Treatment - Lippincott Williams & Wilkins



Proposed Quality Indicators

and Literature Reviews

The Crohn’s and Colitis Foundation of America (CCFA) is committed to the improvement of the quality of care for those suffering from inflammatory bowel disease (IBD). The Professional Education Committee of the CCFA has defined a mission statement toward achieving this objective, which begins with Defining Quality of Care. This project represents the initial step toward achieving this goal, through the Development of Quality Indicators for IBD whereby basic measures of quality are defined.

This initiative has followed methodology developed at RAND/UCLA, which has been previously used to develop quality indicators for a host of medical conditions including rheumatoid arthritis, cirrhosis, and the elderly. The methodology incorporates both expert opinion and an evidence basis for the identification of quality indicators through an iterative process.

CCFA Professional Education,

Quality Subcommittee

Thomas Ullman, M.D. (Chair, Prof Ed)

Corey Siegel, M.D. (Co-Chair, Prof Ed)

Gil Melmed, M.D. (QI Subcommittee)

Clinical Advisory Panel

(December, 2009)

Brennan Spiegel, M.D. (Moderator)

David Rubin, M.D.

John Allen, M.D.

Themos Dassipoules, M.D.

Stephen Hanauer, M.D.

Ted Denson, M.D.

Michael Kappelman, M.D.

Doug Wolf, M.D.

Robert Cima, M.D.

Russell Cohen, M.D.

Multi-Disciplinary Advisory Panel

(December, 2010)

Brennan Spiegel, M.D. (Moderator)

Balfour Sartor, M.D.

James Lewis, M.D.

David Rubin, M.D.

John Allen, M.D.

Stephen Hanauer, M.D.

Michael Kappelman, M.D.

Doug Wolf, M.D.

Russell Cohen, M.D.

Jean-Fred Colombel, M.D.

Ronald Schwartz, M.D.

Amy Moynihan, R.N.

Authors:

Bincy Abraham, M.D. Baylor School of Medicine

Nikhil Agarwal, M.D. Cedars-Sinai Medical Center/UCLA

Garrett Cullen, M.D Beth Israel Deaconess Medical Center

Shani DeSilva, M.D Dartmouth-Hitchcock Medical Center

Shane Devlin, M.D. University of Calgary

Sharyle Fowler, M.D. Massachusetts General Hospital

Gauree Gupta, M.D. Cedars-Sinai Medical Center/UCLA

Gilaad Kaplan, M.D. University of Calgary

David Klibansky, M.D., Dartmouth-Hitchcock Medical Center

Garrett Lawlor, M.D .Beth Israel Deaconesss Medical Center

Campbell Levy, M.D ..Dartmouth-Hitchcock Medical Center

Burr Loew, M.D\ Dartmouth-Hitchcock Medical Center

Millie Long, M.D. University of North Carolina

Nimisha Parekh, M.D .University of California, Irvine

Keely Parisian, M.D Cleveland Clinic

Atsushi Sakuraba, M.D .University of Chicago

Justin Sewell, M.D University of California, San Franscisco

Shamita Shah, M.D .Stanford University

Brijen Shah, M.D Mount Sinai Medical Center, NY

Andrew Tinsely, M.D. Mount Sinai Medical Center, NY

Chad Williams, M.D Cedars-Sinai Medical Center

Project personnel

Thomas Ullman, M.D. Editor

Corey Siegel, M.D. Editor

Gil Melmed, M.D. Project Manager, Editor

Cathy MacLean, M.D, PhD. Advisor

Thomas Mead . Research Librarian

Kimberly Isaacs CCFA

Laura Wingate CCFA

Jennifer Talley Center for Outcomes Research

Review does not imply endorsement of the findings, which remain the sole responsibility of the authors and the review team.

Table of Contents

Methods 2

Diagnosis 2

Q.I. #1: Determine disease phenotype 2

Q.I. #2: Patient Support 2

Q.I. #3: Re-Evaluation Within 6 Weeks 2

Q.I. #4 and #5: Crohn’s Disease and Smoking 2

Q.I. #6 C. Difficile testing during disease flare 2

Q.I. #7: Testing for non-C. Difficile enteric infections 2

Q.I. #8: Counselling against NSAIDs 2

Drug Safety and Monitoring 2

Q.I. #9: Tuberculosis testing before anti-TNF therapy 2

Q.I. #10: Laboratory Monitoring on anti-TNF Therapy 2

Q.I. #11: Assessment of Viral Hepatitis prior to anti-TNF Therapy 2

Q.I. #12: Renal function on 5-ASA 2

Q.I. #13: TPMT Testing before 6MP/AZA 2

IBD Treatment 2

Q.I. #14: Topical and Oral 5-ASA for distal ulcerative colitis 2

Q.I. #15: Oral Aminosalicylate therapy for mild to moderate extensive ulcerative colitis 2

Q.I. #16: Oral therapy for ulcerative proctitis refractory to topical agents 2

Q.I. #17: Steroid-Sparing Therapy for UC 2

Q.I. #18: Oral cyclosporine after IV induction 2

Q.I. #19: Check CMV in hospitalized UC 2

IBD Health-Care Maintenance 2

Q.I. #20: Annual Review 2

Q.I. #21: Influenza vaccine 2

Q.I. #22: Avoid live virus vaccines if immunosuppressed 2

IBD and Colon Cancer 2

Q.I. #23 Surveillance Colonoscopy 2

Q.I. #24: Biopsy of colonic strictures 2

Q.I. #25: Discuss implications of surveillance 2

Q.I. #26: Surveillence in Crohn’s colitis 2

Q.I.#27: Biopsy Adjacent Mucosa of Polypoid Lesions 2

Q.I. #28: Surveillence colonoscopy in P.S.C. 2

Q.I. #29: Flat Low Grade Dysplasia 2

IBD Surgical Issues 2

Q.I. #30: Surgical drainage 2

Q.I. #31: Discuss options for UC surgery 2

Q.I. #32: Surgery for colonic perforation 2

Miscellaneous 2

Q.I. #33: Inquire about CAM 2

Q.I. #34: Ophthalmology referral 2

Q.I. #35: Weight and Nutrition 2

Methods

In this monograph, we present a set of candidate quality indicators for Crohn’s disease and ulcerative colitis, along with a synthesis of the available evidence supporting a link between the indicator and an outcome of interest. We developed potential quality indicators from two sources: Review of existing guidelines, and expert opinion based on an Advisory Panel Meeting in December, 2009.

We constructed potential quality indicators in an “if-then-because” format. “If” refers to the clinical characteristics that describe persons eligible for the quality indicator (For example: If a patient has ulcerative colitis for 8 years, then such-and-such should be done). The “then” portion refers to the actual process that should or should not be performed. The “because” section refers to the expected health impact if the indicator is (or is not) performed. We focused exclusively on quality indicators that measured processes, rather than outcomes, of care because process measures are a more efficient means of assessing quality. Processes are thought to be completely under the control of the health care system and, therefore, are amenable to change. Futhermore, true outcome measures in IBD are difficult to define.

We included potential quality indicators for consideration for two reasons: Either they were believed to have a significant impact on outcomes, or they were widely recommended. To be a valid measure of quality, a proposed process must be linked to an impact on outcome; consequently, we performed a comprehensive search of the literature to assess the available evidence linking the proposed process quality indicators to their impacts on outcome. In some instances, the available evidence did not support some of the widely recommended potential quality indicators; those quality indicators and a summary of the evidence pertaining to them are also included in this monograph. Thus, inclusion of an indicator in this monograph does not necessarily imply that either the authors or the project team believe it to be a valid measure of quality.

Guidelines from which Quality Indicators were extracted

Guidelines published after 2002 were searched for potential quality indicators. Guidelines were obtained that were published by or under the auspices of various specialty organizations including:

▪ American Gastroenterology Association (AGA)

▪ American College of Gastroenterology (ACG)

▪ American Society of Gastroenterology Endoscopy (ASGE)

▪ American Society of Colorectal Surgeons (ASCRS)

▪ British Society of Gastroenterology (BSG)

▪ European Crohn’s and Colitis Organization (ECCO)

▪ Crohn’s and Colitis Foundation of America (CCFA)

Development of this “Candidate Set” of 35 Quality Indicators

All guidelines were read in duplicate, from which over 500 potential quality indicators were extracted by members of the Quality of Care Subcommittee. From this initial set, we developed a set of approximately 100 potential quality indicators. In developing these indicators, we addressed processes that pertained to diagnosis, treatment, and health care maintenance of patients with IBD. Most measures were applicable to both Crohn’s disease (CD) and ulcerative colitis (UC) unless specifically relevant to one disease. We then circulated a preliminary set of process indicators to our Advisory Committee for review. Reviewers electronically rated these ‘top 100’ for validity, and then met in-person for a moderated session (December, 2009) to discuss discrepancies and confidentially re-rate for both validity and feasibility.

On the basis of the re-rating, we subsequently narrowed down the initial set to the 35 highest rated indicators that met approval by the Advisory Committee for both validity and feasibility. We then searched MEDLINE via the National Library of Medicine’s PubMed to identify evidence linking the potential indicators to the outcomes of interest. All searches were limited to English language and human subjects. We performed separate MEDLINE searches for each quality indicator (exact search strategies available from authors on request) and searched the references of key articles to identify over 2,000 titles. Together with a team of literature reviewers, we sequentially reviewed the titles, abstracts, and articles from these searches for relevance to this report. Studies were included if they provided evidence on the potential relationship between the process in question and better outcomes in humans.

Purpose of this Monograph:

This monograph is intended to inform the panelists who will be participating in the Multidisciplinary Advisory Panel on December 9, 2010. Panelists will be asked to confidentially rate the validity of each QI twice – once via internet prior to the December meeting, and once at the meeting itself. The literature summaries provided in this compendium are intended to serve as a reference; the decision to rate an item as valid should be based on the expert interpretation and experience of the individual panelists.

IBD CANDIDATE QUALITY INDICATORS

Diagnosis

Q.I. #1: Determine disease phenotype

Q.I. #1 IF a patient is newly diagnosed with inflammatory bowel disease

THEN the type and extent of disease should be determined

BECAUSE this evaluation is necessary to guide treatment strategies.

Summary: Disease location and severity can influence the management of IBD with respect to choice of medications, type of surgery, and counseling for colorectal cancer surveillance.

Details

The diagnosis of ulcerative colitis and Crohn’s disease is made using clinical history, endoscopic findings, histology, and radiologic imaging. As part of the diagnostic workup, other etiologies of colitis/enteritis should be excluded including infections, ischemic, medication induced, radiation induced, neoplastic and other inflammatory conditions.1-5

Ulcerative Colitis

Endoscopy is used to confirm diagnosis of ulcerative colitis, assess extent of disease, and disease severity. The recommended endoscopic procedure is colonoscopy and ileoscopy with segmental biopsies to evaluate for IBD and to help differentiate between ulcerative colitis and Crohn’s disease.6 However, colonoscopy should be avoided in severe ulcerative colitis and flexible sigmoidoscopy with biopsy should be done to confirm diagnosis and exclude infections.

The extent of disease in ulcerative colitis is determined by endoscopic evaluation and characterized in the Montreal classification as: E1 proctitis, E2 Left sided colitis, E3 Pancolitis.10,11 If disease extent cannot be assessed on initial evaluation, it should be assessed once a patient’s condition permits. It is important to delineate disease inflammation as distal (limited to below the descending colon and within reach of topical therapy) or proximal, with extension to the transverse and ascending colon thus requiring systemic medication.3

In ulcerative colitis, disease severity is generally classified by clinical parameters originally described by Truelove and Witts13 describing disease as mild, moderate and severe. ECCO and ACG recommend the use of clinical parameters to describe severity of disease.14, 15 The Montreal Classification characterizes ulcerative colitis by similar criteria as seen in Table 1.10, 11 Population data suggest that most patients present initially with “moderate to higher” disease activity.12

Table 110, 11: Montreal Classification for Ulcerative Colitis

|Disease Severity |Disease Extent |

|Remission (S0) No more than 3 bowel movements daily, no blood in | |

|stools, and no urgency | |

|Mild (S1) Up to 4 bowel movements daily, trace amounts of blood, |E1 Proctitis |

|normal pulse, temperature, hemoglobin and ESR | |

|Moderate (S2) 4 to 6 bloody bowel movements daily, no signs of |E2 Left sided colitis |

|systemic involvement | |

|Severe (S3) more than 6 bloody bowel movements daily, temperature|E3 Pancolitis |

|>37.5 C, heart rate >90, hemoglobin below 10.5g/dl, ESR >30mm/h | |

The initial approach to therapy for UC is determined by severity and anatomic extent of disease, with the oral or topical 5-aminosalicylate (5-ASA) agents first-line therapy for mild to moderate distal disease.3, 16 In addition, the extent of disease determines the start and frequency of surveillance program for colorectal cancer screening, as pancolitis carries higher risk of colorectal cancer than left sided disease.

Crohn’s Disease

Crohn’s disease has several different phenotypic presentations. Diagnostic testing in Crohn’s disease is guided by presenting symptoms, physical findings, and laboratory parameters.

Endoscopy is also the recommended to confirm diagnosis of Crohn’s disease, document location of disease, and for tissue sampling.17 While colonoscopy and ileoscopy with segmental biopsies is the procedure of choice, patients with severe disease should only have a sigmoidoscopy until clinical symptoms improve.

Esophagogastroduodenoscopy is recommended in patients with upper GI symptoms. In children, the European Society of Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) developed the “Porto Criteria” and recommend that all children suspected with Crohn’s disease should have a complete examination at time of diagnosis to establish diagnosis, assess disease severity and extent before treatment is started.19 Complete examination includes colonoscopy and ileoscopy with biopsy, esophagogastroduodenoscopy with biopsy, and small bowel imaging (small bowel follow through or enteroclysis). The European Crohn’s and Colitis Organisation (ECCO) also supports this recommendation in children.20 To date there are no recommendations for routine upper endoscopy for adult patients with Crohn’s disease.

Crohn’s disease can affect the small bowel that is not in the reach of colonoscope. Several techniques are available to image the small intestine including: small bowel follow through, ultrasound, CT enterography, MR enterography, enteroclysis, CT enteroclysis, MR enteroclysis, and video capsule endoscopy. CT and MR enterography offer the possible ability to differentiate between inflammation and noninflammation.17 Due to risks of radiation, MRI may be preferred over CT.21 Video capsule endoscopy can be considered in patients in whom a stricture/stenosis have been excluded.

Perianal disease should be assessed with exam under anesthesia, pelvic MRI, and or anorectal endoscopic ultrasound.22

The Montreal Classification of Crohn’s disease takes into account the age at time of diagnosis, location of disease and development of complications such as strictures, fistulas and abscesses.10, 11 (see Table 2)

Montreal Classification of Crohn’s Disease10, 11

| | | |

|A1: < 16years at diagnosis |L1: Terminal ileum |B1: Without stricture, nonpenetrating |

|A2: 17 to 40 years at diagnosis |L2: Colon |B2: With stricture formation |

|A3: > 40 years at diagnosis |L3: Ileocolon |B3: Internally penetrating |

| |L4: Upper GI tract |B3p: Perianally penetrating |

| |L4 +: Lower GI tract and distal disease | |

Crohn’s disease activity is also classified by clinical parameters and described as mild, moderate, or severe as described by ECCO and ACG guidelines as follows:4, 23

Mild: Patient able to walk, tolerate oral nutrition, no signs of dehydration, no systemic involvement, no abdominal pain or mass, no ileus, or loss of no more than 10% of body weight, CRP is elevated.

Moderate: Intermittent vomiting, loss of more than 10% of body weight, lack of response to drug therapy for mild Crohn’s disease, no ileus, and elevated CRP

Severe: Cachectic with BMI under 18, ileus, abscess, persistent symptoms despite intensive therapy, and elevated CRP.

