Pub Date : 2022-11-01Epub Date: 2022-09-06DOI: 10.1016/S2468-1253(22)00233-3
Severine Vermeire, Bruce E Sands, Herbert Tilg, Zsolt Tulassay, Radoslaw Kempinski, Silvio Danese, Ivan Bunganič, Josianne Nitcheu, Julien Santo, Didier Scherrer, Sophie Biguenet, Hartmut J Ehrlich, Jean-Marc Steens, Paul Gineste, William J Sandborn
<p><strong>Background: </strong>ABX464 (obefazimod) is a small molecule that selectively upregulates miR-124 in immune cells. We aimed to assess ABX464 as a treatment for patients with moderate-to-severe, active ulcerative colitis.</p><p><strong>Methods: </strong>In this phase 2b, double-blind, randomised, placebo-controlled induction trial, patients were recruited from 95 centres (hospitals and health-care centres) in 16 countries. Eligible patients were aged 18-75 years, with a diagnosis of moderate-to-severe, active ulcerative colitis and a modified Mayo Score (MMS) of 5 points or higher, and a documented non-response or intolerance to previous treatment. Enrolled patients were randomly assigned (1:1:1:1) via an interactive voice and web response system to receive once daily oral ABX464 100 mg, ABX464 50 mg, ABX464 25 mg, or matched placebo. Randomisation was stratified according to study site (US vs non-US) and to whether the patient had previous exposure to second-line treatment with biologics or JAK inhibitors. The primary endpoint was the change from baseline in MMS at week 8. The primary efficacy analysis was done in the full analysis set (FAS), defined as all randomly assigned patients who received at least one dose of study treatment and had baseline data for at least one efficacy variable, and was analysed according to the principles of intention-to-treat. Safety analyses included patients who had been randomly assigned and who received at least one dose of study treatment. The 96 week open-label extension is ongoing. This study is registered with ClinicalTrials.gov, NCT04023396.</p><p><strong>Findings: </strong>Between Aug 13, 2019, and April 16, 2021, 254 patients were randomly allocated to ABX464 100 mg (n=64), ABX464 50 mg (n=63), ABX464 25 mg (n=63), or placebo (n=64). Two patients, both in the ABX464 25 mg group, were excluded from the FAS. In the FAS at week 8, the least squares mean (LSM) change from baseline in MMS was -2·9 (95% CI -3·4 to -2·5) for the ABX464 100 mg group, -3·2 (-3·7 to -2·7) for the ABX464 50 mg group, -3·1 (-3·6 to -2·6) for the ABX464 25 mg group, and -1·9 (-2·4 to -1·5) for placebo group; the magnitude of the difference in MMS from baseline was significantly greater in all three ABX464 groups compared with placebo (p=0·0039 for ABX464 100 mg vs placebo, p=0·0003 for ABX464 50 mg vs placebo, and p=0·0010 for ABX464 25 mg vs placebo). The most frequently reported adverse event was headache, which was reported for 27 (42%) of 64 patients in the ABX464 100 mg group, 19 (30%) of 63 in the 50 mg group, 13 (21%) of 62 in the 25 mg group, and five (8%) of 64 in the placebo group. Severe (grade 3) headache was reported for three (5%) patients in the ABX464 group 100 mg group, two (3%) in the ABX464 50 mg group, one (2%) in the ABX464 25 mg group, and none in the placebo group. The only serious adverse event reported for two or more patients in any group was ulcerative colitis (one in each of the ABX464 100 mg and
{"title":"ABX464 (obefazimod) for moderate-to-severe, active ulcerative colitis: a phase 2b, double-blind, randomised, placebo-controlled induction trial and 48 week, open-label extension.","authors":"Severine Vermeire, Bruce E Sands, Herbert Tilg, Zsolt Tulassay, Radoslaw Kempinski, Silvio Danese, Ivan Bunganič, Josianne Nitcheu, Julien Santo, Didier Scherrer, Sophie Biguenet, Hartmut J Ehrlich, Jean-Marc Steens, Paul Gineste, William J Sandborn","doi":"10.1016/S2468-1253(22)00233-3","DOIUrl":"https://doi.org/10.1016/S2468-1253(22)00233-3","url":null,"abstract":"<p><strong>Background: </strong>ABX464 (obefazimod) is a small molecule that selectively upregulates miR-124 in immune cells. We aimed to assess ABX464 as a treatment for patients with moderate-to-severe, active ulcerative colitis.</p><p><strong>Methods: </strong>In this phase 2b, double-blind, randomised, placebo-controlled induction trial, patients were recruited from 95 centres (hospitals and health-care centres) in 16 countries. Eligible patients were aged 18-75 years, with a diagnosis of moderate-to-severe, active ulcerative colitis and a modified Mayo Score (MMS) of 5 points or higher, and a documented non-response or intolerance to previous treatment. Enrolled patients were randomly assigned (1:1:1:1) via an interactive voice and web response system to receive once daily oral ABX464 100 mg, ABX464 50 mg, ABX464 25 mg, or matched placebo. Randomisation was stratified according to study site (US vs non-US) and to whether the patient had previous exposure to second-line treatment with biologics or JAK inhibitors. The primary endpoint was the change from baseline in MMS at week 8. The primary efficacy analysis was done in the full analysis set (FAS), defined as all randomly assigned patients who received at least one dose of study treatment and had baseline data for at least one efficacy variable, and was analysed according to the principles of intention-to-treat. Safety analyses included patients who had been randomly assigned and who received at least one dose of study treatment. The 96 week open-label extension is ongoing. This study is registered with ClinicalTrials.gov, NCT04023396.</p><p><strong>Findings: </strong>Between Aug 13, 2019, and April 16, 2021, 254 patients were randomly allocated to ABX464 100 mg (n=64), ABX464 50 mg (n=63), ABX464 25 mg (n=63), or placebo (n=64). Two patients, both in the ABX464 25 mg group, were excluded from the FAS. In the FAS at week 8, the least squares mean (LSM) change from baseline in MMS was -2·9 (95% CI -3·4 to -2·5) for the ABX464 100 mg group, -3·2 (-3·7 to -2·7) for the ABX464 50 mg group, -3·1 (-3·6 to -2·6) for the ABX464 25 mg group, and -1·9 (-2·4 to -1·5) for placebo group; the magnitude of the difference in MMS from baseline was significantly greater in all three ABX464 groups compared with placebo (p=0·0039 for ABX464 100 mg vs placebo, p=0·0003 for ABX464 50 mg vs placebo, and p=0·0010 for ABX464 25 mg vs placebo). The most frequently reported adverse event was headache, which was reported for 27 (42%) of 64 patients in the ABX464 100 mg group, 19 (30%) of 63 in the 50 mg group, 13 (21%) of 62 in the 25 mg group, and five (8%) of 64 in the placebo group. Severe (grade 3) headache was reported for three (5%) patients in the ABX464 group 100 mg group, two (3%) in the ABX464 50 mg group, one (2%) in the ABX464 25 mg group, and none in the placebo group. The only serious adverse event reported for two or more patients in any group was ulcerative colitis (one in each of the ABX464 100 mg and ","PeriodicalId":114609,"journal":{"name":"The lancet. Gastroenterology & hepatology","volume":" ","pages":"1024-1035"},"PeriodicalIF":35.7,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33449636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01DOI: 10.1016/s2468-1253(22)00281-3
H. Schellekens
{"title":"All roads lead to the gut-brain microbiome network.","authors":"H. Schellekens","doi":"10.1016/s2468-1253(22)00281-3","DOIUrl":"https://doi.org/10.1016/s2468-1253(22)00281-3","url":null,"abstract":"","PeriodicalId":114609,"journal":{"name":"The lancet. Gastroenterology & hepatology","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122181163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01Epub Date: 2022-07-28DOI: 10.1016/S2468-1253(22)00234-5
Eneyi E Kpokiri, Dalia Elasi, Tiange P Zhang, Claire L Amon, Jessica Hicks, Jack Wallace, Philippa Easterbrook, Nick Walsh, Manal H El-Sayed, Philippa C Matthews, Su H Wang, Joseph D Tucker, Dan Wu
