Feasibility of Reduced Clinical Monitoring in Patients with Inflammatory Bowel Disease Treated with Thiopurine Therapy

Dig Dis Sci. 2023 Jul;68(7):2936-2945. doi: 10.1007/s10620-023-07950-0. Epub 2023 May 2.

Abstract

Background: Outpatient visits and laboratory assessments are routinely scheduled every 3 to 4 months in thiopurine-treated patients with inflammatory bowel disease (IBD) to timely detect thiopurine-related adverse events (AEs). AEs that require therapy adjustment beyond 12 months of treatment are rare.

Aim and methods: This single-center prospective cohort study evaluated the safety of a reduced 6-monthly monitoring strategy in steroid-free patients with quiescent IBD on stable dose of azathioprine, mercaptopurine, or thioguanine monotherapy. The primary outcome was thiopurine-related AEs requiring therapy adjustments during a follow-up period of 24 months. Secondary outcomes included all AEs including laboratory toxicity, disease flares until 12 months, and the net monetary benefit from this strategy concerning IBD-related health care use.

Results: We enrolled 85 patients with IBD (median age 42 years, 61% Crohn's disease, 62% female), with a median disease duration of 12.5 years and median thiopurine treatment duration of 6.7 years. During follow-up, 3 patients (4%) ceased thiopurines due to AEs: recurrent infections, non-melanoma skin cancer, and gastrointestinal complaints (nausea, vomiting). At 12 months, 25 laboratory toxicities were observed (including 13% myelotoxicity, 17% hepatotoxicity); none required therapy adjustments and all were transient. A reduced monitoring strategy had a net benefit of €136 per patient.

Conclusion: Three patients (4%) ceased thiopurine therapy due to thiopurine-related AEs, while no laboratory toxicity required therapy adjustments. Monitoring frequency of every 6 months seems feasible in patients with stable IBD on long-term (median duration > 6 years) maintenance thiopurine therapy and may contribute to reduced patient-burden and health care costs.

Keywords: Adverse events; Inflammatory bowel disease; Monitoring; Safety; Thiopurines.

MeSH terms

  • Adult
  • Azathioprine / adverse effects
  • Feasibility Studies
  • Female
  • Humans
  • Immunosuppressive Agents* / adverse effects
  • Inflammatory Bowel Diseases* / chemically induced
  • Inflammatory Bowel Diseases* / drug therapy
  • Male
  • Mercaptopurine / adverse effects
  • Prospective Studies

Substances

  • Immunosuppressive Agents
  • Azathioprine
  • Mercaptopurine