Amy Karon

For adults with eosinophilic esophagitis, maintenance treatment with swallowed topical steroids was associated with significantly higher remission rates when compared with “steroid holidays” in a single-center retrospective observational study presented in the February issue of Clinical Gastroenterology and Hepatology.

At a median follow-up time of 5 years, the rate of complete (including clinical, endoscopic, and histologic) remission was 16.1% when patients were receiving swallowed topical steroids but only 1.3% when they were not on these or other maintenance therapies (that is, on “drug holidays”), reported Thomas Greuter, MD, of University Hospital Zürich and the Mayo Clinic in Rochester, Minn., and his associates. Swallowed topical steroids also were associated with significantly higher rates of each individual endpoint (P less than .001). Swallowed topical steroid therapy did not appear to cause dysplasia or mucosal atrophy, although esophageal candidiasis was confirmed in 2.7% of visits when patients were on treatment. “Given the good safety profile of low-dose swallowed topical steroid therapy, we advocate for prolonged treatment. Dose-finding trials are needed to achieve higher remission rates,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Several studies have confirmed the efficacy of short-term swallowed topical steroids for treating eosinophilic esophagitis, but only one small randomized trial has evaluated longer-term treatment, and participants were followed for only 1 year. Dr. Greuter and his associates therefore analyzed retrospective data from 229 adults in Switzerland who received swallowed topical steroids for eosinophilic esophagitis between 2000 and 2014. Induction therapy consisted of 1 mg swallowed topical steroids twice daily, allowing 2-4 weeks for a clinical response. Patients then received infinite maintenance therapy with 0.25 mg swallowed topical steroids twice daily. Patients tended to be male and diagnosed in their late 30s. Endoscopy commonly showed corrugated rings, white exudates, edema, and furrows, and 35% of patients had strictures. Peak eosinophil count typically was 25 cells per high-power frame.

Among 819 follow-up visits, 336 (41%) occurred when patients were on maintenance swallowed topical steroid therapy. The median duration of maintenance therapy prior to a follow-up visit was 347 days (interquartile range, 90-750 days) or 677 doses (IQR, 280-1413 doses). The rate of clinical remission was 31% when patients were on maintenance treatment but only 4.5% when they were not (P less than .001). Respective rates of endoscopic and histologic remission were 48.8% versus 17.8% (P less than .001) and 44.8% versus 10.1% (P less than .001). After accounting for numerous demographic and clinical variables, the only significant predictors of clinical remission were treatment with swallowed topical steroids (odds ratio, 16.98; 95% confidence interval, 6.69-43.09) and a negative family history of esophageal eosinophilia (OR, 4.02; 95% CI, 1.41-11.47).

This study excluded patients whose eosinophilic esophagitis had responded to proton pump inhibitor therapy. Also, the maintenance dose of swallowed topical steroid dose (0.25 mg twice daily) probably was too low to achieve efficacious drug levels in the esophageal mucosa, which could explain the high proportion of treatment-refractory cases, according to the researchers. Evaluating a higher maintenance dose “would be of particular interest in the future,” they added.

The Swiss National Science Foundation provided partial funding. Dr. Greuter disclosed a travel grant from Falk Pharma GmbH and Vifor and an unrestricted research grant from Novartis.

SOURCE: Greuter T et al. Clin Gastroenterol Hepatol. 2018 Jun 11.

For adults with eosinophilic esophagitis, maintenance treatment with swallowed topical steroids was associated with significantly higher remission rates when compared with “steroid holidays” in a single-center retrospective observational study presented in the February issue of Clinical Gastroenterology and Hepatology.

At a median follow-up time of 5 years, the rate of complete (including clinical, endoscopic, and histologic) remission was 16.1% when patients were receiving swallowed topical steroids but only 1.3% when they were not on these or other maintenance therapies (that is, on “drug holidays”), reported Thomas Greuter, MD, of University Hospital Zürich and the Mayo Clinic in Rochester, Minn., and his associates. Swallowed topical steroids also were associated with significantly higher rates of each individual endpoint (P less than .001). Swallowed topical steroid therapy did not appear to cause dysplasia or mucosal atrophy, although esophageal candidiasis was confirmed in 2.7% of visits when patients were on treatment. “Given the good safety profile of low-dose swallowed topical steroid therapy, we advocate for prolonged treatment. Dose-finding trials are needed to achieve higher remission rates,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Several studies have confirmed the efficacy of short-term swallowed topical steroids for treating eosinophilic esophagitis, but only one small randomized trial has evaluated longer-term treatment, and participants were followed for only 1 year. Dr. Greuter and his associates therefore analyzed retrospective data from 229 adults in Switzerland who received swallowed topical steroids for eosinophilic esophagitis between 2000 and 2014. Induction therapy consisted of 1 mg swallowed topical steroids twice daily, allowing 2-4 weeks for a clinical response. Patients then received infinite maintenance therapy with 0.25 mg swallowed topical steroids twice daily. Patients tended to be male and diagnosed in their late 30s. Endoscopy commonly showed corrugated rings, white exudates, edema, and furrows, and 35% of patients had strictures. Peak eosinophil count typically was 25 cells per high-power frame.

Among 819 follow-up visits, 336 (41%) occurred when patients were on maintenance swallowed topical steroid therapy. The median duration of maintenance therapy prior to a follow-up visit was 347 days (interquartile range, 90-750 days) or 677 doses (IQR, 280-1413 doses). The rate of clinical remission was 31% when patients were on maintenance treatment but only 4.5% when they were not (P less than .001). Respective rates of endoscopic and histologic remission were 48.8% versus 17.8% (P less than .001) and 44.8% versus 10.1% (P less than .001). After accounting for numerous demographic and clinical variables, the only significant predictors of clinical remission were treatment with swallowed topical steroids (odds ratio, 16.98; 95% confidence interval, 6.69-43.09) and a negative family history of esophageal eosinophilia (OR, 4.02; 95% CI, 1.41-11.47).

This study excluded patients whose eosinophilic esophagitis had responded to proton pump inhibitor therapy. Also, the maintenance dose of swallowed topical steroid dose (0.25 mg twice daily) probably was too low to achieve efficacious drug levels in the esophageal mucosa, which could explain the high proportion of treatment-refractory cases, according to the researchers. Evaluating a higher maintenance dose “would be of particular interest in the future,” they added.

The Swiss National Science Foundation provided partial funding. Dr. Greuter disclosed a travel grant from Falk Pharma GmbH and Vifor and an unrestricted research grant from Novartis.

SOURCE: Greuter T et al. Clin Gastroenterol Hepatol. 2018 Jun 11.

For adults with eosinophilic esophagitis, maintenance treatment with swallowed topical steroids was associated with significantly higher remission rates when compared with “steroid holidays” in a single-center retrospective observational study presented in the February issue of Clinical Gastroenterology and Hepatology.

At a median follow-up time of 5 years, the rate of complete (including clinical, endoscopic, and histologic) remission was 16.1% when patients were receiving swallowed topical steroids but only 1.3% when they were not on these or other maintenance therapies (that is, on “drug holidays”), reported Thomas Greuter, MD, of University Hospital Zürich and the Mayo Clinic in Rochester, Minn., and his associates. Swallowed topical steroids also were associated with significantly higher rates of each individual endpoint (P less than .001). Swallowed topical steroid therapy did not appear to cause dysplasia or mucosal atrophy, although esophageal candidiasis was confirmed in 2.7% of visits when patients were on treatment. “Given the good safety profile of low-dose swallowed topical steroid therapy, we advocate for prolonged treatment. Dose-finding trials are needed to achieve higher remission rates,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Several studies have confirmed the efficacy of short-term swallowed topical steroids for treating eosinophilic esophagitis, but only one small randomized trial has evaluated longer-term treatment, and participants were followed for only 1 year. Dr. Greuter and his associates therefore analyzed retrospective data from 229 adults in Switzerland who received swallowed topical steroids for eosinophilic esophagitis between 2000 and 2014. Induction therapy consisted of 1 mg swallowed topical steroids twice daily, allowing 2-4 weeks for a clinical response. Patients then received infinite maintenance therapy with 0.25 mg swallowed topical steroids twice daily. Patients tended to be male and diagnosed in their late 30s. Endoscopy commonly showed corrugated rings, white exudates, edema, and furrows, and 35% of patients had strictures. Peak eosinophil count typically was 25 cells per high-power frame.

Among 819 follow-up visits, 336 (41%) occurred when patients were on maintenance swallowed topical steroid therapy. The median duration of maintenance therapy prior to a follow-up visit was 347 days (interquartile range, 90-750 days) or 677 doses (IQR, 280-1413 doses). The rate of clinical remission was 31% when patients were on maintenance treatment but only 4.5% when they were not (P less than .001). Respective rates of endoscopic and histologic remission were 48.8% versus 17.8% (P less than .001) and 44.8% versus 10.1% (P less than .001). After accounting for numerous demographic and clinical variables, the only significant predictors of clinical remission were treatment with swallowed topical steroids (odds ratio, 16.98; 95% confidence interval, 6.69-43.09) and a negative family history of esophageal eosinophilia (OR, 4.02; 95% CI, 1.41-11.47).

This study excluded patients whose eosinophilic esophagitis had responded to proton pump inhibitor therapy. Also, the maintenance dose of swallowed topical steroid dose (0.25 mg twice daily) probably was too low to achieve efficacious drug levels in the esophageal mucosa, which could explain the high proportion of treatment-refractory cases, according to the researchers. Evaluating a higher maintenance dose “would be of particular interest in the future,” they added.

The Swiss National Science Foundation provided partial funding. Dr. Greuter disclosed a travel grant from Falk Pharma GmbH and Vifor and an unrestricted research grant from Novartis.

SOURCE: Greuter T et al. Clin Gastroenterol Hepatol. 2018 Jun 11.

Two recent studies highlight the ability of vedolizumab and tofacitinib to rapidly improve symptoms reported by patients with inflammatory bowel disease (IBD).

In a post hoc study of 1,758 patients with ulcerative colitis (UC) or Crohn’s disease (CD) in the phase 3 GEMINI trials, 2 weeks of vedolizumab (Entyvio) therapy effectively improved patient-reported outcomes, and these continued to improve through 6 weeks of treatment, wrote Brian G. Feagan, MD, and his associates in the January issue of Clinical Gastroenterology and Hepatology.

In UC patients who had not previously received tumor necrosis factor (TNF) antagonists, 22% of vedolizumab recipients, compared with 7% of placebo recipients, achieved complete resolution of rectal bleeding together with a meaningful reduction in stool frequency at treatment week 2, the investigators noted. Among CD patients who were naive to TNF antagonists, 15% reported decreases in abdominal pain and loose stools at treatment week 2, compared with 8% of placebo recipients.

Although 2 weeks of vedolizumab also topped placebo for improving patient-reported outcomes among TNF antagonist–exposed patients, the effects were less pronounced, wrote Dr. Feagan, of the University of Western Ontario, London, and his associates. “These data add to the growing evidence that second-generation biologics, such as vedolizumab and ustekinumab, have higher efficacy in TNF antagonist–naive patients in both clinical trials and real-world settings. Recent trends in clinical practice are moving toward incorporating disease-modifying therapy earlier in the treatment of IBD to prevent disease progression and cumulative bowel damage.”

Patient-reported outcomes have become key during both clinical research and regulatory review of claims on proposed drug labels. In the second study, also published in the January issue of Clinical Gastroenterology and Hepatology, Stephen B. Hanauer, MD, of Northwestern University, Chicago, and his associates performed a post hoc analysis of symptoms reported by 1,139 adults with UC who received the oral small-molecule Janus kinase inhibitor tofacitinib (10 g twice daily) or placebo during the 8-week OCTAVE Induction 1 and 2 trials. These were identical phase 3 studies of patients with moderate to severe UC who could not tolerate or had responded inadequately to TNF antagonists, corticosteroids, or thiopurines.

Compared with placebo, 3 days of tofacitinib therapy induced significantly greater reductions from baseline in patient-reported stool frequency and rectal bleeding (P less than .01 for each measure), Dr. Hanauer and his associates reported. The effect was independent of prior treatment for UC or baseline levels of C-reactive protein. These findings reflect the rapid onset of effect of tofacitinib therapy in patients with UC. In contrast, thiopurines (azathioprine and 6-mercaptopurine) can take at least 8 weeks to exhibit steroid-sparing effects.

While corticosteroids can induce UC remission within 5 days, their side effects tend to escalate over time and they “lack maintenance benefits,” the researchers wrote. “In these analyses, onset of tofacitinib efficacy occurred within 3 days, irrespective of concomitant corticosteroid use or prior anti-TNF treatment failure.”

