6-Thioguanine therapy in Crohn's disease--observational data in Swedish patients.
OBJECTIVE
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 x 10(8) 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.
Almer
S H C
SH
Department of Clinical and Experimental Medicine, Division of Gastroenterology and Hepatology, Faculty of Health Sciences, Linköping University, Linköping, Sweden. sven.almer@lio.se
Hjortswang
H
H
Hindorf
U
U
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001379:Azathioprine / Q000009:adverse effects; D003424:Crohn Disease / Q000188:drug therapy*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D012720:Severity of Illness Index; D013548:Sweden; D013866:Thioguanine / Q000627:therapeutic use*; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine