Low-dose thiopurine with allopurinol co-therapy overcomes thiopurine intolerance and allows thiopurine continuation in inflammatory bowel disease

Abstract

Aims: To assess the utility and tolerability of thiopurine-allopurinol co-therapy in inflammatory bowel disease (IBD) patients with intolerance to thiopurine monotherapy.

Methods: A retrospective observational study assessed cases of thiopurine intolerance then switched to thiopurine allopurinol co-therapy between 2011 and 2015 at two centres. Indications for switch, dosing and subsequent clinical outcomes (including thiopurine persistence) were recorded.

Results: Of 767 patients on thiopurines for IBD, 89 (12%) were switched to co-therapy for intolerance. 64/89 (72%) had Crohn's disease, 38 (43%) were males, median age at switch was 40y (range 17-78), median IBD duration 6y (0-29). Median follow-up was 1.9y (0-5). Reasons for switching to co-therapy included fatigue (37%), hepatotoxicity (23%), nausea (23%), arthralgia (10%), headache (12%) and hypersensitivity reaction (4%). Overall, 66 (74%) patients remained on co-therapy until most recent review and achieved a clinical response. High rates of overcoming intolerance (62-100%) occurred with co-therapy for all reasons above, although fatigue was less amenable to switching than non-fatigue indications (62% vs 91%, p = <0.001). Of 34 patients not escalated to biologics with endoscopic data, 15 were in remission (44%) at most recent review.

Conclusion: Low-dose thiopurine combined with allopurinol appears safe and effective in overcoming intolerances to thiopurine monotherapy in many cases.

Keywords: Azathioprine; Colitis; Crohn's; Mercaptopurine; Tolerability.