Crohn’s Disease: Drug Therapy

Therapy goals

  • Remission induction (achieving disease calming in the acute relapse) and maintenance.
  • Mucosal healing should be aimed for.

Therapy recommendations

Therapy recommendation depending on phase and intensity:

  • Remission induction:
    • Acute relapse
      • M. Crohn’s with involvement of the ileocecal region (ileocecal valve: functional closure between the large and small intestines) and/or right-sided colon (large intestine and
        • Mild inflammatory activity: initially budesonide (glucocorticoids; topical steroids/local application) per os and/or klysma budesonide may be given; if contraindications (contraindications) to steroids or patient wishes, therapy with mesalazine/5-ASA (anti-inflammatory/adrenaline) may also be given
        • Moderate inflammatory activity: initially with budesonide or systemically acting glucocorticoids In children: Budesonide instead of systemically active glucocorticoids.
        • High inflammatory activity: initial with systemically acting glucocorticoids.
      • M. Crohn’s:
        • With mild to moderate activity: try therapy with sulfasalazine (mesalazine is the active metabolite of sulfasalazine) or systemically active glucocorticoids In children with active Crohn’s:
          • Mesalazine not for remission induction (achieve disease calming in acute relapse); consider elective surgery early in growth retardation, circumscribed disease, or persistent disease activity
          • In children and adolescents, enteral nutrition therapy should be used instead of glucocorticoid therapy for remission induction of Crohn’s disease
        • High disease activity: initial systemic glucocorticoids In children with moderate or severe Crohn’s disease: early immunosuppressive therapy.
        • In distal involvement: concomitant suppositories, clysms, or foams (5-ASA, steroids).
      • Extensive infestation of the small intestine
        • Initial systemic glucocorticoids
        • And impending malnutrition: additional enteral nutrition therapy (consider early).
      • Infestation of the esophagus and stomach.
        • Primary systemic glucocorticoids.
        • For gastroduodenal involvement: primary systemically acting glucocorticoids in combination with proton pump inhibitors (acid blockers)
    • Therapy escalation
      • Before initiating immunosuppressive therapy or further escalation of therapy, surgical intervention should be considered as an alternative
      • Steroid-refractory Crohn’s disease (nonresponse to steroids/glucocorticoids) with moderate to high disease activity: anti-TNF-α antibodies with or without azathioprine or 6-mercaptopurine.
    • Failure of therapy with immunosuppressants.
      • Failure of therapy with azathioprine or 6-mercaptopurine, methotrexate, or anti-TNF-α antibodies: reevaluation of disease activity, an exclusion of other causes of clinical deterioration (CMV, clostridial, or other bacterial infections, diagnostic certainty), treatment adherence (treatment compliance), and a discussion of surgical treatment options should occur. (IV, ↑ , strong consensus) If active Crohn’s disease is confirmed, ongoing therapy should be optimized (dose, dosing intervals) before switching therapy.
  • Remission maintenance or relapse prophylaxis (in principle, the same therapeutic principles apply to children and adolescents as to adults):
    • Systemic glucocorticosteroids and budesonide should not be used for relapse prophylaxis in the long term!
    • Surgical intervention should be considered as an alternative before initiating immunosuppressive therapy or further escalation of therapy.
    • Azathioprine or 6-mercaptopurine, methotrexate, and anti-TNF-α antibodies (in special risk constellations) are suitable for remission-maintaining therapy. In children and adolescents, nutritional therapy can be used for remission maintenance.
    • In the case of a steroid-dependent course, therapy with azathioprine or 6-mercaptopurine, methotrexate or an anti-TNF-α antibody, if necessary also in combination (I), should be carried out under consideration of the risk profile.
    • If necessary.Ustekinumab (monoclonal antibody targeting interleukins IL-12 and -23) in moderate to severe active Crohn’s disease; in patients who have had an inadequate response to, are intolerant of, or are contraindicated for conventional or anti-TNF-α therapies
    • Remission-maintaining therapy should be given on a long-term basis. (II, ↑ , strong consensus). A general recommendation on the necessary duration of remission-maintaining therapy with azathioprine or 6-mer-captopurine, methotrexate, or anti-TNF-α antibodies cannot be given. (IV, ↔ , strong consensus).
    • If necessary, also supply of probiotics (supplements with probiotic cultures).
  • Postoperative remission maintenance
    • Postoperative remission-maintaining therapy can be initiated, taking into account the individual disease course and risk profile. (I, ↑ , strong consensus).
    • Waiting without postoperative remission-maintaining therapy with endoscopic evaluation after 6 months may be an option. (II, ↑ , strong consensus).
    • Mesalazine may be used in postoperative remission maintenance. (I, ↑ , consensus).
    • Patients with a complicated course should receive postoperative therapy with azathioprine or 6-mercaptopurine. (II, ↑ , strong consensus).

