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Canadian Guidelines for the Medical Management of Ulcerative Colitis in Nonhospitalized Patients
- In patients with mild to moderate active ulcerative proctitis, rectal 5-ASA, at a dosage of 1 g daily, is recommended as first-line therapy to induce symptomatic remission.
- In patients with mild to moderate active left-sided UC, 5-ASA enemas, at a dosage of at least 1 g daily, are recommended as an alternative first-line therapy to induce complete remission.
- In patients with mild to moderate active UC of any disease extent beyond proctitis, an oral 5-ASA preparation, at dosages between 2.0 and 4.8 g/day, is recommended as an alternative first-line therapy to induce complete remission.
- In patients with mild to moderate active UC of any disease extent beyond proctitis, the combination of a rectal and an oral 5-ASA preparation over oral 5-ASA alone is suggested as an alternative first-line therapy to induce complete remission.
- It is recommended that patients with UC be evaluated for lack of symptomatic response to oral/rectal 5-ASA induction therapy in 4 to 8 weeks to determine the need to modify therapy.
- In patients with oral or rectal 5-ASA–induced complete remission of mild to moderate active left-sided UC or proctitis, the same therapy shall be continued to maintain complete remission.
- In patients with oral 5-ASA–induced complete remission of mild to moderate active UC of any disease extent, continued oral therapy of at least 2 g/day is recommended to maintain complete remission.
- In selected 5-ASA–naive patients with UC who have achieved symptomatic remission on oral corticosteroids, an oral 5-ASA preparation of at least 2 g/day is recommended while being assessed for corticosteroid-free complete remission.
- In patients with UC who have failed to respond to oral 5-ASA, switching to another oral 5-ASA formulation to induce remission is not recommended.
- When using oral 5-ASA to induce or maintain complete remission of UC, once-daily dosing is preferred over more frequent dosing.
- In patients with moderate to severe active UC, oral corticosteroids are recommended as first-line therapy to induce complete remission.
- In patients with mild to moderate active UC who fail to respond to 5-ASA therapy, oral corticosteroids are recommended as second-line therapy to induce complete remission.
- In patients with mild to moderate active left-sided UC or proctitis who fail to respond to rectal 5-ASA therapy, rectal corticosteroids are suggested as second-line therapy to induce complete remission.
- In patients with UC, oral corticosteroids are not recommended to maintain complete remission because they are ineffective for this indication and their prolonged use is associated with significant adverse effects.
- In patients with mild to moderate UC of any disease extent, oral budesonide MMX is suggested as an alternative first-line therapy to induce complete remission.
- It is recommended that patients with UC be evaluated for lack of symptomatic response to corticosteroid induction therapy within 2 weeks to determine the need to modify therapy.
- In patients with UC, the use of thiopurine monotherapy to induce complete remission is not recommended.
- In selected patients with UC who have achieved symptomatic remission on oral corticosteroids, thiopurine monotherapy is suggested as an option to maintain complete corticosteroid-free remission.
- In patients with UC, the use of methotrexate monotherapy is not recommended to induce or maintain complete remission.
- In patients with UC who fail to respond to thiopurines or corticosteroids, anti-TNF therapy is recommended to induce complete corticosteroid-free remission.
- Anti-TNF therapy should be combined with a thiopurine or methotrexate rather than used as monotherapy to induce complete remission.
- In patients with UC who are corticosteroid dependent, anti-TNF therapy is recommended to induce and maintain complete corticosteroid-free remission.
- It is recommend that patients with UC be evaluated for lack of symptomatic response to anti-TNF induction therapy in 8 to 12 weeks to determine the need to modify therapy.
- In patients with UC who respond to anti-TNF induction therapy, continued anti-TNF therapy is recommended to maintain complete remission.
- In patients with UC who have a suboptimal response to anti-TNF induction therapy, dose intensification is recommended to achieve complete remission.
- In patients with UC who lose response to anti-TNF maintenance therapy, optimizing dose is recommended to recapture complete remission.
- Dose optimization for patients with UC thjrough therapeutic drug monitoring is recommended.
- In patients with primary failure to an anti-TNF therapy, switching to vedolizumab is recommended over switching to another anti-TNF therapy to induce complete corticosteroid-free remission.
- In patients with secondary failure to an anti-TNF therapy, switching to another anti-TNF therapy or vedolizumab is recommended based on therapeutic drug monitoring results to induce complete corticosteroid-free remission.
- In patients with moderate to severe active UC who fail to respond to corticosteroids, thiopurines, or anti-TNF therapies, vedolizumab is recommended to induce complete corticosteroid-free remission.
- Patients with UC shall be evaluated for lack of symptomatic response to vedolizumab induction therapy in 8 to 14 weeks to determine the need to modify therapy.
- In patients with UC who respond to vedolizumab, continued vedolizumab therapy is recommended to maintain complete corticosteroid- free remission.
- Fecal microbial transplant to induce or maintain complete remission in patients with UC is not recommended outside the setting of a clinical trial.
- In patients with UC, probiotics to induce or maintain complete remission outside the setting of a clinical trial are not recommended.
- 5-ASA failure: Inability of the patient to achieve and maintain complete corticosteroid-free remission despite optimal treatment with oral, rectal, or combination 5-ASA therapy
- Thiopurine failure: Inability of the patient to maintain corticosteroid-free complete remission despite dose optimization
- Biologic failure:
- Primary failure: Inability of the patient to achieve corticosteroid-free complete remission despite dose optimization
- Secondary failure: Inability of the patient to maintain corticosteroid-free complete remission after achieving a symptomatic response
- High disease activity (in acute setting)
- Frequency of hospitalization
- Need for surgery
- Inability to work or participate in leisure activities
- Failure to respond to medication
- Complete remission: Both symptomatic remission and endoscopic healing as defined below
- Endoscopic healing: Normal mucosa, vascular blurring, or chronic changes (eg, inflammatory polyps, scarring) without friability
- Symptomatic remission: Normal stool frequency ( 3/day) and no blood in the stool
- Symptomatic response: Meaningful improvement in symptoms as judged by both the patient and physician in the absence of remission; response should not be considered a desirable final outcome but is useful to assess early response to treatment
- Disease Extent
- The extent of endoscopic disease was categorized as
- proctitis (distal to the rectosigmoid junction or within 18 cm of the anal verge)
- left-sided colitis (extending anywhere from the sigmoid to the splenic flexure), or
- extensive colitis (extending beyond the splenic flexure).
- The extent of endoscopic disease was categorized as
- Disease Activity
- Disease activity is best determined by clinical symptoms and an objective assessment of disease activity through endoscopy. Yet is often necessary to make clinical decisions based on symptoms alone. Ideally, a formal scoring tool such as the Mayo score or a similar disease activity score should be used to determine disease activity in patients with UC. The Mayo score includes 4 measures: stool frequency, rectal bleeding, endoscopic findings, and the physician’s global assessment. Although such a scoring system is desirable for accurate and consistent assessment of disease activity, it is often necessary to make management decisions in the absence of endoscopic information while considering the subjective aspects of disease presentation not captured by the full Mayo score. In such circumstances, the partial Mayo score (which omits the endoscopic subscore) can be informative.
- 0 – Normal number of stools for this patient
- 1 – 1–2 stools more than normal
- 2 – 3–4 stools more than normal
- 3 – 5 or more stools more than normal
- 0 – No blood seen
- 1 – Streaks of blood with stool less than half the time
- 2 – Obvious blood with stool most of the time or more
- 3 – Blood passed alone
- 0 – Normal or inactive disease
- 1 – Mild disease (erythema, decreased vascular pattern, mild friability)
- 2 – Moderate disease (marked erythema, absent vascular pattern, friability, erosions)
- 3 – Severe disease (spontaneous bleeding, ulceration)
- 0 – Normal (there are no symptoms of colitis, the patient feels well, and the flexible proctosigmoidoscopy score is 0) (stool frequency = 0; rectal bleeding = 0; patient’s functional assessment = 0; flexible proctosigmoidoscopy findings = 0)
- 1 – Mild disease (mild symptoms and proctoscopic findings that were mildly abnormal) (the subscores should be mostly 1: stool frequency = 0 or 1; rectal bleeding = 0 or 1; patient’s functional assessment = 0 or 1; flexible proctosigmoidoscopy findings = 0 or 1)
- 2 – Moderate disease (more serious abnormalities and proctosigmoidoscopic and symptom scores of 1 or 2) (the subscores should be mostly 2: stool frequency = 1 or 2; rectal bleeding = 1 or 2; patient’s functional assessment = 1 or 2; flexible proctosigmoidoscopy findings = 1 or 2)
- 3 – Severe disease (the proctosigmoidoscopic and symptom scores are 2 to 3 and the patient probably requires corticosteroid therapy and possibly hospitalization) (the subscores should be mostly 3: stool frequency = 2 or 3; rectal bleeding = 2 or 3; patient’s functional assessment = 2 or 3; flexible proctosigmoidoscopy findings = 2 or 3)
- 0 – Generally well
- 1 – Fair
- 2 – Poor
- 3 – Terrible
Prevention and Treatment of Venous Thromboembolism in Patients with IBD
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Inflammatory Bowel Disease (IBD) patients have about a 3-fold higher risk of Venous Thromboembolism (VTE) compared with the general population.
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Moderate to severe disease activity drives the increased risk of VTE in IBD and should be considered a provoking factor.
- For the prevention of VTE, strong recommendations are made for 1) anticoagulant thromboprophylaxis over no prophylaxis for patients with IBD who are hospitalized with moderate to severe IBD flares without severe bleeding, for 2) anticoagulant thromboprophylaxis over no prophylaxis for inpatients with IBD who have undergone major abdominal-pelvic or general surgery, and 3) against anticoagulant thromboprophylaxis in outpatients with an IBD flare if they have not had a previous VTE.
- For the treatment of VTE, strong recommendations are made for a minimum of 3 months of anticoagulant therapy for adult and pediatric IBD patients with a symptomatic DVT, PE, or splanchnic vein thrombosis. If anticoagulant therapy is being stopped in patients with a reversible provoking factor, it should not be stopped until the risk factor has resolved for at least 1 month.
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Hospitalized patients with moderate-to-severe flares (without severe bleeding) should receive anticoagulant thromboprophylaxis with low-molecular-weight heparin, heparin, or fondaparinux.
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Patients hospitalized for indications unrelated to IBD or for IBD with non-severe gastrointestinal bleeding should receive anticoagulant prophylaxis.
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Hospitalized patients with severe IBD-related bleeding should receive mechanical prophylaxis (preferably intermittent pneumatic compression (IPC)). Once IBD-related bleeding is no longer severe, substitute anticoagulation for mechanical prophylaxis.
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Patients should receive anticoagulant prophylaxis during hospitalization for major abdominopelvic or general surgery.
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Outpatients with IBD flares and no prior VTE do not need prophylaxis.
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Patients with prior VTE and moderate-to-severe flares should receive anticoagulant prophylaxis unless prior episodes occurred only after major surgery.
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Pregnant women with IBD should receive anticoagulant prophylaxis after C-section until hospital discharge.
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Patients with VTE who have coexisting IBD do not need testing for hereditary or acquired hypercoagulable states.
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Patients who experience their first episode of VTE while in remission should receive indefinite anticoagulation unless there is an unrelated reversible provoking factor (then a minimum of 3 months).
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Patients who experience their first episode of VTE in the presence of active disease should be anticoagulated until IBD is in remission for 3 months.
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Recommendations for pediatric patients are similar to those for adults.
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Patients with symptomatic acute splanchnic vein thrombosis (portal, mesenteric, splenic vein thrombosis) should be treated with principles similar to those with VTE in other sites.
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Patients with asymptomatic, incidentally detected splanchnic vein thrombosis (on imaging studies) should not be anticoagulated.
Guideline on the Use of Thiopurines, Methotrexate, and Anti–TNF-a Biologic Drugs for the Induction and Maintenance of Remission in Inflammatory Crohn’s Disease
The American Gastroenterological Association published new guidelines on the use of Thiopurines, Methotrexate, and anti–TNF biologic drugs for the induction and maintenance of remission in Crohn’s Disease. Selecting among immunomodulator monotherapy, anti-TNF-alpha monotherapy and combination therapy is a clinical dilemma. The AGA decision support tool (gastro.org/crohnsdecisiontool) and guidelines on the use of immunomodulators and anti-TNF-alpha biologic agents in inducing and maintaining clinical remission in patients with inflammatory (luminal) Crohn’s disease is of considerable value. The technical review is also available for review, which offers an in-depth analysis of the existing research informing the clinical recommendations.
Recommendations for the induction of remission:
1. The AGA suggests against using thiopurine monotherapy to induce remission in patients with moderately severe Crohn’s disease.
2. The AGA suggests against using methotrexate to induce remission in patients with moderately severe Crohn’s disease.
3. The AGA recommends using anti-TNF-alpha drugs to induce remission in patients with moderately severe Crohn’s disease.
4. The AGA recommends using anti-TNF-alpha monotherapy over thiopurine monotherapy to induce remission in patients who have moderately severe Crohn’s disease.
5. The AGA recommends using anti-TNF-alpha drugs in combination with thiopurines over thiopurine monotherapy to induce remission in patients who have moderately severe Crohn’s disease.
6. The AGA suggests using anti-TNF-alpha drugs in combination with thiopurines over anti-TNF-alpha drug monotherapy to induce remission in patients who have moderately severe Crohn’s disease.
