6-Thioguanine therapy in Crohn′s disease—Observational data in Swedish patients

• Published in: Digestive and liver disease 2009-03, Vol.41 (3), p.194-200
• Main Authors: Almer, S.H.C, Hjortswang, H, Hindorf, U
• Format: Article
• Language: English
• Subjects: 6-thioguanine; Drug toxicity; Gastroenterology and Hepatology; Inflammatory bowel disease; Thiopurine drugs
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/j.dld.2008.07.314

Abstract Background and aims Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9–28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety. Methods We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohn's disease (CD) patients (13 men, median age 41 (19–65) years) with prior intolerance ( n = 18) or resistance ( n = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times. Results Patients were treated with a median daily dose of 40 mg 6-TG (range 20–60) for 259 (15–2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4–26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation ( n = 10) after 85 (15–451) days or dose reduction ( n = 6) after 78 (10–853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance ( p = 0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure ( n = 5) or safety concerns ( n = 3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99–2488) vs. 551 (392–1574) pmol/8 × 108 RBC; p = 0.80. Conclusions In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered.