Crohn's disease medical therapy: Difference between revisions

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Revision as of 19:19, 21 May 2017

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Treatment options include medications, nutrition supplements, surgery, or a combination of these options. The goals of treatment are to control inflammation, correct nutritional deficiencies, and relieve symptoms like abdominal pain, diarrhea, and rectal bleeding. Treatment for Crohn’s disease depends on the location and severity of disease, complications, and the person’s response to previous medical treatments when treated for recurring symptoms. Some people have long periods of remission, sometimes years, when they are free of symptoms. However, the disease usually recurs at various times over a person’s lifetime.

Medical Therapy

1. Mild to Moderate Crohn's Disease
- Ileitis and colitis
  - Preferred regimen for illeitis and rt side colitis: Oral budesonide (9 mg/day)
  - Preferred regimen distal colitis : Topical mesalamine or topical steroids (enemas or suppositories)
  - Preferred regimen other site :Oral mesalamine (4 g/day) or oral sulfasalazine (3-6 g/day)
  - Alternative regimen (1): Mesalamine enemas or suppositories (in patients refractory to topical corticosteroids or oral aminosalicylates.
  - Alternate regimen (2): Oral prednisone up to 40-60 mg/day AND infliximab 5mg/kg at weeks 0, 2, 6 of treatment
    - Note: Effective dose of Sulfasalazine is 4-6g/day in 4 doses; mesalamine is 2-4.6g/day in 3 doses; balasalazine 6.75g/day in 3 doses; mesalamine multimatrix formulation is 2.4 to 4.8 g/day. These drugs are effective within 2.4 weeks.

Oral lesion
- Preferred regimen (1): triamcinolone acetonide
- Preferred regimen (2): mesalamine suppository 500 mg qd or bid
- Preferred regimen (3):mesalamine enema 2-4 g q1-3 days
- Preferred regimen (4):sulfasalazine 2g/day OR mesalamine compounds 1.6g/day OR balsalazide 3-6g/day
- Alternative regimen (1): 6-mercaptopurine OR azathioprine AND infliximab
  - Note: A combination of oral mesalamine 1.6g/day and mesalamine enema 4g twice weekly is more effective than oral treatment alone.
Gastroduodenal disease
- Preferred regimen (1): PPI or H2 antagonist, or sucralfate
- Preferred regimen (2): Oral mesalamine (Pentasa: 2 g/day)

2. Mild to Moderate Extensive Colitis
- Acute Management
  - Preferred regimen (1): oral sulfasalazine titrated up to 4-6g/day OR oral aminosalicylate in doses of up to 4.8g/day of active 5-ASA moiety
  - Alternate regimen (1): Oral steroids (in patients refractory to aminosalicylates in combination with topical therapy)
  - Alternate regimen (2): 6-mercaptopurine AND azathioprine (in patients refractory to oral steroids)
  - Alternative regimen (3): infliximab 5mg/kg I.V. at weeks 0,2, and 6 (steroid refractory or steroid dependent despite adequate 6-MP dosing or intolerant to other regimens)
    - Note (1): Infliximab is contraindicated in patients with untreated latent TB, pre-existing demyelinating disorder, optic neuritis, moderate to severe CHF, current or recent malignancy
    - Note (2): Transdermal nicotine is effective in achieving remission.

Maintenance of Remission
- Preferred regimen (1): Sulfasalazine, olsalazine, mesalamine, and balsalazide
- Alternative regimen (1): 6-mercaptopurine OR azathioprine
- Alternate regimen (2): infliximab (in patients with successful induction with infliximab)
  - Note: Corticosteroids are not recommended for long-term maintenance therapy

3.Severe Colitis

- Acute Management
  - Preferred Regimen (1): Maximal oral treatment with prednisone AND oral aminosalicylate drugs AND topical mesalamine
  - Alternate regimen (2): Infliximab 5mg/kg (if refractory and urgent hospitalization is not necessary)
  - Alternate regimen (3): Intravenous corticosteroids (if patient presents with toxicity)
    - Note: Failure to show significant improvement within 3-5 days is an indication for colectomy. Infliximab may be effective in avoiding colectomy in patients failing to respond to corticosteroids.

- Maintenance of Remission
  - Preferred Regimen (1): 6 mercaptopurine

4.Management of Pouchitis (complication of IPAA surgery)

- Preferred Regimen (1): Metronidazole 400mg q8h OR 20mg/kg daily
- Preferred Regimen (2): Ciprofloxacin 500mg bid
  - Note: Other etiologies mimicking pouchitis include irritable pouch syndrome, cuffitis, CD of the pouch, and postoperative complications such as anastomotic leak or stricture.