By combining disease location, severity and presence of complications describes the phenotype of patient with Crohn’s disease and guides management decisions in terms of medication choice and surgery.24

References:

1. Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 2007;369(9573):1641-57.

2. Thielman NM, Guerrant RL. Clinical practice. Acute infectious diarrhea. The New England journal of medicine 2004;350(1):38-47.

3. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. The American journal of gastroenterology;105(3):501-23; quiz 24.

4. Lichtenstein GR, Hanauer SB, Sandborn WJ. Management of Crohn's disease in adults. The American journal of gastroenterology 2009;104(2):465-83; quiz 4, 84.

5. Sands BE. From symptom to diagnosis: clinical distinctions among various forms of intestinal inflammation. Gastroenterology 2004;126(6):1518-32.

6. Leighton JA, Shen B, Baron TH, et al. ASGE guideline: endoscopy in the diagnosis and treatment of inflammatory bowel disease. Gastrointestinal endoscopy 2006;63(4):558-65.

7. Simpson P, Papadakis KA. Endoscopic evaluation of patients with inflammatory bowel disease. Inflammatory bowel diseases 2008;14(9):1287-97.

8. Fefferman DS, Farrell RJ. Endoscopy in inflammatory bowel disease: indications, surveillance, and use in clinical practice. Clin Gastroenterol Hepatol 2005;3(1):11-24.

9. Ladefoged K, Munck LK, Jorgensen F, Engel P. Skip inflammation of the appendiceal orifice: a prospective endoscopic study. Scandinavian journal of gastroenterology 2005;40(10):1192-6.

10. Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006;55(6):749-53.

11. Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Canadian journal of gastroenterology = Journal canadien de gastroenterologie 2005;19 Suppl A:5-36.

12. Langholz E, Munkholm P, Nielsen OH, Kreiner S, Binder V. Incidence and prevalence of ulcerative colitis in Copenhagen county from 1962 to 1987. Scandinavian journal of gastroenterology 1991;26(12):1247-56.

13. Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. British medical journal 1955;2(4947):1041-8.

14. Stange EF, Travis SP. The European consensus on ulcerative colitis: new horizons? Gut 2008;57(8):1029-31.

15. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee. The American journal of gastroenterology 2004;99(7):1371-85.

16. Safdi M, DeMicco M, Sninsky C, et al. A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis. The American journal of gastroenterology 1997;92(10):1867-71.

17. Stange EF, Travis SP, Vermeire S, et al. European evidence based consensus on the diagnosis and management of Crohn's disease: definitions and diagnosis. Gut 2006;55 Suppl 1:i1-15.

18. Nahon S, Bouhnik Y, Lavergne-Slove A, et al. Colonoscopy accurately predicts the anatomical severity of colonic Crohn's disease attacks: correlation with findings from colectomy specimens. The American journal of gastroenterology 2002;97(12):3102-7.

19. Escher JC, Aml Dias, J, Bochenek, K. Inflammatory Bowel Disease in children and adolescents. Recommendations for Diagnosis: The Porto Criteria. Medical Position Paper. J Pediatri Gastroenterology Nutrition 2005;41:1-7.

20. Caprilli R, Gassull MA, Escher JC, et al. European evidence based consensus on the diagnosis and management of Crohn's disease: special situations. Gut 2006;55 Suppl 1:i36-58.

21. Brenner DJ, Hall EJ. Computed tomography--an increasing source of radiation exposure. The New England journal of medicine 2007;357(22):2277-84.

22. Schwartz DA, Loftus EV, Jr., Tremaine WJ, et al. The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. Gastroenterology 2002;122(4):875-80.

23. Travis SP, Stange EF, Lemann M, et al. European evidence based consensus on the diagnosis and management of Crohn's disease: current management. Gut 2006;55 Suppl 1:i16-35.

24. Walfish A, Sachar D. Phenotype classification in IBD: Is there an impact on therapy? Inflammatory bowel diseases 2007;13(12):1573-5.