{"title":"Expanding community engagement and advocacy in chronic viral hepatitis.","authors":"Eneyi E Kpokiri, Dalia Elasi, Tiange P Zhang, Claire L Amon, Jessica Hicks, Jack Wallace, Philippa Easterbrook, Nick Walsh, Manal H El-Sayed, Philippa C Matthews, Su H Wang, Joseph D Tucker, Dan Wu","doi":"10.1016/S2468-1253(22)00234-5","DOIUrl":"10.1016/S2468-1253(22)00234-5","url":null,"abstract":"","PeriodicalId":114609,"journal":{"name":"The lancet. Gastroenterology & hepatology","volume":" ","pages":"902-904"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40674111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Over the past century, the incidence of inflammatory bowel disease (IBD) in high-income countries has shown a sharp rise that then plateaued, and a similar trend has been observed in newly industrialised countries. IBD has long been considered uncommon in sub-Saharan Africa, possibly reflecting low exposure to environmental risk factors described in high-income populations. Alternatively, individuals living in sub-Saharan Africa might have a different genetic disposition. However, some cases of IBD might remain undetected in sub-Saharan Africa because of a lack of awareness, deficiencies in diagnostic and clinical capacity, and a substantial rate of misdiagnosis due to the high burden of infectious diseases. There are few published data describing the natural history of IBD in sub-Saharan Africa, and the true burden of the disease remains largely unknown, although there is some evidence that the incidence of IBD is rising in this region. This Series paper summarises the present understanding of IBD and challenges facing clinicians when diagnosing this disease in sub-Saharan Africa.
{"title":"Inflammatory bowel disease in sub-Saharan Africa: epidemiology, risk factors, and challenges in diagnosis.","authors":"Gillian Watermeyer, Leolin Katsidzira, Mashiko Setshedi, Smita Devani, Wisdom Mudombi, Chris Kassianides","doi":"10.1016/S2468-1253(22)00047-4","DOIUrl":"https://doi.org/10.1016/S2468-1253(22)00047-4","url":null,"abstract":"<p><p>Over the past century, the incidence of inflammatory bowel disease (IBD) in high-income countries has shown a sharp rise that then plateaued, and a similar trend has been observed in newly industrialised countries. IBD has long been considered uncommon in sub-Saharan Africa, possibly reflecting low exposure to environmental risk factors described in high-income populations. Alternatively, individuals living in sub-Saharan Africa might have a different genetic disposition. However, some cases of IBD might remain undetected in sub-Saharan Africa because of a lack of awareness, deficiencies in diagnostic and clinical capacity, and a substantial rate of misdiagnosis due to the high burden of infectious diseases. There are few published data describing the natural history of IBD in sub-Saharan Africa, and the true burden of the disease remains largely unknown, although there is some evidence that the incidence of IBD is rising in this region. This Series paper summarises the present understanding of IBD and challenges facing clinicians when diagnosing this disease in sub-Saharan Africa.</p>","PeriodicalId":114609,"journal":{"name":"The lancet. Gastroenterology & hepatology","volume":" ","pages":"952-961"},"PeriodicalIF":35.7,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40465404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01DOI: 10.1016/S2468-1253(22)00282-5
Chris Wortley
{"title":"Warburg: father of the metabolic approach to cancer.","authors":"Chris Wortley","doi":"10.1016/S2468-1253(22)00282-5","DOIUrl":"https://doi.org/10.1016/S2468-1253(22)00282-5","url":null,"abstract":"","PeriodicalId":114609,"journal":{"name":"The lancet. Gastroenterology & hepatology","volume":" ","pages":"911"},"PeriodicalIF":35.7,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33458248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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