Pharmacotherapy

Aminosalicylates

Sulfasalazine has been a major agent in the therapy of mild to moderate UC for over 50 years. In 1977 Mastan S.Kalsi et al determined that 5-aminosalicyclic acid (5-ASA and mesalazine) was the therapeutically active compound in sulfasalazine. Since then many 5-ASA compounds have been developed with the aim of maintaining efficacy but reducing the common side effects associated with the sulfapyridine moiety in sulfasalazine.^[1]

Mesalazine, also known as 5-aminosalicylic acid, 5-ASA, Asacol, Pentasa and Mesalamine.
Sulfasalazine, also known as Azulfidine.
Balsalazide, also known as Colazal.
Olsalazine, also known as Dipentum.

Corticosteroids

Immunosuppressive drugs

Mercaptopurine, also known as 6-Mercaptopurine, 6-MP and Purinethol.
Azathioprine, also known as Imuran, Azasan or Azamun, which metabolizes to 6-MP.
Methotrexate, which inhibits folic acid
Tacrolimus

Biological treatment

Contraindicated medications

Crohn's disease is considered an absolute contraindication to the use of the following medications:

Alosetron

References

↑ S. Kane (2006). "Asacol - A Review Focusing on Ulcerative Colitis".

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[1] S. Kane (2006). "Asacol - A Review Focusing on Ulcerative Colitis".

[1]

@@ Line 7: / Line 7: @@
 ==Medical Therapy==
-A number of medical treatments are utilized with the goal of putting and keeping the disease in [[remission (medicine)|remission]].  These include [[mesalazine|5-aminosalicylic acid]] (5-ASA) formulations (Pentasa capsules, Asacol tablets, Lialda tablets, Rowasa retention enemas), [[prednisone|steroid]] medications, immunomodulators (such as [[azathioprine]], [[mercaptopurine]] (6-MP), and [[methotrexate]]), and newer [[biological therapy for inflammatory bowel disease|biological]] medications, such as [[infliximab]] (Remicade) and [[adalimumab]] (Humira).<ref name=Podolsky>{{Cite journal|last=Podolsky|first= Daniel K.|title=Inflammatory bowel disease|journal=New England Journal of Medicine|month=August|year=2002|volume=346|issue=6|pages=417-29
-|url=http://content.nejm.org/cgi/content/extract/347/6/417|accessdate=2006-07-02|id=PMID 12167685}}</ref>Also in January 2008 the U.S. Food and Drug Administration approved a new biological medication known as [[natalizumab]] (Tysabri) for both induction of remission and maintenance of remission in moderate and severe Crohn's Disease.
-Treatment is only needed for people exhibiting symptoms. The therapeutic approach to Crohn's disease is sequential: to treat [[acute (medical)|acute]] disease and then to maintain [[remission]]. Treatment initially involves the use of medications to treat any infection and to reduce inflammation. This usually involves the use of aminosalicylate anti-inflammatory drugs and corticosteroids, and may include antibiotics.
-Once remission is induced, the goal of treatment becomes maintaining remission and avoiding flares. Because of side-effects, the prolonged use of corticosteroids must be avoided. Although some people are able to maintain remission with aminosalicylates alone, many require immunosuppressive drugs.
+:* 1. '''Mild to Moderate Crohn's Disease'''
-On 14 January 2008 the U.S. Food and Drug Administration approved [[natalizumab]] (Tysabri) for both induction of remission and maintenance of remission in Crohns. Natalizumab is humanized monoclonal antibody (MAb), and the first alpha-4 antagonist in a new class of agents called selective adhesion-molecule (SAM) inhibitors. Alpha-4 integrin is required for [[leukocyte]]s to adhere to the walls of blood vessels and migrate into the gut; natalizumab prevents leukocytes from doing that. Natalizumab was previously approved for [[multiple sclerosis]]. However, because it suppresses the [[immune system]], natalizumab has been linked to a very rare adverse effect that is usually fatal if undetected. Leukocytes also protect the body from viruses, and 2 patients on natalizumab, who were also receiving other immuno-suppressive drugs ([[Interferon beta-1a|Avonex]] and Immuran), died of a rare brain infection, [[progressive multifocal leukoencephalopathy]]. Because of this danger, patients must be in a special monitoring program, and natalizumab is given as a mono-therapy.<ref name="FDA-Tysbari">{{cite press release|title=FDA Approves Tysabri to Treat Moderate-to-Severe Crohn's Disease|publisher=U.S. Food and Drug Administration|date=2008-01-14|url=http://www.fda.gov/bbs/topics/NEWS/2008/NEW01775.html|accessdate=2008-01-16
+:** '''Ileitis and colitis'''
-}}</ref> As of late December 2007, more than 21,000 MS patients were receiving natalizumab mono-therapy without a single incidence of PML occurring.<ref>.http://www.elan.com/News/full.asp?ID=1091942</ref>
+:*** Preferred regimen for illeitis and rt side colitis: Oral budesonide (9 mg/day)
+:*** Preferred regimen distal colitis : Topical mesalamine or topical steroids (enemas or suppositories)
-[[Surgery]] may be required for complications such as obstructions, fistulas and/or abscesses, or if the disease does not respond to drugs within a reasonable time. For patients with an obstruction due to a stricture, two options for treatment are strictureplasty and resection of that portion of bowel.  According to a retrospective review at the Cleveland Clinic, there is no [[statistical significance]] between strictureplasty alone versus strictureplasty and resection specifically in cases of duodenal involvement. In these cases, re-operation rates were 31% and 27%, respectively, indicating that strictureplasty is a safe and effective treatment for selected patients with duodenal involvement.<ref name="pmid8918424">{{cite journal | author = Ozuner G, Fazio VW, Lavery IC, Milsom JW, Strong SA | title = Reoperative rates for Crohn's disease following strictureplasty. Long-term analysis | journal = Dis. Colon Rectum | volume = 39 | issue = 11 | pages = 1199-203 | year = 1996 | pmid = 8918424 | doi = }}</ref>
+:*** Preferred regimen other site :Oral mesalamine (4 g/day) or oral sulfasalazine (3-6 g/day)
-Recent studies using [[Helminthic therapy]] or [[hookworm]]s to treat Crohn's Disease and other (non-viral) auto-immune diseases seem to yield promising results.<ref>British Medical Journal [http://gut.bmj.com/cgi/content/full/55/1/136 A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors]</ref><ref name="Daily Mail">Daily Mail. [http://www.dailymail.co.uk/pages/live/articles/technology/technology.html?in_article_id=481875&in_page_id=1965  The bloodsucking worm that fights allergies from inside your tummy] 14-09-2007.</ref><ref>[http://www.kuro5hin.org/story/2006/4/30/91945/8971 How to cure your asthma or hayfever using hookworm - a practical guide]. 01-05-2006.</ref>
-:* 1. '''Mild to Moderate Distal Colitis'''
-:** '''Acute Management'''
-:*** Preferred regimen (1): Topical [[Mesalamine]]
-:*** Preferred regimen (2): Topical [[corticosteroids]]
-:*** Preferred regimen (3):Oral aminosalicylates
 :*** Alternative regimen (1): [[Mesalamine]] enemas or suppositories (in patients refractory to topical [[corticosteroid]]<nowiki/>s or oral aminosalicylates.
 :*** Alternate regimen (2): Oral [[prednisone]] up to 40-60 mg/day '''AND''' infliximab 5mg/kg at weeks 0, 2, 6 of treatment
 :**** Note: Effective dose of [[Sulfasalazine]] is 4-6g/day in 4 doses; [[mesalamine]] is 2-4.6g/day in 3 doses; [[Balsalazide|balasalazine]] 6.75g/day in 3 doses; [[mesalamine]] multimatrix formulation is 2.4 to 4.8 g/day. These drugs are effective within 2.4 weeks.
-:::*'''Maintenance of Remission'''
+:::*'''Oral lesion'''
-:::**Preferred regimen (1): [[Mesalamine|mesalamin]]<nowiki/>e suppository 500 mg qd or bid
+:::**Preferred regimen (1): triamcinolone acetonide
-:::** Preferred regimen (2):[[Mesalamine (rectal)|mesalamin]]<nowiki/>e enema 2-4 g  q1-3 days
+:::**Preferred regimen (2): [[Mesalamine|mesalamin]]<nowiki/>e suppository 500 mg qd or bid
-:::** Preferred regimen (3):[[sulfasalazine]] 2g/day '''OR''' [[Mesalamine (oral)|mesalamine compounds]] 1.6g/day '''OR''' [[balsalazide]] 3-6g/day
+:::** Preferred regimen (3):[[Mesalamine (rectal)|mesalamin]]<nowiki/>e enema 2-4 g  q1-3 days
+:::** Preferred regimen (4):[[sulfasalazine]] 2g/day '''OR''' [[Mesalamine (oral)|mesalamine compounds]] 1.6g/day '''OR''' [[balsalazide]] 3-6g/day
 :::** Alternative regimen (1): [[6-mercaptopurine]] '''OR''' [[azathioprine]] '''AND''' [[infliximab]]
 :::*** Note: A combination of oral [[Mesalamine (oral)|mesalamine]] 1.6g/day and [[Mesalamine (rectal)|mesalamine enema]] 4g twice weekly is more effective than oral treatment alone.
+:::*'''Gastroduodenal disease'''
+:::**Preferred regimen (1):  PPI or H2 antagonist, or sucralfate
+:::**Preferred regimen (2):  Oral mesalamine (Pentasa: 2 g/day)
 :*'''2. Mild to Moderate Extensive Colitis'''
 :**'''Acute Management'''