Crohn's disease medical therapy

Crohn's disease
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Crohn's Disease from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
CT
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Crohn's disease medical therapy On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Crohn's disease medical therapy All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Crohn's disease medical therapy
CDC on Crohn's disease medical therapy
Crohn's disease medical therapy in the news
Blogs on Crohn's disease medical therapy
Directions to Hospitals Treating Crohn's disease
Risk calculators and risk factors for Crohn's disease medical therapy

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

Overiew

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

A number of medical treatments are utilized with the goal of putting and keeping the disease in remission. These include 5-aminosalicylic acid (5-ASA) formulations (Pentasa capsules, Asacol tablets, Lialda tablets, Rowasa retention enemas), steroid medications, immunomodulators (such as azathioprine, mercaptopurine (6-MP), and methotrexate), and newer biological medications, such as infliximab (Remicade) and adalimumab (Humira).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 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. 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 leukocytes 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 (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. As of late December 2007, more than 21,000 MS patients were receiving natalizumab mono-therapy without a single incidence of PML occurring.

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.

Recent studies using Helminthic therapy or hookworms to treat Crohn's Disease and other (non-viral) auto-immune diseases seem to yield promising results.

• 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 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.

• Maintenance of Remission
  • Preferred regimen (1): mesalamine suppository 500 mg qd or bid
  • Preferred regimen (2):mesalamine enema 2-4 g q1-3 days
  • Preferred regimen (3):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.

• 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.

• 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

• Cortisone
• Prednisone
• Prednisolone
• Hydrocortisone
• Methylprednisolone
• Beclometasone
• Budesonide

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

• Infliximab
• Visilizumab

Contraindicated medications

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

• Alosetron