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Probably okay to skip SIBO breath test before starting rifaximin in IBS-D
MAUI, HAWAII – , according to IBS expert Lin Chang, MD, a professor and vice chief of the division of digestive diseases at the University of California, Los Angeles.
Rifaximin is an antibiotic that works in the intestines but is not absorbed by the body, and is approved for irritable bowel syndrome with diarrhea (IBS-D). It’s a second-line option for moderate illness when diet, OTC medications, and other easier options don’t do the trick. Endpoints were met by about 10% more patients on rifaximin than placebo in randomized trials, perhaps by resetting gut microbiota.
“It was a small therapeutic gain, but it was statistically significant,” Dr. Chang said at the Gastroenterology Updates, IBD, Liver Disease Conference. In her own practice, she said it sometimes helps even with bloating and abdominal distension, two of the most vexing problems in IBS-D.
However, symptoms come back after 3-6 months, and prices approach $2,000 for the 2-week IBS-D course. Insurance doesn’t always fully cover it, and the Food and Drug Administration has capped treatments at three.
That’s left providers wondering what to do when people ask for rifaximin after seeing it advertised and eager for some way to predict if it will work or not. Some clinicians have turned to a breath test for small-intestinal bacterial overgrowth (SIBO) before prescribing rifaximin because there is evidence that SIBO contributes to IBS-D, but others have not. It’s a contentious issue in IBS medicine, Dr. Chang said.
A recent open-label study funded by rifaximin maker Salix Pharmaceuticals made a case for testing. Among 93 IBS-D patients, 60% with a positive breath test at baseline had reduced pain, diarrhea, and other symptoms after 550 mg three times daily for 2 weeks, versus 26% with a negative test (Am J Gastroenterol. 2019 Dec;114[12]:1886-93).
Even so, when asked after her IBS presentation, Dr. Chang said she doesn’t breath test because it doesn’t make sense. Even with positive results, “you don’t really know if they have SIBO or not. Sometimes healthy controls have a positive test, and some people with IBS who end up responding to rifaximin have a negative breath test. It’s up to you, [but] it doesn’t correlate” with outcomes, she said.
Indeed, a letter in response to the study made a strong case that nine of the subjects should have been counted as having a negative, not positive, breath test, and if they had, the difference in outcome would have disappeared (Am J Gastroenterol. 2020 Mar 2. doi: 10.14309/ajg.0000000000000569).
Dr. Chang has opted for an empiric approach. “I just treat patients who meet the criteria used in the clinical trials,” such as moderate abdominal pain and bloating, she said (for example, N Engl J Med. 2011 Jan 6;364[1]:22-32).
And she doesn’t push if people can’t afford rifaximin. Some turn to other antibiotics, like metronidazole (Flagyl) or ciprofloxacin (Cipro), which are absorbed in the GI tract, but Dr. Chang said symptoms will recur after a few months regardless of the antibiotic. “You don’t want all these young women to be given antibiotics over and over again. Their symptoms are just going to come back, and you are going to have to learn how to treat them anyway,” she said.
Instead, she moves on to other options when patients are at the point where they need prescription pharmaceuticals. One of her top choices is the tricyclic antidepressant amitriptyline. It helps with the pain; the anticholinergic effects counter the diarrhea; and the sedative effects help patients who have a hard time sleeping. Sleep problems make IBS-D symptoms worse, Dr. Chang said.
MAUI, HAWAII – , according to IBS expert Lin Chang, MD, a professor and vice chief of the division of digestive diseases at the University of California, Los Angeles.
Rifaximin is an antibiotic that works in the intestines but is not absorbed by the body, and is approved for irritable bowel syndrome with diarrhea (IBS-D). It’s a second-line option for moderate illness when diet, OTC medications, and other easier options don’t do the trick. Endpoints were met by about 10% more patients on rifaximin than placebo in randomized trials, perhaps by resetting gut microbiota.
“It was a small therapeutic gain, but it was statistically significant,” Dr. Chang said at the Gastroenterology Updates, IBD, Liver Disease Conference. In her own practice, she said it sometimes helps even with bloating and abdominal distension, two of the most vexing problems in IBS-D.
However, symptoms come back after 3-6 months, and prices approach $2,000 for the 2-week IBS-D course. Insurance doesn’t always fully cover it, and the Food and Drug Administration has capped treatments at three.
That’s left providers wondering what to do when people ask for rifaximin after seeing it advertised and eager for some way to predict if it will work or not. Some clinicians have turned to a breath test for small-intestinal bacterial overgrowth (SIBO) before prescribing rifaximin because there is evidence that SIBO contributes to IBS-D, but others have not. It’s a contentious issue in IBS medicine, Dr. Chang said.
A recent open-label study funded by rifaximin maker Salix Pharmaceuticals made a case for testing. Among 93 IBS-D patients, 60% with a positive breath test at baseline had reduced pain, diarrhea, and other symptoms after 550 mg three times daily for 2 weeks, versus 26% with a negative test (Am J Gastroenterol. 2019 Dec;114[12]:1886-93).
Even so, when asked after her IBS presentation, Dr. Chang said she doesn’t breath test because it doesn’t make sense. Even with positive results, “you don’t really know if they have SIBO or not. Sometimes healthy controls have a positive test, and some people with IBS who end up responding to rifaximin have a negative breath test. It’s up to you, [but] it doesn’t correlate” with outcomes, she said.
Indeed, a letter in response to the study made a strong case that nine of the subjects should have been counted as having a negative, not positive, breath test, and if they had, the difference in outcome would have disappeared (Am J Gastroenterol. 2020 Mar 2. doi: 10.14309/ajg.0000000000000569).
Dr. Chang has opted for an empiric approach. “I just treat patients who meet the criteria used in the clinical trials,” such as moderate abdominal pain and bloating, she said (for example, N Engl J Med. 2011 Jan 6;364[1]:22-32).
And she doesn’t push if people can’t afford rifaximin. Some turn to other antibiotics, like metronidazole (Flagyl) or ciprofloxacin (Cipro), which are absorbed in the GI tract, but Dr. Chang said symptoms will recur after a few months regardless of the antibiotic. “You don’t want all these young women to be given antibiotics over and over again. Their symptoms are just going to come back, and you are going to have to learn how to treat them anyway,” she said.
Instead, she moves on to other options when patients are at the point where they need prescription pharmaceuticals. One of her top choices is the tricyclic antidepressant amitriptyline. It helps with the pain; the anticholinergic effects counter the diarrhea; and the sedative effects help patients who have a hard time sleeping. Sleep problems make IBS-D symptoms worse, Dr. Chang said.
MAUI, HAWAII – , according to IBS expert Lin Chang, MD, a professor and vice chief of the division of digestive diseases at the University of California, Los Angeles.
Rifaximin is an antibiotic that works in the intestines but is not absorbed by the body, and is approved for irritable bowel syndrome with diarrhea (IBS-D). It’s a second-line option for moderate illness when diet, OTC medications, and other easier options don’t do the trick. Endpoints were met by about 10% more patients on rifaximin than placebo in randomized trials, perhaps by resetting gut microbiota.
“It was a small therapeutic gain, but it was statistically significant,” Dr. Chang said at the Gastroenterology Updates, IBD, Liver Disease Conference. In her own practice, she said it sometimes helps even with bloating and abdominal distension, two of the most vexing problems in IBS-D.
However, symptoms come back after 3-6 months, and prices approach $2,000 for the 2-week IBS-D course. Insurance doesn’t always fully cover it, and the Food and Drug Administration has capped treatments at three.
That’s left providers wondering what to do when people ask for rifaximin after seeing it advertised and eager for some way to predict if it will work or not. Some clinicians have turned to a breath test for small-intestinal bacterial overgrowth (SIBO) before prescribing rifaximin because there is evidence that SIBO contributes to IBS-D, but others have not. It’s a contentious issue in IBS medicine, Dr. Chang said.
A recent open-label study funded by rifaximin maker Salix Pharmaceuticals made a case for testing. Among 93 IBS-D patients, 60% with a positive breath test at baseline had reduced pain, diarrhea, and other symptoms after 550 mg three times daily for 2 weeks, versus 26% with a negative test (Am J Gastroenterol. 2019 Dec;114[12]:1886-93).
Even so, when asked after her IBS presentation, Dr. Chang said she doesn’t breath test because it doesn’t make sense. Even with positive results, “you don’t really know if they have SIBO or not. Sometimes healthy controls have a positive test, and some people with IBS who end up responding to rifaximin have a negative breath test. It’s up to you, [but] it doesn’t correlate” with outcomes, she said.
Indeed, a letter in response to the study made a strong case that nine of the subjects should have been counted as having a negative, not positive, breath test, and if they had, the difference in outcome would have disappeared (Am J Gastroenterol. 2020 Mar 2. doi: 10.14309/ajg.0000000000000569).
Dr. Chang has opted for an empiric approach. “I just treat patients who meet the criteria used in the clinical trials,” such as moderate abdominal pain and bloating, she said (for example, N Engl J Med. 2011 Jan 6;364[1]:22-32).
And she doesn’t push if people can’t afford rifaximin. Some turn to other antibiotics, like metronidazole (Flagyl) or ciprofloxacin (Cipro), which are absorbed in the GI tract, but Dr. Chang said symptoms will recur after a few months regardless of the antibiotic. “You don’t want all these young women to be given antibiotics over and over again. Their symptoms are just going to come back, and you are going to have to learn how to treat them anyway,” she said.
Instead, she moves on to other options when patients are at the point where they need prescription pharmaceuticals. One of her top choices is the tricyclic antidepressant amitriptyline. It helps with the pain; the anticholinergic effects counter the diarrhea; and the sedative effects help patients who have a hard time sleeping. Sleep problems make IBS-D symptoms worse, Dr. Chang said.
REPORTING FROM GUILD 2020
Genetic variants in nudix hydrolase linked to thiopurine myelosuppression
MAUI, HAWAII – There’s a new kid on the block to worry about when it comes to thiopurine pharmacogenetics: Genetic variants in the thiopurine-metabolizing enzyme nudix hydrolase 15 have been linked to a markedly increased risk of thiopurine myelosuppression among inflammatory bowel disease patients.
The Food and Drug Administration and others already recommend screening for genetic variants in thiopurine methyltransferase (TPMT), another enzyme that metabolizes thiopurine. Polymorphisms lead to TMPT dysfunction, accumulation of cytotoxic metabolites, and increased risk of thiopurine-induced myelosuppression (TIM). Carriers are advised to use reduced doses with careful drug monitoring, or to skip thiopurines altogether.
A similar picture is emerging for nudix hydrolase 15 (NUDT15). It’s been known for several years that genetic variants are not uncommon among East Asian people and lead to TIM, but their prevalence and impact among people of European decent wasn’t clearly understood until now.
Investigators led by Gareth Walker, MBBS, of the Royal Devon and Exeter Hospital in Exeter, England, compared rates of problematic TMPT and NUDT15 variants among European inflammatory bowel disease patients who had developed TIM and those who had not, about 1,000 patients in all. The majority were on azathioprine and had Crohn’s disease. Finnish people were excluded because “their unique genetic background ... has led to the enrichment of some disease-causing gene variants and losses of others,” according to the study, which was published in JAMA.
Carriage of any of three coding NUDT15 variants greatly increased the risk of TIM (odds ratio, 27.3; 95% confidence interval, 9.3-116.7), independent of TPMT genotype and thiopurine dose. A particular variant – an in-frame deletion in NUDT15 – increased the risk 38-fold (95% CI, 5.1-286.1), and was carried by 5.8% of TIM patients.
The analysis also confirmed the importance of TPMT variants, which were found in 30.5% of TIM patients (95/311) versus 16.4% (100/608) of patients who did not develop TIM.
“Patients with variants of either NUDT15 or TPMT, or among those with variants of both genes, had a faster onset of TIM, more severe TIM, and had a greater need for granulocyte colony–stimulating factor rescue therapy. ... Our data suggest that pretreatment sequencing of the NUDT15 gene ... may be considered prior to initiation of thiopurine therapy,” the team concluded.
The prevalence of problematic NUDT15 variants among non-Finnish Europeans is about 1.6%, 6.9% among people from Finland, and almost 30% among East Asians. The team estimated NUDT15 would have to be genotyped in 95 non-Finnish Europeans to prevent one case of TIM; the number is 123 for TPMT. “Given the widespread use of thiopurines” – primarily in rheumatology and transplant medicine, in addition to gastroenterology – “these findings may have ramifications beyond the management of IBD,” the investigators wrote.
“I do think it’s worthwhile” to screen for NUDT15, said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., who reviewed the study at the Gastroenterology Updates, IBD, Liver Disease Conference. “If you are a homozygote for this, your chance of getting profound leukopenia is very high, so I would probably not use a thiopurine.”
“If you are going to start low dose on everyone” with careful blood monitoring, “I suppose you could just do that, but I would say if you can get” the test and “are reassured the patient is not” carrying problematic NUDT15 or TMPT variants, “then I think you just go ahead and do full dose,” he said.
Testing for the relevant variants is available through the Mayo Clinic and several commercial labs.
“Even though the thiopurine dose is adjusted based on genotype, patients still need to be monitored closely for the development of thiopurine-induced myelosuppression as” TMPT and NUDT15 variants “do not explain all cases of” TIM, Marieke Coenen, PhD, an associate professor of pharmacogenetics at Radboud University Medical Center in Nijmegen, the Netherlands, cautioned in an editorial (Transl Gastroenterol Hepatol. 2019 Dec 12;4:81).
The prevalence of problematic NUDT15 variants is 0.7% among African and 20.7% among Hispanic people.
The work was funded by the National Institutes of Health, Crohn’s & Colitis UK, the Wellcome Trust, and others. Dr. Walker and other investigators reported numerous industry ties. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies. Dr. Coenen had no disclosures.
SOURCE: Walker GJ et al. JAMA. 2019 Feb 26;321(8):773-85.
MAUI, HAWAII – There’s a new kid on the block to worry about when it comes to thiopurine pharmacogenetics: Genetic variants in the thiopurine-metabolizing enzyme nudix hydrolase 15 have been linked to a markedly increased risk of thiopurine myelosuppression among inflammatory bowel disease patients.
The Food and Drug Administration and others already recommend screening for genetic variants in thiopurine methyltransferase (TPMT), another enzyme that metabolizes thiopurine. Polymorphisms lead to TMPT dysfunction, accumulation of cytotoxic metabolites, and increased risk of thiopurine-induced myelosuppression (TIM). Carriers are advised to use reduced doses with careful drug monitoring, or to skip thiopurines altogether.
A similar picture is emerging for nudix hydrolase 15 (NUDT15). It’s been known for several years that genetic variants are not uncommon among East Asian people and lead to TIM, but their prevalence and impact among people of European decent wasn’t clearly understood until now.
Investigators led by Gareth Walker, MBBS, of the Royal Devon and Exeter Hospital in Exeter, England, compared rates of problematic TMPT and NUDT15 variants among European inflammatory bowel disease patients who had developed TIM and those who had not, about 1,000 patients in all. The majority were on azathioprine and had Crohn’s disease. Finnish people were excluded because “their unique genetic background ... has led to the enrichment of some disease-causing gene variants and losses of others,” according to the study, which was published in JAMA.
Carriage of any of three coding NUDT15 variants greatly increased the risk of TIM (odds ratio, 27.3; 95% confidence interval, 9.3-116.7), independent of TPMT genotype and thiopurine dose. A particular variant – an in-frame deletion in NUDT15 – increased the risk 38-fold (95% CI, 5.1-286.1), and was carried by 5.8% of TIM patients.
The analysis also confirmed the importance of TPMT variants, which were found in 30.5% of TIM patients (95/311) versus 16.4% (100/608) of patients who did not develop TIM.
“Patients with variants of either NUDT15 or TPMT, or among those with variants of both genes, had a faster onset of TIM, more severe TIM, and had a greater need for granulocyte colony–stimulating factor rescue therapy. ... Our data suggest that pretreatment sequencing of the NUDT15 gene ... may be considered prior to initiation of thiopurine therapy,” the team concluded.
