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

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

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn's disease: long-term outcomes for 11928 patients in the UK inflammatory bowel disease bioresource

© 2020 The Authors. Published by BMJ. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.1136/gutjnl-2019-320185Objective 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.The IBD BioResource is co-funded by the Medical Research Council (Grant number MR/M00533X/1), the Wellcome Sanger Institute, Open Targets, Crohn’s and Colitis UK (Grant number M14/1), National Institute for Health Research (NIHR, Grant/Portfolio number 20664) and the Cambridge Biomedical Research Centre (BRC). The Cambridge BRC is a partnership between Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and is funded by the NIHR.Published versio

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.

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

Genetic mosaic of the Mediterranean fig: comprehensive genomic insights from a gene bank collection

High-depth whole-genome resequencing of 53 diverse fig tree genotypes yielded a rich dataset of genetic variants. We successfully identified 5,501,460 single-nucleotide polymorphisms (SNPs) and 1,228,537 insertions and deletions (InDels), providing a high-density and excellent-quality genetic map of the fig tree. We also performed a detailed population structure analysis, dividing the 53 genotypes into three geographical groups and assessing their genetic diversity and divergence. Analysis of structural variants (SVs) and copy number variations (CNVs) revealed their potential functional impact, particularly in plant-pathogen interaction and secondary metabolism. Metabolomic fingerprinting of fig genotypes uncovered extensive variation in primary metabolites and polyphenolic compounds, highlighting the influence of genotype on fruit quality traits such as nutritional content and bioactive compound composition. The genome-wide association study (GWAS) identified critical SNPs associated with fruit quality and morphological features. The discovery of significant candidate genes, such as AGL62, GDSL, and COBRA-like protein 4 genes, offers promising targets for marker-assisted selection and genome editing approaches to improve fig fruit morphological and quality traits. This extensive genomic analysis of fig trees enhances our understanding of the genetic basis of important agronomic traits and provides a rich resource for future research in this economically and nutritionally significant fruit.This research was co-financed by the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation under the call RESEARCH – CREATE – INNOVATE (2nd cycle) (Project Code: Τ2ΕΔΚ-03933).info:eu-repo/semantics/publishedVersio