Recommendations for maintenance of remission:
1. The AGA recommends using thiopurines over no immunomodulator therapy to maintain a steroid-induced remission in patients with Crohn’s disease.
2. The AGA suggests using methotrexate over no immunomodulator therapy to maintain a steroid-induced remission in patients with Crohn’s disease.
3. The AGA suggests using anti-TNF-alpha drugs over no anti-TNF-alpha drugs to maintain a steroid or anti-TNF-alpha drug-induced remission in patients with Crohn’s disease.
4. The AGA makes no recommendation for or against the combination of an anti-TNF-alpha drug and a thiopurine versus an anti-TNF-alpha drug alone to maintain remission induced by a combination of these drugs in patients with Crohn’s disease.
http://download.journals.elsevierhealth.com/pdfs/journals/0016-5085/PIIS0016508513015217.pdf
http://download.journals.elsevierhealth.com/pdfs/journals/0016-5085/PIIS0016508513015205.pdf
Inflammatory Bowel Disease – Introduction and Overview
To write about Inflammatory Bowel Disease (IBD) for our UG patient information blog is a daunting task and this blog can at best provide a general overview as a starting point for an educated open discussion between patients and providers. Certain internet-sites will also give guidance, such as the Crohn’s and Colitis Foundation of America (CCFA) or the patient education portals of the American College of Gastroenterology (ACG) and the American Gastroenterological Association (AGA).
When talking about IBD, one refers to two inflammatory conditions of the gut, either Ulcerative Colitis (UC) or Crohn’s Disease (CD). While UC will only affect the large intestine (colon) and does not skip lesions (always starting at the anus/rectum), CD can involve the entire GI tract from mouth to anus, may skip areas of the gut, and often involves the terminal ileum. Extraintestinal manifestations of IBD include joints (IBD related arthritis), eye problems (iritis) and skin lesions (such as erythema nodosum or pyoderma gangrenosum). In addition, IBD can be associated with a liver condition called primary sclerosing cholangitis (PSC), a related autoimmune disorder of the bile ducts.
A clear cause of IBD has not yet been discovered, with multifactorial genetic and environmental influences being investigated. While significant research is being conducted and multiple gene loci have been found, a definitive cure is not yet in sight. IBD is felt to be an autoimmune disorder with abnormal immune response and inflammation arising from a pathologic response to a viral, bacterial, or possibly allergic intestinal injury in genetic susceptible individuals. Since about 10% of IBD patients have affected family members, a genetic predisposition is indeed likely. UC occurs more frequently in younger individuals (15 to 40 years old); CD can have a bimodal distribution, affecting the young and old. Indeed reports of newly diagnosed CD in 80 year olds are not uncommon. While an estimated 130-240 per 100,000 people may be affected, there appears to be neither male nor female predominance.
UC will typically only affect the lining (mucosa) of the large intestine, but CD (potentially affecting the entire GI-tract) can be a transmural illness, involving the entire thickness of the bowel wall. This difference in mucosal and transmural inflammation also affects the varying presentations of these similar yet different diseases. While both may present with pain, diarrhea, bleeding (both diseases may at times only be limited to the large intestine), patients with CD are more likely to develop abscesses and/or fistulas to the abdominal wall, anus and perineum, or other organs (i.e. bowel, bladder, vagina). Due to the transmural inflammation of CD, strictures and obstructions can form, leading to possible bowel obstructions. While both UC and CD can present with periods of remission and relapse, only UC can be “cured” with surgery.
Trigger factors of these diseases are being debated. Stress may have a negative influence but this is difficult to measure or prove. Nicotine use is of grave concern, especially in CD and smoking must be stopped if at all possible. NSAIDs may trigger a flare and should be avoided.
Diagnosis: Given a great variety of symptoms and a possible overlap with the Irritable Bowel Syndrome, a diagnosis can be difficult to make or confirm. Symptoms such as abdominal pain, diarrhea, weight loss, rectal bleeding, or fever should be taken seriously and should be worked up by a health care provider. Other issues such as fatigue, loss of appetite, joint pains, liver disease, unexplained anemia, aphthous oral ulcers and iritis (redness and swelling of the eyes) should also raise concerns.
In order to make a diagnosis, multiple modalities may be used such as laboratory work-up, stool samples (to rule out infections), cross-sectional x-ray images (CT-enteroclysis or MR-enteroclysis) and endoscopic work up (EGD, Colonoscopy, Enteroscopy, Camera-Pill Endoscopy). There is no single test that can definitively diagnose or exclude IBD. A detailed patient history and physical exam as well as an established “time-line” of symptoms and findings can be useful to establish a diagnosis of IBD.