Q.I. #2: Patient Support

QI#2 IF a patient is newly diagnosed with IBD

THEN information about patient support groups and sources of help should be made available

BECAUSE IBD patients who feel well supported and well informed are more likely to positively cope with and manage their illness.

SUMMARY

Despite the lack of studies on this issue, expert opinion advocates that IBD patients should receive information about support groups and other sources of help. According to expert opinion, patients who are educated about their disease and have adequate social support experience a better quality of life and may also be more likely to adhere to medical therapy resulting in management of disease.

DETAILS

Our search revealed one study that assessed the effect of patient support in patients with IBD[pic](1). This study was prospective but neither randomized nor controlled. Investigations prospectively assessed 61 children and adolescents with IBD before and after a one week long support-group camp. Questionnaires were administered pre and post camp to assess quality of life variables, the IMPACT II (a tool to assess health-related quality of life) and the State-Trait Anxiety Inventory for Children. Significant improvements in quality of life and bowel symptoms were noted at the completion of the support camp. There was no significant change in the level of anxiety. There may also be an association between patient support and adherence to medication. Patients who do not feel well supported, particularly by the medical team, are less likely to adhere to medical therapy for their IBD(2). This may translate into poorer disease control.

Expert opinion advocates for providing patients with adequate resources and support. The British Society of Gastroenterology guidelines for the management of IBD and The IBD Standards Group both recommend that providers give educational information about IBD and support to patients and their families[pic](3, 4). They cite that such measures are important to allow patients better manage their IBD, have a better quality of life and to be more involved in their own care. Recent World Gastroenterology Organization (WGO) guidelines, based on expert opinion, also state that patients should be educated about their disease at the time of diagnosis(5).

References:

1. Shepanski MA, Hurd LB, Culton K, et al. Health-related quality of life improves in children and adolescents with inflammatory bowel disease after attending a camp sponsored by the Crohn's and Colitis Foundation of America. Inflamm Bowel Dis 2005;11:164-70.

2. Robinson A. Review article: improving adherence to medication in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2008;27 Suppl 1:9-14.

3. Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of inflammatory bowel disease in adults. Gut 2004;53 Suppl 5:V1-16.

4. IBD Standards Group. Quality Care Service standard for the healthcare of people who have Inflammatory Bowel Disease (IBD). 2009.

5. Bernstein CN, Fried M, Krabshuis JH, et al. World Gastroenterology Organization Practice Guidelines for the diagnosis and management of IBD in 2010. Inflamm Bowel Dis;16:112-24.

Q.I. #3: RE-EVALUATION WITHIN 6 WEEKS

QI #3 IF a patient with CD is started on therapy

THEN he or she should be re-evaluated within 6 weeks

BECAUSE evaluation is necessary to assess symptoms, physical signs, laboratory and other investigations that may indicate treatment response, failure or adverse events

Summary: There has been no prospective study evaluating the impact of review 6 weeks after starting a new therapy on outcomes in CD. However, based on the pharmacology of commonly used therapies, 6 weeks seems to be an appropriate interval for assessment of both tolerability and efficacy of treatment relevant to many commonly used therapies.

Details

A variety of therapies are used in Crohn’s disease (CD) with the aim of inducing and maintaining remissionRecent data have suggested that early introduction of immunosuppressant therapy may alter the natural history of Crohn’s disease1. While this has not been widely adopted at this time, many practitioners are aware of the need to be aggressive early in the disease course, particularly in those with complicated disease (extensive, stricturing or penetrating). In light of this, early assessment of response to therapy is important so that patients are quickly transitioned to effective treatment.

Aminosalicylates are a mainstay of therapy for UC and (despite a strong evidence base) are frequently used in CD. Typically, patients with UC treated with 5-ASAs have a response within 2 weeks of starting the drug.

Corticosteroids are effective agents for induction of remission4, but they are not suitable for maintenance therapy and should be tapered following response. If there has been no response to by 7-10 days, the patient should change therapy (or be admitted to hospital for intravenous therapy in certain circumstances). Budesonide is a topically active glucocorticoid that is effective for the induction of remission in ileal or ileocolonic CD5. Its efficacy in the induction of remission is comparable to prednisone and it has an onset of action of approximately 2 weeks6.

