bioRxiv (Cold Spring Harbor Laboratory), Feb 16, 2024
We describe a data-driven computational approach for quantifying the microbial functional pathway... more We describe a data-driven computational approach for quantifying the microbial functional pathways in the gastrointestinal tract, based on an analysis of stool metatranscriptomic data within a large and diverse adult human population (n = 66,545). We develop a suite of eight gut microbial pathway scores, each of which represents the activity of a well-defined set of microbial functional features relevant to known gut biochemical activities. We use a normative approach within a subpopulation (n = 9,350) to determine the optimal and non-optimal levels of activity of these functional pathway scores. We hypothesize that non-optimal scores are associated with irritable bowel syndrome (IBS) and its subtypes (i.e., IBS-Constipation, IBS-Diarrhea, IBS-Mixed Type). We show that non-optimal scores within these microbial functional pathways are associated with higher odds of IBS or its subtypes within an independent cohort (n = 57,195). Given these findings, these gut pathway scores can be used to deliver meaningful health insights from simple, non-invasive stool samples, as potential molecular endpoints to measure the efficacy of practical interventions, and develop data-driven personalized algorithms aimed at providing nutritional recommendations, diagnostics, and treatments for IBS as well as related conditions.
Recent studies have identified microbial components in most tumors and invoked microorganisms in ... more Recent studies have identified microbial components in most tumors and invoked microorganisms in cancer onset and progression. The microbial functions responsible for these effects likely include production of genotoxins, modification of human gene expression, and protection of cancer cells from immune surveillance. Metatranscriptomics (MT) is a powerful tool for the development of potential cancer diagnostics and therapeutics, as well as investigating cancer initiation and progression. This is because MT data can quantify human and microbial gene expression, as well as provide strain level taxonomic classification of the microorganisms in the tumor microenvironment (TME). In addition, the microbial data derived from the MT method can easily be normalized across different samples, since many human transcripts can act as internal standards. When collecting tissue samples for clinical studies, researchers have the option of using fresh or Formalin-Fixed Paraffin-Embedded (FFPE) sample...
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phas... more BACKGROUND Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab for maintenance of remission in patients with moderately to severely active ulcerative colitis. METHODS We conducted a randomised, placebo-controlled, double-blind, phase 3 study (LAUREL) across 111 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. During open-label induction, participants received subcutaneous etrolizumab 105 mg once every 4 weeks. Participants who had clinical response at week 10 (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) proceeded into the double-blind maintenance phase and were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or matched placebo until week 62. Randomisation was stratified by baseline concomitant treatment with corticosteroids, treatment with immunosuppressants, baseline disease activity, and week 10 remission status. All participants and study site personnel were masked to treatment assignment. The primary endpoint was remission at week 62 (MCS ≤2, with individual subscores ≤1, and rectal bleeding subscore of 0) among patients with a clinical response at week 10, measured in the modified intention-to-treat population (all randomised patients who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, NCT02165215, and is now closed to recruitment. FINDINGS Between Aug 12, 2014, and June 4, 2020, 658 patients were screened for eligibility and 359 were enrolled into the induction phase. 214 (60%) patients had a clinical response at week 10 and were randomly assigned to receive etrolizumab (n=108) or placebo (n=106) in the maintenance phase. 80 (74%) patients in the etrolizumab group and 42 (40%) in the placebo group completed the study through week 62. Four patients in the placebo group did not receive study treatment and were excluded from the analyses. At week 62, 32 (29·6%) of 108 patients in the etrolizumab group and 21 (20·6%) of 102 in the placebo group were in remission (adjusted treatment difference 7·7% [95% CI -4·2 to 19·2]; p=0·19). A greater proportion of patients reported one or more adverse events in the placebo group (82 [80%] of 102) than in the etrolizumab group (70 [65%] of 108); the most common adverse event in both groups was ulcerative colitis (16 [15%] patients in the etrolizumab group and 37 [36%] in the placebo group). Ten (9%) patients in the etrolizumab group and eight (8%) in the placebo group reported one or more serious adverse events. No deaths were reported in either treatment group. INTERPRETATION No significant differences were observed between maintenance etrolizumab and placebo in the primary endpoint of remission at week 62 among patients who had a clinical response at week 10. Etrolizumab was well tolerated in this population and no new safety signals were identified. FUNDING F Hoffmann-La Roche.
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier ph... more BACKGROUND Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. METHODS HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18-80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov, NCT02100696. FINDINGS HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). INTERPRETATION HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. FUNDING F Hoffmann-La Roche.
INTRODUCTION: The COVID-19 pandemic has led to immediate, profound, and potentially permanent cha... more INTRODUCTION: The COVID-19 pandemic has led to immediate, profound, and potentially permanent changes to the practice of gastroenterology Here, we describe the progression of change in a large community practice gastroenterology clinic resulting from COVID-19 Additionally, we examine implications on staffing, requirements for personal protection equipment and the use of telemedicine METHODS: We looked at practice data from a vertically integrated community-based gastroenterology practice of 30 physicians, and 16 non-physician providers (NPPs) based in the Puget Sound Region of the Pacific Northwest The practice operates 9 clinics, 7 endoscopy centers and 2 ambulatory infusion centers In 2019 collectively, the practice performed approximately 3800 endoscopic procedures, 350 infusions and 4300 clinic visits per month We examined data in the immediate months before March 19, 2020 state mandated closure for Covid-19 and two months following RESULTS: At the height of its impact in April, we saw an approximate decrease of 75% in RVU's, 45% in clinic visits, and 100% reduction in endoscopic procedures Telemedicine, which previously was not utilized in our practice, evolved rapidly within less than a week to approximately 90% of clinical visits and was embraced by both physicians and patients There was an increase in clinic visits per MD as clinical contact increased and procedure volume was reduced With the reopening of the endoscopy centers in May, we noted a 15 25% increase in costs per procedure, secondary to utilization of PPE, increasing staffing per procedure and a reduction of the average number of cases per physician per month from 130 to 50 Infusion volumes were minimally impacted by the epidemic and stay at home orders CONCLUSION: The COVID-19 pandemic has led to immediate and profound changes on the practice and delivery of gastroenterology care Many of these changes will be temporary as we embrace efficiencies However, there will be fundamental alterations to the practice of gastroenterology that will remain even after a vaccine or very effective treatment for COVID-19 has been secured such as the use of PPE, requirements for clinical space and the use of telemedicine We anticipate PPE cost will decrease over time, with efficiency of AEC throughput, and testing/ screening requirements Future studies will be valuable to look at those trends and changes in practice patterns as this epidemic evolves
Gluten ingestion leads to symptoms and small intestinal mucosal injury in patients with celiac di... more Gluten ingestion leads to symptoms and small intestinal mucosal injury in patients with celiac disease. The only option is the strict lifelong exclusion of dietary gluten, which is difficult to accomplish. Many patients following a gluten-free diet continue to have symptoms and have small intestinal mucosal injury. Non-dietary therapies are needed. We performed a phase 2 study of the ability of latiglutenase, an orally administered mixture of 2 recombinant gluten-targeting proteases, to reduce mucosal morphometric measures in biopsies from patients with celiac disease. We performed a double-blind, placebo-controlled, dose-ranging study to assess the efficacy and safety of latiglutenase in 494 patients with celiac disease (with moderate or severe symptoms) in North America and Europe, from August 2013 until December 2014. Participants reported following a gluten-free diet for at least 1 year before the study began. Patients with documented moderate or severe symptoms and villous atro...
bioRxiv (Cold Spring Harbor Laboratory), Feb 16, 2024
We describe a data-driven computational approach for quantifying the microbial functional pathway... more We describe a data-driven computational approach for quantifying the microbial functional pathways in the gastrointestinal tract, based on an analysis of stool metatranscriptomic data within a large and diverse adult human population (n = 66,545). We develop a suite of eight gut microbial pathway scores, each of which represents the activity of a well-defined set of microbial functional features relevant to known gut biochemical activities. We use a normative approach within a subpopulation (n = 9,350) to determine the optimal and non-optimal levels of activity of these functional pathway scores. We hypothesize that non-optimal scores are associated with irritable bowel syndrome (IBS) and its subtypes (i.e., IBS-Constipation, IBS-Diarrhea, IBS-Mixed Type). We show that non-optimal scores within these microbial functional pathways are associated with higher odds of IBS or its subtypes within an independent cohort (n = 57,195). Given these findings, these gut pathway scores can be used to deliver meaningful health insights from simple, non-invasive stool samples, as potential molecular endpoints to measure the efficacy of practical interventions, and develop data-driven personalized algorithms aimed at providing nutritional recommendations, diagnostics, and treatments for IBS as well as related conditions.
Recent studies have identified microbial components in most tumors and invoked microorganisms in ... more Recent studies have identified microbial components in most tumors and invoked microorganisms in cancer onset and progression. The microbial functions responsible for these effects likely include production of genotoxins, modification of human gene expression, and protection of cancer cells from immune surveillance. Metatranscriptomics (MT) is a powerful tool for the development of potential cancer diagnostics and therapeutics, as well as investigating cancer initiation and progression. This is because MT data can quantify human and microbial gene expression, as well as provide strain level taxonomic classification of the microorganisms in the tumor microenvironment (TME). In addition, the microbial data derived from the MT method can easily be normalized across different samples, since many human transcripts can act as internal standards. When collecting tissue samples for clinical studies, researchers have the option of using fresh or Formalin-Fixed Paraffin-Embedded (FFPE) sample...
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phas... more BACKGROUND Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab for maintenance of remission in patients with moderately to severely active ulcerative colitis. METHODS We conducted a randomised, placebo-controlled, double-blind, phase 3 study (LAUREL) across 111 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. During open-label induction, participants received subcutaneous etrolizumab 105 mg once every 4 weeks. Participants who had clinical response at week 10 (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) proceeded into the double-blind maintenance phase and were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or matched placebo until week 62. Randomisation was stratified by baseline concomitant treatment with corticosteroids, treatment with immunosuppressants, baseline disease activity, and week 10 remission status. All participants and study site personnel were masked to treatment assignment. The primary endpoint was remission at week 62 (MCS ≤2, with individual subscores ≤1, and rectal bleeding subscore of 0) among patients with a clinical response at week 10, measured in the modified intention-to-treat population (all randomised patients who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, NCT02165215, and is now closed to recruitment. FINDINGS Between Aug 12, 2014, and June 4, 2020, 658 patients were screened for eligibility and 359 were enrolled into the induction phase. 214 (60%) patients had a clinical response at week 10 and were randomly assigned to receive etrolizumab (n=108) or placebo (n=106) in the maintenance phase. 80 (74%) patients in the etrolizumab group and 42 (40%) in the placebo group completed the study through week 62. Four patients in the placebo group did not receive study treatment and were excluded from the analyses. At week 62, 32 (29·6%) of 108 patients in the etrolizumab group and 21 (20·6%) of 102 in the placebo group were in remission (adjusted treatment difference 7·7% [95% CI -4·2 to 19·2]; p=0·19). A greater proportion of patients reported one or more adverse events in the placebo group (82 [80%] of 102) than in the etrolizumab group (70 [65%] of 108); the most common adverse event in both groups was ulcerative colitis (16 [15%] patients in the etrolizumab group and 37 [36%] in the placebo group). Ten (9%) patients in the etrolizumab group and eight (8%) in the placebo group reported one or more serious adverse events. No deaths were reported in either treatment group. INTERPRETATION No significant differences were observed between maintenance etrolizumab and placebo in the primary endpoint of remission at week 62 among patients who had a clinical response at week 10. Etrolizumab was well tolerated in this population and no new safety signals were identified. FUNDING F Hoffmann-La Roche.
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier ph... more BACKGROUND Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. METHODS HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18-80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov, NCT02100696. FINDINGS HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). INTERPRETATION HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. FUNDING F Hoffmann-La Roche.
INTRODUCTION: The COVID-19 pandemic has led to immediate, profound, and potentially permanent cha... more INTRODUCTION: The COVID-19 pandemic has led to immediate, profound, and potentially permanent changes to the practice of gastroenterology Here, we describe the progression of change in a large community practice gastroenterology clinic resulting from COVID-19 Additionally, we examine implications on staffing, requirements for personal protection equipment and the use of telemedicine METHODS: We looked at practice data from a vertically integrated community-based gastroenterology practice of 30 physicians, and 16 non-physician providers (NPPs) based in the Puget Sound Region of the Pacific Northwest The practice operates 9 clinics, 7 endoscopy centers and 2 ambulatory infusion centers In 2019 collectively, the practice performed approximately 3800 endoscopic procedures, 350 infusions and 4300 clinic visits per month We examined data in the immediate months before March 19, 2020 state mandated closure for Covid-19 and two months following RESULTS: At the height of its impact in April, we saw an approximate decrease of 75% in RVU's, 45% in clinic visits, and 100% reduction in endoscopic procedures Telemedicine, which previously was not utilized in our practice, evolved rapidly within less than a week to approximately 90% of clinical visits and was embraced by both physicians and patients There was an increase in clinic visits per MD as clinical contact increased and procedure volume was reduced With the reopening of the endoscopy centers in May, we noted a 15 25% increase in costs per procedure, secondary to utilization of PPE, increasing staffing per procedure and a reduction of the average number of cases per physician per month from 130 to 50 Infusion volumes were minimally impacted by the epidemic and stay at home orders CONCLUSION: The COVID-19 pandemic has led to immediate and profound changes on the practice and delivery of gastroenterology care Many of these changes will be temporary as we embrace efficiencies However, there will be fundamental alterations to the practice of gastroenterology that will remain even after a vaccine or very effective treatment for COVID-19 has been secured such as the use of PPE, requirements for clinical space and the use of telemedicine We anticipate PPE cost will decrease over time, with efficiency of AEC throughput, and testing/ screening requirements Future studies will be valuable to look at those trends and changes in practice patterns as this epidemic evolves
Gluten ingestion leads to symptoms and small intestinal mucosal injury in patients with celiac di... more Gluten ingestion leads to symptoms and small intestinal mucosal injury in patients with celiac disease. The only option is the strict lifelong exclusion of dietary gluten, which is difficult to accomplish. Many patients following a gluten-free diet continue to have symptoms and have small intestinal mucosal injury. Non-dietary therapies are needed. We performed a phase 2 study of the ability of latiglutenase, an orally administered mixture of 2 recombinant gluten-targeting proteases, to reduce mucosal morphometric measures in biopsies from patients with celiac disease. We performed a double-blind, placebo-controlled, dose-ranging study to assess the efficacy and safety of latiglutenase in 494 patients with celiac disease (with moderate or severe symptoms) in North America and Europe, from August 2013 until December 2014. Participants reported following a gluten-free diet for at least 1 year before the study began. Patients with documented moderate or severe symptoms and villous atro...
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Papers by robert wohlman