Takeda funded the GEMINI studies. Dr. Feagan reported advisory relationships with Takeda, AbbVie, Amgen, AstraZeneca, and several other pharmaceutical companies. Dr. Hanauer also reported ties to numerous pharmaceutical companies, including Pfizer, which funded the OCTAVE trials.
 

SOURCES: Feagan BG et al. Clin Gastroenterol Hepatol. 2018 May 29. doi: 10.1016/j.cgh.2018.05.026; Hanauer SB et al. Clin Gastroenterol Hepatol. 2018 Jul 15. doi: 10.1016/j.cgh.2018.07.009.

Two recent studies highlight the ability of vedolizumab and tofacitinib to rapidly improve symptoms reported by patients with inflammatory bowel disease (IBD).

In a post hoc study of 1,758 patients with ulcerative colitis (UC) or Crohn’s disease (CD) in the phase 3 GEMINI trials, 2 weeks of vedolizumab (Entyvio) therapy effectively improved patient-reported outcomes, and these continued to improve through 6 weeks of treatment, wrote Brian G. Feagan, MD, and his associates in the January issue of Clinical Gastroenterology and Hepatology.

In UC patients who had not previously received tumor necrosis factor (TNF) antagonists, 22% of vedolizumab recipients, compared with 7% of placebo recipients, achieved complete resolution of rectal bleeding together with a meaningful reduction in stool frequency at treatment week 2, the investigators noted. Among CD patients who were naive to TNF antagonists, 15% reported decreases in abdominal pain and loose stools at treatment week 2, compared with 8% of placebo recipients.

Although 2 weeks of vedolizumab also topped placebo for improving patient-reported outcomes among TNF antagonist–exposed patients, the effects were less pronounced, wrote Dr. Feagan, of the University of Western Ontario, London, and his associates. “These data add to the growing evidence that second-generation biologics, such as vedolizumab and ustekinumab, have higher efficacy in TNF antagonist–naive patients in both clinical trials and real-world settings. Recent trends in clinical practice are moving toward incorporating disease-modifying therapy earlier in the treatment of IBD to prevent disease progression and cumulative bowel damage.”

Patient-reported outcomes have become key during both clinical research and regulatory review of claims on proposed drug labels. In the second study, also published in the January issue of Clinical Gastroenterology and Hepatology, Stephen B. Hanauer, MD, of Northwestern University, Chicago, and his associates performed a post hoc analysis of symptoms reported by 1,139 adults with UC who received the oral small-molecule Janus kinase inhibitor tofacitinib (10 g twice daily) or placebo during the 8-week OCTAVE Induction 1 and 2 trials. These were identical phase 3 studies of patients with moderate to severe UC who could not tolerate or had responded inadequately to TNF antagonists, corticosteroids, or thiopurines.

Compared with placebo, 3 days of tofacitinib therapy induced significantly greater reductions from baseline in patient-reported stool frequency and rectal bleeding (P less than .01 for each measure), Dr. Hanauer and his associates reported. The effect was independent of prior treatment for UC or baseline levels of C-reactive protein. These findings reflect the rapid onset of effect of tofacitinib therapy in patients with UC. In contrast, thiopurines (azathioprine and 6-mercaptopurine) can take at least 8 weeks to exhibit steroid-sparing effects.

While corticosteroids can induce UC remission within 5 days, their side effects tend to escalate over time and they “lack maintenance benefits,” the researchers wrote. “In these analyses, onset of tofacitinib efficacy occurred within 3 days, irrespective of concomitant corticosteroid use or prior anti-TNF treatment failure.”

Takeda funded the GEMINI studies. Dr. Feagan reported advisory relationships with Takeda, AbbVie, Amgen, AstraZeneca, and several other pharmaceutical companies. Dr. Hanauer also reported ties to numerous pharmaceutical companies, including Pfizer, which funded the OCTAVE trials.
 

SOURCES: Feagan BG et al. Clin Gastroenterol Hepatol. 2018 May 29. doi: 10.1016/j.cgh.2018.05.026; Hanauer SB et al. Clin Gastroenterol Hepatol. 2018 Jul 15. doi: 10.1016/j.cgh.2018.07.009.

Two recent studies highlight the ability of vedolizumab and tofacitinib to rapidly improve symptoms reported by patients with inflammatory bowel disease (IBD).

In a post hoc study of 1,758 patients with ulcerative colitis (UC) or Crohn’s disease (CD) in the phase 3 GEMINI trials, 2 weeks of vedolizumab (Entyvio) therapy effectively improved patient-reported outcomes, and these continued to improve through 6 weeks of treatment, wrote Brian G. Feagan, MD, and his associates in the January issue of Clinical Gastroenterology and Hepatology.

In UC patients who had not previously received tumor necrosis factor (TNF) antagonists, 22% of vedolizumab recipients, compared with 7% of placebo recipients, achieved complete resolution of rectal bleeding together with a meaningful reduction in stool frequency at treatment week 2, the investigators noted. Among CD patients who were naive to TNF antagonists, 15% reported decreases in abdominal pain and loose stools at treatment week 2, compared with 8% of placebo recipients.

Although 2 weeks of vedolizumab also topped placebo for improving patient-reported outcomes among TNF antagonist–exposed patients, the effects were less pronounced, wrote Dr. Feagan, of the University of Western Ontario, London, and his associates. “These data add to the growing evidence that second-generation biologics, such as vedolizumab and ustekinumab, have higher efficacy in TNF antagonist–naive patients in both clinical trials and real-world settings. Recent trends in clinical practice are moving toward incorporating disease-modifying therapy earlier in the treatment of IBD to prevent disease progression and cumulative bowel damage.”

Patient-reported outcomes have become key during both clinical research and regulatory review of claims on proposed drug labels. In the second study, also published in the January issue of Clinical Gastroenterology and Hepatology, Stephen B. Hanauer, MD, of Northwestern University, Chicago, and his associates performed a post hoc analysis of symptoms reported by 1,139 adults with UC who received the oral small-molecule Janus kinase inhibitor tofacitinib (10 g twice daily) or placebo during the 8-week OCTAVE Induction 1 and 2 trials. These were identical phase 3 studies of patients with moderate to severe UC who could not tolerate or had responded inadequately to TNF antagonists, corticosteroids, or thiopurines.

Compared with placebo, 3 days of tofacitinib therapy induced significantly greater reductions from baseline in patient-reported stool frequency and rectal bleeding (P less than .01 for each measure), Dr. Hanauer and his associates reported. The effect was independent of prior treatment for UC or baseline levels of C-reactive protein. These findings reflect the rapid onset of effect of tofacitinib therapy in patients with UC. In contrast, thiopurines (azathioprine and 6-mercaptopurine) can take at least 8 weeks to exhibit steroid-sparing effects.

While corticosteroids can induce UC remission within 5 days, their side effects tend to escalate over time and they “lack maintenance benefits,” the researchers wrote. “In these analyses, onset of tofacitinib efficacy occurred within 3 days, irrespective of concomitant corticosteroid use or prior anti-TNF treatment failure.”

Takeda funded the GEMINI studies. Dr. Feagan reported advisory relationships with Takeda, AbbVie, Amgen, AstraZeneca, and several other pharmaceutical companies. Dr. Hanauer also reported ties to numerous pharmaceutical companies, including Pfizer, which funded the OCTAVE trials.
 

SOURCES: Feagan BG et al. Clin Gastroenterol Hepatol. 2018 May 29. doi: 10.1016/j.cgh.2018.05.026; Hanauer SB et al. Clin Gastroenterol Hepatol. 2018 Jul 15. doi: 10.1016/j.cgh.2018.07.009.

For patients with early-stage esophageal squamous cell carcinoma, minimally invasive esophageal submucosal dissection (ESD) led to significantly fewer severe adverse perioperative events than esophagectomy and was associated with similar rates of all-cause mortality and cancer recurrence or metastasis, according to the findings of a single-center retrospective cohort study.

After a median of 21 months of follow-up (range, 6-73 months), rates of all-cause mortality were 7% with ESD and 11% with esophagectomy, said Yiqun Zhang of Zhongshan Hospital, Shanghai, China, and his associates. Rates of cancer recurrence or metastasis were 9.1% and 8.9%, respectively, while disease-specific mortality was lower with ESD (3.4% vs. 7.4% with esophagectomy; P = .049). Severe nonfatal adverse perioperative events occurred in 15% of ESD cases versus 28% of esophagectomy cases (P less than .001). The findings justify more studies of ESD in carefully selected patients with early-stage (T1a-m2/m3 or T1b) esophageal squamous cell carcinoma, the researchers wrote in Clinical Gastroenterology and Hepatology.

Esophagectomy is standard for managing early-stage esophageal squamous cell carcinoma but is associated with high rates of morbidity and mortality. While ESD is minimally invasive, it is considered risky because esophageal squamous cell carcinoma so frequently metastasizes to the lymph nodes, the investigators noted. For the study, they retrospectively compared 322 ESDs and 274 esophagectomies performed during 2011-2016 in patients with T1a-m2/m3 or T1b esophageal squamous cell carcinoma. All cases were pathologically confirmed, and none were premalignant (that is, high-grade intraepithelial neoplasias).

Endoscopic submucosal dissection was associated with significantly lower rates of esophageal fistula (0.3% with ESD vs. 16% with esophagectomy; P less than .001) and pulmonary complications (0.3% vs. 3.6%, respectively; P less than .001), which explained its overall superiority in terms of severe adverse perioperative events, the researchers wrote. Perioperative deaths were rare but occurred more often with esophagectomy (four patients) than with ESD (one patient). Depth of tumor invasion was the only significant correlate of all-cause mortality (hazard ratio for T1a–m3 or deeper tumors versus T1a–m2 tumors, 3.54; 95% confidence interval, 1.08-11.62; P = .04) in a Cox regression analysis that accounted for many potential confounders, such as demographic and tumor characteristics, hypertension, chronic obstructive pulmonary disease (COPD), nodal metastasis, chemotherapy, and radiotherapy.

Perhaps esophagectomy did not improve survival in this retrospective study because follow-up time was too short, because adjuvant therapy compensated for the increased risk of tumor relapse with ESD, or because of the confounding effects of unmeasured variables, such as submucosal stages of T1b cancer, lymphovascular invasion, or tumor morphology, the researchers wrote. “Since a randomized study comparing esophagectomy and ESD alone would not be practical, a potential strategy for future research may include serial treatments – that is, ESD first, followed by esophagectomy, radiotherapy, or chemotherapy, depending on the ESD pathology findings,” they added. “A quality-of-life analysis of ESD would also be helpful because this might be one of the biggest advantages of ESD over esophagectomy and was beyond the scope of this study.”

The study was supported by the National Natural Science Foundation of China, the Shanghai Committee of Science and Technology, and Zhongshan Hospital. The investigators reported having no relevant conflicts of interest.

SOURCE: Zhang Y et al. Clin Gastroenterol Hepatol. 2018 Apr 25. doi: 10.1016/j.cgh.2018.04.038.

For patients with early-stage esophageal squamous cell carcinoma, minimally invasive esophageal submucosal dissection (ESD) led to significantly fewer severe adverse perioperative events than esophagectomy and was associated with similar rates of all-cause mortality and cancer recurrence or metastasis, according to the findings of a single-center retrospective cohort study.

After a median of 21 months of follow-up (range, 6-73 months), rates of all-cause mortality were 7% with ESD and 11% with esophagectomy, said Yiqun Zhang of Zhongshan Hospital, Shanghai, China, and his associates. Rates of cancer recurrence or metastasis were 9.1% and 8.9%, respectively, while disease-specific mortality was lower with ESD (3.4% vs. 7.4% with esophagectomy; P = .049). Severe nonfatal adverse perioperative events occurred in 15% of ESD cases versus 28% of esophagectomy cases (P less than .001). The findings justify more studies of ESD in carefully selected patients with early-stage (T1a-m2/m3 or T1b) esophageal squamous cell carcinoma, the researchers wrote in Clinical Gastroenterology and Hepatology.

Esophagectomy is standard for managing early-stage esophageal squamous cell carcinoma but is associated with high rates of morbidity and mortality. While ESD is minimally invasive, it is considered risky because esophageal squamous cell carcinoma so frequently metastasizes to the lymph nodes, the investigators noted. For the study, they retrospectively compared 322 ESDs and 274 esophagectomies performed during 2011-2016 in patients with T1a-m2/m3 or T1b esophageal squamous cell carcinoma. All cases were pathologically confirmed, and none were premalignant (that is, high-grade intraepithelial neoplasias).