The thiopurines (azathioprine and 6-mercaptopurine) can take up to 3 (and even 6) months to reach maximum efficacy7. However, 20% can have a response by 2 weeks and this can be assessed at 6-week follow-up8. The main short-term concern with these agents is related to adverse events and patients should have a white blood count and liver tests checked early in the course of therapy.

Methotrexate is typically started at 25mg subcutaneously weekly for the first 16 weeks before being reduced to 15mg weekly. The onset of action is thought to be similar to that of the thiopurines although it has been suggested that it may even be slightly earlier9. Review at 6 weeks allows for assessment of tolerability and early response.

Anti-TNF agents (infliximab, adalimumab and certolizumab pegol) are frequently assessed for symptomatic benefit at 6 weeks. In the case of all 3 agents, the induction regimen is for 4 (adalimumab and certolizumab pegol) to 6 (infliximab) weeks and a complete lack of any response at this point suggests a primary non-response.. The AGA Institute suggest that a complete lack of response after 2 doses of infliximab should be an indication for discontinuation10. Those who have had an attenuated response may benefit from a reduction in dosing interval or an increase in dose10.

The monoclonal antibody against alpha-4 integrin, natalizumab, is licensed for Crohn’s disease under the TOUCH program whereby clinicians are obliged to discontinue it if there has been no response after 12 weeks of therapy (because of the risk of progressive multifocal leukoencephalopathy). The drug is given at 4 week intervals and so a 6 week interval is a good time to evaluate tolerability and possible early response to the first 2 doses,

Data from large randomized controlled trials in CD have shown that endoscopically-visualised mucosal healing is possible with certain therapies11, 12. Furthermore, there are data to suggest improved outcomes in those with mucosal healing offering an additional therapeutic goal to that of symptomatic improvement13, 14. Although this is currently an important focus of research and is increasingly used as an endpoint in clinical trials it not typically assessed as early as 6 weeks and is more likely to be checked at 3, 6 or 12 months in those who have symptomatic response.

References

1. D'Haens G, Baert F, van Assche G, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet 2008;371:660-7.

2. Pinczowski D, Ekbom A, Baron J, Yuen J, Adami HO. Risk factors for colorectal cancer in patients with ulcerative colitis: a case-control study. Gastroenterology 1994;107:117-20.

3. Jess T, Gamborg M, Matzen P, Munkholm P, Sorensen TI. Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. The American journal of gastroenterology 2005;100:2724-9.

4. Faubion WA, Jr., Loftus EV, Jr., Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology 2001;121:255-60.

5. Greenberg GR, Feagan BG, Martin F, et al. Oral budesonide for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group. The New England journal of medicine 1994;331:836-41.

6. Campieri M, Ferguson A, Doe W, Persson T, Nilsson LG. Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group. Gut 1997;41:209-14.

7. Su C, Lichtenstein GR. Treatment of inflammatory bowel disease with azathioprine and 6-mercaptopurine. Gastroenterol Clin North Am 2004;33:209-34, viii.

8. Sandborn WJ, Tremaine WJ, Wolf DC, et al. Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn's disease. North American Azathioprine Study Group. Gastroenterology 1999;117:527-35.

9. Feagan BG, Rochon J, Fedorak RN, et al. Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. The New England journal of medicine 1995;332:292-7.

10. Clark M, Colombel JF, Feagan BC, et al. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23, 2006. Gastroenterology 2007;133:312-39.

11. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002;359:1541-9.

12. Rutgeerts P, Diamond RH, Bala M, et al. Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease. Gastrointestinal endoscopy 2006;63:433-42; quiz 64.

13. Baert F, Moortgat L, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. Gastroenterology;138:463-8; quiz e10-1.

14. Schnitzler F, Fidder H, Ferrante M, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn's disease. Inflammatory bowel diseases 2009;15:1295-301.

Q.I. #4 and #5: Crohn’s Disease and Smoking

Q.I. #4 IF a patient who is newly diagnosed with Crohn’s disease (CD)

THEN he or she should be educated about the risks of disease exacerbation from cigarette smoking

BECAUSE cigarette smoking has been associated with CD exacerbation, recurrence after surgery, and resistance to anti-TNF therapy.

