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. 2021 Apr;70(4):677-686.
doi: 10.1136/gutjnl-2019-320185. Epub 2020 Oct 1.

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn's disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Evangelos Stournaras #  1 , Wendi Qian #  2 , Apostolos Pappas  1 , You Yi Hong  1 , Rasha Shawky  3 ; UK IBD BioResource Investigators; Tim Raine #  1   4 , Miles Parkes #  5   3   4 ; UK IBD Bioresource Investigators
Collaborators, Affiliations

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn's disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Evangelos Stournaras et al. Gut. 2021 Apr.

Abstract

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn's disease (CD), including their impact on need for surgery.

Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines.

Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015).

Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD.

Keywords: 6-mercaptopurine; azathioprine; crohn's disease; tolerance; ulcerative colitis.

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Conflict of interest statement

Competing interests: MP is in receipt of grant funding from Pfizer, Gilead and Roche, and has received speaker fees from Takeda. TR has received research/educational grants and/or speaker/consultation fees from Abbvie, BMS, Celgene, Ferring, Gilead, GSK, Mylan, LabGenius, Janssen, MSD, Novartis, Pfizer, Sandoz, Takeda and UCB.

Figures

Figure 1
Figure 1
Study flow chart.
Figure 2
Figure 2
Time (years) from IBD diagnosis to thiopurine initiation in the 11 928 subjects. IBD, inflammatory bowel disease.
Figure 3
Figure 3
Kaplan-Meier plots of time during which thiopurine monotherapy was effective in UC and CD, without requirement for treatment escalation (p<0.0001 for log-rank test). CD, Crohn’s disease; UC, ulcerative colitis.
Figure 4
Figure 4
Kaplan-Meier plot showing the proportion of patients with UC not requiring colectomy relative to time since initiation of thiopurines, stratified by ability to tolerate thiopurines. Patients unable to tolerate thiopurine had a significantly shorter time to colectomy (log-rank <0.0001). UC, ulcerative colitis.
Figure 5
Figure 5
Kaplan-Meier plot showing the proportion of patients with CD not requiring surgery relative to time since initiation of thiopurines, stratified by ability to tolerate thiopurines. Patients unable to tolerate thiopurine had a significantly shorter time to surgery (log-rank=0.002). CD, Crohn’s disease.
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Comment in

References

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