The prevalence of problematic NUDT15 variants among non-Finnish Europeans is about 1.6%, 6.9% among people from Finland, and almost 30% among East Asians. The team estimated NUDT15 would have to be genotyped in 95 non-Finnish Europeans to prevent one case of TIM; the number is 123 for TPMT. “Given the widespread use of thiopurines” – primarily in rheumatology and transplant medicine, in addition to gastroenterology – “these findings may have ramifications beyond the management of IBD,” the investigators wrote.
“I do think it’s worthwhile” to screen for NUDT15, said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., who reviewed the study at the Gastroenterology Updates, IBD, Liver Disease Conference. “If you are a homozygote for this, your chance of getting profound leukopenia is very high, so I would probably not use a thiopurine.”
“If you are going to start low dose on everyone” with careful blood monitoring, “I suppose you could just do that, but I would say if you can get” the test and “are reassured the patient is not” carrying problematic NUDT15 or TMPT variants, “then I think you just go ahead and do full dose,” he said.
Testing for the relevant variants is available through the Mayo Clinic and several commercial labs.
“Even though the thiopurine dose is adjusted based on genotype, patients still need to be monitored closely for the development of thiopurine-induced myelosuppression as” TMPT and NUDT15 variants “do not explain all cases of” TIM, Marieke Coenen, PhD, an associate professor of pharmacogenetics at Radboud University Medical Center in Nijmegen, the Netherlands, cautioned in an editorial (Transl Gastroenterol Hepatol. 2019 Dec 12;4:81).
The prevalence of problematic NUDT15 variants is 0.7% among African and 20.7% among Hispanic people.
The work was funded by the National Institutes of Health, Crohn’s & Colitis UK, the Wellcome Trust, and others. Dr. Walker and other investigators reported numerous industry ties. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies. Dr. Coenen had no disclosures.
SOURCE: Walker GJ et al. JAMA. 2019 Feb 26;321(8):773-85.
MAUI, HAWAII – There’s a new kid on the block to worry about when it comes to thiopurine pharmacogenetics: Genetic variants in the thiopurine-metabolizing enzyme nudix hydrolase 15 have been linked to a markedly increased risk of thiopurine myelosuppression among inflammatory bowel disease patients.
The Food and Drug Administration and others already recommend screening for genetic variants in thiopurine methyltransferase (TPMT), another enzyme that metabolizes thiopurine. Polymorphisms lead to TMPT dysfunction, accumulation of cytotoxic metabolites, and increased risk of thiopurine-induced myelosuppression (TIM). Carriers are advised to use reduced doses with careful drug monitoring, or to skip thiopurines altogether.
A similar picture is emerging for nudix hydrolase 15 (NUDT15). It’s been known for several years that genetic variants are not uncommon among East Asian people and lead to TIM, but their prevalence and impact among people of European decent wasn’t clearly understood until now.
Investigators led by Gareth Walker, MBBS, of the Royal Devon and Exeter Hospital in Exeter, England, compared rates of problematic TMPT and NUDT15 variants among European inflammatory bowel disease patients who had developed TIM and those who had not, about 1,000 patients in all. The majority were on azathioprine and had Crohn’s disease. Finnish people were excluded because “their unique genetic background ... has led to the enrichment of some disease-causing gene variants and losses of others,” according to the study, which was published in JAMA.
Carriage of any of three coding NUDT15 variants greatly increased the risk of TIM (odds ratio, 27.3; 95% confidence interval, 9.3-116.7), independent of TPMT genotype and thiopurine dose. A particular variant – an in-frame deletion in NUDT15 – increased the risk 38-fold (95% CI, 5.1-286.1), and was carried by 5.8% of TIM patients.
The analysis also confirmed the importance of TPMT variants, which were found in 30.5% of TIM patients (95/311) versus 16.4% (100/608) of patients who did not develop TIM.
“Patients with variants of either NUDT15 or TPMT, or among those with variants of both genes, had a faster onset of TIM, more severe TIM, and had a greater need for granulocyte colony–stimulating factor rescue therapy. ... Our data suggest that pretreatment sequencing of the NUDT15 gene ... may be considered prior to initiation of thiopurine therapy,” the team concluded.
The prevalence of problematic NUDT15 variants among non-Finnish Europeans is about 1.6%, 6.9% among people from Finland, and almost 30% among East Asians. The team estimated NUDT15 would have to be genotyped in 95 non-Finnish Europeans to prevent one case of TIM; the number is 123 for TPMT. “Given the widespread use of thiopurines” – primarily in rheumatology and transplant medicine, in addition to gastroenterology – “these findings may have ramifications beyond the management of IBD,” the investigators wrote.
“I do think it’s worthwhile” to screen for NUDT15, said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., who reviewed the study at the Gastroenterology Updates, IBD, Liver Disease Conference. “If you are a homozygote for this, your chance of getting profound leukopenia is very high, so I would probably not use a thiopurine.”
“If you are going to start low dose on everyone” with careful blood monitoring, “I suppose you could just do that, but I would say if you can get” the test and “are reassured the patient is not” carrying problematic NUDT15 or TMPT variants, “then I think you just go ahead and do full dose,” he said.
Testing for the relevant variants is available through the Mayo Clinic and several commercial labs.
“Even though the thiopurine dose is adjusted based on genotype, patients still need to be monitored closely for the development of thiopurine-induced myelosuppression as” TMPT and NUDT15 variants “do not explain all cases of” TIM, Marieke Coenen, PhD, an associate professor of pharmacogenetics at Radboud University Medical Center in Nijmegen, the Netherlands, cautioned in an editorial (Transl Gastroenterol Hepatol. 2019 Dec 12;4:81).