Endoscopic submucosal dissection was associated with significantly lower rates of esophageal fistula (0.3% with ESD vs. 16% with esophagectomy; P less than .001) and pulmonary complications (0.3% vs. 3.6%, respectively; P less than .001), which explained its overall superiority in terms of severe adverse perioperative events, the researchers wrote. Perioperative deaths were rare but occurred more often with esophagectomy (four patients) than with ESD (one patient). Depth of tumor invasion was the only significant correlate of all-cause mortality (hazard ratio for T1a–m3 or deeper tumors versus T1a–m2 tumors, 3.54; 95% confidence interval, 1.08-11.62; P = .04) in a Cox regression analysis that accounted for many potential confounders, such as demographic and tumor characteristics, hypertension, chronic obstructive pulmonary disease (COPD), nodal metastasis, chemotherapy, and radiotherapy.

Perhaps esophagectomy did not improve survival in this retrospective study because follow-up time was too short, because adjuvant therapy compensated for the increased risk of tumor relapse with ESD, or because of the confounding effects of unmeasured variables, such as submucosal stages of T1b cancer, lymphovascular invasion, or tumor morphology, the researchers wrote. “Since a randomized study comparing esophagectomy and ESD alone would not be practical, a potential strategy for future research may include serial treatments – that is, ESD first, followed by esophagectomy, radiotherapy, or chemotherapy, depending on the ESD pathology findings,” they added. “A quality-of-life analysis of ESD would also be helpful because this might be one of the biggest advantages of ESD over esophagectomy and was beyond the scope of this study.”

The study was supported by the National Natural Science Foundation of China, the Shanghai Committee of Science and Technology, and Zhongshan Hospital. The investigators reported having no relevant conflicts of interest.

SOURCE: Zhang Y et al. Clin Gastroenterol Hepatol. 2018 Apr 25. doi: 10.1016/j.cgh.2018.04.038.

For patients with early-stage esophageal squamous cell carcinoma, minimally invasive esophageal submucosal dissection (ESD) led to significantly fewer severe adverse perioperative events than esophagectomy and was associated with similar rates of all-cause mortality and cancer recurrence or metastasis, according to the findings of a single-center retrospective cohort study.

After a median of 21 months of follow-up (range, 6-73 months), rates of all-cause mortality were 7% with ESD and 11% with esophagectomy, said Yiqun Zhang of Zhongshan Hospital, Shanghai, China, and his associates. Rates of cancer recurrence or metastasis were 9.1% and 8.9%, respectively, while disease-specific mortality was lower with ESD (3.4% vs. 7.4% with esophagectomy; P = .049). Severe nonfatal adverse perioperative events occurred in 15% of ESD cases versus 28% of esophagectomy cases (P less than .001). The findings justify more studies of ESD in carefully selected patients with early-stage (T1a-m2/m3 or T1b) esophageal squamous cell carcinoma, the researchers wrote in Clinical Gastroenterology and Hepatology.

Esophagectomy is standard for managing early-stage esophageal squamous cell carcinoma but is associated with high rates of morbidity and mortality. While ESD is minimally invasive, it is considered risky because esophageal squamous cell carcinoma so frequently metastasizes to the lymph nodes, the investigators noted. For the study, they retrospectively compared 322 ESDs and 274 esophagectomies performed during 2011-2016 in patients with T1a-m2/m3 or T1b esophageal squamous cell carcinoma. All cases were pathologically confirmed, and none were premalignant (that is, high-grade intraepithelial neoplasias).

Endoscopic submucosal dissection was associated with significantly lower rates of esophageal fistula (0.3% with ESD vs. 16% with esophagectomy; P less than .001) and pulmonary complications (0.3% vs. 3.6%, respectively; P less than .001), which explained its overall superiority in terms of severe adverse perioperative events, the researchers wrote. Perioperative deaths were rare but occurred more often with esophagectomy (four patients) than with ESD (one patient). Depth of tumor invasion was the only significant correlate of all-cause mortality (hazard ratio for T1a–m3 or deeper tumors versus T1a–m2 tumors, 3.54; 95% confidence interval, 1.08-11.62; P = .04) in a Cox regression analysis that accounted for many potential confounders, such as demographic and tumor characteristics, hypertension, chronic obstructive pulmonary disease (COPD), nodal metastasis, chemotherapy, and radiotherapy.

Perhaps esophagectomy did not improve survival in this retrospective study because follow-up time was too short, because adjuvant therapy compensated for the increased risk of tumor relapse with ESD, or because of the confounding effects of unmeasured variables, such as submucosal stages of T1b cancer, lymphovascular invasion, or tumor morphology, the researchers wrote. “Since a randomized study comparing esophagectomy and ESD alone would not be practical, a potential strategy for future research may include serial treatments – that is, ESD first, followed by esophagectomy, radiotherapy, or chemotherapy, depending on the ESD pathology findings,” they added. “A quality-of-life analysis of ESD would also be helpful because this might be one of the biggest advantages of ESD over esophagectomy and was beyond the scope of this study.”

The study was supported by the National Natural Science Foundation of China, the Shanghai Committee of Science and Technology, and Zhongshan Hospital. The investigators reported having no relevant conflicts of interest.

SOURCE: Zhang Y et al. Clin Gastroenterol Hepatol. 2018 Apr 25. doi: 10.1016/j.cgh.2018.04.038.

Two recent studies highlight the ability of vedolizumab and tofacitinib to rapidly improve symptoms reported by patients with inflammatory bowel disease.

In a post hoc study of 1,758 patients with ulcerative colitis (UC) or Crohn’s disease (CD) in the phase 3 GEMINI trials, 2 weeks of vedolizumab (Entyvio) therapy effectively improved patient-reported outcomes, and these continued to improve through 6 weeks of treatment, wrote Brian G. Feagan, MD, and his associates in Clinical Gastroenterology and Hepatology.

Among UC patients who had not previously received tumor necrosis factor (TNF) antagonist therapy, 22% of vedolizumab recipients, compared with only 7% of placebo recipients, achieved complete resolution of rectal bleeding together with a meaningful reduction in stool frequency at treatment week 2, the investigators noted. Among CD patients who were naive to TNF antagonists, 15% reported meaningful decreases in abdominal pain and loose stools at treatment week 2, compared with only 8% of placebo recipients.

Although 2 weeks of vedolizumab also topped placebo for improving patient-reported outcomes among TNF antagonist–exposed patients, the effects were less pronounced, wrote Dr. Feagan, of the University of Western Ontario, London, and his associates. “These data add to the growing evidence that second-generation biologics, such as vedolizumab and ustekinumab, have higher efficacy in TNF antagonist–naive patients in both clinical trials and real-world settings. Recent trends in clinical practice are moving toward incorporating disease-modifying therapy earlier in the treatment of IBD to prevent disease progression and cumulative bowel damage; hence, the importance of evaluating the treatment effects of vedolizumab in biologic-naive patients.”

Patient-reported outcomes have become key during both clinical research and regulatory review of claims on proposed drug labels. In the second study, also published in Clinical Gastroenterology and Hepatology, Stephen B. Hanauer, MD, of Northwestern University, Chicago, and his associates performed a post hoc analysis of symptoms reported by 1,139 adults with UC who received the oral small-molecule Janus kinase inhibitor tofacitinib (10 g twice daily) or placebo during the 8-week OCTAVE Induction 1 and 2 trials. These were identical phase 3 studies of patients with moderate to severe UC who could not tolerate or had responded inadequately to TNF antagonists, corticosteroids, or thiopurines.

Compared with placebo, 3 days of tofacitinib therapy induced significantly greater reductions from baseline in patient-reported stool frequency and rectal bleeding (P less than .01 for each measure), Dr. Hanauer and his associates reported. The effect was independent of prior treatment for UC or baseline levels of C-reactive protein. These findings reflect the rapid onset of effect of tofacitinib therapy in patients with UC. In contrast, thiopurines (azathioprine and 6-mercaptopurine) can take at least 8 weeks to exhibit steroid-sparing effects.

While corticosteroids can induce UC remission within 5 days, their side effects tend to escalate over time and they “lack maintenance benefits,” the researchers wrote. “In these analyses, onset of tofacitinib efficacy occurred within 3 days, irrespective of concomitant corticosteroid use or prior anti-TNF treatment failure.”

Takeda funded the GEMINI studies. Dr. Feagan reported advisory relationships with Takeda, AbbVie, Amgen, AstraZeneca, and several other pharmaceutical companies. Dr. Hanauer also reported ties to numerous pharmaceutical companies, including Pfizer, which funded the OCTAVE trials.

SOURCES: Feagan BG et al. Clin Gastroenterol Hepatol. 2018 May 29. doi: 10.1016/j.cgh.2018.05.026; Hanauer S et al. Clin Gastroenterol Hepatol. 2018 Jul 15. doi: 10.1016/j.cgh.2018.07.009.

Two recent studies highlight the ability of vedolizumab and tofacitinib to rapidly improve symptoms reported by patients with inflammatory bowel disease.

In a post hoc study of 1,758 patients with ulcerative colitis (UC) or Crohn’s disease (CD) in the phase 3 GEMINI trials, 2 weeks of vedolizumab (Entyvio) therapy effectively improved patient-reported outcomes, and these continued to improve through 6 weeks of treatment, wrote Brian G. Feagan, MD, and his associates in Clinical Gastroenterology and Hepatology.

Among UC patients who had not previously received tumor necrosis factor (TNF) antagonist therapy, 22% of vedolizumab recipients, compared with only 7% of placebo recipients, achieved complete resolution of rectal bleeding together with a meaningful reduction in stool frequency at treatment week 2, the investigators noted. Among CD patients who were naive to TNF antagonists, 15% reported meaningful decreases in abdominal pain and loose stools at treatment week 2, compared with only 8% of placebo recipients.

Although 2 weeks of vedolizumab also topped placebo for improving patient-reported outcomes among TNF antagonist–exposed patients, the effects were less pronounced, wrote Dr. Feagan, of the University of Western Ontario, London, and his associates. “These data add to the growing evidence that second-generation biologics, such as vedolizumab and ustekinumab, have higher efficacy in TNF antagonist–naive patients in both clinical trials and real-world settings. Recent trends in clinical practice are moving toward incorporating disease-modifying therapy earlier in the treatment of IBD to prevent disease progression and cumulative bowel damage; hence, the importance of evaluating the treatment effects of vedolizumab in biologic-naive patients.”

Patient-reported outcomes have become key during both clinical research and regulatory review of claims on proposed drug labels. In the second study, also published in Clinical Gastroenterology and Hepatology, Stephen B. Hanauer, MD, of Northwestern University, Chicago, and his associates performed a post hoc analysis of symptoms reported by 1,139 adults with UC who received the oral small-molecule Janus kinase inhibitor tofacitinib (10 g twice daily) or placebo during the 8-week OCTAVE Induction 1 and 2 trials. These were identical phase 3 studies of patients with moderate to severe UC who could not tolerate or had responded inadequately to TNF antagonists, corticosteroids, or thiopurines.

Compared with placebo, 3 days of tofacitinib therapy induced significantly greater reductions from baseline in patient-reported stool frequency and rectal bleeding (P less than .01 for each measure), Dr. Hanauer and his associates reported. The effect was independent of prior treatment for UC or baseline levels of C-reactive protein. These findings reflect the rapid onset of effect of tofacitinib therapy in patients with UC. In contrast, thiopurines (azathioprine and 6-mercaptopurine) can take at least 8 weeks to exhibit steroid-sparing effects.

While corticosteroids can induce UC remission within 5 days, their side effects tend to escalate over time and they “lack maintenance benefits,” the researchers wrote. “In these analyses, onset of tofacitinib efficacy occurred within 3 days, irrespective of concomitant corticosteroid use or prior anti-TNF treatment failure.”

Takeda funded the GEMINI studies. Dr. Feagan reported advisory relationships with Takeda, AbbVie, Amgen, AstraZeneca, and several other pharmaceutical companies. Dr. Hanauer also reported ties to numerous pharmaceutical companies, including Pfizer, which funded the OCTAVE trials.

SOURCES: Feagan BG et al. Clin Gastroenterol Hepatol. 2018 May 29. doi: 10.1016/j.cgh.2018.05.026; Hanauer S et al. Clin Gastroenterol Hepatol. 2018 Jul 15. doi: 10.1016/j.cgh.2018.07.009.

Two recent studies highlight the ability of vedolizumab and tofacitinib to rapidly improve symptoms reported by patients with inflammatory bowel disease.

In a post hoc study of 1,758 patients with ulcerative colitis (UC) or Crohn’s disease (CD) in the phase 3 GEMINI trials, 2 weeks of vedolizumab (Entyvio) therapy effectively improved patient-reported outcomes, and these continued to improve through 6 weeks of treatment, wrote Brian G. Feagan, MD, and his associates in Clinical Gastroenterology and Hepatology.

