Favourable tolerability and drug survival of tioguanine versus methotrexate after failure of conventional thiopurines in Crohn's disease

BACKGROUND AND AIMS: Both methotrexate and tioguanine can be considered as treatment options in patients with Crohn's disease after failure of conventional thiopurines. This study aimed to compare tolerability and drug survival of methotrexate and tioguanine therapy after failure of conventional thiopurines in patients with Crohn's disease. METHODS: We conducted a retrospective, multi-centre study, including patients with Crohn's disease initiating monotherapy methotrexate or tioguanine after failure (all causes) of conventional thiopurines. Follow-up duration was 104 weeks or until treatment discontinuation. The primary outcome was cumulative therapy discontinuation incidence due to adverse events. Secondary outcomes included total number of (serious) adverse events, and ongoing monotherapy. RESULTS: In total, 219 patients starting either methotrexate (n=105) or tioguanine (n=114) were included. Sixty-five (29.7%) patients (methotrexate 43.8% [46/105 people]; tioguanine 16.7% [19/114 people], p<0.001) discontinued their treatment due to adverse events during follow-up. Median time until discontinuation due to adverse events was 16 weeks (interquartile range [IQR] 7-38, p=0.812). Serious adverse events were not significantly different. Patients treated with methotrexate experienced adverse events more often (methotrexate 83%; tioguanine 46%, p<0.001). Total monotherapy drug survival after 104 weeks was 22% for methotrexate and 46% for tioguanine (p