User login
Referral centers varied significantly in IBD treatment approaches
Even high-volume referral centers varied significantly in their use of immunomodulators and some other therapies for patients with inflammatory bowel disease, particularly Crohn’s disease, a prospective cohort study found.
“The development and implementation of evidence-based standards of care may reduce variations and improve patient outcomes,” Dr. Ashwin Ananthakrishnan of Massachusetts General Hospital in Boston and his associates wrote in the June issue of Clinical Gastroenterology and Hepatology (2014 Nov. 21 [doi: 10.1016/j.cgh.2014.11.020]). “Because adherence to guidelines frequently is inadequate, a reduction of practice variation also requires continual improvement, including setting goals and repeated measurement of processes to identify how standardizing care impacts outcomes.”
New biologics have created increasingly diverse treatment options for patients with inflammatory bowel disease (IBD), but few studies have looked at how clinicians and patients choose treatment regimens in daily practice, the researchers noted. To explore the issue, they prospectively studied 1,659 adults with Crohn’s disease (CD) and 946 patients with ulcerative colitis who were treated at one of seven academic medical centers, all of which see a high volume of IBD patients.
Referral centers varied about threefold in their use of immunomodulators for CD (odds ratio for between-center differences, 3.34; 95% confidence interval, 2.09-5.32) in a model that controlled for age at diagnosis, sex, race, smoking status, and duration and extent or behavior of disease, the researchers reported. Use of immunomodulators for ulcerative colitis varied by more than twofold, they found (OR, 2.32; 95% CI, 1.05 to 5.13). Furthermore, they uncovered significant differences in use of oral mesalamine in both forms of IBD, and in the use of corticosteroids and immunomodulator-tumor necrosis factor antagonist combinations for CD, they said.
Treatment practices tended to vary more for CD than for ulcerative colitis, perhaps because CD spans a broader spectrum of pathologies or because clinicians have not yet reached consensus on early aggressive therapy or treatment strategies for CD, the researchers said. “Variations in treatment generally occur when there is uncertainty about the best practice,” they commented. “It is possible that the variations will diminish as evidence on effective IBD therapy grows and evidence-based guidelines become available and are implemented. The continued variation suggests that there is significant potential for standardization of care across referral and community practices.”
The study did not pinpoint reasons for discrepancies in practice, which could have reflected differences related to referring physicians’ or patients’ behaviors or expectations, the researchers said. But the findings did not reflect a single outlier center, and the cohort was not chosen to study variations between centers, which should have helped eliminate selection bias, they added.
The Leona M. and Harry B. Helmsley Charitable Trust funded the study. Dr. Ananthakrishnan reported advisory board payments from Cubist Pharmaceuticals and AbbVe. One coauthor reported financial conflicts of interest with numerous pharmaceutical companies. The other authors reported no conflicts of interest.
Jack Wennberg, a pioneer in quality improvement, was the first to recognize the association between significant variation in health care utilization and poor quality of care. The problem is that Wennberg published this in Science in 1973 (182:1102-8), and now, over 40 years later, we are just making progress for patients with Crohn’s disease and ulcerative colitis.
As a field, we now need to catch up and learn how to address this variation. It won’t be by solely measuring the differences between practices. As a proverb that was taught to me by experts at the Institute for Healthcare Improvement says, “You can’t fatten a cow by weighing it.” We could measure our practice patterns, quality metrics, and report them every day to claim our appropriate reimbursement from the Centers for Medicare & Medicaid Services, but this won’t improve patient outcomes or our understanding of what drives a better quality of life for our patients.
We need to take what Dr. Ananthakrishnan and his team have taught us to the next level. We need to learn from the Model for Improvement (Langley G.J., The improvement guide: A practical approach to enhancing organizational performance. San Francisco: Jossey-Bass, 2009), which teaches us that, to improve, we need to answer three questions: What are we trying to accomplish? How will we know that a change is an improvement? and What changes can we make that will result in an improvement? If we can apply these questions to changes that we want to make in our practices and systematically pursue answers, we will start to improve the quality of care delivered to our patients, as opposed to simply reporting that it is poor.
Dr. Corey A. Siegel, M.S., is director of the Dartmouth-Hitchcock Inflammatory Bowel Disease Center at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He is supported by AHRQ grant 1R01HS021747-01 and serves as consultant or on an advisory board for Abbvie, Amgen, Lilly, Janssen, Salix, Pfizer, Prometheus, Takeda, Theradiag, and UCB. He serves as a speaker for CME activities for AbbVie, Janssen, and Takeda, and has received grant support from Abbvie, Janssen, Salix, Takeda, and UCB. He is cochair of the Crohn’s and Colitis Foundation of America’s Quality of Care Program.
Jack Wennberg, a pioneer in quality improvement, was the first to recognize the association between significant variation in health care utilization and poor quality of care. The problem is that Wennberg published this in Science in 1973 (182:1102-8), and now, over 40 years later, we are just making progress for patients with Crohn’s disease and ulcerative colitis.
As a field, we now need to catch up and learn how to address this variation. It won’t be by solely measuring the differences between practices. As a proverb that was taught to me by experts at the Institute for Healthcare Improvement says, “You can’t fatten a cow by weighing it.” We could measure our practice patterns, quality metrics, and report them every day to claim our appropriate reimbursement from the Centers for Medicare & Medicaid Services, but this won’t improve patient outcomes or our understanding of what drives a better quality of life for our patients.
We need to take what Dr. Ananthakrishnan and his team have taught us to the next level. We need to learn from the Model for Improvement (Langley G.J., The improvement guide: A practical approach to enhancing organizational performance. San Francisco: Jossey-Bass, 2009), which teaches us that, to improve, we need to answer three questions: What are we trying to accomplish? How will we know that a change is an improvement? and What changes can we make that will result in an improvement? If we can apply these questions to changes that we want to make in our practices and systematically pursue answers, we will start to improve the quality of care delivered to our patients, as opposed to simply reporting that it is poor.
Dr. Corey A. Siegel, M.S., is director of the Dartmouth-Hitchcock Inflammatory Bowel Disease Center at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He is supported by AHRQ grant 1R01HS021747-01 and serves as consultant or on an advisory board for Abbvie, Amgen, Lilly, Janssen, Salix, Pfizer, Prometheus, Takeda, Theradiag, and UCB. He serves as a speaker for CME activities for AbbVie, Janssen, and Takeda, and has received grant support from Abbvie, Janssen, Salix, Takeda, and UCB. He is cochair of the Crohn’s and Colitis Foundation of America’s Quality of Care Program.
Jack Wennberg, a pioneer in quality improvement, was the first to recognize the association between significant variation in health care utilization and poor quality of care. The problem is that Wennberg published this in Science in 1973 (182:1102-8), and now, over 40 years later, we are just making progress for patients with Crohn’s disease and ulcerative colitis.
As a field, we now need to catch up and learn how to address this variation. It won’t be by solely measuring the differences between practices. As a proverb that was taught to me by experts at the Institute for Healthcare Improvement says, “You can’t fatten a cow by weighing it.” We could measure our practice patterns, quality metrics, and report them every day to claim our appropriate reimbursement from the Centers for Medicare & Medicaid Services, but this won’t improve patient outcomes or our understanding of what drives a better quality of life for our patients.
We need to take what Dr. Ananthakrishnan and his team have taught us to the next level. We need to learn from the Model for Improvement (Langley G.J., The improvement guide: A practical approach to enhancing organizational performance. San Francisco: Jossey-Bass, 2009), which teaches us that, to improve, we need to answer three questions: What are we trying to accomplish? How will we know that a change is an improvement? and What changes can we make that will result in an improvement? If we can apply these questions to changes that we want to make in our practices and systematically pursue answers, we will start to improve the quality of care delivered to our patients, as opposed to simply reporting that it is poor.
Dr. Corey A. Siegel, M.S., is director of the Dartmouth-Hitchcock Inflammatory Bowel Disease Center at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. He is supported by AHRQ grant 1R01HS021747-01 and serves as consultant or on an advisory board for Abbvie, Amgen, Lilly, Janssen, Salix, Pfizer, Prometheus, Takeda, Theradiag, and UCB. He serves as a speaker for CME activities for AbbVie, Janssen, and Takeda, and has received grant support from Abbvie, Janssen, Salix, Takeda, and UCB. He is cochair of the Crohn’s and Colitis Foundation of America’s Quality of Care Program.
Even high-volume referral centers varied significantly in their use of immunomodulators and some other therapies for patients with inflammatory bowel disease, particularly Crohn’s disease, a prospective cohort study found.
“The development and implementation of evidence-based standards of care may reduce variations and improve patient outcomes,” Dr. Ashwin Ananthakrishnan of Massachusetts General Hospital in Boston and his associates wrote in the June issue of Clinical Gastroenterology and Hepatology (2014 Nov. 21 [doi: 10.1016/j.cgh.2014.11.020]). “Because adherence to guidelines frequently is inadequate, a reduction of practice variation also requires continual improvement, including setting goals and repeated measurement of processes to identify how standardizing care impacts outcomes.”
New biologics have created increasingly diverse treatment options for patients with inflammatory bowel disease (IBD), but few studies have looked at how clinicians and patients choose treatment regimens in daily practice, the researchers noted. To explore the issue, they prospectively studied 1,659 adults with Crohn’s disease (CD) and 946 patients with ulcerative colitis who were treated at one of seven academic medical centers, all of which see a high volume of IBD patients.
Referral centers varied about threefold in their use of immunomodulators for CD (odds ratio for between-center differences, 3.34; 95% confidence interval, 2.09-5.32) in a model that controlled for age at diagnosis, sex, race, smoking status, and duration and extent or behavior of disease, the researchers reported. Use of immunomodulators for ulcerative colitis varied by more than twofold, they found (OR, 2.32; 95% CI, 1.05 to 5.13). Furthermore, they uncovered significant differences in use of oral mesalamine in both forms of IBD, and in the use of corticosteroids and immunomodulator-tumor necrosis factor antagonist combinations for CD, they said.
Treatment practices tended to vary more for CD than for ulcerative colitis, perhaps because CD spans a broader spectrum of pathologies or because clinicians have not yet reached consensus on early aggressive therapy or treatment strategies for CD, the researchers said. “Variations in treatment generally occur when there is uncertainty about the best practice,” they commented. “It is possible that the variations will diminish as evidence on effective IBD therapy grows and evidence-based guidelines become available and are implemented. The continued variation suggests that there is significant potential for standardization of care across referral and community practices.”
The study did not pinpoint reasons for discrepancies in practice, which could have reflected differences related to referring physicians’ or patients’ behaviors or expectations, the researchers said. But the findings did not reflect a single outlier center, and the cohort was not chosen to study variations between centers, which should have helped eliminate selection bias, they added.
The Leona M. and Harry B. Helmsley Charitable Trust funded the study. Dr. Ananthakrishnan reported advisory board payments from Cubist Pharmaceuticals and AbbVe. One coauthor reported financial conflicts of interest with numerous pharmaceutical companies. The other authors reported no conflicts of interest.
Even high-volume referral centers varied significantly in their use of immunomodulators and some other therapies for patients with inflammatory bowel disease, particularly Crohn’s disease, a prospective cohort study found.