Among UC patients who had not previously received tumor necrosis factor (TNF) antagonist therapy, 22% of vedolizumab recipients, compared with only 7% of placebo recipients, achieved complete resolution of rectal bleeding together with a meaningful reduction in stool frequency at treatment week 2, the investigators noted. Among CD patients who were naive to TNF antagonists, 15% reported meaningful decreases in abdominal pain and loose stools at treatment week 2, compared with only 8% of placebo recipients.

Although 2 weeks of vedolizumab also topped placebo for improving patient-reported outcomes among TNF antagonist–exposed patients, the effects were less pronounced, wrote Dr. Feagan, of the University of Western Ontario, London, and his associates. “These data add to the growing evidence that second-generation biologics, such as vedolizumab and ustekinumab, have higher efficacy in TNF antagonist–naive patients in both clinical trials and real-world settings. Recent trends in clinical practice are moving toward incorporating disease-modifying therapy earlier in the treatment of IBD to prevent disease progression and cumulative bowel damage; hence, the importance of evaluating the treatment effects of vedolizumab in biologic-naive patients.”

Patient-reported outcomes have become key during both clinical research and regulatory review of claims on proposed drug labels. In the second study, also published in Clinical Gastroenterology and Hepatology, Stephen B. Hanauer, MD, of Northwestern University, Chicago, and his associates performed a post hoc analysis of symptoms reported by 1,139 adults with UC who received the oral small-molecule Janus kinase inhibitor tofacitinib (10 g twice daily) or placebo during the 8-week OCTAVE Induction 1 and 2 trials. These were identical phase 3 studies of patients with moderate to severe UC who could not tolerate or had responded inadequately to TNF antagonists, corticosteroids, or thiopurines.

Compared with placebo, 3 days of tofacitinib therapy induced significantly greater reductions from baseline in patient-reported stool frequency and rectal bleeding (P less than .01 for each measure), Dr. Hanauer and his associates reported. The effect was independent of prior treatment for UC or baseline levels of C-reactive protein. These findings reflect the rapid onset of effect of tofacitinib therapy in patients with UC. In contrast, thiopurines (azathioprine and 6-mercaptopurine) can take at least 8 weeks to exhibit steroid-sparing effects.

While corticosteroids can induce UC remission within 5 days, their side effects tend to escalate over time and they “lack maintenance benefits,” the researchers wrote. “In these analyses, onset of tofacitinib efficacy occurred within 3 days, irrespective of concomitant corticosteroid use or prior anti-TNF treatment failure.”

Takeda funded the GEMINI studies. Dr. Feagan reported advisory relationships with Takeda, AbbVie, Amgen, AstraZeneca, and several other pharmaceutical companies. Dr. Hanauer also reported ties to numerous pharmaceutical companies, including Pfizer, which funded the OCTAVE trials.

SOURCES: Feagan BG et al. Clin Gastroenterol Hepatol. 2018 May 29. doi: 10.1016/j.cgh.2018.05.026; Hanauer S et al. Clin Gastroenterol Hepatol. 2018 Jul 15. doi: 10.1016/j.cgh.2018.07.009.

Routine clinical and laboratory markers predicted histologic response to obeticholic acid therapy among patients with nonalcoholic steatohepatitis (NASH), investigators reported in Gastroenterology.

In a secondary analysis of data from the FLINT trial, histologic response at treatment week 24 correlated significantly with baseline nonalcoholic fatty liver disease activity score (NAS) greater than 5, baseline triglycerides 154 mg/dL or less, baseline international normalized ratio no greater than 1, baseline aspartate aminotransferase (AST) level no greater than 49 U/L, and at least a 17-U/L decrease from baseline in alanine aminotransferase (ALT) level.

A stepwise logistic regression model including these variables and receipt of obeticholic acid distinguished histologic responders from nonresponders with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% confidence interval, 0.77-0.89; P less than .0001). These parameters “are readily available clinical and biochemical characteristics that are routinely available to clinicians and may be applied to daily practice,” wrote Rohit Loomba, MD, of the University of California, San Diego, with his associates. They may show “that the patients most likely to achieve histologic response are those with higher disease activity, but still with largely conserved liver function, allowing for potential healing or improvement.”

NASH is expected to become the leading reason for liver transplantation in the next few decades. Several treatments can induce histologic hepatic improvement, but none are approved for NASH. Obeticholic acid (Ocaliva) is a selective agonist of the farsenoid X receptor ligand and is indicated for treating primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA).

In the 72-week, multicenter, randomized, double-blind FLINT trial, noncirrhotic adults with biopsy-confirmed NASH received once-daily obeticholic acid (25 mg) or placebo. Blinded pathologists interpreted biopsies. The primary endpoint (improvement in liver histology) was met in the interim analysis, so the researchers stopped collecting final liver biopsies.

The secondary analysis included all patients with baseline and final biopsies, including 73 histologic responders and 127 nonresponders. “[The] trends for each of the selected predictors was the same when comparing histologic responders to nonresponders, regardless of treatment group (obeticholic acid versus placebo),” the researchers wrote. The predictors are biologically feasible, the researchers contended – for example, high baseline NAS would be more susceptible to significant improvement, while lower baseline triglyceride levels might reflect a liver that “is less burdened by triglyceride secretion” and, therefore, might have greater capacity to heal. Both AST and ALT “are metrics of liver injury,” and lower baseline AST, in combination with greater reduction in ALT at week 24, probably reflected “AST and ALT levels that are closer to normal,” they added.

Nonetheless, the researchers acknowledged several possible sources of bias. Trial participants were recruited from tertiary care settings and had complete biopsy data, which might not reflect the overall NASH population. Overfitting also could have biased the model because the number of variables assessed approached the number of events being predicted. Furthermore, the model assessed no treatment other than obeticholic acid. “A more robust model could potentially be developed if multiple pharmacological interventions could be considered simultaneously,” the researchers noted. The ongoing phase 3 REGENERATE trial aims to confirm the benefit of obeticholic acid in patients with NASH, they added. Topline results are expected in October 2022.

The FLINT trial was funded by Intercept Pharmaceuticals and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Loomba cochaired the FLINT trial protocol writing committee, is on the steering committee of the ongoing REGENERATE trial, and has received research funding from Intercept Pharmaceuticals, which developed and markets obeticholic acid. Several other coinvestigators reported ties to Intercept and to other pharmaceutical companies.

SOURCE: Loomba R et al. Gastroenterology. 2018 Sep 14. doi: 10.1053/j.gastro.2018.09.021.

Routine clinical and laboratory markers predicted histologic response to obeticholic acid therapy among patients with nonalcoholic steatohepatitis (NASH), investigators reported in Gastroenterology.

In a secondary analysis of data from the FLINT trial, histologic response at treatment week 24 correlated significantly with baseline nonalcoholic fatty liver disease activity score (NAS) greater than 5, baseline triglycerides 154 mg/dL or less, baseline international normalized ratio no greater than 1, baseline aspartate aminotransferase (AST) level no greater than 49 U/L, and at least a 17-U/L decrease from baseline in alanine aminotransferase (ALT) level.

A stepwise logistic regression model including these variables and receipt of obeticholic acid distinguished histologic responders from nonresponders with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% confidence interval, 0.77-0.89; P less than .0001). These parameters “are readily available clinical and biochemical characteristics that are routinely available to clinicians and may be applied to daily practice,” wrote Rohit Loomba, MD, of the University of California, San Diego, with his associates. They may show “that the patients most likely to achieve histologic response are those with higher disease activity, but still with largely conserved liver function, allowing for potential healing or improvement.”

NASH is expected to become the leading reason for liver transplantation in the next few decades. Several treatments can induce histologic hepatic improvement, but none are approved for NASH. Obeticholic acid (Ocaliva) is a selective agonist of the farsenoid X receptor ligand and is indicated for treating primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA).

In the 72-week, multicenter, randomized, double-blind FLINT trial, noncirrhotic adults with biopsy-confirmed NASH received once-daily obeticholic acid (25 mg) or placebo. Blinded pathologists interpreted biopsies. The primary endpoint (improvement in liver histology) was met in the interim analysis, so the researchers stopped collecting final liver biopsies.

The secondary analysis included all patients with baseline and final biopsies, including 73 histologic responders and 127 nonresponders. “[The] trends for each of the selected predictors was the same when comparing histologic responders to nonresponders, regardless of treatment group (obeticholic acid versus placebo),” the researchers wrote. The predictors are biologically feasible, the researchers contended – for example, high baseline NAS would be more susceptible to significant improvement, while lower baseline triglyceride levels might reflect a liver that “is less burdened by triglyceride secretion” and, therefore, might have greater capacity to heal. Both AST and ALT “are metrics of liver injury,” and lower baseline AST, in combination with greater reduction in ALT at week 24, probably reflected “AST and ALT levels that are closer to normal,” they added.

Nonetheless, the researchers acknowledged several possible sources of bias. Trial participants were recruited from tertiary care settings and had complete biopsy data, which might not reflect the overall NASH population. Overfitting also could have biased the model because the number of variables assessed approached the number of events being predicted. Furthermore, the model assessed no treatment other than obeticholic acid. “A more robust model could potentially be developed if multiple pharmacological interventions could be considered simultaneously,” the researchers noted. The ongoing phase 3 REGENERATE trial aims to confirm the benefit of obeticholic acid in patients with NASH, they added. Topline results are expected in October 2022.

The FLINT trial was funded by Intercept Pharmaceuticals and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Loomba cochaired the FLINT trial protocol writing committee, is on the steering committee of the ongoing REGENERATE trial, and has received research funding from Intercept Pharmaceuticals, which developed and markets obeticholic acid. Several other coinvestigators reported ties to Intercept and to other pharmaceutical companies.

SOURCE: Loomba R et al. Gastroenterology. 2018 Sep 14. doi: 10.1053/j.gastro.2018.09.021.

Routine clinical and laboratory markers predicted histologic response to obeticholic acid therapy among patients with nonalcoholic steatohepatitis (NASH), investigators reported in Gastroenterology.

In a secondary analysis of data from the FLINT trial, histologic response at treatment week 24 correlated significantly with baseline nonalcoholic fatty liver disease activity score (NAS) greater than 5, baseline triglycerides 154 mg/dL or less, baseline international normalized ratio no greater than 1, baseline aspartate aminotransferase (AST) level no greater than 49 U/L, and at least a 17-U/L decrease from baseline in alanine aminotransferase (ALT) level.

A stepwise logistic regression model including these variables and receipt of obeticholic acid distinguished histologic responders from nonresponders with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% confidence interval, 0.77-0.89; P less than .0001). These parameters “are readily available clinical and biochemical characteristics that are routinely available to clinicians and may be applied to daily practice,” wrote Rohit Loomba, MD, of the University of California, San Diego, with his associates. They may show “that the patients most likely to achieve histologic response are those with higher disease activity, but still with largely conserved liver function, allowing for potential healing or improvement.”

NASH is expected to become the leading reason for liver transplantation in the next few decades. Several treatments can induce histologic hepatic improvement, but none are approved for NASH. Obeticholic acid (Ocaliva) is a selective agonist of the farsenoid X receptor ligand and is indicated for treating primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA).

In the 72-week, multicenter, randomized, double-blind FLINT trial, noncirrhotic adults with biopsy-confirmed NASH received once-daily obeticholic acid (25 mg) or placebo. Blinded pathologists interpreted biopsies. The primary endpoint (improvement in liver histology) was met in the interim analysis, so the researchers stopped collecting final liver biopsies.

The secondary analysis included all patients with baseline and final biopsies, including 73 histologic responders and 127 nonresponders. “[The] trends for each of the selected predictors was the same when comparing histologic responders to nonresponders, regardless of treatment group (obeticholic acid versus placebo),” the researchers wrote. The predictors are biologically feasible, the researchers contended – for example, high baseline NAS would be more susceptible to significant improvement, while lower baseline triglyceride levels might reflect a liver that “is less burdened by triglyceride secretion” and, therefore, might have greater capacity to heal. Both AST and ALT “are metrics of liver injury,” and lower baseline AST, in combination with greater reduction in ALT at week 24, probably reflected “AST and ALT levels that are closer to normal,” they added.

Nonetheless, the researchers acknowledged several possible sources of bias. Trial participants were recruited from tertiary care settings and had complete biopsy data, which might not reflect the overall NASH population. Overfitting also could have biased the model because the number of variables assessed approached the number of events being predicted. Furthermore, the model assessed no treatment other than obeticholic acid. “A more robust model could potentially be developed if multiple pharmacological interventions could be considered simultaneously,” the researchers noted. The ongoing phase 3 REGENERATE trial aims to confirm the benefit of obeticholic acid in patients with NASH, they added. Topline results are expected in October 2022.

The FLINT trial was funded by Intercept Pharmaceuticals and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Loomba cochaired the FLINT trial protocol writing committee, is on the steering committee of the ongoing REGENERATE trial, and has received research funding from Intercept Pharmaceuticals, which developed and markets obeticholic acid. Several other coinvestigators reported ties to Intercept and to other pharmaceutical companies.

SOURCE: Loomba R et al. Gastroenterology. 2018 Sep 14. doi: 10.1053/j.gastro.2018.09.021.

Patients who died from colorectal cancer were significantly more likely than controls not to have been screened, to have missed screenings, or not to have followed up on an abnormal result, according to the results of a large retrospective case-control study.

Source: American Gastroenterological Association

The findings signify “potentially modifiable” screening failures in a population known for relatively high uptake of colorectal cancer screening, wrote Chyke A. Doubeni, MD, MPH, of the University of Pennsylvania, Philadelphia, and his associates in Gastroenterology. Strikingly, 76% of patients who died from colorectal cancer were not current on screening versus 55% of cancer-free patients, they said. Being up to date on screening decreased the odds of dying from colorectal cancer by 62% (odds ratio, 0.38; 95% confidence interval, 0.33-0.44), even after adjustment for race, ethnicity, socioeconomic status, comorbidities, and frequency of contact with primary care providers, they added.

Colonoscopy, sigmoidoscopy, and fecal testing are effective and recommended screening techniques that help prevent deaths from colorectal cancer. Therefore, most such deaths are thought to result from “breakdowns in the screening process,” the researchers wrote. However, interval cancers and missed lesions also play a role, and no prior study has examined detailed screening histories and their association with colorectal cancer mortality.

Accordingly, the researchers reviewed medical records and registry data for 1,750 enrollees in the Kaiser Permanente Northern and Southern California systems who died from colorectal cancer during 2002-2012 and were part of the health plan for at least 5 years before their cancer diagnosis. They compared these patients with 3,486 cancer-free controls matched by age, sex, study site, and numbers of years enrolled in the health plan. Patients were considered up to date on screening if they were screened at intervals recommended by the 2008 multisociety colorectal cancer screening guidelines – that is, if they had received a colonoscopy within 10 years of colorectal cancer diagnosis or sigmoidoscopy or barium enema within 5 years of it. For fecal testing, the investigators used a 2-year interval based on its efficacy in clinical trials.

Among patients who died from colorectal cancer, only 24% were up to date on screening versus 45% of cancer-free-patients, the investigators determined. Furthermore, 68% of patients who died from colorectal cancer were never screened or were not screened at appropriate intervals, compared with 53% of cancer-free patients.

Additionally, while 8% of colorectal cancer deaths occurred in patients who had not followed up on abnormal screening results, only 2% of controls who had received abnormal screening results had failed to follow up.

“In two health systems with high rates of screening, we observed that most patients dying from colorectal cancer had potentially modifiable failures of the screening process,” the researchers concluded. “This study suggests that, even in settings with high screening uptake, access to and timely uptake of screening, regular rescreening, appropriate use of testing given patient characteristics, completion of timely diagnostic testing when screening is positive, and improving the effectiveness of screening tests, particularly for right colon cancer, remain important areas of focus for further decreasing colorectal cancer deaths.”

The National Institutes of Health funded the work. The investigators reported having no conflicts of interest except that one coinvestigator is editor in chief of the journal Gastroenterology.

SOURCE: Doubeni CA et al. Gastroenterology. 2018 Sep 27. doi: 10.1053/j.gastro.2018.09.040.

Patients who died from colorectal cancer were significantly more likely than controls not to have been screened, to have missed screenings, or not to have followed up on an abnormal result, according to the results of a large retrospective case-control study.

Source: American Gastroenterological Association

The findings signify “potentially modifiable” screening failures in a population known for relatively high uptake of colorectal cancer screening, wrote Chyke A. Doubeni, MD, MPH, of the University of Pennsylvania, Philadelphia, and his associates in Gastroenterology. Strikingly, 76% of patients who died from colorectal cancer were not current on screening versus 55% of cancer-free patients, they said. Being up to date on screening decreased the odds of dying from colorectal cancer by 62% (odds ratio, 0.38; 95% confidence interval, 0.33-0.44), even after adjustment for race, ethnicity, socioeconomic status, comorbidities, and frequency of contact with primary care providers, they added.

Colonoscopy, sigmoidoscopy, and fecal testing are effective and recommended screening techniques that help prevent deaths from colorectal cancer. Therefore, most such deaths are thought to result from “breakdowns in the screening process,” the researchers wrote. However, interval cancers and missed lesions also play a role, and no prior study has examined detailed screening histories and their association with colorectal cancer mortality.

Accordingly, the researchers reviewed medical records and registry data for 1,750 enrollees in the Kaiser Permanente Northern and Southern California systems who died from colorectal cancer during 2002-2012 and were part of the health plan for at least 5 years before their cancer diagnosis. They compared these patients with 3,486 cancer-free controls matched by age, sex, study site, and numbers of years enrolled in the health plan. Patients were considered up to date on screening if they were screened at intervals recommended by the 2008 multisociety colorectal cancer screening guidelines – that is, if they had received a colonoscopy within 10 years of colorectal cancer diagnosis or sigmoidoscopy or barium enema within 5 years of it. For fecal testing, the investigators used a 2-year interval based on its efficacy in clinical trials.

Among patients who died from colorectal cancer, only 24% were up to date on screening versus 45% of cancer-free-patients, the investigators determined. Furthermore, 68% of patients who died from colorectal cancer were never screened or were not screened at appropriate intervals, compared with 53% of cancer-free patients.

Additionally, while 8% of colorectal cancer deaths occurred in patients who had not followed up on abnormal screening results, only 2% of controls who had received abnormal screening results had failed to follow up.

“In two health systems with high rates of screening, we observed that most patients dying from colorectal cancer had potentially modifiable failures of the screening process,” the researchers concluded. “This study suggests that, even in settings with high screening uptake, access to and timely uptake of screening, regular rescreening, appropriate use of testing given patient characteristics, completion of timely diagnostic testing when screening is positive, and improving the effectiveness of screening tests, particularly for right colon cancer, remain important areas of focus for further decreasing colorectal cancer deaths.”

The National Institutes of Health funded the work. The investigators reported having no conflicts of interest except that one coinvestigator is editor in chief of the journal Gastroenterology.

SOURCE: Doubeni CA et al. Gastroenterology. 2018 Sep 27. doi: 10.1053/j.gastro.2018.09.040.

Patients who died from colorectal cancer were significantly more likely than controls not to have been screened, to have missed screenings, or not to have followed up on an abnormal result, according to the results of a large retrospective case-control study.

Source: American Gastroenterological Association

The findings signify “potentially modifiable” screening failures in a population known for relatively high uptake of colorectal cancer screening, wrote Chyke A. Doubeni, MD, MPH, of the University of Pennsylvania, Philadelphia, and his associates in Gastroenterology. Strikingly, 76% of patients who died from colorectal cancer were not current on screening versus 55% of cancer-free patients, they said. Being up to date on screening decreased the odds of dying from colorectal cancer by 62% (odds ratio, 0.38; 95% confidence interval, 0.33-0.44), even after adjustment for race, ethnicity, socioeconomic status, comorbidities, and frequency of contact with primary care providers, they added.

Colonoscopy, sigmoidoscopy, and fecal testing are effective and recommended screening techniques that help prevent deaths from colorectal cancer. Therefore, most such deaths are thought to result from “breakdowns in the screening process,” the researchers wrote. However, interval cancers and missed lesions also play a role, and no prior study has examined detailed screening histories and their association with colorectal cancer mortality.

Accordingly, the researchers reviewed medical records and registry data for 1,750 enrollees in the Kaiser Permanente Northern and Southern California systems who died from colorectal cancer during 2002-2012 and were part of the health plan for at least 5 years before their cancer diagnosis. They compared these patients with 3,486 cancer-free controls matched by age, sex, study site, and numbers of years enrolled in the health plan. Patients were considered up to date on screening if they were screened at intervals recommended by the 2008 multisociety colorectal cancer screening guidelines – that is, if they had received a colonoscopy within 10 years of colorectal cancer diagnosis or sigmoidoscopy or barium enema within 5 years of it. For fecal testing, the investigators used a 2-year interval based on its efficacy in clinical trials.

Among patients who died from colorectal cancer, only 24% were up to date on screening versus 45% of cancer-free-patients, the investigators determined. Furthermore, 68% of patients who died from colorectal cancer were never screened or were not screened at appropriate intervals, compared with 53% of cancer-free patients.

Additionally, while 8% of colorectal cancer deaths occurred in patients who had not followed up on abnormal screening results, only 2% of controls who had received abnormal screening results had failed to follow up.

“In two health systems with high rates of screening, we observed that most patients dying from colorectal cancer had potentially modifiable failures of the screening process,” the researchers concluded. “This study suggests that, even in settings with high screening uptake, access to and timely uptake of screening, regular rescreening, appropriate use of testing given patient characteristics, completion of timely diagnostic testing when screening is positive, and improving the effectiveness of screening tests, particularly for right colon cancer, remain important areas of focus for further decreasing colorectal cancer deaths.”

The National Institutes of Health funded the work. The investigators reported having no conflicts of interest except that one coinvestigator is editor in chief of the journal Gastroenterology.

SOURCE: Doubeni CA et al. Gastroenterology. 2018 Sep 27. doi: 10.1053/j.gastro.2018.09.040.

Among patients with lymphocytic colitis, 8 weeks of oral budesonide therapy was associated with significantly higher rates of clinical and histologic remission versus placebo in a multicenter, double-blind clinical trial.

Fully 79% of patients achieved clinical remission with budesonide, compared with only 42% of patients in the placebo arm (P = .01), reported Stephan Miehlke, MD, of the Center for Digestive Diseases in Hamburg, Germany, and his associates. A third group of patients received oral mesalazine therapy, which induced clinical remission in 68% of cases (P = .09). Budesonide also induced histologic remission significantly more often (68%) than did mesalazine (26%; P = .02) or placebo (21%; P = .008).

“The study population was not large, but the trial was adequately powered,” the researchers wrote. The report was published online in Gastroenterology. “These results confirm the efficacy of budesonide for the induction of remission in active lymphocytic colitis and are consistent with expert recommendations for its use as first-line therapy.”

Lymphocytic colitis is a subtype of microscopic colitis that is characterized by an increase in intraepithelial lymphocytes. This condition has substantial negative effects on quality of life – the most common symptom is chronic diarrhea, and some patients also experience fecal incontinence and abdominal pain. Expert guidelines recommend first-line treatment with budesonide and second-line treatment with mesalazine, but evidence supporting either recommendation is sparse and low-quality, the investigators wrote.

For the study, they compared 8 weeks of treatment with pH-modified release oral budesonide granules (9 mg once daily), oral mesalazine granules (3 g once daily) or placebo in 57 patients (19 per arm) with histologically confirmed, newly diagnosed or relapsed lymphocytic colitis. All patients had at least a 12-week history of watery, nonbloody diarrhea, no other documented diarrheal conditions, and no recent history of antidiarrheal therapy. Nearly three-quarters were female and the mean age was 59 years. The primary endpoint was clinical remission, defined as no more than 21 stools in the 7 days before week 8, including no more than 6 watery stools.

After 8 weeks of double-blinded treatment, all clinically remitted patients stopped treatment and were followed for another 16 weeks. Those who were not in remission or who relapsed were offered 4 weeks of open-label budesonide therapy, which led to clinical remission in 88% of cases, the researchers said. “This study confirms that budesonide is effective for the induction of remission in active lymphocytic colitis,” they concluded. “Strikingly, a substantial improvement in symptoms, including a profound reduction in the number of watery stools, was seen within a median of 3 days after starting budesonide therapy.”

Serious adverse events were uncommon in all three groups, and each arm had a similar rate of adverse events considered secondary to treatment. In the budesonide group, these included one case each of weight gain, transient ischemic attack, and affective disturbance with sleep disorder. In the mesalazine group, three patients developed acute pancreatitis, increased hepatic enzymes, or dizziness. Eleven percent of budesonide recipients and 16% of mesalazine recipients stopped treatment because of adverse events. “No patient in any group had a clinically significant shift in cortisol level between baseline and week 8 that was considered related to the study drug,” the investigators said. “Other changes in laboratory parameters were not considered clinically relevant in any treatment group.”