Further notes

  • A systematic review with network meta-analysis demonstrated that budesonide (9 mg/d or higher) is the first-line treatment for induction of remission in active mild or moderate Crohn’s disease and for remission maintenance or relapse prophylaxis (6 mg /d).
  • In a meta-analysis of five randomized controlled trials (147 children with Crohn’s disease), nutritional therapy was shown to be equivalent to glucocorticoid treatment. The effect had been independent of whether an elemental, semielemental, or polymeric diet had been used.Another trial of nutritional therapy showed remission in:
    • Purely ileal Crohn’s disease: 93%.
    • Ileocolitis: 82.1 %
  • In the disease flare-up, the administration of glucocorticoids may also be necessary during pregnancy. The risk to the child experts classify prednisone as low.
  • Long-term systemic steroid therapy should be avoided. (I, ↓↓ , strong consensus).
  • After discontinuation of TNTα-blocker therapy (elective or because of UAW or because of top-down strategy), the incidence rate of relapse (recurrence of disease) was 19% per patient-year. The median time to relapse after discontinuation of therapy was eleven months. After relapse, clinical remission was achieved in 69-79% by re-treatment with the same TNF-α blocker (infliximab: 79%; adalimumab: 69%).

Notes on extraintestinal manifestations (diseases outside the intestine).

  • Long-term systemic steroid therapy should be avoided. (I, ↓↓ , strong consensus).
  • Pubertal developmental delays should not be treated with growth-promoting hormones in adolescent Crohn’s disease patients.
  • Anemia/blood deficiency (iron and B12 deficiency; iron deficiency anemia: pregnant women ≤ 11 g/dL, nonpregnant women ≤ 12 g/dL, men ≤ 13 g/dL); most common manifestation in Crohn’s disease)Iron deficiency anemia (hemoglobin ≥ 10 g/dL):
    • Oral iron substitution; if intolerant or not responding to oral substitution or severe anemia (hemoglobin < 10 /dl / 6.3mmol/l) intravenous administration of iron.
    • Vitamin B 12 substitution should be parenteral in cases of proven vitamin B 12 deficiency anemia.
  • In peripheral arthritides (joint inflammation), sulfasalazine should be used primarily. (II, ↑ , strong consensus).
  • Severe refractory polyarthritides (inflammation of five or more joints) and severe refractory spondyloarthropathy (ankylosing spondylitis) should be treated with anti-TNF-α antibodies. (II, ↑ , consensus).
  • Selective COX-2 inhibitors can be used for inflammatory spinal pain and/or refractory peripheral joint pain. (I, ↑ , consensus).
  • High-dose systemic steroid therapy should be given for erythema nodosum (see “Symptoms – Complaints” below) and pyoderma gangraenosum (painful disease of the skin in which ulceration or ulceration (ulceration or ulceration) and gangrene (tissue death due to reduced blood flow or other damage) occur over a large area, usually in one location). (IV, ↑ , strong consensus).
  • See also under “Further therapy.”

Supplements (dietary supplements; vital substances)

Suitable dietary supplements should contain the following vital substances:

Note: The listed vital substances are not a substitute for drug therapy. Food supplements are intended to supplement the general diet in the particular life situation.