P4452 - Dramatic Changes in Thiopurine Metabolite Levels in a Patient with Inflammatory Bowel Disease Treated with Tirzepatide for Weight Loss: A Case Report
Jeremy A. Klein, MD1, Joelle St-Pierre, MD, PhD2, David T. Choi, PharmD2, Jacqueline Lopez, RN, BSN2, David T.. Rubin, MD, FACG2 1University of Chicago Medical Center, Chicago, IL; 2University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, IL
Introduction: Thiopurines are used to maintain remission in IBD and require regular monitoring for myelotoxicity or liver enzyme abnormalities. We present a patient with IBD who experienced a significant increase in thiopurine metabolite levels and mild hepatotoxicity following tirzepatide initiation, which we hypothesize was related to delayed transit and increased absorption. This case underlines the importance of closely monitoring thiopurine metabolites levels in patients with IBD when initiating glucagon-like peptide-1 (GLP-1) therapies.
Case Description/Methods: A 42-year-old woman with Crohn’s disease (CD) of an ileal pouch anal anastomosis presented for routine follow-up. She was diagnosed with ulcerative pancolitis in 2011 treated with mesalamines, infliximab, and thiopurine prior to total proctocolectomy in 2018 due to persistent invisible dysplasia. In 2021, due to significant pre-pouch ileal ulcers, she was diagnosed with CD of the pouch that responded to prednisone for induction. TPMT enzyme activity was in the normal range and she started 75 mg/day of 6-MP for maintenance, with 6-TG and 6-MMP levels at 281 pmol/8 × 108 RBC and 3,932 pmol/8 × 108 RBC respectively. Routine blood count and liver chemistries were normal. She subsequently started tirzepatide 2.5 mg per week in October 2023 for weight loss, tolerated up to 7.5 mg, and lost 14.1 kg in 4 months. In February 2024, her 6-TG was elevated to 512 pmol/8 × 108 RBC, 6-MMP elevated to 11,704 pmol/8 × 108 RBC, AST 44 U/L, ALT 75 U/L. We instructed her to stop 6-MP for one week and then decrease to 50 mg/day (she remained on tirzepatide). Repeat labs 6 weeks later showed resolution of transaminitis (AST 23 U/L, ALT 32 U/L) along with normalization of 6-TG 434 pmol/8 × 108 RBC and 6-MMP 1,608 pmol/8 × 108 RBC (Figure 1). She subsequently continued 50 mg/day of 6-MP and her IBD remained stable in 6 months of follow-up (so far).
Discussion: This case details how tirzepatide, a dual GLP-1 receptor agonist and glucose-dependent insulinotropic polypeptide (GIP), can increase thiopurine metabolite levels. There are no current studies showing the effect of tirzepatide on thiopurine metabolism. We hypothesize that slower gastric/duodenal transit time from GLP-1 allowed for increased 6-MP absorption. In addition, 6-MP has a high volume of distribution that is increased with adipose tissue loss. Due to widespread use of GLP-1 for diabetes and weight loss, it is important that gastroenterologists closely monitor patients with IBD on thiopurine therapy.
Figure: Figure 1. Transaminase and thiopurine metabolite levels pre-tirzepatide, while on maintenance tirzepatide (7.5 mg/week), and six weeks after 6-MP dose decrease from 75 to 50 mg/day.
Disclosures:
Jeremy Klein indicated no relevant financial relationships.
Joelle St-Pierre indicated no relevant financial relationships.
Jacqueline Lopez indicated no relevant financial relationships.
David Rubin: AbbVie – Consultant. AltruBio – Consultant. Apex – Consultant. Avalo Therapeutics – Consultant. Bausch Health – Consultant. Bristol Myers Squibb – Consultant. Buhlmann Diagnostics Corp – Consultant. Celgene – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. Cornerstones Health – Board of Directors. Crohn's & Colitis Foundation – Board of Trustees. Douglas Therapeutics – Consultant. Eli Lilly – Consultant. InDex Pharmaceuticals – Consultant. Intouch Group – Consultant. Iterative Health – Consultant. Janssen Pharmaceuticals – Consultant. Odyssey Thera – Consultant. Pfizer – Consultant. Prometheus Biosciences – Consultant. Samsung Neurologica – Consultant. Takeda – Consultant, Grant/Research Support.
Jeremy A. Klein, MD1, Joelle St-Pierre, MD, PhD2, David T. Choi, PharmD2, Jacqueline Lopez, RN, BSN2, David T.. Rubin, MD, FACG2. P4452 - Dramatic Changes in Thiopurine Metabolite Levels in a Patient with Inflammatory Bowel Disease Treated with Tirzepatide for Weight Loss: A Case Report, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.
