature, each guideline is extensively reviewed by the CAG Practice Affairs Committee, composed of practitioners from across Canada. Changes are made, and once the guideline is felt to be appropriate, it is then circulated for further review by recognized Canadian experts and then amended further. Finally, the guideline is presented to the CAG Governing Board for further review and final approval. Practice guidelines are intended to give an understanding of a clinical problem and outline one or more preferred approaches to investigation and management of the problem. While practice guidelines are intended to be useful to all physicians, it is recognized that specialists may rely less on practice guidelines than those in more general practice. These guidelines are intended to give a practical approach to a problem based on the current literature, but are not intended to be state-of-the-art reviews with extensive references. Practice guidelines are developed to be of assistance to practising clinicians and are not intended to be the only approach to the management of clinical problems, nor are they intended to be considered as a standard of care. The CAG Practice Affairs Committee recognizes that clinical circumstances may at times justify an approach different from that outlined in a practice guideline. It is also recognized that new developments in medical research and clinical practice may require subsequent changes to the practice guideline. 370 Can J Gastroenterol Vol 15 No 6 June 2001

5 MEDIATORS of INFLAMMATION The Scientific World Journal Gastroenterology Research and Practice Diabetes Research International Endocrinology Immunology Research Disease Markers Submit your manuscripts at BioMed Research International PPAR Research Obesity Ophthalmology Evidence-Based Complementary and Alternative Medicine Stem Cells International Oncology Parkinson s Disease Computational and Mathematical Methods in Medicine AIDS Behavioural Neurology Research and Treatment Oxidative Medicine and Cellular Longevity