Treatment: The medical treatment of IBD (UC and CD) is very similar for both conditions; drugs approved for one disease will often be used for the other.
- 5-ASA formulations [aminosalicylates: sulfasalazine (Azulfidine®), balsalazide (Colazal®), mesalamine (Delzicol®, Asacol HD®, Lialda®, Pentasa®, Apriso®, Rowasa® enema, Canasa®), olsalazine (Dipentum®)] have been used for decades and are available as oral medications, suppositories, or enemas. It is understood that 5-ASA molecules affect the disease process on an intraluminal-local mucosal level. They are usually well tolerated, but like any medications can have serious side effects and should be discussed with and monitored by the treating provider.
- Corticosteroids, such as prednisone/hydrocortisone, are often used if 5-ASA products are insufficient to control inflammation. While steroids can be given iv, orally, as suppositories, or as enemas, the long-term side effect profile (infections, cataract formation, bone-loss, weight gain, fat redistribution, skin break-down) is unfavorable and therefore steroids should be avoided if possible. Furthermore steroids may alter the natural history or CD, changing the disease from a fibrostenotic stricturing process to a fistulizing process. Newer steroid preparations such as budesonide (Entocort®, Uceris®) may have a more favorable side effect profile but must still be viewed with caution.
- Immunomodulating medications such as azathioprine (Imuran®), 6-mercaptopurine (Purinethol®), or methotrexate (Trexall®) are used for more advanced disease states. These drugs, although well tolerated, must be monitored carefully as they can increase infectious complications, bone marrow suppression, liver injury and even cancer. METHOTREXATE MAY NEVER BE USED DURING PREGNANCY.
- Biologic treatments like infliximab (Remicade®), adalimumab (Humira®) and certolizumab pegol (Cimzia®) have traditionally been used for patients with moderate to severe CD. Infliximab (Remicade®) and adalimumab (Humira®) are also indicated and approved for UC. There drugs target specific proteins in the immune system to control inflammation. These anti-tumor necrosis factor (Anti-TNF) medications recognize, attach to and block certain actions of the immune system. Like all other drugs, they do not cure IBD, but reduce the level of inflammation. Like immunomodulators, these drugs can cause rare but serious side effects such as infections or cancer, and must be closely monitored by the treating provider.
- Natalizumab (Tysabri®) may be used in CD patients who have failed two biologics.
Step-Up vs. Step-Down Therapy: Traditionally, a step-up approach was used, i.e. mesalamine and steroid preparations to be used first, followed by immunomodulators and then “topped-off” by biologic agents, as these were initially only used for the treatment of moderate to severe CD if not responding to the standard step-up approach (aminosalicylates, corticosteroids or immunosuppressive agents). Given the severe potential complications of CD, a step-down approach is now being considered in CD, where early initiation of immunomodulator and biologic therapy is recommended to prevent fistulizing or fibrostenotic disease.
Diet: No single diet is uniformly recommended by the US GI-societies; a well-balanced healthy diet is still the best option. A low-roughage diet is suggested during disease activity; lactose intolerance may develop due to small bowel inflammation. Given concerns for potential bone loss, calcium supplementation can be considered with 400-800 IU Vitamin D and 800-1000 mg calcium as a daily dose being preferred. Too much calcium supplementation may be of concern as cardiac and overall morbidity and mortality may increase if over 1400 mg calcium is taken daily. A multi-vitamin may be of benefit to address micronutrient losses. Although we do not endorse a specific product, Forvia appears to address potential losses in IBD patients and it may be worthwhile for our patients to research that product and compare it to other MVI brands.
General Health Management: Regular provider follow-up is key to good health and disease control. In general all IBD patients should follow routine health maintenance protocols (i.e. management of screening, hypertension etc), routine vaccinations are advised; LIVE VACCINATIONS MUST BE AVOIDED, if patients are on biologics and/or immunomodulators. Yearly Dermatology visits are advised for those on biologics and/or immunomodulators to minimize skin cancer risks; women should see their OBGYNs regularly (including routine pap-smears etc.).
Surgery in IBD: Surgeons and Gastroenterologists work closely together for patients with IBD. A multi-specialty approach offers the best overall outcome for fistulizing as well as fibrostenotic CD. While surgery can not cure CD, significant positive impact can be expected for appropriately selected patients (ie complications of obstruction, abscess, fistula, failure to respond to medical treatment). Surgery can “cure” UC by removing the entire colon. This is usually done in a two-stage operation, creating first an “ileostomy” (the ileum is attached to the abdominal wall) while creating an ileal pouch; in a second operation the ileostomy is then “taken down” and the pouch is attached to the anus.
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