Azathioprine in Crohn's disease and ulcerative colitis

azathioprine:

• may be used in patients with Crohn's disease or ulcerative colitis that are steroid dependent or steroid resistant
• this is a very effective, safe and well-tolerated drug with no definite associated risk of cancer
• may also be useful for fistulating Crohn's disease
• inhibits DNA synthesis and lymphocyte proliferation
• azathioprine has a slow onset of action and requires continuing steroid cover for 8-12 weeks (1)
• the principle side-effects of azathioprine are idiosyncratic acute pancreatitis and bone-marrow suppression

NICE state with respect to the use of azathioprine in Crohn's disease:

• add on therapy in order to induce remission in Crohn's
  • azathioprine or mercaptopurine should be considered as an add-on to a conventional glucocorticosteroid or budesonide to induce remission of Crohn's disease if:
    • there are two or more inflammatory exacerbations in a 12-month period,
    • or the glucocorticosteroid dose cannot be tapered
      
    • thiopurine methyltransferase (TPMT) activity should assessed before offering azathioprine or mercaptopurine
      • do not offer azathioprine or mercaptopurine if TPMT activity is deficient (very low or absent). Consider azathioprine or mercaptopurine at a lower dose if TPMT activity is below normal but not deficient (according to local laboratory reference values)
• maintenance treatment for those who choose this option
  • azathioprine or mercaptopurine
    • should be offered as monotherapy to maintain remission when previously used with a conventional glucocorticosteroid or budesonide to induce remission
      • azathioprine or mercaptopurine should be considered to maintain remission in people who have not previously received these drugs (particularly those with adverse prognostic factors such as early age of onset, perianal disease, glucocorticosteroid use at presentation and severe presentations)
    • only consider methotrexate to maintain remission in people who:
      • needed methotrexate to induce remission, or
      • have tried but did not tolerate azathioprine ormercaptopurine for maintenance or
      • have contraindications to azathioprine or mercaptopurine (for example, deficient TPMT activity or previous episodes of pancreatitis)
    • do not offer a conventional glucocorticosteroid or budesonide to maintain remission
  • maintaining remission in Crohn's disease after surgery
    • azathioprine or mercaptopurine should be considered to maintain remission after surgery in people with adverse prognostic factors such as:
      • more than one resection, or
      • previously complicated or debilitating disease (for example, abscess, involvement of adjacent structures, fistulising or penetrating disease)
    • consider 5-ASA treatment to maintain remission after surgery
    • do not offer budesonide or enteral nutrition to maintain remission after surgery

Notes (3):

• the toxicity of azathioprine (and 6-mercaptopurine) is increased with allopurinol, which inhibits xanthine oxidase, the enzyme responsible for their metabolism
• the onset of action of immunomodulators (such as azathioprine) is prolonged, with the clinical response sometimes delayed for up to four months
  • thus other therapies are often co-prescribed until the benefits become apparent

Reference:

1. Prescriber (2001), 12 (20), 43-58.
2. NICE (October 2012). Crohn's disease Management in adults, children and young people
3. Prescriber (2004); 15(5).