“The development and implementation of evidence-based standards of care may reduce variations and improve patient outcomes,” Dr. Ashwin Ananthakrishnan of Massachusetts General Hospital in Boston and his associates wrote in the June issue of Clinical Gastroenterology and Hepatology (2014 Nov. 21 [doi: 10.1016/j.cgh.2014.11.020]). “Because adherence to guidelines frequently is inadequate, a reduction of practice variation also requires continual improvement, including setting goals and repeated measurement of processes to identify how standardizing care impacts outcomes.”
New biologics have created increasingly diverse treatment options for patients with inflammatory bowel disease (IBD), but few studies have looked at how clinicians and patients choose treatment regimens in daily practice, the researchers noted. To explore the issue, they prospectively studied 1,659 adults with Crohn’s disease (CD) and 946 patients with ulcerative colitis who were treated at one of seven academic medical centers, all of which see a high volume of IBD patients.
Referral centers varied about threefold in their use of immunomodulators for CD (odds ratio for between-center differences, 3.34; 95% confidence interval, 2.09-5.32) in a model that controlled for age at diagnosis, sex, race, smoking status, and duration and extent or behavior of disease, the researchers reported. Use of immunomodulators for ulcerative colitis varied by more than twofold, they found (OR, 2.32; 95% CI, 1.05 to 5.13). Furthermore, they uncovered significant differences in use of oral mesalamine in both forms of IBD, and in the use of corticosteroids and immunomodulator-tumor necrosis factor antagonist combinations for CD, they said.
Treatment practices tended to vary more for CD than for ulcerative colitis, perhaps because CD spans a broader spectrum of pathologies or because clinicians have not yet reached consensus on early aggressive therapy or treatment strategies for CD, the researchers said. “Variations in treatment generally occur when there is uncertainty about the best practice,” they commented. “It is possible that the variations will diminish as evidence on effective IBD therapy grows and evidence-based guidelines become available and are implemented. The continued variation suggests that there is significant potential for standardization of care across referral and community practices.”
The study did not pinpoint reasons for discrepancies in practice, which could have reflected differences related to referring physicians’ or patients’ behaviors or expectations, the researchers said. But the findings did not reflect a single outlier center, and the cohort was not chosen to study variations between centers, which should have helped eliminate selection bias, they added.
The Leona M. and Harry B. Helmsley Charitable Trust funded the study. Dr. Ananthakrishnan reported advisory board payments from Cubist Pharmaceuticals and AbbVe. One coauthor reported financial conflicts of interest with numerous pharmaceutical companies. The other authors reported no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: High-volume referral centers varied significantly in use of immunomodulators and other therapies for inflammatory bowel disease, especially Crohn’s disease.
Major finding: Centers varied as much as threefold in use of immunomodulators for CD (OR, 3.34; 95% CI, 2.09-4.32).
Data source: Prospective cohort study of 1,659 patients with Crohn’s disease and 946 patients with ulcerative colitis.
Disclosures: The Leona M. and Harry B. Helmsley Charitable Trust funded the study. Dr. Ananthakrishnan reported advisory board payments from Cubist Pharmaceuticals and AbbVie. One coauthor reported financial conflicts of interest with numerous pharmaceutical companies. The other authors reported no conflicts of interest.
Experts advocate ‘treat-to-target’ approach for Crohn’s disease
Patients with Crohn’s disease could benefit from a “treat-to-target” approach based on intervening early to reverse inflammation and gathering objective data to guide clinical decisions, according to a review article published in the June issue of Clinical Gastroenterology and Hepatology (2015 [doi:10.1016/j.cgh.2013.09.006]).
“In spite of available effective treatments, the development of complications such as stricture, fistula, and abscess that result in surgery and lead to a disabling course of Crohn’s disease remain common,” said Dr. Guillame Bouguen at the University of California, San Diego, and his associates. “This ‘natural history’ is not likely to improve unless the overall symptom-based therapeutic strategy for Crohn’s disease is changed,” they wrote.
Clinicians have historically managed Crohn’s disease (CD) by gradually intensifying treatments based on patients’ symptoms, but this approach has failed to achieve good long-term outcomes and puts patients at risk of bowel damage, the reviewers said. The advent of better drugs for other chronic inflammatory diseases, such as rheumatoid arthritis, “reinvigorated” treatment strategies to focus on intervening earlier and controlling inflammation as much as possible, including by augmenting the novel biologics with methotrexate or other older disease-modifying antirheumatic drugs, they said.A similar “treat-to-target” approach to CD would mean responding to objective evidence of inflammation before patients developed irreversible bowel damage, Dr. Bouguen and his associates said. The main treatment goal would be mucosal healing, but the target level would reflect individual comorbidities, demographic and behavioral factors, and risks of side effects. After refining the mucosal healing target, gastroenterologists would stick to it throughout treatment, and would adjust treatment based on imaging and other objective measures of bowel inflammation. Colonoscopies and related procedures would be performed every 6 months until ulcerations resolved, and every 1-2 years after that. To improve trust and adherence to treatment, gastroenterologists also would need to educate patients about the mucosal healing target and the plan for achieving that goal, the reviewers said.
Based on preliminary data, patients on azathioprine and tumor necrosis factor antagonists might be able to taper them after achieving sustained mucosal healing, although larger studies on the topic are lacking, said the reviewers. A treat-to-target approach also might help symptomatic CD patients who already have permanent bowel damage enhance their long-term quality of life and prevent worsening disability, the investigators said.The International Organization on Inflammatory Bowel Disease is leading a consensus effort to define the therapeutic target in the treatment of inflammatory bowel disease. “However, the principles of the treat-to-target strategy that uses both systematic follow-up of patients and therapy optimization focusing on inflammation and damage may persist,” they added. To better clarify whether a treat-to-target approach is useful in CD, researchers are enrolling patients in the REACT II trial, which will compare treatments that target mucosal healing with the conventional symptoms-based paradigm, they noted.The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial relationships with numerous pharmaceutical companies.
Patients with Crohn’s disease could benefit from a “treat-to-target” approach based on intervening early to reverse inflammation and gathering objective data to guide clinical decisions, according to a review article published in the June issue of Clinical Gastroenterology and Hepatology (2015 [doi:10.1016/j.cgh.2013.09.006]).
“In spite of available effective treatments, the development of complications such as stricture, fistula, and abscess that result in surgery and lead to a disabling course of Crohn’s disease remain common,” said Dr. Guillame Bouguen at the University of California, San Diego, and his associates. “This ‘natural history’ is not likely to improve unless the overall symptom-based therapeutic strategy for Crohn’s disease is changed,” they wrote.
Clinicians have historically managed Crohn’s disease (CD) by gradually intensifying treatments based on patients’ symptoms, but this approach has failed to achieve good long-term outcomes and puts patients at risk of bowel damage, the reviewers said. The advent of better drugs for other chronic inflammatory diseases, such as rheumatoid arthritis, “reinvigorated” treatment strategies to focus on intervening earlier and controlling inflammation as much as possible, including by augmenting the novel biologics with methotrexate or other older disease-modifying antirheumatic drugs, they said.A similar “treat-to-target” approach to CD would mean responding to objective evidence of inflammation before patients developed irreversible bowel damage, Dr. Bouguen and his associates said. The main treatment goal would be mucosal healing, but the target level would reflect individual comorbidities, demographic and behavioral factors, and risks of side effects. After refining the mucosal healing target, gastroenterologists would stick to it throughout treatment, and would adjust treatment based on imaging and other objective measures of bowel inflammation. Colonoscopies and related procedures would be performed every 6 months until ulcerations resolved, and every 1-2 years after that. To improve trust and adherence to treatment, gastroenterologists also would need to educate patients about the mucosal healing target and the plan for achieving that goal, the reviewers said.
Based on preliminary data, patients on azathioprine and tumor necrosis factor antagonists might be able to taper them after achieving sustained mucosal healing, although larger studies on the topic are lacking, said the reviewers. A treat-to-target approach also might help symptomatic CD patients who already have permanent bowel damage enhance their long-term quality of life and prevent worsening disability, the investigators said.The International Organization on Inflammatory Bowel Disease is leading a consensus effort to define the therapeutic target in the treatment of inflammatory bowel disease. “However, the principles of the treat-to-target strategy that uses both systematic follow-up of patients and therapy optimization focusing on inflammation and damage may persist,” they added. To better clarify whether a treat-to-target approach is useful in CD, researchers are enrolling patients in the REACT II trial, which will compare treatments that target mucosal healing with the conventional symptoms-based paradigm, they noted.The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial relationships with numerous pharmaceutical companies.
Patients with Crohn’s disease could benefit from a “treat-to-target” approach based on intervening early to reverse inflammation and gathering objective data to guide clinical decisions, according to a review article published in the June issue of Clinical Gastroenterology and Hepatology (2015 [doi:10.1016/j.cgh.2013.09.006]).
“In spite of available effective treatments, the development of complications such as stricture, fistula, and abscess that result in surgery and lead to a disabling course of Crohn’s disease remain common,” said Dr. Guillame Bouguen at the University of California, San Diego, and his associates. “This ‘natural history’ is not likely to improve unless the overall symptom-based therapeutic strategy for Crohn’s disease is changed,” they wrote.
Clinicians have historically managed Crohn’s disease (CD) by gradually intensifying treatments based on patients’ symptoms, but this approach has failed to achieve good long-term outcomes and puts patients at risk of bowel damage, the reviewers said. The advent of better drugs for other chronic inflammatory diseases, such as rheumatoid arthritis, “reinvigorated” treatment strategies to focus on intervening earlier and controlling inflammation as much as possible, including by augmenting the novel biologics with methotrexate or other older disease-modifying antirheumatic drugs, they said.A similar “treat-to-target” approach to CD would mean responding to objective evidence of inflammation before patients developed irreversible bowel damage, Dr. Bouguen and his associates said. The main treatment goal would be mucosal healing, but the target level would reflect individual comorbidities, demographic and behavioral factors, and risks of side effects. After refining the mucosal healing target, gastroenterologists would stick to it throughout treatment, and would adjust treatment based on imaging and other objective measures of bowel inflammation. Colonoscopies and related procedures would be performed every 6 months until ulcerations resolved, and every 1-2 years after that. To improve trust and adherence to treatment, gastroenterologists also would need to educate patients about the mucosal healing target and the plan for achieving that goal, the reviewers said.
Based on preliminary data, patients on azathioprine and tumor necrosis factor antagonists might be able to taper them after achieving sustained mucosal healing, although larger studies on the topic are lacking, said the reviewers. A treat-to-target approach also might help symptomatic CD patients who already have permanent bowel damage enhance their long-term quality of life and prevent worsening disability, the investigators said.The International Organization on Inflammatory Bowel Disease is leading a consensus effort to define the therapeutic target in the treatment of inflammatory bowel disease. “However, the principles of the treat-to-target strategy that uses both systematic follow-up of patients and therapy optimization focusing on inflammation and damage may persist,” they added. To better clarify whether a treat-to-target approach is useful in CD, researchers are enrolling patients in the REACT II trial, which will compare treatments that target mucosal healing with the conventional symptoms-based paradigm, they noted.The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial relationships with numerous pharmaceutical companies.
Key clinical point: A treat-to-target approach based on early control of inflammation and objective clinical data might benefit patients with Crohn’s disease.
Major finding: Using only symptoms to guide treatment decisions in Crohn’s disease has failed to achieve good long-term outcomes.
Data source: A review of 15 primary research and review articles.
Disclosures: The authors reported no funding sources. Dr. Bouguen reported receiving lecture fees from Abbott Laboratories, Ferring, and MSD Pharma. The other authors reported financial disclosures from numerous pharmaceutical companies.
DDW: Anti-MAdCAM antibody hits endpoints in treatment-refractory UC
WASHINGTON – The anti-MAdCAM candidate, PF-00547659, induced responses in up to 54% of patients with moderately to severely active ulcerative colitis failing at least one prior therapy.
At the optimal dose of 22.5 mg, 16.7% of all patients and 25.8% of patients naive to anti–tumor necrosis factor (TNF) therapy achieved remission with the anti-mucosal addressin cell adhesion molecule 1 (MAdCAM-1) monoclonal antibody in the phase II TURANDOT trial, Dr. Walter Reinisch reported in a late-breaking abstract session at the annual Digestive Disease Week.
Selective blockade of adhesion molecules is an attractive treatment strategy for inflammatory bowel disease, with one approach shown to improve clinical outcomes by blocking alpha4beta7 integrin. Drugs that bind to alpha4beta7 include the ulcerative colitis (UC) drug vedolizumab (Entyvio), the experimental UC drug etrolizumab, and the Crohn’s disease and multiple sclerosis drug natalizumab (Tysabri).
Natalizumab, which also binds to alpha4beta1 integrin on endothelial cells expressing VCAM-1, however, has raised concerns because it increases the risk of progressive multifocal leukoencephalopathy (PML), a rare and fatal viral infection of the brain.
PF-00547659 has no cross-reactivity with vascular cell adhesion proten-1 (VCAM-1) and has no effect on central nervous system immune surveillance, said Dr. Reinisch of McMaster University, Hamilton, Ont.
The phase II double-blind TURANDOT trial randomly assigned 357 patients with moderate to severe UC who had failed or were intolerant to at least one conventional therapy to one of four doses of PF-00547659 (7.5 mg, 22.5 mg, 75 mg, or 225 mg) or placebo delivered by subcutaneous injection in three doses separated by 4 weeks. The primary endpoint was clinical remission, defined by a total Mayo Score at week 12 of ≤ 2 points with no individual subscore > 1. More than half of patients had received prior anti-TNF therapy, the average baseline total Mayo Score was 8.4, and average age was 40 years.
Clinical remission rates followed a bell-shaped curve, occurring in 2.7% of patients on placebo, 11.3% on PF-00547659 at the 7.5-mg dose, 16.7% at 22.5 mg, 15.5% at 75 mg, and 5.7% at 225 mg. The difference between placebo and active treatment was statistically significant at a P value of less than .05 for all but the 225-mg dose, Dr. Reinisch reported.
Clinical responses were seen in 28.8%, 38%, 54.2%, 45%, and 50% of patients, respectively, with the three highest PF-00547659 doses achieving significance (P values < .05).
Compared with placebo, mucosal healing was significantly more common at the 22.5-mgdose (8.2% vs. 27.8%; P < .05) and 75-mg dose (8.2% vs. 25.4%; P < .05) and trended higher for the 7.5-mg dose (15.5%) and 225-mg dose (14.3%).
Mucosal healing may be driving the bell-shaped dose-response curve, but additional analyses are ongoing to determine whether the curve is a robust finding, he said.
Fetal calprotectin declined in all treatment groups versus placebo, with the nadir reached at week 8 and maintained.
No major differences in safety signals between placebo and active treatment were seen, including infections (18% vs. 21%), GI infections (1% vs. 4%), and infections in ex-GI MAdCAM bearing tissues (7% vs. 6%), Dr. Reinisch said.
During a discussion of the findings, concerns were raised about a theoretical risk for PML akin to natalizumab because MAdCAM is not that specific. Dr. Reinisch repeated that there’s no evidence to suggest this, and cited a vedolizumab trial showing no PML in patients with Crohn’s disease (N. Engl. J. Med. 2013;369:711-21).
Dr. Reinisch disclosed ties with several drug companies, including Pfizer, which sponsored the study.
On Twitter @pwendl
WASHINGTON – The anti-MAdCAM candidate, PF-00547659, induced responses in up to 54% of patients with moderately to severely active ulcerative colitis failing at least one prior therapy.
At the optimal dose of 22.5 mg, 16.7% of all patients and 25.8% of patients naive to anti–tumor necrosis factor (TNF) therapy achieved remission with the anti-mucosal addressin cell adhesion molecule 1 (MAdCAM-1) monoclonal antibody in the phase II TURANDOT trial, Dr. Walter Reinisch reported in a late-breaking abstract session at the annual Digestive Disease Week.
Selective blockade of adhesion molecules is an attractive treatment strategy for inflammatory bowel disease, with one approach shown to improve clinical outcomes by blocking alpha4beta7 integrin. Drugs that bind to alpha4beta7 include the ulcerative colitis (UC) drug vedolizumab (Entyvio), the experimental UC drug etrolizumab, and the Crohn’s disease and multiple sclerosis drug natalizumab (Tysabri).
Natalizumab, which also binds to alpha4beta1 integrin on endothelial cells expressing VCAM-1, however, has raised concerns because it increases the risk of progressive multifocal leukoencephalopathy (PML), a rare and fatal viral infection of the brain.
PF-00547659 has no cross-reactivity with vascular cell adhesion proten-1 (VCAM-1) and has no effect on central nervous system immune surveillance, said Dr. Reinisch of McMaster University, Hamilton, Ont.
The phase II double-blind TURANDOT trial randomly assigned 357 patients with moderate to severe UC who had failed or were intolerant to at least one conventional therapy to one of four doses of PF-00547659 (7.5 mg, 22.5 mg, 75 mg, or 225 mg) or placebo delivered by subcutaneous injection in three doses separated by 4 weeks. The primary endpoint was clinical remission, defined by a total Mayo Score at week 12 of ≤ 2 points with no individual subscore > 1. More than half of patients had received prior anti-TNF therapy, the average baseline total Mayo Score was 8.4, and average age was 40 years.
Clinical remission rates followed a bell-shaped curve, occurring in 2.7% of patients on placebo, 11.3% on PF-00547659 at the 7.5-mg dose, 16.7% at 22.5 mg, 15.5% at 75 mg, and 5.7% at 225 mg. The difference between placebo and active treatment was statistically significant at a P value of less than .05 for all but the 225-mg dose, Dr. Reinisch reported.
Clinical responses were seen in 28.8%, 38%, 54.2%, 45%, and 50% of patients, respectively, with the three highest PF-00547659 doses achieving significance (P values < .05).
Compared with placebo, mucosal healing was significantly more common at the 22.5-mgdose (8.2% vs. 27.8%; P < .05) and 75-mg dose (8.2% vs. 25.4%; P < .05) and trended higher for the 7.5-mg dose (15.5%) and 225-mg dose (14.3%).
Mucosal healing may be driving the bell-shaped dose-response curve, but additional analyses are ongoing to determine whether the curve is a robust finding, he said.
Fetal calprotectin declined in all treatment groups versus placebo, with the nadir reached at week 8 and maintained.
No major differences in safety signals between placebo and active treatment were seen, including infections (18% vs. 21%), GI infections (1% vs. 4%), and infections in ex-GI MAdCAM bearing tissues (7% vs. 6%), Dr. Reinisch said.
During a discussion of the findings, concerns were raised about a theoretical risk for PML akin to natalizumab because MAdCAM is not that specific. Dr. Reinisch repeated that there’s no evidence to suggest this, and cited a vedolizumab trial showing no PML in patients with Crohn’s disease (N. Engl. J. Med. 2013;369:711-21).
Dr. Reinisch disclosed ties with several drug companies, including Pfizer, which sponsored the study.
On Twitter @pwendl
WASHINGTON – The anti-MAdCAM candidate, PF-00547659, induced responses in up to 54% of patients with moderately to severely active ulcerative colitis failing at least one prior therapy.
At the optimal dose of 22.5 mg, 16.7% of all patients and 25.8% of patients naive to anti–tumor necrosis factor (TNF) therapy achieved remission with the anti-mucosal addressin cell adhesion molecule 1 (MAdCAM-1) monoclonal antibody in the phase II TURANDOT trial, Dr. Walter Reinisch reported in a late-breaking abstract session at the annual Digestive Disease Week.
Selective blockade of adhesion molecules is an attractive treatment strategy for inflammatory bowel disease, with one approach shown to improve clinical outcomes by blocking alpha4beta7 integrin. Drugs that bind to alpha4beta7 include the ulcerative colitis (UC) drug vedolizumab (Entyvio), the experimental UC drug etrolizumab, and the Crohn’s disease and multiple sclerosis drug natalizumab (Tysabri).
Natalizumab, which also binds to alpha4beta1 integrin on endothelial cells expressing VCAM-1, however, has raised concerns because it increases the risk of progressive multifocal leukoencephalopathy (PML), a rare and fatal viral infection of the brain.
PF-00547659 has no cross-reactivity with vascular cell adhesion proten-1 (VCAM-1) and has no effect on central nervous system immune surveillance, said Dr. Reinisch of McMaster University, Hamilton, Ont.
The phase II double-blind TURANDOT trial randomly assigned 357 patients with moderate to severe UC who had failed or were intolerant to at least one conventional therapy to one of four doses of PF-00547659 (7.5 mg, 22.5 mg, 75 mg, or 225 mg) or placebo delivered by subcutaneous injection in three doses separated by 4 weeks. The primary endpoint was clinical remission, defined by a total Mayo Score at week 12 of ≤ 2 points with no individual subscore > 1. More than half of patients had received prior anti-TNF therapy, the average baseline total Mayo Score was 8.4, and average age was 40 years.
Clinical remission rates followed a bell-shaped curve, occurring in 2.7% of patients on placebo, 11.3% on PF-00547659 at the 7.5-mg dose, 16.7% at 22.5 mg, 15.5% at 75 mg, and 5.7% at 225 mg. The difference between placebo and active treatment was statistically significant at a P value of less than .05 for all but the 225-mg dose, Dr. Reinisch reported.
Clinical responses were seen in 28.8%, 38%, 54.2%, 45%, and 50% of patients, respectively, with the three highest PF-00547659 doses achieving significance (P values < .05).
Compared with placebo, mucosal healing was significantly more common at the 22.5-mgdose (8.2% vs. 27.8%; P < .05) and 75-mg dose (8.2% vs. 25.4%; P < .05) and trended higher for the 7.5-mg dose (15.5%) and 225-mg dose (14.3%).
Mucosal healing may be driving the bell-shaped dose-response curve, but additional analyses are ongoing to determine whether the curve is a robust finding, he said.
Fetal calprotectin declined in all treatment groups versus placebo, with the nadir reached at week 8 and maintained.
No major differences in safety signals between placebo and active treatment were seen, including infections (18% vs. 21%), GI infections (1% vs. 4%), and infections in ex-GI MAdCAM bearing tissues (7% vs. 6%), Dr. Reinisch said.
During a discussion of the findings, concerns were raised about a theoretical risk for PML akin to natalizumab because MAdCAM is not that specific. Dr. Reinisch repeated that there’s no evidence to suggest this, and cited a vedolizumab trial showing no PML in patients with Crohn’s disease (N. Engl. J. Med. 2013;369:711-21).
Dr. Reinisch disclosed ties with several drug companies, including Pfizer, which sponsored the study.
On Twitter @pwendl
AT DDW 2015
Key clinical point: PF-00547659 is clinically active in treatment-refractory ulcerative colitis and appears to skirt the PML safety concern seen with natalizumab.
Major finding: Up to 54% of patients had a clinical response and up to 25.8% achieved complete remission with PF-00547659.
Data source: Double-blind, placebo-controlled phase II trial of 357 patients with moderate to severe ulcerative colitis.
Disclosures: Dr. Reinisch disclosed ties with several drug companies, including Pfizer, which sponsored the study.
FDA approves Viberzi and Xifaxan for IBS
The Food and Drug Administration has approved Viberzi (eluxadoline) and Xifaxan (rifaximin) to treat irritable bowel syndrome with diarrhea (IBS-D) in adults, the agency announced May 27.
Viberzi is a locally active mixed mu-opioid–receptor agonist and delta-opioid–receptor antagonist that targets nervous system receptors to lessen bowel contractions. The medication is taken twice daily with food, the FDA said in a statement.
Phase III clinical trial results presented at the 2014 Digestive Disease Week showed that 31% of IBS-D patients who took Viberzi had improved abdominal pain and stool consistency at 26 weeks, compared with 19.5% of placebo patients. Xifaxan is an antibiotic originally approved as a therapy for travelers’ diarrhea caused by Escherichia coli, and for recurring overt hepatic encephalopathy. It is taken orally three times per day for 14 days, and can be re-administered up to two times in patients who experience symptom recurrence. Its efficacy was established in three clinical trials, including a phase III trial of 636 patients with recurrence which showed greater improvement of symptoms in patients taking Xifaxan than in those who received placebo, the FDA statement said.
Viberzi should not be taken by patients with a history of bile duct obstruction, pancreatitis, severe liver impairment, or severe constipation, or patients who drink more than three alcoholic beverages per day. Common side effects in patients treated with Viberzi were constipation, nausea, and abdominal pain.
In patients treated with Xifaxan for IBS-D, common side effects included nausea and an increase in the liver enzyme alanine aminotransferase (ALT).
Viberzi is manufactured by Patheon Pharmaceuticals. Xifaxan is marketed by Salix Pharmaceuticals, based in Raleigh, N.C.
For more safety information, please visit the FDA website.
The Food and Drug Administration has approved Viberzi (eluxadoline) and Xifaxan (rifaximin) to treat irritable bowel syndrome with diarrhea (IBS-D) in adults, the agency announced May 27.
Viberzi is a locally active mixed mu-opioid–receptor agonist and delta-opioid–receptor antagonist that targets nervous system receptors to lessen bowel contractions. The medication is taken twice daily with food, the FDA said in a statement.
Phase III clinical trial results presented at the 2014 Digestive Disease Week showed that 31% of IBS-D patients who took Viberzi had improved abdominal pain and stool consistency at 26 weeks, compared with 19.5% of placebo patients. Xifaxan is an antibiotic originally approved as a therapy for travelers’ diarrhea caused by Escherichia coli, and for recurring overt hepatic encephalopathy. It is taken orally three times per day for 14 days, and can be re-administered up to two times in patients who experience symptom recurrence. Its efficacy was established in three clinical trials, including a phase III trial of 636 patients with recurrence which showed greater improvement of symptoms in patients taking Xifaxan than in those who received placebo, the FDA statement said.
Viberzi should not be taken by patients with a history of bile duct obstruction, pancreatitis, severe liver impairment, or severe constipation, or patients who drink more than three alcoholic beverages per day. Common side effects in patients treated with Viberzi were constipation, nausea, and abdominal pain.
In patients treated with Xifaxan for IBS-D, common side effects included nausea and an increase in the liver enzyme alanine aminotransferase (ALT).
Viberzi is manufactured by Patheon Pharmaceuticals. Xifaxan is marketed by Salix Pharmaceuticals, based in Raleigh, N.C.
For more safety information, please visit the FDA website.
The Food and Drug Administration has approved Viberzi (eluxadoline) and Xifaxan (rifaximin) to treat irritable bowel syndrome with diarrhea (IBS-D) in adults, the agency announced May 27.
Viberzi is a locally active mixed mu-opioid–receptor agonist and delta-opioid–receptor antagonist that targets nervous system receptors to lessen bowel contractions. The medication is taken twice daily with food, the FDA said in a statement.
Phase III clinical trial results presented at the 2014 Digestive Disease Week showed that 31% of IBS-D patients who took Viberzi had improved abdominal pain and stool consistency at 26 weeks, compared with 19.5% of placebo patients. Xifaxan is an antibiotic originally approved as a therapy for travelers’ diarrhea caused by Escherichia coli, and for recurring overt hepatic encephalopathy. It is taken orally three times per day for 14 days, and can be re-administered up to two times in patients who experience symptom recurrence. Its efficacy was established in three clinical trials, including a phase III trial of 636 patients with recurrence which showed greater improvement of symptoms in patients taking Xifaxan than in those who received placebo, the FDA statement said.
Viberzi should not be taken by patients with a history of bile duct obstruction, pancreatitis, severe liver impairment, or severe constipation, or patients who drink more than three alcoholic beverages per day. Common side effects in patients treated with Viberzi were constipation, nausea, and abdominal pain.
In patients treated with Xifaxan for IBS-D, common side effects included nausea and an increase in the liver enzyme alanine aminotransferase (ALT).
Viberzi is manufactured by Patheon Pharmaceuticals. Xifaxan is marketed by Salix Pharmaceuticals, based in Raleigh, N.C.
For more safety information, please visit the FDA website.
VIDEO: Is it IBS? Blood test may offer conclusive answer
WASHINGTON – A new blood test could conclusively determine if a patient with chronic diarrhea has diarrhea-predominant irritable bowel syndrome (D-IBS).
The IBSchek blood test detects the presence of antibodies to cytolethal distending toxin B and vinculin. In a study presented at the annual Digestive Disease Week and published in PLoS ONE, the positive predictive value for D-IBS of just one of the antibodies was greater than 98%, explained study lead author Dr. Mark Pimentel of Cedars-Sinai Medical Center, Los Angeles. If the test is positive for both antibodies, “the post-test probability is 95% that you have IBS.”
In a video interview, Dr. Pimentel discussed the study’s findings and the potential impact for physicians and patients. The search for diagnostic answers leads to “a lot of doctor-shopping, certainly a lot of colonoscopies and unnecessary testing that are always negative with these patients,” he noted. “Maybe this will put an end to that.
“People used to think this is all psychological,” Dr. Pimentel added. “Now we can say, No, it’s organic. There’s something real going on; I’ve got a test that proves that.”
Dr. Pimentel has received consulting fees from Commonwealth Laboratories, which makes the IBSchek blood test.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – A new blood test could conclusively determine if a patient with chronic diarrhea has diarrhea-predominant irritable bowel syndrome (D-IBS).
The IBSchek blood test detects the presence of antibodies to cytolethal distending toxin B and vinculin. In a study presented at the annual Digestive Disease Week and published in PLoS ONE, the positive predictive value for D-IBS of just one of the antibodies was greater than 98%, explained study lead author Dr. Mark Pimentel of Cedars-Sinai Medical Center, Los Angeles. If the test is positive for both antibodies, “the post-test probability is 95% that you have IBS.”
In a video interview, Dr. Pimentel discussed the study’s findings and the potential impact for physicians and patients. The search for diagnostic answers leads to “a lot of doctor-shopping, certainly a lot of colonoscopies and unnecessary testing that are always negative with these patients,” he noted. “Maybe this will put an end to that.
“People used to think this is all psychological,” Dr. Pimentel added. “Now we can say, No, it’s organic. There’s something real going on; I’ve got a test that proves that.”
Dr. Pimentel has received consulting fees from Commonwealth Laboratories, which makes the IBSchek blood test.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – A new blood test could conclusively determine if a patient with chronic diarrhea has diarrhea-predominant irritable bowel syndrome (D-IBS).
The IBSchek blood test detects the presence of antibodies to cytolethal distending toxin B and vinculin. In a study presented at the annual Digestive Disease Week and published in PLoS ONE, the positive predictive value for D-IBS of just one of the antibodies was greater than 98%, explained study lead author Dr. Mark Pimentel of Cedars-Sinai Medical Center, Los Angeles. If the test is positive for both antibodies, “the post-test probability is 95% that you have IBS.”
In a video interview, Dr. Pimentel discussed the study’s findings and the potential impact for physicians and patients. The search for diagnostic answers leads to “a lot of doctor-shopping, certainly a lot of colonoscopies and unnecessary testing that are always negative with these patients,” he noted. “Maybe this will put an end to that.
“People used to think this is all psychological,” Dr. Pimentel added. “Now we can say, No, it’s organic. There’s something real going on; I’ve got a test that proves that.”
Dr. Pimentel has received consulting fees from Commonwealth Laboratories, which makes the IBSchek blood test.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT DDW 2015
DDW: Ozanimod active in moderate-severe UC, without cardiac signal in TOUCHSTONE trial
WASHINGTON– The oral S1P receptor modulator ozanimod is clinically active and well tolerated in patients with moderate to severe ulcerative colitis (UC), phase II study results show.
Importantly, no notable cardiac, opthalmologic, or infectious treatment-related adverse events were observed, Dr. William Sandborn said at the annual Digestive Disease Week.
The first sphingosine-1-phosphate (S1P) receptor modulator, Fingolimod (Gilenya), carries a warning for first-dose cardiac effects, liver function test elevations, and macular edema and targets S1P receptors 1, 3, 4, and 5. Ozanimod is a next-generation S1P receptor modulator that has increased selectivity for the S1P receptors 1 and 5, compared with receptor 3, which may be related to safety concerns with fingolimod, said Dr. Sandborn, chief of gastroenterology at the University of California-San Diego.
He reported on the double-blind, phase II TOUCHSTONE trial involving 197 adults with moderate to severe UC who were receiving oral aminosalicylates and/or prednisone, and were randomly assigned to receive ozanimod 0.5 mg (n = 65) or 1 mg (n = 67) or placebo (n = 65). Doses were titrated through week 1, followed by 8 weeks of full-dose therapy.
The study’s primary efficacy endpoint was the proportion of patients in clinical remission at week 8, defined as a Mayo score of 2 or less, with no subscore of more than 1.
At week 8, 16.4% of patients on ozanimod 1 mg were in remission vs. 6.2% on placebo (P = .0482) and 13.8% on ozanimod 0.5 mg (P = .1422), Dr. Sandborn reported.
Rates of clinical response at 8 weeks were 56.7% with the high-dose ozanimod, 53.8% with the low dose, and 37% with placebo. Once again, the between-group difference was significant only for high-dose ozanimod (P = .0207).
Mucosal improvement was significantly more common with either high-dose ozanimod (34.3% vs. 12.3% placebo; P = .0023) or low-dose ozanimod (27.7% vs. 12.3% placebo; P = .0348), he said.
The most common adverse events were anemia/decreased hemoglobin, occurring in four patients in the placebo and low-dose ozanimod groups, and worsening of UC, occurring in three patients on placebo, two on low-dose ozanimod, and one on high-dose ozanimod.
Serious treatment-related adverse events were reported in four patients on placebo, one on ozanimod 0.5 mg (hyperpyrexia), and one on ozanimod 1 mg (UC).