The prevalence of problematic NUDT15 variants is 0.7% among African and 20.7% among Hispanic people.
The work was funded by the National Institutes of Health, Crohn’s & Colitis UK, the Wellcome Trust, and others. Dr. Walker and other investigators reported numerous industry ties. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies. Dr. Coenen had no disclosures.
SOURCE: Walker GJ et al. JAMA. 2019 Feb 26;321(8):773-85.
REPORTING FROM GUILD 2020
HLA gene variant predicts anti-TNF antibodies in Crohn’s
MAUI, HAWAII – A variant in the human leukocyte antigen gene – DQA1*05 – almost doubled the risk of antibodies forming against tumor necrosis factor (TNF) inhibitors in Crohn’s disease patients, irrespective of concomitant immunomodulator use, according to a report in Gastroenterology.
“Pretreatment genetic testing for HLA-DQA1*05 may help personalize the choice of anti-TNF and the need for combination therapy,” concluded investigators led by Aleksejs Sazonovs, of the Wellcome Sanger Institute in Hinxton, England.
The same variant increases the risk of celiac disease, and it is included in commercial celiac genotyping assays. The allele is carried by about 40% of Europeans.
“This is turning into a hot topic; people are talking about it, [and it’s] blowing up on Twitter,” said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. “It turns out this is really a significant predictor of immunogenicity. Whatever your risk of developing antibodies, it’s going to double if you have this HLA marker, and it’s common.
“I think we are going to start [stratifying] our decision on combination [or] monotherapy based on this,” added Dr. Loftus, speaking at the Gastroenterology Updates, IBD, Liver Disease Conference. “I would argue that, if your patient has this marker, it would be criminal to give that patient infliximab monotherapy.”
The finding also begs the question of whether to bypass anti-TNFs altogether if a patient has the marker, Dr. Loftus noted, and just use ustekinumab, vedolizumab, or another agent.
Checking for celiac disease in inflammatory bowel disease isn’t unusual and involves the same gene variant, he added, so payer coverage shouldn’t be much of a problem.
The investigators ran a genome-wide association study on 1,418 biologic-naive Crohn’s patients starting infliximab or adalimumab therapy. Patients were in their 30s, on average, with a disease duration of about 3 years; there were about equal numbers of men and women.
A total of 44% of patients developed antidrug antibodies within a year. Overall, the rate of immunogenicity – defined as an antidrug antibody titer of at least 10 AU/mL – was nearly doubled in HLA-DQA1*05 carriers (hazard ratio, 1.90; 95% confidence interval, 1.60-2.25).
The association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33) and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator, usually azathioprine (HR, 2.01; 95% CI, 1.57-2.58).
The highest rates of immunogenicity, 92% at 1 year, were in HLA-DQA1*05 carriers on infliximab monotherapy. The lowest rates, 10% at 1 year, were in adalimumab patients on combination therapy who didn’t carry the variant. HLA-DQA1*05 was also associated with lower drug persistence rates.
The specific alleles HLA-DQA1*05:01 and HLA-DQA1*05:05 mediated most of the risk.
The study authors advised that “all patients treated with an anti-TNF should be prescribed an immunomodulator to lower the risk of immunogenicity.” Among HLA-DQA1*05 carriers “in whom immunomodulators are contraindicated or not tolerated, clinicians might advise against the use of anti-TNF drugs, particularly infliximab.”
In contrast, “patients who do not carry HLA-DQA1*05 might be given the choice between adalimumab or infliximab combination therapy,” the investigators said. “Patients without the risk allele and a history of adverse drug reactions to thiopurines and/or methotrexate, or who are at high risk of opportunistic infections, might be spared the additional risks of combination therapy and treated with adalimumab monotherapy.”
The mechanism for the association is unknown, the authors said.
The work was funded by the British Society of Gastroenterology, AbbVie, Merck, Pfizer, and others. The authors disclosed numerous ties to those or other pharmaceutical companies. Two authors were employees of AbbVie, marketer of the branded adalimumab Humira.
SOURCE: Sazonovs A et al. Gastroenterology. 2020 Jan;158(1):189-99.
MAUI, HAWAII – A variant in the human leukocyte antigen gene – DQA1*05 – almost doubled the risk of antibodies forming against tumor necrosis factor (TNF) inhibitors in Crohn’s disease patients, irrespective of concomitant immunomodulator use, according to a report in Gastroenterology.
“Pretreatment genetic testing for HLA-DQA1*05 may help personalize the choice of anti-TNF and the need for combination therapy,” concluded investigators led by Aleksejs Sazonovs, of the Wellcome Sanger Institute in Hinxton, England.
The same variant increases the risk of celiac disease, and it is included in commercial celiac genotyping assays. The allele is carried by about 40% of Europeans.
“This is turning into a hot topic; people are talking about it, [and it’s] blowing up on Twitter,” said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. “It turns out this is really a significant predictor of immunogenicity. Whatever your risk of developing antibodies, it’s going to double if you have this HLA marker, and it’s common.
“I think we are going to start [stratifying] our decision on combination [or] monotherapy based on this,” added Dr. Loftus, speaking at the Gastroenterology Updates, IBD, Liver Disease Conference. “I would argue that, if your patient has this marker, it would be criminal to give that patient infliximab monotherapy.”
The finding also begs the question of whether to bypass anti-TNFs altogether if a patient has the marker, Dr. Loftus noted, and just use ustekinumab, vedolizumab, or another agent.
