A prospective, open-label trial of 6-thioguanine in patients with ulcerative or indeterminate colitis.
OBJECTIVE
6-thioguanine (6-TG) has emerged as a promising therapeutic alternative in patients with Crohn's disease intolerant or resistant to azathioprine (AZA) and/or 6-mercaptopurine (6-MP). The aim of the present study was to evaluate the safety and efficacy of 6-TG in patients with ulcerative colitis (UC) or indeterminate colitis (IC) intolerant or resistant to AZA/6-MP.


METHODS
Twenty patients with an acute flare, steroid-dependent or steroid-refractory disease attending our outpatient department were included in the study. Measurement of 6-TG nucleotide levels was done to check compliance. Complete, partial and non-response were defined by means of the clinical activity index and the daily steroid demand. Secondary outcome parameters included changes in cumulative steroid doses, C-reactive protein (CRP) levels, and an endoscopic score.


RESULTS
Out of 20 patients 4 were excluded owing to noncompliance; 2/16 compliant patients (13%) had to be prematurely withdrawn because of adverse events, which ceased upon drug discontinuation. By per-protocol analysis, 5/14 patients (36%) were complete, 6/14 (43%) partial and 3/14 (21%) non-responders. In addition to the reduction of the cumulative steroid dose over 3 months, CRP decreased in the study population and the endoscopic score decreased in treatment responders.


CONCLUSIONS
Treatment with 6-TG was effective in patients with UC or IC previously intolerant or resistant to AZA/6-MP. Future work is needed to define a subpopulation of patients at low risk for its potential hepatotoxicity, which we assume will benefit from 6-TG.
Teml
Alexander
A
Universitätsklinik für Innere Medizin IV, Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien, Vienna, Austria.
Schwab
Matthias
M
Harrer
Marieluise
M
Miehsler
Wolfgang
W
Schaeffeler
Elke
E
Dejaco
Clemens
C
Mantl
Martina
M
Schneider
Barbara
B
Vogelsang
Harald
H
Reinisch
Walter
W
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001379:Azathioprine / Q000009:adverse effects / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005838:Genotype; D006150:Guanine Nucleotides / Q000097:blood; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000378:metabolism; D008778:Methylthioinosine / Q000097:blood; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism; D010349:Patient Compliance; D011446:Prospective Studies; D011788:Quality of Life; D013866:Thioguanine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013873:Thionucleotides / Q000097:blood; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D006150:Guanine Nucleotides; D009961:Orosomucoid; D013873:Thionucleotides; C003964:6-thioguanylic acid; D008778:Methylthioinosine; D002097:C-Reactive Protein; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine