- Low-dose thioguanine (TG; ≤40 mg/day) can be effective and well-tolerated in more than 50% of difficult-to-treat patients with inflammatory bowel disease (IBD) failing conventional thiopurine therapy (azathioprine [AZA]/mercaptopurine [MP]) and other immunomodulation or biological therapy.
- Hepatotoxicity was not common and the incidence rate of nodular regenerative hyperplasia (NRH) was within the background incidence.
Why this matters
- Findings warrant future prospective trial to further establish the role of TG in patients with IBD as first-line or rescue treatment.
- This retrospective, multicentre study included 193 patients with IBD (57% female and 64% Crohn’s disease) who had failed prior treatment with conventional thiopurine and other immunomodulation or biological therapy and were subsequently treated with TG as rescue monotherapy between 2003 and 2019.
- Clinical response, adverse events, laboratory results, imaging, and liver biopsies were collected.
- Funding: None.
- The median daily dose of TG was 20 mg (range, 20-40 mg); median treatment duration was 23 months (interquartile range [IQR], 10-47 months); and the median follow-up time was 36 months (IQR, 22-53 months).
- Clinical response at 6 and 12 months of TG therapy was seen in 71% (n=137) and 65% (n=125) of patients, respectively.
- 54% of patients remained on TG until the end of follow-up.
- Adverse events mainly included elevated liver function tests (6%), myelotoxicity (7%), and rash (5%).
- Liver biopsies were performed in 33 patients (17%); NRH was histologically diagnosed in two patients and 2 other patients developed non-cirrhotic portal hypertension.
- The median 6-thioguanine nucleotides and thiopurine methyltransferase levels were 953 (IQR, 145-1761) pmoL/8×105 RBC and 47 (IQR, 34.5-96) mU/L, respectively.
- Retrospective design.