Fernando Magro1,2,3,4, Maria Manuela Estevinho1,5, Cláudia Camila Dias6,7, Luís Correia8, Paula Lago9, Paula Ministro10, Francisco Portela11, Roger Feakins12, Silvio Danese13,14, Laurent Peyrin-Biroulet15. 1. Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal. 2. Department of Gastroenterology, São João Hospital Center, Porto, Portugal. 3. MedInUP, Center for Drug Discovery and Innovative Medicines, Porto, Portugal. 4. Clinical Pharmacology Unit, São João Hospital University Center, Porto, Portugal. 5. Department of Gastroenterology, Vila Nova de Gaia/Espinho Hospital Center, Vila Nova de Gaia, Portugal. 6. Department of Community Medicine, Information and Decision in Health, Faculty of Medicine of the University of Porto, Porto, Portugal. 7. Centre for Health Technology and Services Research, Porto, Portugal. 8. Department of Gastroenterology and Hepatology, Santa Maria Hospital, University of Lisbon, Lisbon, Portugal. 9. Department of Gastroenterology, Porto Hospital Center, Porto, Portugal. 10. Department of Gastroenterology, Tondela-Viseu Hospital Center, Viseu, Portugal. 11. Department of Gastroenterology, University Hospital Center of Coimbra, Coimbra, Portugal. 12. Department of Histopathology, Royal Free London NHS Foundation Trust, London, UK. 13. IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center- IRCCS-, Rozzano, Milan, Italy. 14. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. 15. Institut National de la Santé et de la Recherche Médicale U954 and Department of Gastroenterology, Nancy University Hospital, Lorraine University, Nancy, France.
Abstract
BACKGROUND AND AIMS: Interest in histology for ulcerative colitis [UC] has increased recently. This systematic review and meta-analysis aims to assess, for the first time, whether histological outcomes are more informative than endoscopic and clinical outcomes in distinguishing the impact of intervention over placebo in induction trials. METHODS: MEDLINE, ScienceDirect and Cochrane Central Register of Controlled Trials were searched to identify randomized placebo-controlled trials [RCTs] enrolling moderate-to-severe UC patients. Studies were assessed using the Quality Assessment Tool for Studies with Diverse Designs. We analysed the pooled proportion of patients achieving clinical, endoscopic and histological remission and response after a pharmacological intervention and compared the results with those of placebo-treated patients by using a random-effects model. RESULTS: From 889 identified records, 13 RCTs were included. The odds ratio [OR] for remission was higher in patients receiving intervention than in those under placebo for clinical (OR 2.13, 95% confidence interval [CI] 1.33-3.43), endoscopic [OR 1.46, 95% CI 0.19-11.18] and histological remission [OR 1.85, 95% CI 1.20-2.84]. Significant differences were observed for all response outcomes [clinical: OR 2.27, 95% CI 1.84-2.85; endoscopic: OR 2.16, 95% CI 1.51-3.10; histological: OR 3.63, 95% CI, 1.41-9.36]. No significant heterogeneity existed; no subgroup effects were found for duration of the induction or histological scale [p > 0.05]. Clinical and histological remission and endoscopic response were concordant in discriminating interventions from placebo. CONCLUSION: Histological outcomes are informative in trials of moderate-to-severe UC. Further studies analysing histology at the end of induction are needed to confirm its relevance in distinguishing the efficacy of an intervention over placebo in comparison to clinical and endoscopic outcomes and to explore its prognostic value.
BACKGROUND AND AIMS: Interest in histology for ulcerative colitis [UC] has increased recently. This systematic review and meta-analysis aims to assess, for the first time, whether histological outcomes are more informative than endoscopic and clinical outcomes in distinguishing the impact of intervention over placebo in induction trials. METHODS: MEDLINE, ScienceDirect and Cochrane Central Register of Controlled Trials were searched to identify randomized placebo-controlled trials [RCTs] enrolling moderate-to-severe UC patients. Studies were assessed using the Quality Assessment Tool for Studies with Diverse Designs. We analysed the pooled proportion of patients achieving clinical, endoscopic and histological remission and response after a pharmacological intervention and compared the results with those of placebo-treated patients by using a random-effects model. RESULTS: From 889 identified records, 13 RCTs were included. The odds ratio [OR] for remission was higher in patients receiving intervention than in those under placebo for clinical (OR 2.13, 95% confidence interval [CI] 1.33-3.43), endoscopic [OR 1.46, 95% CI 0.19-11.18] and histological remission [OR 1.85, 95% CI 1.20-2.84]. Significant differences were observed for all response outcomes [clinical: OR 2.27, 95% CI 1.84-2.85; endoscopic: OR 2.16, 95% CI 1.51-3.10; histological: OR 3.63, 95% CI, 1.41-9.36]. No significant heterogeneity existed; no subgroup effects were found for duration of the induction or histological scale [p > 0.05]. Clinical and histological remission and endoscopic response were concordant in discriminating interventions from placebo. CONCLUSION: Histological outcomes are informative in trials of moderate-to-severe UC. Further studies analysing histology at the end of induction are needed to confirm its relevance in distinguishing the efficacy of an intervention over placebo in comparison to clinical and endoscopic outcomes and to explore its prognostic value.