Usefulness of Thiopurine Monotherapy for Crohn's Disease in the Era of Biologics: A Long-Term Single-Center Experience

Dig Dis Sci. 2019 Mar;64(3):875-879. doi: 10.1007/s10620-018-5381-0. Epub 2018 Dec 12.

Abstract

Background: Thiopurines are classically used in Crohn's disease (CD). Treatment fails in a proportion of patients either due to adverse events (AE) or lack of efficacy. Increasing use of anti-TNFα biologic drugs may have had impact on thiopurines usage.

Aim: To evaluate the evolving use of azathioprine (AZA) monotherapy in the era of biologics.

Methods: The study retrospectively analyzed clinical records of all CD patients who started treatment with AZA monotherapy at our center since 1990. Dates of starting AZA and treatment failure (TF) were collected. We defined AZA TF if it was withdrawn due to lack of efficacy or AE, or biologics were added.

Results: A total of 383 patients were included: 46.5% were males and mean age was 31 (range 17-84) years. Median follow-up was 43 (range 0.2-289) months. Overall, 147 patients (38%) experienced TF. Median cumulative survival time of AZA was 126 (95% CI 105-147) months. Proportion of patients with AZA TF increased along time: 7 patients in 1990-1995 (4.7% of all TF); 8 in 1996-2000 (5.4%); 22 in 2001-2005(15%); 41 in 2006-2010 (28%); 69 in 2011-2014 (47%) (p = 0.04). 7%, 21%, 4%, 45%, and 33.3% of patients moved to biologics in each period, respectively (χ2 = 13.07; p < 0.05). Seventy-four patients (18.4%) stopped AZA due to AE, and 73(19%) due to lack of efficacy. Regarding AZA indication, prevention of postoperative recurrence obtained better results than steroid dependency (p = 0.001); perianal fistulizing CD predicted poorer outcomes (p = 0.002).

Conclusion: An important proportion of CD patients under AZA monotherapy experienced TF in our experience. Although AZA monotherapy remains useful for CD in the era of biologics, current clinical practice is shifting to anti-TNFα biologic drugs in an increasing proportion of patients.

Keywords: Crohn’s disease; Thiopurine IBD; Thiopurine maintenance in Crohn’s disease.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Azathioprine / adverse effects
  • Azathioprine / therapeutic use*
  • Biological Products / therapeutic use
  • Crohn Disease / diagnosis
  • Crohn Disease / drug therapy*
  • Crohn Disease / immunology
  • Female
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Spain
  • Time Factors
  • Treatment Failure
  • Young Adult

Substances

  • Biological Products
  • Gastrointestinal Agents
  • Immunosuppressive Agents
  • Azathioprine