Safety and effectiveness of long-term allopurinol-thiopurine maintenance treatment in inflammatory bowel disease

• Published in: Inflammatory bowel diseases 2013-02, Vol.19 (2), p.363-369
• Main Authors: Hoentjen, Frank, Seinen, Margien L, Hanauer, Stephen B, de Boer, Nanne K H, Rubin, David T, Bouma, Gerd, Harrell, Laura E, van Bodegraven, Adriaan A
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Allopurinol - metabolism; Allopurinol - therapeutic use; Azathioprine - metabolism; Azathioprine - therapeutic use; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - metabolism; Crohn Disease - drug therapy; Crohn Disease - metabolism; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents - metabolism; Immunosuppressive Agents - therapeutic use; Maintenance Chemotherapy; Male; Medication Adherence; Mercaptopurine - metabolism; Mercaptopurine - therapeutic use; Middle Aged; Treatment Outcome; Young Adult
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1002/ibd.23021

Thiopurines are the mainstay of conventional maintenance therapy in inflammatory bowel disease (IBD). Unfortunately, up to 50% of patients discontinue immunosuppressive therapy within 2 years due to intolerance or lack of efficacy. Allopurinol with low-dose thiopurine can optimize thiopurine metabolism for IBD patients with preferential shunting toward 6-methyl mercaptopurine (6-MMP) formation. The aim of this study was to assess long-term maintenance effectiveness and tolerability of allopurinol-thiopurine therapy in a larger multicenter cohort of IBD patients. Enrolled patients who failed monotherapy with thiopurines due to a skewed metabolism were subsequently treated with a combination therapy of allopurinol and low-dose thiopurine. Adverse events were monitored and therapeutic adherence was assessed. Seventy-seven IBD patients were enrolled with a mean follow-up of 19 months. The median 6-thioguanine nucleotide concentration increased from 145 during monotherapy to 271 pmol/8 × 10(8) red blood cell (RBC) after at least 8 weeks of combination therapy while reducing the thiopurine dosage (P < 0.001). In contrast, median 6-MMP concentrations decreased from 10,110 to 265 pmol/8 × 10(8) RBC (P < 0.001). Leukopenia occurred in 12 patients (16%), requiring dose adaptation. Liver test abnormalities normalized in 81% of patients after the addition of allopurinol. Sixteen (21%) patients had to discontinue combination therapy. The percentage of patients still using combination therapy at 6, 12, 24, and 60 months was 87%, 85%, 76%, and 65%, respectively. Long-term combination therapy with allopurinol and low-dose thiopurines is an effective and well-tolerated treatment in IBD patients with a skewed thiopurine metabolism.