The overall incidence of cardiac events was low, with two palpitations reported in the placebo group, one sinus bradycardia and one first-degree AV block in the ozanimod 0.5-mg group, and none in the 1-mg group.
“Ozanimod was well tolerated with a favorable benefit-risk profile supporting the planned phase III trial in ulcerative colitis and the phase II study in Crohn’s disease,” said Dr. Sandborn, who also reported the results earlier this year in Europe.
On Twitter@pwendl
WASHINGTON– The oral S1P receptor modulator ozanimod is clinically active and well tolerated in patients with moderate to severe ulcerative colitis (UC), phase II study results show.
Importantly, no notable cardiac, opthalmologic, or infectious treatment-related adverse events were observed, Dr. William Sandborn said at the annual Digestive Disease Week.
The first sphingosine-1-phosphate (S1P) receptor modulator, Fingolimod (Gilenya), carries a warning for first-dose cardiac effects, liver function test elevations, and macular edema and targets S1P receptors 1, 3, 4, and 5. Ozanimod is a next-generation S1P receptor modulator that has increased selectivity for the S1P receptors 1 and 5, compared with receptor 3, which may be related to safety concerns with fingolimod, said Dr. Sandborn, chief of gastroenterology at the University of California-San Diego.
He reported on the double-blind, phase II TOUCHSTONE trial involving 197 adults with moderate to severe UC who were receiving oral aminosalicylates and/or prednisone, and were randomly assigned to receive ozanimod 0.5 mg (n = 65) or 1 mg (n = 67) or placebo (n = 65). Doses were titrated through week 1, followed by 8 weeks of full-dose therapy.
The study’s primary efficacy endpoint was the proportion of patients in clinical remission at week 8, defined as a Mayo score of 2 or less, with no subscore of more than 1.
At week 8, 16.4% of patients on ozanimod 1 mg were in remission vs. 6.2% on placebo (P = .0482) and 13.8% on ozanimod 0.5 mg (P = .1422), Dr. Sandborn reported.
Rates of clinical response at 8 weeks were 56.7% with the high-dose ozanimod, 53.8% with the low dose, and 37% with placebo. Once again, the between-group difference was significant only for high-dose ozanimod (P = .0207).
Mucosal improvement was significantly more common with either high-dose ozanimod (34.3% vs. 12.3% placebo; P = .0023) or low-dose ozanimod (27.7% vs. 12.3% placebo; P = .0348), he said.
The most common adverse events were anemia/decreased hemoglobin, occurring in four patients in the placebo and low-dose ozanimod groups, and worsening of UC, occurring in three patients on placebo, two on low-dose ozanimod, and one on high-dose ozanimod.
Serious treatment-related adverse events were reported in four patients on placebo, one on ozanimod 0.5 mg (hyperpyrexia), and one on ozanimod 1 mg (UC).
The overall incidence of cardiac events was low, with two palpitations reported in the placebo group, one sinus bradycardia and one first-degree AV block in the ozanimod 0.5-mg group, and none in the 1-mg group.
“Ozanimod was well tolerated with a favorable benefit-risk profile supporting the planned phase III trial in ulcerative colitis and the phase II study in Crohn’s disease,” said Dr. Sandborn, who also reported the results earlier this year in Europe.
On Twitter@pwendl
WASHINGTON– The oral S1P receptor modulator ozanimod is clinically active and well tolerated in patients with moderate to severe ulcerative colitis (UC), phase II study results show.
Importantly, no notable cardiac, opthalmologic, or infectious treatment-related adverse events were observed, Dr. William Sandborn said at the annual Digestive Disease Week.
The first sphingosine-1-phosphate (S1P) receptor modulator, Fingolimod (Gilenya), carries a warning for first-dose cardiac effects, liver function test elevations, and macular edema and targets S1P receptors 1, 3, 4, and 5. Ozanimod is a next-generation S1P receptor modulator that has increased selectivity for the S1P receptors 1 and 5, compared with receptor 3, which may be related to safety concerns with fingolimod, said Dr. Sandborn, chief of gastroenterology at the University of California-San Diego.
He reported on the double-blind, phase II TOUCHSTONE trial involving 197 adults with moderate to severe UC who were receiving oral aminosalicylates and/or prednisone, and were randomly assigned to receive ozanimod 0.5 mg (n = 65) or 1 mg (n = 67) or placebo (n = 65). Doses were titrated through week 1, followed by 8 weeks of full-dose therapy.
The study’s primary efficacy endpoint was the proportion of patients in clinical remission at week 8, defined as a Mayo score of 2 or less, with no subscore of more than 1.
At week 8, 16.4% of patients on ozanimod 1 mg were in remission vs. 6.2% on placebo (P = .0482) and 13.8% on ozanimod 0.5 mg (P = .1422), Dr. Sandborn reported.
Rates of clinical response at 8 weeks were 56.7% with the high-dose ozanimod, 53.8% with the low dose, and 37% with placebo. Once again, the between-group difference was significant only for high-dose ozanimod (P = .0207).
Mucosal improvement was significantly more common with either high-dose ozanimod (34.3% vs. 12.3% placebo; P = .0023) or low-dose ozanimod (27.7% vs. 12.3% placebo; P = .0348), he said.
The most common adverse events were anemia/decreased hemoglobin, occurring in four patients in the placebo and low-dose ozanimod groups, and worsening of UC, occurring in three patients on placebo, two on low-dose ozanimod, and one on high-dose ozanimod.
Serious treatment-related adverse events were reported in four patients on placebo, one on ozanimod 0.5 mg (hyperpyrexia), and one on ozanimod 1 mg (UC).
The overall incidence of cardiac events was low, with two palpitations reported in the placebo group, one sinus bradycardia and one first-degree AV block in the ozanimod 0.5-mg group, and none in the 1-mg group.
“Ozanimod was well tolerated with a favorable benefit-risk profile supporting the planned phase III trial in ulcerative colitis and the phase II study in Crohn’s disease,” said Dr. Sandborn, who also reported the results earlier this year in Europe.
On Twitter@pwendl
AT DDW 2015
Key clinical point: Ozanimod 1 mg induced clinical remission at week 8 in patients with moderate to severe ulcerative colitis.
Major finding: At week 8, 16.4% of patients on ozanimod 1 mg were in remission vs. 6.2% on placebo (P = .0482) and 13.8% on ozanimod 0.5 mg (P = .1422).
Data source: Randomized, double-blind trial of 197 patients with moderate to severe ulcerative colitis.
Disclosures: Dr. Sandborn reported financial relationships with numerous firms including Receptos, which funded the study.
DDW: Recurrent C. difficile infections take heavy toll on IBD patients
WASHINGTON – Patients with inflammatory bowel disease had a one-third higher risk for having a recurrent Clostridium difficile infection than did the general population, and a 20-fold higher risk for needing a total colectomy because of the infection, a study showed.
Risk factors for recurrent C. difficile infection (rCDI) in patients with inflammatory bowel disease (IBD) include a recent hospitalization, immunosuppressive drugs, and antibiotics, but which drugs are most culpable is unclear, according to Dr. Roshan Razik of Mount Sinai Hospital, Toronto, and the University of Toronto.
“The drugs that we’re using do place patients at higher risk for recurrent C. difficile, but it’s yet to come out which drugs within drug categories – immunomodulators, antibiotics, biologics – pose a higher risk, although we are beginning to see evidence, for example, that azathioprine is higher risk than methotrexate, infliximab might be higher risk than adalimumab, so we have to continue to parse through the data,” he said in an interview.
He and his colleagues conducted two retrospective studies to assess the effects of rCDI on patients with IBD.
The first study used a case-control design, including patients with IBD who had two or more documented instances of rCDI from 2010 through 2013 as cases, and IBD patients with only one infection as controls.
The second study used a retrospective cohort to calculate the incidence of rCDI in patients with IBD, compared with patients without IBD, Dr. Razik reported at the annual Digestive Disease Week.
There were a total of 503 patients who tested positive for CDI included in the studies: 110 patients with IBD (49% with Crohn’s disease and 51% with ulcerative colitis) and 393 without. The mean age was 58.8 years, and 61.4% were female.
Compared with patients without IBD, patients with Crohn’s disease or ulcerative colitis developed CDI at a younger age (39 years vs. 64 years, P < .001), used more steroids (39.1% vs. 12%, P < .001), used more immunosuppressive agents (42.7% vs. 13.2%, P < .001), and were more likely to have a prior bowel resection (28.2% vs. 11.5%, P < .001).
In all, 32% of patients with IBD had a recurrent CDI, compared with 24% of non-IBD patients (P < .01). There were no significant differences between the groups in the number of hospitalizations due to CDI, but patients with IBD were significantly more likely to require colectomy because of the infections (6.4% vs. 0.3%, P < .001).
In a multivariate analysis, risk factors for rCDI in patients with IBD included nonileal Crohn’s disease (odds ratio, 2.59; P < .001), recent antibiotic therapy (OR, 2.60; P < .001), use of a 5-aminosalicylic acid drug (OR, 3.06; P < .001), steroid use (OR, 2.94; P < .001), biologic therapy (OR, 2.50; P = .001), a recent hospitalization (OR, 2.62; P < .001), and no previous bowel resections (OR, 1.72; P = .020).
Clinicians need to look beyond the usual suspects, antibiotics, as causative agents for rCDI. Immunomodulators and biologic agents also were strongly associated with rCDI in the study, Dr. Razik noted.
The study source was not disclosed. He reported having no relevant financial conflicts of interest.
WASHINGTON – Patients with inflammatory bowel disease had a one-third higher risk for having a recurrent Clostridium difficile infection than did the general population, and a 20-fold higher risk for needing a total colectomy because of the infection, a study showed.
Risk factors for recurrent C. difficile infection (rCDI) in patients with inflammatory bowel disease (IBD) include a recent hospitalization, immunosuppressive drugs, and antibiotics, but which drugs are most culpable is unclear, according to Dr. Roshan Razik of Mount Sinai Hospital, Toronto, and the University of Toronto.
“The drugs that we’re using do place patients at higher risk for recurrent C. difficile, but it’s yet to come out which drugs within drug categories – immunomodulators, antibiotics, biologics – pose a higher risk, although we are beginning to see evidence, for example, that azathioprine is higher risk than methotrexate, infliximab might be higher risk than adalimumab, so we have to continue to parse through the data,” he said in an interview.
He and his colleagues conducted two retrospective studies to assess the effects of rCDI on patients with IBD.
The first study used a case-control design, including patients with IBD who had two or more documented instances of rCDI from 2010 through 2013 as cases, and IBD patients with only one infection as controls.
The second study used a retrospective cohort to calculate the incidence of rCDI in patients with IBD, compared with patients without IBD, Dr. Razik reported at the annual Digestive Disease Week.
There were a total of 503 patients who tested positive for CDI included in the studies: 110 patients with IBD (49% with Crohn’s disease and 51% with ulcerative colitis) and 393 without. The mean age was 58.8 years, and 61.4% were female.
Compared with patients without IBD, patients with Crohn’s disease or ulcerative colitis developed CDI at a younger age (39 years vs. 64 years, P < .001), used more steroids (39.1% vs. 12%, P < .001), used more immunosuppressive agents (42.7% vs. 13.2%, P < .001), and were more likely to have a prior bowel resection (28.2% vs. 11.5%, P < .001).
