6-Thioguanine therapy in Crohn's disease--observational data in Swedish patients

• Published in: Digestive and liver disease Vol. 41; no. 3; p. 194
• Main Authors: Almer, S H C, Hjortswang, H, Hindorf, U
• Format: Journal Article
• Language: English
• Published: Netherlands 01.03.2009
• Subjects: 6-thioguanine; Adult; Aged; Antimetabolites, Antineoplastic - therapeutic use; Azathioprine - adverse effects; Clinical Medicine; Crohn Disease - drug therapy; Drug; Drug Resistance; Drug toxicity; Female; Gastroenterologi; Gastroenterology and Hepatology; Humans; Immunosuppressive Agents - adverse effects; Inflammatory bowel disease; Klinisk medicin; Male; Medical and Health Sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Mercaptopurine - adverse effects; Middle Aged; Prospective Studies; Remission Induction; Severity of Illness Index; Sweden; Thioguanine - therapeutic use; Thiopurine drugs; toxicity; Young Adult
• ISSN: 1878-3562; 1590-8658; 1878-3562
• DOI: 10.1016/j.dld.2008.07.314

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. 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. 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 x 10(8) RBC; p=0.80. 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.