Q.I. #5 IF you have a patient with Crohn’s disease who is an active smoker

THEN smoking cessation should be recommended, including referral for counseling or nicotine substitutes

BECAUSE smoking cessation lowers the risk of disease flares and lowers the need for corticosteroids, immunomodulators, and dose increase in immunomodulators

Summary: Smoking has a negative effect on patients with CD. Several studies have reported that smokers have a more severe disease course and are more likely to develop a more complicated form of CD. A large meta-analysis of observational studies indicates a significantly increased risk of surgical recurrence and clinical exacerbation in CD patients who are smokers. Published literature is mixed in terms of whether smoking affects the efficacy of anti-TNF therapy. Three studies reported a negative association whereas most others showed no difference or reported mixed results.

Furthermore, ex-smokers have a more favorable disease course that resembles that of non-smokers. The risk of endoscopic and clinical recurrence in former smokers who have not smoked for at least 1 year is similar to that of non-smokers1, and the benefit of smoking cessation may be seen within the year following cessation. Thus, data suggests that smoking cessation should be recommended for active smokers with Crohn’s disease. There is only one prospective intervention study that supports these recommendations in CD patients.

Details

Cigarette Smoking and Crohn’s exacerbation including risk of complicated CD:

We have identified five studies, which report current cigarette smokers experience higher risk of relapses and more severe disease. Four of these studies are prospective cohort studies. In 1992 Wright et al observed 239 patients and found cigarette smokers were more likely to have ileocolitis that nonsmokers (47% vs 32% p=0.028), and ileocolitis was linked to an increased number of inflammatory attacks (47% for ileocolitis vs. 35% for ileitis and 14% for colitis; p=.001). In another prospective cohort of 74 patients Duffy et al reported that current smoking increases the risk of relapse for Crohn’s patients. The risk increased by 1.6 times that of nonsmokers (p100)|No |

|2005 | | | |and long-term remission (CDAI3 at evaluation | |

| | | | |compared to the baseline | |

PNR prospective non-randomized, R retrospective; IFX=infliximab; ADA=adalimumab; CDAI- Crohn’s disease activity index

HBI-Harvey Bradshaw index

1. Cottone M, Rosselli M, Orlando A, et al. Smoking habits and recurrence in Crohn's disease. Gastroenterology 1994; 106: 643-648

2. Cosnes J, Beaugerie L, Carbonnel F, et al. Smoking cessation and the course of Crohn’s disease: An Intervention Study

3. Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1999;340:685– 691.

Q.I. #6 C. Difficile testing during disease flare

Q.I. #6: IF you have a patient in whom a severe or refractory flare of IBD is suspected with increased stool frequency

THEN the patient should undergo C difficile testing,

BECAUSE patients with symptoms of disease exacerbation may have C difficile infection. C difficile infection increases risk of adverse outcomes among hospitalized IBD patients, including mortality, and this risk increases when patients are treated concomitantly with antibiotics and immunosuppressive agents.

Summary: Several studies of large national datasets identified higher and more rapidly increasing prevalence of C difficile infection among hospitalized IBD inpatients compared with other inpatients. Hospitalized IBD patients with C difficile infection have elevated mortality rates; among C difficile-infected UC patients the in-hospital mortality risk is four percent. The use of combination antibiotics and immunosuppressive agents among such patients also increases mortality risk. More than 10% of ambulatory IBD patients are C difficile carriers, and 8-20% percent of ambulatory flares may be associated with C difficile infection.

Details

The majority of studies investigating C difficile infection among IBD patients were performed in hospitalized patients. The incidence of C difficile infection continues to rise among all hospitalized patients, but temporal increases are more marked among patients with IBD.1 In a study using Nationwide Inpatient Sample data, the prevalence of C difficile infection among hospitalized patients with UC nearly doubled from 26.6 per 1,000 discharges in 1998 to 51.2 per 1,000 in 2004 (P ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download