In all, 32% of patients with IBD had a recurrent CDI, compared with 24% of non-IBD patients (P < .01). There were no significant differences between the groups in the number of hospitalizations due to CDI, but patients with IBD were significantly more likely to require colectomy because of the infections (6.4% vs. 0.3%, P < .001).
In a multivariate analysis, risk factors for rCDI in patients with IBD included nonileal Crohn’s disease (odds ratio, 2.59; P < .001), recent antibiotic therapy (OR, 2.60; P < .001), use of a 5-aminosalicylic acid drug (OR, 3.06; P < .001), steroid use (OR, 2.94; P < .001), biologic therapy (OR, 2.50; P = .001), a recent hospitalization (OR, 2.62; P < .001), and no previous bowel resections (OR, 1.72; P = .020).
Clinicians need to look beyond the usual suspects, antibiotics, as causative agents for rCDI. Immunomodulators and biologic agents also were strongly associated with rCDI in the study, Dr. Razik noted.
The study source was not disclosed. He reported having no relevant financial conflicts of interest.
WASHINGTON – Patients with inflammatory bowel disease had a one-third higher risk for having a recurrent Clostridium difficile infection than did the general population, and a 20-fold higher risk for needing a total colectomy because of the infection, a study showed.
Risk factors for recurrent C. difficile infection (rCDI) in patients with inflammatory bowel disease (IBD) include a recent hospitalization, immunosuppressive drugs, and antibiotics, but which drugs are most culpable is unclear, according to Dr. Roshan Razik of Mount Sinai Hospital, Toronto, and the University of Toronto.
“The drugs that we’re using do place patients at higher risk for recurrent C. difficile, but it’s yet to come out which drugs within drug categories – immunomodulators, antibiotics, biologics – pose a higher risk, although we are beginning to see evidence, for example, that azathioprine is higher risk than methotrexate, infliximab might be higher risk than adalimumab, so we have to continue to parse through the data,” he said in an interview.
He and his colleagues conducted two retrospective studies to assess the effects of rCDI on patients with IBD.
The first study used a case-control design, including patients with IBD who had two or more documented instances of rCDI from 2010 through 2013 as cases, and IBD patients with only one infection as controls.
The second study used a retrospective cohort to calculate the incidence of rCDI in patients with IBD, compared with patients without IBD, Dr. Razik reported at the annual Digestive Disease Week.
There were a total of 503 patients who tested positive for CDI included in the studies: 110 patients with IBD (49% with Crohn’s disease and 51% with ulcerative colitis) and 393 without. The mean age was 58.8 years, and 61.4% were female.
Compared with patients without IBD, patients with Crohn’s disease or ulcerative colitis developed CDI at a younger age (39 years vs. 64 years, P < .001), used more steroids (39.1% vs. 12%, P < .001), used more immunosuppressive agents (42.7% vs. 13.2%, P < .001), and were more likely to have a prior bowel resection (28.2% vs. 11.5%, P < .001).
In all, 32% of patients with IBD had a recurrent CDI, compared with 24% of non-IBD patients (P < .01). There were no significant differences between the groups in the number of hospitalizations due to CDI, but patients with IBD were significantly more likely to require colectomy because of the infections (6.4% vs. 0.3%, P < .001).
In a multivariate analysis, risk factors for rCDI in patients with IBD included nonileal Crohn’s disease (odds ratio, 2.59; P < .001), recent antibiotic therapy (OR, 2.60; P < .001), use of a 5-aminosalicylic acid drug (OR, 3.06; P < .001), steroid use (OR, 2.94; P < .001), biologic therapy (OR, 2.50; P = .001), a recent hospitalization (OR, 2.62; P < .001), and no previous bowel resections (OR, 1.72; P = .020).
Clinicians need to look beyond the usual suspects, antibiotics, as causative agents for rCDI. Immunomodulators and biologic agents also were strongly associated with rCDI in the study, Dr. Razik noted.
The study source was not disclosed. He reported having no relevant financial conflicts of interest.
AT DDW 2015
Key clinical point: Patients with inflammatory bowel disease are at higher risk for recurrent Clostridium difficile infections.
Major finding: 32% of patients with IBD had a recurrent CDI, compared with 24% of non-IBD patients
Data source: Retrospective case-control studies with 503 patients, comparing patients with IBD with and without recurrent C. difficile infections and comparing patients with IBD with non-IBD patients.
Disclosures: The study source was not disclosed. Dr. Razik reported having no relevant financial conflicts of interest.
DDW: Biologic agents improve Crohn’s disease picture
WASHINGTON – The course of Crohn’s disease has changed for the better since the introduction of biological therapies and other treatments in the late 1990s.
“In an era of novel treatment options and strategies for Crohn’s disease, we are seeing that the hospitalization and surgery rates have declined, but progression to a complicated phenotype is unfortunately still common nowadays,” said Dr. Steven Jeuring from Maastricht (the Netherlands) University Medical Center.
A community-based study comparing outcomes for patients with Crohn’s Disease (CD) before and after the introduction of infliximab (Remicade) in the Netherlands in 1999 showed the risk of hospitalization was 55% lower for patients treated after 1999, and the risk for hospitalization during the course of the disease was 35% lower. Similarly, the risk for requiring surgery was 77% lower for patients treated in the modern era, and the risk for surgery at any time in the disease course was 54% lower, Dr. Jeuring said at the annual Digestive Disease Week.
The prevalence of a complicated CD phenotype, marked by the presence of bowel stricturing and/or penetration, was also 48% lower at the time of diagnosis among patients treated within the last two decades, but the rate of progression from an inflammatory to complicated phenotype remained unchanged from the pre-biologics era, Dr. Jeuring said.
He and his colleagues conducted a retrospective study with a population-based cohort of adults with incident inflammatory bowel disease diagnosed from 1991 through 1998 (342 patients) and from 1999 through 2011 (820 patients). The cohort represented 93% of all patients in the IBD registry of the South Limburg region of the Netherlands.
They found that the distribution of disease phenotypes was significantly different between the two time periods, with 45% of patients having complicated disease in the pre-biologics era, compared with 37% during the biologics era, translating into a 23% reduction over time. However, in both cohorts, a fairly large proportion of patients already had complicated disease at the time of diagnosis, Dr. Jeuring noted.
When the investigators looked at the risk of developing stricturing or penetrating disease during 8 years of follow-up, however, they found that there was no difference between the groups, with 30% of patients in the earlier cohort having disease progression, compared with 28% of patients in the later cohort, translating into a non-significant hazard ratio (HR) of 0.95.
Dr. Jeuring said that this finding was “very, very disappointing.”
More encouraging, however was the finding that hospitalization rates in the modern era were significantly lower than in the pre-biologics period. For example, the likelihood of being hospitalized at any time during 8 years of follow-up was 72% in the earlier cohort, compared with 52% in the later cohort.
The HR for being hospitalized at the time of diagnosis among the later vs. earlier cohorts was 0.45, and was statistically significant. Similarly, the HR for being hospitalized at any time over 8 years was 0.65 for patients in the modern era (also significant, with a 95% confidence interval that did not cross 1).
Even more dramatically, more modern therapies were associated with a significant reduction in the risk of being rehospitalized, with a significant HR of 0.29.
The risk for surgical resection either at diagnosis or during the 8-year follow-up period was 52% among patients diagnosed and started on treatment in the 1990s, compared with 25% for patients treated in the new millennium. For the latter cohort, the HRs for surgery at the time of diagnosis and for surgery during follow-up were 0.23 and 0.46, respectively. Both were statistically significant.
The lower risk for surgery for patients in the modern era is primarily driven by decreased risk for surgery for inflammatory disease, Dr, Jeuring said.
The study was supported by Maastricht University Medical Center. Dr. Jeuring reported having no conflicts of interest.
WASHINGTON – The course of Crohn’s disease has changed for the better since the introduction of biological therapies and other treatments in the late 1990s.
“In an era of novel treatment options and strategies for Crohn’s disease, we are seeing that the hospitalization and surgery rates have declined, but progression to a complicated phenotype is unfortunately still common nowadays,” said Dr. Steven Jeuring from Maastricht (the Netherlands) University Medical Center.
A community-based study comparing outcomes for patients with Crohn’s Disease (CD) before and after the introduction of infliximab (Remicade) in the Netherlands in 1999 showed the risk of hospitalization was 55% lower for patients treated after 1999, and the risk for hospitalization during the course of the disease was 35% lower. Similarly, the risk for requiring surgery was 77% lower for patients treated in the modern era, and the risk for surgery at any time in the disease course was 54% lower, Dr. Jeuring said at the annual Digestive Disease Week.
The prevalence of a complicated CD phenotype, marked by the presence of bowel stricturing and/or penetration, was also 48% lower at the time of diagnosis among patients treated within the last two decades, but the rate of progression from an inflammatory to complicated phenotype remained unchanged from the pre-biologics era, Dr. Jeuring said.
He and his colleagues conducted a retrospective study with a population-based cohort of adults with incident inflammatory bowel disease diagnosed from 1991 through 1998 (342 patients) and from 1999 through 2011 (820 patients). The cohort represented 93% of all patients in the IBD registry of the South Limburg region of the Netherlands.
They found that the distribution of disease phenotypes was significantly different between the two time periods, with 45% of patients having complicated disease in the pre-biologics era, compared with 37% during the biologics era, translating into a 23% reduction over time. However, in both cohorts, a fairly large proportion of patients already had complicated disease at the time of diagnosis, Dr. Jeuring noted.
When the investigators looked at the risk of developing stricturing or penetrating disease during 8 years of follow-up, however, they found that there was no difference between the groups, with 30% of patients in the earlier cohort having disease progression, compared with 28% of patients in the later cohort, translating into a non-significant hazard ratio (HR) of 0.95.
Dr. Jeuring said that this finding was “very, very disappointing.”
More encouraging, however was the finding that hospitalization rates in the modern era were significantly lower than in the pre-biologics period. For example, the likelihood of being hospitalized at any time during 8 years of follow-up was 72% in the earlier cohort, compared with 52% in the later cohort.
The HR for being hospitalized at the time of diagnosis among the later vs. earlier cohorts was 0.45, and was statistically significant. Similarly, the HR for being hospitalized at any time over 8 years was 0.65 for patients in the modern era (also significant, with a 95% confidence interval that did not cross 1).
Even more dramatically, more modern therapies were associated with a significant reduction in the risk of being rehospitalized, with a significant HR of 0.29.
The risk for surgical resection either at diagnosis or during the 8-year follow-up period was 52% among patients diagnosed and started on treatment in the 1990s, compared with 25% for patients treated in the new millennium. For the latter cohort, the HRs for surgery at the time of diagnosis and for surgery during follow-up were 0.23 and 0.46, respectively. Both were statistically significant.
The lower risk for surgery for patients in the modern era is primarily driven by decreased risk for surgery for inflammatory disease, Dr, Jeuring said.
The study was supported by Maastricht University Medical Center. Dr. Jeuring reported having no conflicts of interest.
WASHINGTON – The course of Crohn’s disease has changed for the better since the introduction of biological therapies and other treatments in the late 1990s.
“In an era of novel treatment options and strategies for Crohn’s disease, we are seeing that the hospitalization and surgery rates have declined, but progression to a complicated phenotype is unfortunately still common nowadays,” said Dr. Steven Jeuring from Maastricht (the Netherlands) University Medical Center.