Checking for celiac disease in inflammatory bowel disease isn’t unusual and involves the same gene variant, he added, so payer coverage shouldn’t be much of a problem.
The investigators ran a genome-wide association study on 1,418 biologic-naive Crohn’s patients starting infliximab or adalimumab therapy. Patients were in their 30s, on average, with a disease duration of about 3 years; there were about equal numbers of men and women.
A total of 44% of patients developed antidrug antibodies within a year. Overall, the rate of immunogenicity – defined as an antidrug antibody titer of at least 10 AU/mL – was nearly doubled in HLA-DQA1*05 carriers (hazard ratio, 1.90; 95% confidence interval, 1.60-2.25).
The association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33) and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator, usually azathioprine (HR, 2.01; 95% CI, 1.57-2.58).
The highest rates of immunogenicity, 92% at 1 year, were in HLA-DQA1*05 carriers on infliximab monotherapy. The lowest rates, 10% at 1 year, were in adalimumab patients on combination therapy who didn’t carry the variant. HLA-DQA1*05 was also associated with lower drug persistence rates.
The specific alleles HLA-DQA1*05:01 and HLA-DQA1*05:05 mediated most of the risk.
The study authors advised that “all patients treated with an anti-TNF should be prescribed an immunomodulator to lower the risk of immunogenicity.” Among HLA-DQA1*05 carriers “in whom immunomodulators are contraindicated or not tolerated, clinicians might advise against the use of anti-TNF drugs, particularly infliximab.”
In contrast, “patients who do not carry HLA-DQA1*05 might be given the choice between adalimumab or infliximab combination therapy,” the investigators said. “Patients without the risk allele and a history of adverse drug reactions to thiopurines and/or methotrexate, or who are at high risk of opportunistic infections, might be spared the additional risks of combination therapy and treated with adalimumab monotherapy.”
The mechanism for the association is unknown, the authors said.
The work was funded by the British Society of Gastroenterology, AbbVie, Merck, Pfizer, and others. The authors disclosed numerous ties to those or other pharmaceutical companies. Two authors were employees of AbbVie, marketer of the branded adalimumab Humira.
SOURCE: Sazonovs A et al. Gastroenterology. 2020 Jan;158(1):189-99.
MAUI, HAWAII – A variant in the human leukocyte antigen gene – DQA1*05 – almost doubled the risk of antibodies forming against tumor necrosis factor (TNF) inhibitors in Crohn’s disease patients, irrespective of concomitant immunomodulator use, according to a report in Gastroenterology.
“Pretreatment genetic testing for HLA-DQA1*05 may help personalize the choice of anti-TNF and the need for combination therapy,” concluded investigators led by Aleksejs Sazonovs, of the Wellcome Sanger Institute in Hinxton, England.
The same variant increases the risk of celiac disease, and it is included in commercial celiac genotyping assays. The allele is carried by about 40% of Europeans.
“This is turning into a hot topic; people are talking about it, [and it’s] blowing up on Twitter,” said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. “It turns out this is really a significant predictor of immunogenicity. Whatever your risk of developing antibodies, it’s going to double if you have this HLA marker, and it’s common.
“I think we are going to start [stratifying] our decision on combination [or] monotherapy based on this,” added Dr. Loftus, speaking at the Gastroenterology Updates, IBD, Liver Disease Conference. “I would argue that, if your patient has this marker, it would be criminal to give that patient infliximab monotherapy.”
The finding also begs the question of whether to bypass anti-TNFs altogether if a patient has the marker, Dr. Loftus noted, and just use ustekinumab, vedolizumab, or another agent.
Checking for celiac disease in inflammatory bowel disease isn’t unusual and involves the same gene variant, he added, so payer coverage shouldn’t be much of a problem.
The investigators ran a genome-wide association study on 1,418 biologic-naive Crohn’s patients starting infliximab or adalimumab therapy. Patients were in their 30s, on average, with a disease duration of about 3 years; there were about equal numbers of men and women.
A total of 44% of patients developed antidrug antibodies within a year. Overall, the rate of immunogenicity – defined as an antidrug antibody titer of at least 10 AU/mL – was nearly doubled in HLA-DQA1*05 carriers (hazard ratio, 1.90; 95% confidence interval, 1.60-2.25).
The association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33) and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator, usually azathioprine (HR, 2.01; 95% CI, 1.57-2.58).
The highest rates of immunogenicity, 92% at 1 year, were in HLA-DQA1*05 carriers on infliximab monotherapy. The lowest rates, 10% at 1 year, were in adalimumab patients on combination therapy who didn’t carry the variant. HLA-DQA1*05 was also associated with lower drug persistence rates.
The specific alleles HLA-DQA1*05:01 and HLA-DQA1*05:05 mediated most of the risk.
The study authors advised that “all patients treated with an anti-TNF should be prescribed an immunomodulator to lower the risk of immunogenicity.” Among HLA-DQA1*05 carriers “in whom immunomodulators are contraindicated or not tolerated, clinicians might advise against the use of anti-TNF drugs, particularly infliximab.”
In contrast, “patients who do not carry HLA-DQA1*05 might be given the choice between adalimumab or infliximab combination therapy,” the investigators said. “Patients without the risk allele and a history of adverse drug reactions to thiopurines and/or methotrexate, or who are at high risk of opportunistic infections, might be spared the additional risks of combination therapy and treated with adalimumab monotherapy.”
The mechanism for the association is unknown, the authors said.
The work was funded by the British Society of Gastroenterology, AbbVie, Merck, Pfizer, and others. The authors disclosed numerous ties to those or other pharmaceutical companies. Two authors were employees of AbbVie, marketer of the branded adalimumab Humira.
SOURCE: Sazonovs A et al. Gastroenterology. 2020 Jan;158(1):189-99.
REPORTING FROM GUILD 2020
Obesity expert: Time to embrace growing array of options
MAUI, HAWAII – Specialists who study obesity and embrace the increasing number of treatment options are poised to lead the way in stemming the disease, which Andres Acosta, MD, PhD, calls the “epidemic of the century.”
“Gastroenterologists are in the first line of treatment for obesity management,” said Acosta, who runs the precision medicine for obesity lab at the Mayo Clinic in Rochester, Minn.
“Patients with obesity are already in our clinics,” he said in an interview. And too many physicians “are ignoring the problem.”
The vast majority of people with acid reflux have obesity, as do those with nonalcoholic fatty liver disease, he explained. “By targeting those two areas, we’ll be targeting more than 50% of our patients.” Recurring polyps and colon cancer are also often associated with obesity, he said.
Because of their skill as endoscopists, internists, and nutrition experts, gastroenterologists are uniquely positioned to care for obesity, said Acosta, who is first author of a white paper – Practice Guide on Obesity and Weight Management, Education and Resources – developed by the American Gastroenterological Association with input from nine medical societies.
More treatment choices
Physicians heard an update on options available in the continuum of obesity care from Christopher Thompson, MD, director of endoscopy at Brigham and Women’s Hospital in Boston, at the Gastroenterology Updates IBD Liver Disease Conference 2020. He discussed the potential weight-loss range and safety profile of each.
Some medications result in a body-weight loss of 5%, whereas gastric bypass surgeries can result in a loss of up to 40%, he said in an interview. And weight loss is typically 10% with intragastric balloon, 15%-20% with aspiration therapies and with endoscopic suturing techniques, and 25%-30% with sleeve gastrectomy.
“It’s nice to be able to offer all of those to patients,” he said, adding that he wants to get the message across to hesitant physicians that obesity management “is not as difficult as they think.”
Physicians can be reluctant to address obesity because of the social stigma associated with excess weight and a discomfort in talking about it.
But “there are ways to open that conversation, and it needs to start happening more,” said Thompson, who pointed out that obesity is the underlying cause of many other illnesses, including diabetes and heart diseases.
And new strategies are in the offing, he explained. His team at Brigham is currently involved in clinical trials to test whether the diversion of food and bile to the lower part of the bowel will generate a metabolic signal that affects insulin resistance and weight, he reported.
They are also testing whether gastric procedures can be combined with small bowel procedures to achieve the weight loss seen with bariatric surgery.
As treatment options for obesity increase, precision medicine will help maximize their potential, said Acosta.
Precision medicine will amp up treatments
Acosta outlined the four categories that patients who are obese generally fall into: those with a “hungry brain,” who think they need to eat more than they do; those with a “hungry gut,” whose gut is not sending the proper signal to the brain that it is full; those with “emotional hunger”; and those with abnormal metabolism.
“For each of those, there are genetic circumstances, metabolism, a hormonal profile, as well as pathophysiologic aspects of obesity, that make these groups unique,” he said.
Deciding which patients should get which treatment is the next frontier, he explained. “For example, if you give an intragastric balloon to all comers, patients will lose about 12% of their body weight. But if you separate responders from nonresponders and you select the right intervention, you can achieve an 18% loss of body weight in the right responders.”
At Mayo, they are working on a blood test to break down phenotypes and identify who will respond best to which treatment, he reported. That could lead to a much more efficient use of scarce resources.
“At the same time, I hope that more insurance companies will cover more obesity treatments,” said Acosta.
This article first appeared on Medscape.com.
MAUI, HAWAII – Specialists who study obesity and embrace the increasing number of treatment options are poised to lead the way in stemming the disease, which Andres Acosta, MD, PhD, calls the “epidemic of the century.”
“Gastroenterologists are in the first line of treatment for obesity management,” said Acosta, who runs the precision medicine for obesity lab at the Mayo Clinic in Rochester, Minn.
“Patients with obesity are already in our clinics,” he said in an interview. And too many physicians “are ignoring the problem.”
The vast majority of people with acid reflux have obesity, as do those with nonalcoholic fatty liver disease, he explained. “By targeting those two areas, we’ll be targeting more than 50% of our patients.” Recurring polyps and colon cancer are also often associated with obesity, he said.
Because of their skill as endoscopists, internists, and nutrition experts, gastroenterologists are uniquely positioned to care for obesity, said Acosta, who is first author of a white paper – Practice Guide on Obesity and Weight Management, Education and Resources – developed by the American Gastroenterological Association with input from nine medical societies.
More treatment choices
Physicians heard an update on options available in the continuum of obesity care from Christopher Thompson, MD, director of endoscopy at Brigham and Women’s Hospital in Boston, at the Gastroenterology Updates IBD Liver Disease Conference 2020. He discussed the potential weight-loss range and safety profile of each.
Some medications result in a body-weight loss of 5%, whereas gastric bypass surgeries can result in a loss of up to 40%, he said in an interview. And weight loss is typically 10% with intragastric balloon, 15%-20% with aspiration therapies and with endoscopic suturing techniques, and 25%-30% with sleeve gastrectomy.
“It’s nice to be able to offer all of those to patients,” he said, adding that he wants to get the message across to hesitant physicians that obesity management “is not as difficult as they think.”
Physicians can be reluctant to address obesity because of the social stigma associated with excess weight and a discomfort in talking about it.