The study was funded by Dr. Falk Pharma GmbH, Freiburg, Germany. Dr. Miehlke and two coauthors received speaker fees from Dr. Falk Pharma. Dr. Miehlke and one coauthor received consultancy fees from Tillots. One coauthor received speaker fees, has been a member of the advisory board, and has received grants from Tillots.

SOURCE: Miehlke S et al. Gastroenterology. 2018 Sep 6. doi: 10.1053/j.gastro.2018.08.042.

Among patients with lymphocytic colitis, 8 weeks of oral budesonide therapy was associated with significantly higher rates of clinical and histologic remission versus placebo in a multicenter, double-blind clinical trial.

Fully 79% of patients achieved clinical remission with budesonide, compared with only 42% of patients in the placebo arm (P = .01), reported Stephan Miehlke, MD, of the Center for Digestive Diseases in Hamburg, Germany, and his associates. A third group of patients received oral mesalazine therapy, which induced clinical remission in 68% of cases (P = .09). Budesonide also induced histologic remission significantly more often (68%) than did mesalazine (26%; P = .02) or placebo (21%; P = .008).

“The study population was not large, but the trial was adequately powered,” the researchers wrote. The report was published online in Gastroenterology. “These results confirm the efficacy of budesonide for the induction of remission in active lymphocytic colitis and are consistent with expert recommendations for its use as first-line therapy.”

Lymphocytic colitis is a subtype of microscopic colitis that is characterized by an increase in intraepithelial lymphocytes. This condition has substantial negative effects on quality of life – the most common symptom is chronic diarrhea, and some patients also experience fecal incontinence and abdominal pain. Expert guidelines recommend first-line treatment with budesonide and second-line treatment with mesalazine, but evidence supporting either recommendation is sparse and low-quality, the investigators wrote.

For the study, they compared 8 weeks of treatment with pH-modified release oral budesonide granules (9 mg once daily), oral mesalazine granules (3 g once daily) or placebo in 57 patients (19 per arm) with histologically confirmed, newly diagnosed or relapsed lymphocytic colitis. All patients had at least a 12-week history of watery, nonbloody diarrhea, no other documented diarrheal conditions, and no recent history of antidiarrheal therapy. Nearly three-quarters were female and the mean age was 59 years. The primary endpoint was clinical remission, defined as no more than 21 stools in the 7 days before week 8, including no more than 6 watery stools.

After 8 weeks of double-blinded treatment, all clinically remitted patients stopped treatment and were followed for another 16 weeks. Those who were not in remission or who relapsed were offered 4 weeks of open-label budesonide therapy, which led to clinical remission in 88% of cases, the researchers said. “This study confirms that budesonide is effective for the induction of remission in active lymphocytic colitis,” they concluded. “Strikingly, a substantial improvement in symptoms, including a profound reduction in the number of watery stools, was seen within a median of 3 days after starting budesonide therapy.”

Serious adverse events were uncommon in all three groups, and each arm had a similar rate of adverse events considered secondary to treatment. In the budesonide group, these included one case each of weight gain, transient ischemic attack, and affective disturbance with sleep disorder. In the mesalazine group, three patients developed acute pancreatitis, increased hepatic enzymes, or dizziness. Eleven percent of budesonide recipients and 16% of mesalazine recipients stopped treatment because of adverse events. “No patient in any group had a clinically significant shift in cortisol level between baseline and week 8 that was considered related to the study drug,” the investigators said. “Other changes in laboratory parameters were not considered clinically relevant in any treatment group.”

The study was funded by Dr. Falk Pharma GmbH, Freiburg, Germany. Dr. Miehlke and two coauthors received speaker fees from Dr. Falk Pharma. Dr. Miehlke and one coauthor received consultancy fees from Tillots. One coauthor received speaker fees, has been a member of the advisory board, and has received grants from Tillots.

SOURCE: Miehlke S et al. Gastroenterology. 2018 Sep 6. doi: 10.1053/j.gastro.2018.08.042.

Among patients with lymphocytic colitis, 8 weeks of oral budesonide therapy was associated with significantly higher rates of clinical and histologic remission versus placebo in a multicenter, double-blind clinical trial.

Fully 79% of patients achieved clinical remission with budesonide, compared with only 42% of patients in the placebo arm (P = .01), reported Stephan Miehlke, MD, of the Center for Digestive Diseases in Hamburg, Germany, and his associates. A third group of patients received oral mesalazine therapy, which induced clinical remission in 68% of cases (P = .09). Budesonide also induced histologic remission significantly more often (68%) than did mesalazine (26%; P = .02) or placebo (21%; P = .008).

“The study population was not large, but the trial was adequately powered,” the researchers wrote. The report was published online in Gastroenterology. “These results confirm the efficacy of budesonide for the induction of remission in active lymphocytic colitis and are consistent with expert recommendations for its use as first-line therapy.”

Lymphocytic colitis is a subtype of microscopic colitis that is characterized by an increase in intraepithelial lymphocytes. This condition has substantial negative effects on quality of life – the most common symptom is chronic diarrhea, and some patients also experience fecal incontinence and abdominal pain. Expert guidelines recommend first-line treatment with budesonide and second-line treatment with mesalazine, but evidence supporting either recommendation is sparse and low-quality, the investigators wrote.

For the study, they compared 8 weeks of treatment with pH-modified release oral budesonide granules (9 mg once daily), oral mesalazine granules (3 g once daily) or placebo in 57 patients (19 per arm) with histologically confirmed, newly diagnosed or relapsed lymphocytic colitis. All patients had at least a 12-week history of watery, nonbloody diarrhea, no other documented diarrheal conditions, and no recent history of antidiarrheal therapy. Nearly three-quarters were female and the mean age was 59 years. The primary endpoint was clinical remission, defined as no more than 21 stools in the 7 days before week 8, including no more than 6 watery stools.

After 8 weeks of double-blinded treatment, all clinically remitted patients stopped treatment and were followed for another 16 weeks. Those who were not in remission or who relapsed were offered 4 weeks of open-label budesonide therapy, which led to clinical remission in 88% of cases, the researchers said. “This study confirms that budesonide is effective for the induction of remission in active lymphocytic colitis,” they concluded. “Strikingly, a substantial improvement in symptoms, including a profound reduction in the number of watery stools, was seen within a median of 3 days after starting budesonide therapy.”

Serious adverse events were uncommon in all three groups, and each arm had a similar rate of adverse events considered secondary to treatment. In the budesonide group, these included one case each of weight gain, transient ischemic attack, and affective disturbance with sleep disorder. In the mesalazine group, three patients developed acute pancreatitis, increased hepatic enzymes, or dizziness. Eleven percent of budesonide recipients and 16% of mesalazine recipients stopped treatment because of adverse events. “No patient in any group had a clinically significant shift in cortisol level between baseline and week 8 that was considered related to the study drug,” the investigators said. “Other changes in laboratory parameters were not considered clinically relevant in any treatment group.”

The study was funded by Dr. Falk Pharma GmbH, Freiburg, Germany. Dr. Miehlke and two coauthors received speaker fees from Dr. Falk Pharma. Dr. Miehlke and one coauthor received consultancy fees from Tillots. One coauthor received speaker fees, has been a member of the advisory board, and has received grants from Tillots.

SOURCE: Miehlke S et al. Gastroenterology. 2018 Sep 6. doi: 10.1053/j.gastro.2018.08.042.

Patients with chronic hepatitis B virus infection and decompensated cirrhosis who immediately initiated entecavir or lamivudine therapy and maintained a virologic response (MVR) had significantly longer transplant-free survival than did nonresponders, according to the results of a multicenter observational study published in the December issue of Clinical Gastroenterology and Hepatology.

CDC/Dr. Erskine Palmer

Survival times were “excellent” if patients survived the first 6 months of antiviral therapy and did not develop hepatocellular carcinoma, said Jeong Won Jang, MD, of the Catholic University of Korea College of Medicine in Seoul, South Korea, and his associates. Patients who developed hepatocellular carcinoma had persistent declines in survival over time, they said. Predictors of short-term mortality included a baseline Model for End-Stage Liver Disease score above 20 and multiple complications.

Chronic hepatitis B virus (HBV) infection is the most common cause of liver-related disease and death in Asia, and complications such as decompensated cirrhosis affect up to 40% of chronically infected persons. Five-year survival rates are as low as 14% if patients develop decompensated cirrhosis.

To explore whether virologic suppression with oral nucleoside or nucleotide analog therapy improves outcomes in these decompensated patients, the researchers studied 295 such individuals from the Epidemiology and Natural History of Liver Cirrhosis in Korea Study. At baseline, these patients did not have documented chronic hepatitis C virus infection, hepatocellular carcinoma, other cancers, autoimmune hepatitis, or alcohol use disorders. All patients initiated entecavir or lamivudine therapy immediately after their cirrhosis became decompensated. The primary outcome was transplant-free survival.

A total of 60.1% of patients survived 5 years and 45.7% survived 10 years without undergoing transplantation, for a median transplant-free survival time of 7.7 years. The 116 patients (39%) who consistently had undetectable HBV DNA levels (less than 20 IU/mL) throughout treatment had significantly longer transplant-free survival than did patients who did not maintain a virologic response (P less than .001). In addition, a maintained virologic response (MVR) was the strongest predictor of long-term transplant-free survival, the researchers said.

A significantly greater proportion of patients who received entecavir survived 10 years compared with patients who received lamivudine. However, there was no significant difference in long-term survival among patients with MVRs to either drug. “Importantly, it appears that improvement in patient survival is attained by antiviral response, not by the type of nucleos(t)ide analogue per se,” the researchers wrote.

Patients who achieved MVR also showed significant improvements in hepatic function, but “the preventive effects of MVR on the incidence of hepatocellular carcinoma appeared only modest,” the investigators said. “Survival of patients without hepatocellular carcinoma who survived the first 6 months after initiation of antiviral therapy was excellent, with only a 25.3% mortality rate occurring between 6 months and 10 years.”

Based on their findings, Dr. Jang and his associates recommended aiming for an HBV DNA load less than 20 IU/mL in patients with decompensated cirrhosis to significantly improve the chances of long-term survival. Survival curves were similar regardless of whether patients had HBV DNA levels less than 10 IU/mL or between and 10 and 20 IU/mL, they noted.

Funders included Korea Healthcare Technology R&D Project and the Catholic Research Coordinating Center of the Korea Health 21 R&D Project, both of the Ministry of Health and Welfare, Republic of Korea. Dr. Jang disclosed ties to Bristol-Myers Squibb, Gilead, and Merck Sharp & Dohme. Three coinvestigators also disclosed ties to Gilead, MSD, and several other pharmaceutical companies.

SOURCE: Jang JW et al. Clin Gastroenterol Hepatol. 2018 May 18. doi: 10.1016/j.cgh.2018.04.063

Patients with chronic hepatitis B virus infection and decompensated cirrhosis who immediately initiated entecavir or lamivudine therapy and maintained a virologic response (MVR) had significantly longer transplant-free survival than did nonresponders, according to the results of a multicenter observational study published in the December issue of Clinical Gastroenterology and Hepatology.

CDC/Dr. Erskine Palmer

Survival times were “excellent” if patients survived the first 6 months of antiviral therapy and did not develop hepatocellular carcinoma, said Jeong Won Jang, MD, of the Catholic University of Korea College of Medicine in Seoul, South Korea, and his associates. Patients who developed hepatocellular carcinoma had persistent declines in survival over time, they said. Predictors of short-term mortality included a baseline Model for End-Stage Liver Disease score above 20 and multiple complications.

Chronic hepatitis B virus (HBV) infection is the most common cause of liver-related disease and death in Asia, and complications such as decompensated cirrhosis affect up to 40% of chronically infected persons. Five-year survival rates are as low as 14% if patients develop decompensated cirrhosis.

To explore whether virologic suppression with oral nucleoside or nucleotide analog therapy improves outcomes in these decompensated patients, the researchers studied 295 such individuals from the Epidemiology and Natural History of Liver Cirrhosis in Korea Study. At baseline, these patients did not have documented chronic hepatitis C virus infection, hepatocellular carcinoma, other cancers, autoimmune hepatitis, or alcohol use disorders. All patients initiated entecavir or lamivudine therapy immediately after their cirrhosis became decompensated. The primary outcome was transplant-free survival.

A total of 60.1% of patients survived 5 years and 45.7% survived 10 years without undergoing transplantation, for a median transplant-free survival time of 7.7 years. The 116 patients (39%) who consistently had undetectable HBV DNA levels (less than 20 IU/mL) throughout treatment had significantly longer transplant-free survival than did patients who did not maintain a virologic response (P less than .001). In addition, a maintained virologic response (MVR) was the strongest predictor of long-term transplant-free survival, the researchers said.

A significantly greater proportion of patients who received entecavir survived 10 years compared with patients who received lamivudine. However, there was no significant difference in long-term survival among patients with MVRs to either drug. “Importantly, it appears that improvement in patient survival is attained by antiviral response, not by the type of nucleos(t)ide analogue per se,” the researchers wrote.

Patients who achieved MVR also showed significant improvements in hepatic function, but “the preventive effects of MVR on the incidence of hepatocellular carcinoma appeared only modest,” the investigators said. “Survival of patients without hepatocellular carcinoma who survived the first 6 months after initiation of antiviral therapy was excellent, with only a 25.3% mortality rate occurring between 6 months and 10 years.”

Based on their findings, Dr. Jang and his associates recommended aiming for an HBV DNA load less than 20 IU/mL in patients with decompensated cirrhosis to significantly improve the chances of long-term survival. Survival curves were similar regardless of whether patients had HBV DNA levels less than 10 IU/mL or between and 10 and 20 IU/mL, they noted.

Funders included Korea Healthcare Technology R&D Project and the Catholic Research Coordinating Center of the Korea Health 21 R&D Project, both of the Ministry of Health and Welfare, Republic of Korea. Dr. Jang disclosed ties to Bristol-Myers Squibb, Gilead, and Merck Sharp & Dohme. Three coinvestigators also disclosed ties to Gilead, MSD, and several other pharmaceutical companies.

SOURCE: Jang JW et al. Clin Gastroenterol Hepatol. 2018 May 18. doi: 10.1016/j.cgh.2018.04.063

Patients with chronic hepatitis B virus infection and decompensated cirrhosis who immediately initiated entecavir or lamivudine therapy and maintained a virologic response (MVR) had significantly longer transplant-free survival than did nonresponders, according to the results of a multicenter observational study published in the December issue of Clinical Gastroenterology and Hepatology.

CDC/Dr. Erskine Palmer

Survival times were “excellent” if patients survived the first 6 months of antiviral therapy and did not develop hepatocellular carcinoma, said Jeong Won Jang, MD, of the Catholic University of Korea College of Medicine in Seoul, South Korea, and his associates. Patients who developed hepatocellular carcinoma had persistent declines in survival over time, they said. Predictors of short-term mortality included a baseline Model for End-Stage Liver Disease score above 20 and multiple complications.

Chronic hepatitis B virus (HBV) infection is the most common cause of liver-related disease and death in Asia, and complications such as decompensated cirrhosis affect up to 40% of chronically infected persons. Five-year survival rates are as low as 14% if patients develop decompensated cirrhosis.

To explore whether virologic suppression with oral nucleoside or nucleotide analog therapy improves outcomes in these decompensated patients, the researchers studied 295 such individuals from the Epidemiology and Natural History of Liver Cirrhosis in Korea Study. At baseline, these patients did not have documented chronic hepatitis C virus infection, hepatocellular carcinoma, other cancers, autoimmune hepatitis, or alcohol use disorders. All patients initiated entecavir or lamivudine therapy immediately after their cirrhosis became decompensated. The primary outcome was transplant-free survival.

A total of 60.1% of patients survived 5 years and 45.7% survived 10 years without undergoing transplantation, for a median transplant-free survival time of 7.7 years. The 116 patients (39%) who consistently had undetectable HBV DNA levels (less than 20 IU/mL) throughout treatment had significantly longer transplant-free survival than did patients who did not maintain a virologic response (P less than .001). In addition, a maintained virologic response (MVR) was the strongest predictor of long-term transplant-free survival, the researchers said.

A significantly greater proportion of patients who received entecavir survived 10 years compared with patients who received lamivudine. However, there was no significant difference in long-term survival among patients with MVRs to either drug. “Importantly, it appears that improvement in patient survival is attained by antiviral response, not by the type of nucleos(t)ide analogue per se,” the researchers wrote.

Patients who achieved MVR also showed significant improvements in hepatic function, but “the preventive effects of MVR on the incidence of hepatocellular carcinoma appeared only modest,” the investigators said. “Survival of patients without hepatocellular carcinoma who survived the first 6 months after initiation of antiviral therapy was excellent, with only a 25.3% mortality rate occurring between 6 months and 10 years.”

Based on their findings, Dr. Jang and his associates recommended aiming for an HBV DNA load less than 20 IU/mL in patients with decompensated cirrhosis to significantly improve the chances of long-term survival. Survival curves were similar regardless of whether patients had HBV DNA levels less than 10 IU/mL or between and 10 and 20 IU/mL, they noted.

Funders included Korea Healthcare Technology R&D Project and the Catholic Research Coordinating Center of the Korea Health 21 R&D Project, both of the Ministry of Health and Welfare, Republic of Korea. Dr. Jang disclosed ties to Bristol-Myers Squibb, Gilead, and Merck Sharp & Dohme. Three coinvestigators also disclosed ties to Gilead, MSD, and several other pharmaceutical companies.

SOURCE: Jang JW et al. Clin Gastroenterol Hepatol. 2018 May 18. doi: 10.1016/j.cgh.2018.04.063

Six months of once-daily norfloxacin therapy did not reduce 6-month mortality among patients with Child-Pugh class C cirrhosis who had not recently received fluoroquinolone therapy.

Mortality based on the Kaplan-Meier method was 14.8% in the norfloxacin group versus 19.7% for patients receiving placebo (P = .21). “Norfloxacin, however, appear[ed] to increase survival of patients with low ascites fluid protein concentrations,” wrote Richard Moreau, MD, of Hôpital Beaujon, Paris, and his associates. The results of the multicenter, double-blind trial of 291 patients were published in the December issue of Gastroenterology.

Patients with advanced cirrhosis often develop spontaneous bacterial peritonitis and other severe bacterial infections, with potentially grave outcomes. These are often enteric gram-negative bacteria that cross the intestinal barrier, enter the systemic circulation, and travel to the site of infection.

Long-term fluoroquinolone therapy (typically with norfloxacin) might help prevent these bacterial infections, the translocation of bacterial products, systemic inflammation, and consequent end-organ dysfunction, such as acute kidney disease. However, long-term antibiotic therapy also raises the specter of multidrug resistance, which is especially concerning when it involves a crucial antibiotic class such as fluoroquinolones, the researchers noted. “[In] patients receiving prolonged fluoroquinolone therapy, the development of infections by multidrug resistant bacteria might obscure the beneficial effect of fluoroquinolones on survival,” they added.

Four previous blinded and placebo-controlled trials have investigated fluoroquinolone therapy and mortality patients with cirrhosis, but they were small, usually included mortality only as a secondary outcome, and yielded mixed results. Hence, the researchers enrolled 291 patients with advanced (Child-Pugh class C) cirrhosis from 18 clinical sites in France and randomly assigned them to receive either norfloxacin (400 mg once daily) or placebo for 6 months. Patients were evaluated monthly during treatment and then at 9 months and 12 months. The primary outcome was survival at 6 months.

In a post hoc analysis, the researchers examined cumulative death rates at 6 months after accounting for liver transplantation as a competing risk of death and including survival data for patients who developed spontaneous bacterial peritonitis. Taking this approach, the estimated cumulative rate of death at 6 months was 15.5% (95% confidence interval, 10.1-21.9) in the norfloxacin group and 24.8% (95% CI, 18.1-32.1) in the placebo group, for a hazard ratio of 0.59 (95% CI, 0.35-0.99). Among patients whose ascites fluid levels were less than 15 g/L, the hazard ratio for death at 6 months was 65% lower in the norfloxacin group than in the placebo group (HR, 0.35; 95% CI, 0.13-0.93). Norfloxacin showed no such benefit for patients with ascites fluid protein levels above 15 g/L.

Norfloxacin therapy “could reduce the incidence of death among patients with ascitic fluid protein concentrations of less than 15 g/L but not among those with ascitic fluid protein concentration of 15 g/L or more,” the researchers concluded. “Norfloxacin may prevent some infections, especially gram-negative bacterial infections, but not the development of [spontaneous bacterial peritonitis] and other noninfectious, liver-related complications.”

The study was funded by Programme Hospitalier de Recherche Clinique National 2008 of the French Ministry of Health. Dr. Moreau reported having no conflicts of interest. Two coinvestigators disclosed ties to Gore Norgine, Exalenz, and Conatus.

SOURCE: Moreau R et al. Gastroenterology. 2018 Aug 22. doi: 10.1053/j.gastro.2018.08.026.

Six months of once-daily norfloxacin therapy did not reduce 6-month mortality among patients with Child-Pugh class C cirrhosis who had not recently received fluoroquinolone therapy.

Mortality based on the Kaplan-Meier method was 14.8% in the norfloxacin group versus 19.7% for patients receiving placebo (P = .21). “Norfloxacin, however, appear[ed] to increase survival of patients with low ascites fluid protein concentrations,” wrote Richard Moreau, MD, of Hôpital Beaujon, Paris, and his associates. The results of the multicenter, double-blind trial of 291 patients were published in the December issue of Gastroenterology.

Patients with advanced cirrhosis often develop spontaneous bacterial peritonitis and other severe bacterial infections, with potentially grave outcomes. These are often enteric gram-negative bacteria that cross the intestinal barrier, enter the systemic circulation, and travel to the site of infection.

Long-term fluoroquinolone therapy (typically with norfloxacin) might help prevent these bacterial infections, the translocation of bacterial products, systemic inflammation, and consequent end-organ dysfunction, such as acute kidney disease. However, long-term antibiotic therapy also raises the specter of multidrug resistance, which is especially concerning when it involves a crucial antibiotic class such as fluoroquinolones, the researchers noted. “[In] patients receiving prolonged fluoroquinolone therapy, the development of infections by multidrug resistant bacteria might obscure the beneficial effect of fluoroquinolones on survival,” they added.

Four previous blinded and placebo-controlled trials have investigated fluoroquinolone therapy and mortality patients with cirrhosis, but they were small, usually included mortality only as a secondary outcome, and yielded mixed results. Hence, the researchers enrolled 291 patients with advanced (Child-Pugh class C) cirrhosis from 18 clinical sites in France and randomly assigned them to receive either norfloxacin (400 mg once daily) or placebo for 6 months. Patients were evaluated monthly during treatment and then at 9 months and 12 months. The primary outcome was survival at 6 months.

In a post hoc analysis, the researchers examined cumulative death rates at 6 months after accounting for liver transplantation as a competing risk of death and including survival data for patients who developed spontaneous bacterial peritonitis. Taking this approach, the estimated cumulative rate of death at 6 months was 15.5% (95% confidence interval, 10.1-21.9) in the norfloxacin group and 24.8% (95% CI, 18.1-32.1) in the placebo group, for a hazard ratio of 0.59 (95% CI, 0.35-0.99). Among patients whose ascites fluid levels were less than 15 g/L, the hazard ratio for death at 6 months was 65% lower in the norfloxacin group than in the placebo group (HR, 0.35; 95% CI, 0.13-0.93). Norfloxacin showed no such benefit for patients with ascites fluid protein levels above 15 g/L.

Norfloxacin therapy “could reduce the incidence of death among patients with ascitic fluid protein concentrations of less than 15 g/L but not among those with ascitic fluid protein concentration of 15 g/L or more,” the researchers concluded. “Norfloxacin may prevent some infections, especially gram-negative bacterial infections, but not the development of [spontaneous bacterial peritonitis] and other noninfectious, liver-related complications.”

The study was funded by Programme Hospitalier de Recherche Clinique National 2008 of the French Ministry of Health. Dr. Moreau reported having no conflicts of interest. Two coinvestigators disclosed ties to Gore Norgine, Exalenz, and Conatus.

SOURCE: Moreau R et al. Gastroenterology. 2018 Aug 22. doi: 10.1053/j.gastro.2018.08.026.

Six months of once-daily norfloxacin therapy did not reduce 6-month mortality among patients with Child-Pugh class C cirrhosis who had not recently received fluoroquinolone therapy.

Mortality based on the Kaplan-Meier method was 14.8% in the norfloxacin group versus 19.7% for patients receiving placebo (P = .21). “Norfloxacin, however, appear[ed] to increase survival of patients with low ascites fluid protein concentrations,” wrote Richard Moreau, MD, of Hôpital Beaujon, Paris, and his associates. The results of the multicenter, double-blind trial of 291 patients were published in the December issue of Gastroenterology.

Patients with advanced cirrhosis often develop spontaneous bacterial peritonitis and other severe bacterial infections, with potentially grave outcomes. These are often enteric gram-negative bacteria that cross the intestinal barrier, enter the systemic circulation, and travel to the site of infection.

Long-term fluoroquinolone therapy (typically with norfloxacin) might help prevent these bacterial infections, the translocation of bacterial products, systemic inflammation, and consequent end-organ dysfunction, such as acute kidney disease. However, long-term antibiotic therapy also raises the specter of multidrug resistance, which is especially concerning when it involves a crucial antibiotic class such as fluoroquinolones, the researchers noted. “[In] patients receiving prolonged fluoroquinolone therapy, the development of infections by multidrug resistant bacteria might obscure the beneficial effect of fluoroquinolones on survival,” they added.

Four previous blinded and placebo-controlled trials have investigated fluoroquinolone therapy and mortality patients with cirrhosis, but they were small, usually included mortality only as a secondary outcome, and yielded mixed results. Hence, the researchers enrolled 291 patients with advanced (Child-Pugh class C) cirrhosis from 18 clinical sites in France and randomly assigned them to receive either norfloxacin (400 mg once daily) or placebo for 6 months. Patients were evaluated monthly during treatment and then at 9 months and 12 months. The primary outcome was survival at 6 months.

In a post hoc analysis, the researchers examined cumulative death rates at 6 months after accounting for liver transplantation as a competing risk of death and including survival data for patients who developed spontaneous bacterial peritonitis. Taking this approach, the estimated cumulative rate of death at 6 months was 15.5% (95% confidence interval, 10.1-21.9) in the norfloxacin group and 24.8% (95% CI, 18.1-32.1) in the placebo group, for a hazard ratio of 0.59 (95% CI, 0.35-0.99). Among patients whose ascites fluid levels were less than 15 g/L, the hazard ratio for death at 6 months was 65% lower in the norfloxacin group than in the placebo group (HR, 0.35; 95% CI, 0.13-0.93). Norfloxacin showed no such benefit for patients with ascites fluid protein levels above 15 g/L.

Norfloxacin therapy “could reduce the incidence of death among patients with ascitic fluid protein concentrations of less than 15 g/L but not among those with ascitic fluid protein concentration of 15 g/L or more,” the researchers concluded. “Norfloxacin may prevent some infections, especially gram-negative bacterial infections, but not the development of [spontaneous bacterial peritonitis] and other noninfectious, liver-related complications.”

The study was funded by Programme Hospitalier de Recherche Clinique National 2008 of the French Ministry of Health. Dr. Moreau reported having no conflicts of interest. Two coinvestigators disclosed ties to Gore Norgine, Exalenz, and Conatus.

SOURCE: Moreau R et al. Gastroenterology. 2018 Aug 22. doi: 10.1053/j.gastro.2018.08.026.

Crohn’s disease was significantly associated with anal canal high-risk human papillomavirus (HPV) infection in a prospective, single-center study of patients undergoing colonoscopy for various indications.

xrender/Thinkstock

High-risk HPV and HPV strain 16 were detected in 30% of patients with Crohn’s disease and 18% of patients without Crohn’s disease (P = .005), said Lucine Vuitton, MD, of University Hospital of Besançon (France) and her associates. “Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening,” the investigators wrote in the November issue of Clinical Gastroenterology and Hepatology.

Most anal cancers are squamous cell carcinomas, for which infection with high-risk HPV (especially high-risk HPV16) is a driving risk factor. Case studies and literature reviews have linked Crohn’s disease to increased rates of anal canal cancers, but population-based data were lacking, the researchers wrote. Therefore, they prospectively analyzed anal tissue samples from 467 consecutive patients undergoing colonoscopy at a tertiary care center in France. Median age was 54 years (interquartile range, 18-86 years), and 52% of patients were women. No patient had detectable macroscopic neoplastic lesions at the anal margin at baseline.

The researchers used the QIAamp DNA Blood minikit (Qiagen) for DNA extraction and the INNO-LiPA HPV Genotyping Extra kit (Fujirebio Diagnostics) for HPV DNA detection and genotyping. These methods identified HPV DNA in anal tissue samples from 34% of the patients and high-risk HPV DNA in 18% of patients. The most prevalent genotype was HPV16 (detected in 7% of samples), followed by HPV51, HPV52, and HPV39.

A total of 112 patients were receiving at least one immunosuppressive treatment for inflammatory bowel disease or another condition. Seventy patients had Crohn’s disease, and 29 patients had ulcerative colitis. The prevalence of anal canal high-risk HPV and HPV16 infection in patients with ulcerative colitis was similar to that seen in those without inflammatory bowel disease. However, patients with Crohn’s disease were more likely to have anal canal high-risk HPV infection (30%) and HPV16 infection (14%), compared with patients without Crohn’s disease (18% and 7%, respectively). Additionally, among 22 patients with Crohn’s disease and perianal involvement, 11 had HPV DNA in the anal canal versus 30% of other patients with inflammatory bowel disease.

Women were more likely to have anal canal high-risk HPV (23%) infection than were men (13%; P = .004). In a multivariable analysis of self-reported data and medical data, significant risk factors for high-risk HPV infection included female sex, a history of sexually transmitted infections, having more than 10 sexual partners over the life course, having at least one sexual partner during the past year, current smoking, and immunosuppressive therapy. The multivariable analysis also linked Crohn’s disease with anal canal high-risk HPV16 infection (odds ratio, 3.8), but the association did not reach statistical significance (95% confidence interval, 0.9-16.9).

Most patients with Crohn’s disease were on immunosuppressive therapy, “which markedly affected statistical power,” the researchers commented. Nonetheless, their findings support HPV vaccination for patients with Crohn’s disease, as well as efforts to target high-risk patients who could benefit from anal cancer screening, they said.

The work was funded by the APICHU research grant from Besançon (France) University Hospital and by the Région de Franche-Comté. Dr. Vuitton disclosed ties to AbbVie, Ferring, MSD, Hospira, Janssen, and Takeda. Three coinvestigators disclosed relationships with AbbVie, MSD, Hospira, Mayoli, and Roche.

SOURCE: Vuitton L et al. Clin Gastroenterol Hepatol. 2018 Nov. doi: 10.1016/j.cgh.2018.03.008.

Crohn’s disease was significantly associated with anal canal high-risk human papillomavirus (HPV) infection in a prospective, single-center study of patients undergoing colonoscopy for various indications.

xrender/Thinkstock

High-risk HPV and HPV strain 16 were detected in 30% of patients with Crohn’s disease and 18% of patients without Crohn’s disease (P = .005), said Lucine Vuitton, MD, of University Hospital of Besançon (France) and her associates. “Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening,” the investigators wrote in the November issue of Clinical Gastroenterology and Hepatology.

Most anal cancers are squamous cell carcinomas, for which infection with high-risk HPV (especially high-risk HPV16) is a driving risk factor. Case studies and literature reviews have linked Crohn’s disease to increased rates of anal canal cancers, but population-based data were lacking, the researchers wrote. Therefore, they prospectively analyzed anal tissue samples from 467 consecutive patients undergoing colonoscopy at a tertiary care center in France. Median age was 54 years (interquartile range, 18-86 years), and 52% of patients were women. No patient had detectable macroscopic neoplastic lesions at the anal margin at baseline.

The researchers used the QIAamp DNA Blood minikit (Qiagen) for DNA extraction and the INNO-LiPA HPV Genotyping Extra kit (Fujirebio Diagnostics) for HPV DNA detection and genotyping. These methods identified HPV DNA in anal tissue samples from 34% of the patients and high-risk HPV DNA in 18% of patients. The most prevalent genotype was HPV16 (detected in 7% of samples), followed by HPV51, HPV52, and HPV39.

A total of 112 patients were receiving at least one immunosuppressive treatment for inflammatory bowel disease or another condition. Seventy patients had Crohn’s disease, and 29 patients had ulcerative colitis. The prevalence of anal canal high-risk HPV and HPV16 infection in patients with ulcerative colitis was similar to that seen in those without inflammatory bowel disease. However, patients with Crohn’s disease were more likely to have anal canal high-risk HPV infection (30%) and HPV16 infection (14%), compared with patients without Crohn’s disease (18% and 7%, respectively). Additionally, among 22 patients with Crohn’s disease and perianal involvement, 11 had HPV DNA in the anal canal versus 30% of other patients with inflammatory bowel disease.

Women were more likely to have anal canal high-risk HPV (23%) infection than were men (13%; P = .004). In a multivariable analysis of self-reported data and medical data, significant risk factors for high-risk HPV infection included female sex, a history of sexually transmitted infections, having more than 10 sexual partners over the life course, having at least one sexual partner during the past year, current smoking, and immunosuppressive therapy. The multivariable analysis also linked Crohn’s disease with anal canal high-risk HPV16 infection (odds ratio, 3.8), but the association did not reach statistical significance (95% confidence interval, 0.9-16.9).

Most patients with Crohn’s disease were on immunosuppressive therapy, “which markedly affected statistical power,” the researchers commented. Nonetheless, their findings support HPV vaccination for patients with Crohn’s disease, as well as efforts to target high-risk patients who could benefit from anal cancer screening, they said.

The work was funded by the APICHU research grant from Besançon (France) University Hospital and by the Région de Franche-Comté. Dr. Vuitton disclosed ties to AbbVie, Ferring, MSD, Hospira, Janssen, and Takeda. Three coinvestigators disclosed relationships with AbbVie, MSD, Hospira, Mayoli, and Roche.

SOURCE: Vuitton L et al. Clin Gastroenterol Hepatol. 2018 Nov. doi: 10.1016/j.cgh.2018.03.008.

Crohn’s disease was significantly associated with anal canal high-risk human papillomavirus (HPV) infection in a prospective, single-center study of patients undergoing colonoscopy for various indications.

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High-risk HPV and HPV strain 16 were detected in 30% of patients with Crohn’s disease and 18% of patients without Crohn’s disease (P = .005), said Lucine Vuitton, MD, of University Hospital of Besançon (France) and her associates. “Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening,” the investigators wrote in the November issue of Clinical Gastroenterology and Hepatology.

Most anal cancers are squamous cell carcinomas, for which infection with high-risk HPV (especially high-risk HPV16) is a driving risk factor. Case studies and literature reviews have linked Crohn’s disease to increased rates of anal canal cancers, but population-based data were lacking, the researchers wrote. Therefore, they prospectively analyzed anal tissue samples from 467 consecutive patients undergoing colonoscopy at a tertiary care center in France. Median age was 54 years (interquartile range, 18-86 years), and 52% of patients were women. No patient had detectable macroscopic neoplastic lesions at the anal margin at baseline.

The researchers used the QIAamp DNA Blood minikit (Qiagen) for DNA extraction and the INNO-LiPA HPV Genotyping Extra kit (Fujirebio Diagnostics) for HPV DNA detection and genotyping. These methods identified HPV DNA in anal tissue samples from 34% of the patients and high-risk HPV DNA in 18% of patients. The most prevalent genotype was HPV16 (detected in 7% of samples), followed by HPV51, HPV52, and HPV39.

A total of 112 patients were receiving at least one immunosuppressive treatment for inflammatory bowel disease or another condition. Seventy patients had Crohn’s disease, and 29 patients had ulcerative colitis. The prevalence of anal canal high-risk HPV and HPV16 infection in patients with ulcerative colitis was similar to that seen in those without inflammatory bowel disease. However, patients with Crohn’s disease were more likely to have anal canal high-risk HPV infection (30%) and HPV16 infection (14%), compared with patients without Crohn’s disease (18% and 7%, respectively). Additionally, among 22 patients with Crohn’s disease and perianal involvement, 11 had HPV DNA in the anal canal versus 30% of other patients with inflammatory bowel disease.

Women were more likely to have anal canal high-risk HPV (23%) infection than were men (13%; P = .004). In a multivariable analysis of self-reported data and medical data, significant risk factors for high-risk HPV infection included female sex, a history of sexually transmitted infections, having more than 10 sexual partners over the life course, having at least one sexual partner during the past year, current smoking, and immunosuppressive therapy. The multivariable analysis also linked Crohn’s disease with anal canal high-risk HPV16 infection (odds ratio, 3.8), but the association did not reach statistical significance (95% confidence interval, 0.9-16.9).

Most patients with Crohn’s disease were on immunosuppressive therapy, “which markedly affected statistical power,” the researchers commented. Nonetheless, their findings support HPV vaccination for patients with Crohn’s disease, as well as efforts to target high-risk patients who could benefit from anal cancer screening, they said.

The work was funded by the APICHU research grant from Besançon (France) University Hospital and by the Région de Franche-Comté. Dr. Vuitton disclosed ties to AbbVie, Ferring, MSD, Hospira, Janssen, and Takeda. Three coinvestigators disclosed relationships with AbbVie, MSD, Hospira, Mayoli, and Roche.

SOURCE: Vuitton L et al. Clin Gastroenterol Hepatol. 2018 Nov. doi: 10.1016/j.cgh.2018.03.008.