A community-based study comparing outcomes for patients with Crohn’s Disease (CD) before and after the introduction of infliximab (Remicade) in the Netherlands in 1999 showed the risk of hospitalization was 55% lower for patients treated after 1999, and the risk for hospitalization during the course of the disease was 35% lower. Similarly, the risk for requiring surgery was 77% lower for patients treated in the modern era, and the risk for surgery at any time in the disease course was 54% lower, Dr. Jeuring said at the annual Digestive Disease Week.
The prevalence of a complicated CD phenotype, marked by the presence of bowel stricturing and/or penetration, was also 48% lower at the time of diagnosis among patients treated within the last two decades, but the rate of progression from an inflammatory to complicated phenotype remained unchanged from the pre-biologics era, Dr. Jeuring said.
He and his colleagues conducted a retrospective study with a population-based cohort of adults with incident inflammatory bowel disease diagnosed from 1991 through 1998 (342 patients) and from 1999 through 2011 (820 patients). The cohort represented 93% of all patients in the IBD registry of the South Limburg region of the Netherlands.
They found that the distribution of disease phenotypes was significantly different between the two time periods, with 45% of patients having complicated disease in the pre-biologics era, compared with 37% during the biologics era, translating into a 23% reduction over time. However, in both cohorts, a fairly large proportion of patients already had complicated disease at the time of diagnosis, Dr. Jeuring noted.
When the investigators looked at the risk of developing stricturing or penetrating disease during 8 years of follow-up, however, they found that there was no difference between the groups, with 30% of patients in the earlier cohort having disease progression, compared with 28% of patients in the later cohort, translating into a non-significant hazard ratio (HR) of 0.95.
Dr. Jeuring said that this finding was “very, very disappointing.”
More encouraging, however was the finding that hospitalization rates in the modern era were significantly lower than in the pre-biologics period. For example, the likelihood of being hospitalized at any time during 8 years of follow-up was 72% in the earlier cohort, compared with 52% in the later cohort.
The HR for being hospitalized at the time of diagnosis among the later vs. earlier cohorts was 0.45, and was statistically significant. Similarly, the HR for being hospitalized at any time over 8 years was 0.65 for patients in the modern era (also significant, with a 95% confidence interval that did not cross 1).
Even more dramatically, more modern therapies were associated with a significant reduction in the risk of being rehospitalized, with a significant HR of 0.29.
The risk for surgical resection either at diagnosis or during the 8-year follow-up period was 52% among patients diagnosed and started on treatment in the 1990s, compared with 25% for patients treated in the new millennium. For the latter cohort, the HRs for surgery at the time of diagnosis and for surgery during follow-up were 0.23 and 0.46, respectively. Both were statistically significant.
The lower risk for surgery for patients in the modern era is primarily driven by decreased risk for surgery for inflammatory disease, Dr, Jeuring said.
The study was supported by Maastricht University Medical Center. Dr. Jeuring reported having no conflicts of interest.
AT DDW 2015
Key clinical point: The advent of biologic agents has improved hospitalization and surgery rates for patients with Crohn’s disease.
Major finding: The risk of hospitalization for patients treated after 1999 or for hospitalization during the course of the disease was 55% and 35% lower, respectively. and the risks for requiring surgery in the modern era or at any time in the disease course was 77% and 54% lower.
Data source: Population-based cohort study of 1,162 patients with inflammatory bowel disease in the South Limburg region of the Netherlands.
Disclosures: The study was supported by Maastricht University Medical Center. Dr. Jeuring reported having no conflicts of interest.
DDW: Statin use associated with significantly lower risk of new-onset IBD
WASHINGTON – A prescription for a statin was associated with about a 40% lower risk of new-onset inflammatory bowel disease in a study that evaluated data from a large U.S. health claims database over a 5-year period, Dr. Ryan Ungaro said at the annual Digestive Disease Week.
The protective effect was seen with different statins and was not associated with the intensity of statin treatment, said Dr. Ungaro, a gastroenterologist at Mount Sinai Hospital, New York.
He and his associates conducted a case-control study by using a national medical claims and pharmacy database, identifying 87,579 patients aged 18 and older with an ICD-9 code for a diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) from January 2008 through December 2012, and 189,526 controls (each case was matched with up to 10 controls, matched for age, gender, race, and state of residence). The median age of cases and controls was about 51 years, and about 41% were male. About 47% were diagnosed with CD, and about 44% were diagnosed with UC. A smaller group of patients who were new-onset cases were included who had at least 1 year with no IBD-related diagnostic code or prescription before the index diagnosis.
Statin use was associated with about a 40% reduced risk of new-onset IBD (odds ratio, 0.59), with similar trends for UC and CD, Dr. Ungaro reported. Separately, the risks of new-onset CD (OR, 0.55) and new-onset UC (OR, 0.62) associated with having a prescription for a statin were also significantly lower.
This association was maintained “regardless of which specific statin a patient was exposed to,” he noted. There was no significant difference in risk of IBD based on the intensity of statin treatment, according to American Heart Association guidelines for low-, moderate-, and high-intensity treatment.
Another finding was that the strongest protective effect was seen in older people, with an OR of 0.55 among those aged 60 years and older. There was no significant effect among those aged 18-30 years, but there were a limited number of statin prescriptions for younger patients, Dr. Ungaro noted.
Limitations of the study include the retrospective design, the inability to directly validate cases, and the reliance on a prescription as a surrogate for the patient actually taking the medication, he said.
Based on the results, “we think that future studies should confirm this protective effect, as well as continue to investigate statins in established IBD,” he concluded.
He referred to recent research demonstrating that statins have immunomodulatory effects “and may actually potentially be beneficial in established IBD.” In addition, a few clinical studies that have looked at the effects of statins in people with established IBD have found that statins are associated with a decreased need for oral steroids and may be associated with improvements in clinical indices and disease and inflammatory markers. Basic science studies indicate that statins are associated with amelioration of disease in mouse models of IBD, may decrease mediators of inflammation, such as tumor necrosis factor-alpha, and may also suppress antigen presentation and T-cell proliferation, he noted.
Dr. Ungaro and his coauthors had no relevant financial disclosures.
WASHINGTON – A prescription for a statin was associated with about a 40% lower risk of new-onset inflammatory bowel disease in a study that evaluated data from a large U.S. health claims database over a 5-year period, Dr. Ryan Ungaro said at the annual Digestive Disease Week.
The protective effect was seen with different statins and was not associated with the intensity of statin treatment, said Dr. Ungaro, a gastroenterologist at Mount Sinai Hospital, New York.
He and his associates conducted a case-control study by using a national medical claims and pharmacy database, identifying 87,579 patients aged 18 and older with an ICD-9 code for a diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) from January 2008 through December 2012, and 189,526 controls (each case was matched with up to 10 controls, matched for age, gender, race, and state of residence). The median age of cases and controls was about 51 years, and about 41% were male. About 47% were diagnosed with CD, and about 44% were diagnosed with UC. A smaller group of patients who were new-onset cases were included who had at least 1 year with no IBD-related diagnostic code or prescription before the index diagnosis.
Statin use was associated with about a 40% reduced risk of new-onset IBD (odds ratio, 0.59), with similar trends for UC and CD, Dr. Ungaro reported. Separately, the risks of new-onset CD (OR, 0.55) and new-onset UC (OR, 0.62) associated with having a prescription for a statin were also significantly lower.
This association was maintained “regardless of which specific statin a patient was exposed to,” he noted. There was no significant difference in risk of IBD based on the intensity of statin treatment, according to American Heart Association guidelines for low-, moderate-, and high-intensity treatment.
Another finding was that the strongest protective effect was seen in older people, with an OR of 0.55 among those aged 60 years and older. There was no significant effect among those aged 18-30 years, but there were a limited number of statin prescriptions for younger patients, Dr. Ungaro noted.
Limitations of the study include the retrospective design, the inability to directly validate cases, and the reliance on a prescription as a surrogate for the patient actually taking the medication, he said.
Based on the results, “we think that future studies should confirm this protective effect, as well as continue to investigate statins in established IBD,” he concluded.
He referred to recent research demonstrating that statins have immunomodulatory effects “and may actually potentially be beneficial in established IBD.” In addition, a few clinical studies that have looked at the effects of statins in people with established IBD have found that statins are associated with a decreased need for oral steroids and may be associated with improvements in clinical indices and disease and inflammatory markers. Basic science studies indicate that statins are associated with amelioration of disease in mouse models of IBD, may decrease mediators of inflammation, such as tumor necrosis factor-alpha, and may also suppress antigen presentation and T-cell proliferation, he noted.
Dr. Ungaro and his coauthors had no relevant financial disclosures.
WASHINGTON – A prescription for a statin was associated with about a 40% lower risk of new-onset inflammatory bowel disease in a study that evaluated data from a large U.S. health claims database over a 5-year period, Dr. Ryan Ungaro said at the annual Digestive Disease Week.
The protective effect was seen with different statins and was not associated with the intensity of statin treatment, said Dr. Ungaro, a gastroenterologist at Mount Sinai Hospital, New York.
He and his associates conducted a case-control study by using a national medical claims and pharmacy database, identifying 87,579 patients aged 18 and older with an ICD-9 code for a diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) from January 2008 through December 2012, and 189,526 controls (each case was matched with up to 10 controls, matched for age, gender, race, and state of residence). The median age of cases and controls was about 51 years, and about 41% were male. About 47% were diagnosed with CD, and about 44% were diagnosed with UC. A smaller group of patients who were new-onset cases were included who had at least 1 year with no IBD-related diagnostic code or prescription before the index diagnosis.
Statin use was associated with about a 40% reduced risk of new-onset IBD (odds ratio, 0.59), with similar trends for UC and CD, Dr. Ungaro reported. Separately, the risks of new-onset CD (OR, 0.55) and new-onset UC (OR, 0.62) associated with having a prescription for a statin were also significantly lower.
This association was maintained “regardless of which specific statin a patient was exposed to,” he noted. There was no significant difference in risk of IBD based on the intensity of statin treatment, according to American Heart Association guidelines for low-, moderate-, and high-intensity treatment.
Another finding was that the strongest protective effect was seen in older people, with an OR of 0.55 among those aged 60 years and older. There was no significant effect among those aged 18-30 years, but there were a limited number of statin prescriptions for younger patients, Dr. Ungaro noted.
Limitations of the study include the retrospective design, the inability to directly validate cases, and the reliance on a prescription as a surrogate for the patient actually taking the medication, he said.
Based on the results, “we think that future studies should confirm this protective effect, as well as continue to investigate statins in established IBD,” he concluded.
He referred to recent research demonstrating that statins have immunomodulatory effects “and may actually potentially be beneficial in established IBD.” In addition, a few clinical studies that have looked at the effects of statins in people with established IBD have found that statins are associated with a decreased need for oral steroids and may be associated with improvements in clinical indices and disease and inflammatory markers. Basic science studies indicate that statins are associated with amelioration of disease in mouse models of IBD, may decrease mediators of inflammation, such as tumor necrosis factor-alpha, and may also suppress antigen presentation and T-cell proliferation, he noted.
Dr. Ungaro and his coauthors had no relevant financial disclosures.
AT DDW 2015
Key clinical point: A reduced risk of new onset inflammatory bowel disease (IBD) may be another benefit of statin therapy.
Major finding: A prescription for a statin was associated with about a 40% lower risk of new-onset IBD, an effect that was seen with different statins and only in older people, in a large case-control study.
Data source: The retrospective study evaluated the risk of new-onset Crohn’s disease (CD) and new-onset ulcerative colitis (UC), in about 87,500 patients with a diagnostic code for UC or CD, and controls using a US national medical claims and pharmacy database from 2008-2012.
Disclosures: Dr. Ungaro and his coauthors had no relevant disclosures.
Celiac disease more than doubles neuropathy risk
Individuals with biopsy-confirmed celiac disease have more than double the risk of receiving a diagnosis of neuropathy when compared with the general population, and the risk persists even when other potentially contributing conditions and lifestyle factors are considered.
The use of Swedish population registries enabled first author Dr. Sujata P. Thawani of Columbia University, New York, and her colleagues to find that the risk of neuropathy was increased both before and after a diagnosis of celiac disease (CD).
“We found an increased risk of neuropathy in patients with CD that persists after CD diagnosis. Although absolute risks for neuropathy are low, CD is a potentially treatable condition with a young age of onset. Our findings suggest that screening could be beneficial in patients with neuropathy,” they wrote (JAMA Neurol. 2015 May 11 [doi:10.1001/jamaneurol.2015.0475]).Neuropathy has a known association with CD, an immune-mediated disorder characterized by sensitivity to gluten with an incidence of about 1% in Western Europe. Previous studies had reported that up to one-third of celiac disease patients also experienced neuropathy, but the literature had not completely characterized the prevalence of neuropathy in the CD population.
Dr. Thawani and her associates used Swedish pathology registers to identify individuals whose small intestine biopsies showed villous atrophy between 1969 and 2008 (Marsh stage 3, n = 28,232). These individuals were categorized as having CD. Neuropathy diagnoses were drawn from national patient and pharmacy registers. Each CD patient was matched with up to five age- and sex-matched controls (n = 139,473) from the Swedish Total Population Registry, all of whom were diagnosed in the same year and were from the same county as the matched CD patient.
Although 41.7% of CD patients were diagnosed in childhood, the median age at diagnosis was 29 years. About 62% of patients in both groups were female. For CD patients, the absolute risk of neuropathy was 64 per 100,000 patient-years, compared with 15 per 100,000 patients-years in the control group (hazard ratio, 2.5; 95% confidence interval, 2.0-2.9; P < .001).
The risk of neuropathy for patients with CD was not affected by gender, absolute age, or age at diagnosis. The risk of neuropathy for those with CD remained about 2.5 times higher than the matched controls, even after accounting for diabetes status, the presence of other autoimmune disorders, vitamin deficiencies, and alcohol use. Although vitamin B12 deficiency has been associated with CD and may contribute to neuropathy, the investigators noted that, “in our analysis, the influence of vitamin deficiencies did not significantly affect our risk estimate.”
Nonspecified neuropathy was the most commonly reported type of neuropathy. Other subtypes of neuropathy were tracked, but limitations of coding and reporting prevented tracking sensory ganglionopathy, the second most commonly reported neuropathy in CD.
The strengths of the study included the large sample size and the study’s statistical strengths. The retrospective nature of the study was an overall limitation, and the homogeneous study population (over 90% of patients in both arms were of Nordic heritage) limited the study’s generalizability.
Surveillance bias may account for some of the increased risk for neuropathy, noted Dr. Thawani and her colleagues. This was hinted at by the fact that a diagnosis of neuropathy tended to follow closely on the CD diagnosis; physicians may have been more attuned to detecting potential sequelae of the CD diagnosis during this time period. Notably, though, patients with a prior neuropathy diagnosis also were more likely to be diagnosed with CD, showing a bidirectional relationship.
“These data may also suggest that the two diseases may share risk factors or a common underlying etiology for the development of neuropathy, such as a potential role of immunologic mechanisms,” they wrote.
The authors reported no conflicts of interest. The investigators received support from the Swedish Society of Medicine, the Swedish Research Council, and the National Center for Advancing Translational Sciences.
Individuals with biopsy-confirmed celiac disease have more than double the risk of receiving a diagnosis of neuropathy when compared with the general population, and the risk persists even when other potentially contributing conditions and lifestyle factors are considered.
The use of Swedish population registries enabled first author Dr. Sujata P. Thawani of Columbia University, New York, and her colleagues to find that the risk of neuropathy was increased both before and after a diagnosis of celiac disease (CD).
“We found an increased risk of neuropathy in patients with CD that persists after CD diagnosis. Although absolute risks for neuropathy are low, CD is a potentially treatable condition with a young age of onset. Our findings suggest that screening could be beneficial in patients with neuropathy,” they wrote (JAMA Neurol. 2015 May 11 [doi:10.1001/jamaneurol.2015.0475]).Neuropathy has a known association with CD, an immune-mediated disorder characterized by sensitivity to gluten with an incidence of about 1% in Western Europe. Previous studies had reported that up to one-third of celiac disease patients also experienced neuropathy, but the literature had not completely characterized the prevalence of neuropathy in the CD population.
Dr. Thawani and her associates used Swedish pathology registers to identify individuals whose small intestine biopsies showed villous atrophy between 1969 and 2008 (Marsh stage 3, n = 28,232). These individuals were categorized as having CD. Neuropathy diagnoses were drawn from national patient and pharmacy registers. Each CD patient was matched with up to five age- and sex-matched controls (n = 139,473) from the Swedish Total Population Registry, all of whom were diagnosed in the same year and were from the same county as the matched CD patient.
Although 41.7% of CD patients were diagnosed in childhood, the median age at diagnosis was 29 years. About 62% of patients in both groups were female. For CD patients, the absolute risk of neuropathy was 64 per 100,000 patient-years, compared with 15 per 100,000 patients-years in the control group (hazard ratio, 2.5; 95% confidence interval, 2.0-2.9; P < .001).
The risk of neuropathy for patients with CD was not affected by gender, absolute age, or age at diagnosis. The risk of neuropathy for those with CD remained about 2.5 times higher than the matched controls, even after accounting for diabetes status, the presence of other autoimmune disorders, vitamin deficiencies, and alcohol use. Although vitamin B12 deficiency has been associated with CD and may contribute to neuropathy, the investigators noted that, “in our analysis, the influence of vitamin deficiencies did not significantly affect our risk estimate.”
Nonspecified neuropathy was the most commonly reported type of neuropathy. Other subtypes of neuropathy were tracked, but limitations of coding and reporting prevented tracking sensory ganglionopathy, the second most commonly reported neuropathy in CD.
The strengths of the study included the large sample size and the study’s statistical strengths. The retrospective nature of the study was an overall limitation, and the homogeneous study population (over 90% of patients in both arms were of Nordic heritage) limited the study’s generalizability.
Surveillance bias may account for some of the increased risk for neuropathy, noted Dr. Thawani and her colleagues. This was hinted at by the fact that a diagnosis of neuropathy tended to follow closely on the CD diagnosis; physicians may have been more attuned to detecting potential sequelae of the CD diagnosis during this time period. Notably, though, patients with a prior neuropathy diagnosis also were more likely to be diagnosed with CD, showing a bidirectional relationship.
“These data may also suggest that the two diseases may share risk factors or a common underlying etiology for the development of neuropathy, such as a potential role of immunologic mechanisms,” they wrote.
The authors reported no conflicts of interest. The investigators received support from the Swedish Society of Medicine, the Swedish Research Council, and the National Center for Advancing Translational Sciences.
Individuals with biopsy-confirmed celiac disease have more than double the risk of receiving a diagnosis of neuropathy when compared with the general population, and the risk persists even when other potentially contributing conditions and lifestyle factors are considered.
The use of Swedish population registries enabled first author Dr. Sujata P. Thawani of Columbia University, New York, and her colleagues to find that the risk of neuropathy was increased both before and after a diagnosis of celiac disease (CD).
“We found an increased risk of neuropathy in patients with CD that persists after CD diagnosis. Although absolute risks for neuropathy are low, CD is a potentially treatable condition with a young age of onset. Our findings suggest that screening could be beneficial in patients with neuropathy,” they wrote (JAMA Neurol. 2015 May 11 [doi:10.1001/jamaneurol.2015.0475]).Neuropathy has a known association with CD, an immune-mediated disorder characterized by sensitivity to gluten with an incidence of about 1% in Western Europe. Previous studies had reported that up to one-third of celiac disease patients also experienced neuropathy, but the literature had not completely characterized the prevalence of neuropathy in the CD population.
Dr. Thawani and her associates used Swedish pathology registers to identify individuals whose small intestine biopsies showed villous atrophy between 1969 and 2008 (Marsh stage 3, n = 28,232). These individuals were categorized as having CD. Neuropathy diagnoses were drawn from national patient and pharmacy registers. Each CD patient was matched with up to five age- and sex-matched controls (n = 139,473) from the Swedish Total Population Registry, all of whom were diagnosed in the same year and were from the same county as the matched CD patient.
Although 41.7% of CD patients were diagnosed in childhood, the median age at diagnosis was 29 years. About 62% of patients in both groups were female. For CD patients, the absolute risk of neuropathy was 64 per 100,000 patient-years, compared with 15 per 100,000 patients-years in the control group (hazard ratio, 2.5; 95% confidence interval, 2.0-2.9; P < .001).
The risk of neuropathy for patients with CD was not affected by gender, absolute age, or age at diagnosis. The risk of neuropathy for those with CD remained about 2.5 times higher than the matched controls, even after accounting for diabetes status, the presence of other autoimmune disorders, vitamin deficiencies, and alcohol use. Although vitamin B12 deficiency has been associated with CD and may contribute to neuropathy, the investigators noted that, “in our analysis, the influence of vitamin deficiencies did not significantly affect our risk estimate.”
Nonspecified neuropathy was the most commonly reported type of neuropathy. Other subtypes of neuropathy were tracked, but limitations of coding and reporting prevented tracking sensory ganglionopathy, the second most commonly reported neuropathy in CD.
The strengths of the study included the large sample size and the study’s statistical strengths. The retrospective nature of the study was an overall limitation, and the homogeneous study population (over 90% of patients in both arms were of Nordic heritage) limited the study’s generalizability.
Surveillance bias may account for some of the increased risk for neuropathy, noted Dr. Thawani and her colleagues. This was hinted at by the fact that a diagnosis of neuropathy tended to follow closely on the CD diagnosis; physicians may have been more attuned to detecting potential sequelae of the CD diagnosis during this time period. Notably, though, patients with a prior neuropathy diagnosis also were more likely to be diagnosed with CD, showing a bidirectional relationship.
“These data may also suggest that the two diseases may share risk factors or a common underlying etiology for the development of neuropathy, such as a potential role of immunologic mechanisms,” they wrote.
The authors reported no conflicts of interest. The investigators received support from the Swedish Society of Medicine, the Swedish Research Council, and the National Center for Advancing Translational Sciences.
FROM JAMA NEUROLOGY
Key clinical point: Screening for celiac disease could be beneficial in patients with neuropathy.
Major findings: The risk of neuropathy for individuals with celiac disease was 2.5 times that of controls, even after adjusting for comorbidities and patient characteristics.
Data source: Review of 28,232 patients with biopsy-confirmed celiac disease and 139,473 matched controls from 1969 to 2008, drawn from Swedish patient registries.
Disclosures: The authors reported no conflicts of interest. The investigators received support from the Swedish Society of Medicine, the Swedish Research Council, and the National Center for Advancing Translational Sciences.