But “there are ways to open that conversation, and it needs to start happening more,” said Thompson, who pointed out that obesity is the underlying cause of many other illnesses, including diabetes and heart diseases.
And new strategies are in the offing, he explained. His team at Brigham is currently involved in clinical trials to test whether the diversion of food and bile to the lower part of the bowel will generate a metabolic signal that affects insulin resistance and weight, he reported.
They are also testing whether gastric procedures can be combined with small bowel procedures to achieve the weight loss seen with bariatric surgery.
As treatment options for obesity increase, precision medicine will help maximize their potential, said Acosta.
Precision medicine will amp up treatments
Acosta outlined the four categories that patients who are obese generally fall into: those with a “hungry brain,” who think they need to eat more than they do; those with a “hungry gut,” whose gut is not sending the proper signal to the brain that it is full; those with “emotional hunger”; and those with abnormal metabolism.
“For each of those, there are genetic circumstances, metabolism, a hormonal profile, as well as pathophysiologic aspects of obesity, that make these groups unique,” he said.
Deciding which patients should get which treatment is the next frontier, he explained. “For example, if you give an intragastric balloon to all comers, patients will lose about 12% of their body weight. But if you separate responders from nonresponders and you select the right intervention, you can achieve an 18% loss of body weight in the right responders.”
At Mayo, they are working on a blood test to break down phenotypes and identify who will respond best to which treatment, he reported. That could lead to a much more efficient use of scarce resources.
“At the same time, I hope that more insurance companies will cover more obesity treatments,” said Acosta.
This article first appeared on Medscape.com.
MAUI, HAWAII – Specialists who study obesity and embrace the increasing number of treatment options are poised to lead the way in stemming the disease, which Andres Acosta, MD, PhD, calls the “epidemic of the century.”
“Gastroenterologists are in the first line of treatment for obesity management,” said Acosta, who runs the precision medicine for obesity lab at the Mayo Clinic in Rochester, Minn.
“Patients with obesity are already in our clinics,” he said in an interview. And too many physicians “are ignoring the problem.”
The vast majority of people with acid reflux have obesity, as do those with nonalcoholic fatty liver disease, he explained. “By targeting those two areas, we’ll be targeting more than 50% of our patients.” Recurring polyps and colon cancer are also often associated with obesity, he said.
Because of their skill as endoscopists, internists, and nutrition experts, gastroenterologists are uniquely positioned to care for obesity, said Acosta, who is first author of a white paper – Practice Guide on Obesity and Weight Management, Education and Resources – developed by the American Gastroenterological Association with input from nine medical societies.
More treatment choices
Physicians heard an update on options available in the continuum of obesity care from Christopher Thompson, MD, director of endoscopy at Brigham and Women’s Hospital in Boston, at the Gastroenterology Updates IBD Liver Disease Conference 2020. He discussed the potential weight-loss range and safety profile of each.
Some medications result in a body-weight loss of 5%, whereas gastric bypass surgeries can result in a loss of up to 40%, he said in an interview. And weight loss is typically 10% with intragastric balloon, 15%-20% with aspiration therapies and with endoscopic suturing techniques, and 25%-30% with sleeve gastrectomy.
“It’s nice to be able to offer all of those to patients,” he said, adding that he wants to get the message across to hesitant physicians that obesity management “is not as difficult as they think.”
Physicians can be reluctant to address obesity because of the social stigma associated with excess weight and a discomfort in talking about it.
But “there are ways to open that conversation, and it needs to start happening more,” said Thompson, who pointed out that obesity is the underlying cause of many other illnesses, including diabetes and heart diseases.
And new strategies are in the offing, he explained. His team at Brigham is currently involved in clinical trials to test whether the diversion of food and bile to the lower part of the bowel will generate a metabolic signal that affects insulin resistance and weight, he reported.
They are also testing whether gastric procedures can be combined with small bowel procedures to achieve the weight loss seen with bariatric surgery.
As treatment options for obesity increase, precision medicine will help maximize their potential, said Acosta.
Precision medicine will amp up treatments
Acosta outlined the four categories that patients who are obese generally fall into: those with a “hungry brain,” who think they need to eat more than they do; those with a “hungry gut,” whose gut is not sending the proper signal to the brain that it is full; those with “emotional hunger”; and those with abnormal metabolism.
“For each of those, there are genetic circumstances, metabolism, a hormonal profile, as well as pathophysiologic aspects of obesity, that make these groups unique,” he said.
Deciding which patients should get which treatment is the next frontier, he explained. “For example, if you give an intragastric balloon to all comers, patients will lose about 12% of their body weight. But if you separate responders from nonresponders and you select the right intervention, you can achieve an 18% loss of body weight in the right responders.”
At Mayo, they are working on a blood test to break down phenotypes and identify who will respond best to which treatment, he reported. That could lead to a much more efficient use of scarce resources.
“At the same time, I hope that more insurance companies will cover more obesity treatments,” said Acosta.
This article first appeared on Medscape.com.
EXPERT ANALYSIS FROM GUILD 2020
Older adults with IBD often undertreated
MAUI, HAWAII – said Christina Ha, MD, from the Inflammatory Bowel Disease Center at Cedars-Sinai in Los Angeles.
Clinicians sometimes fall back on steroids because they are typically inexpensive and because there are fears that the new anti-TNF biologics can cause adverse events in older patients, Ha said at the Gastroenterology Updates, IBD, Liver Disease Conference.
“There are not a lot of safety data for the age group, which is not well represented in clinical trials,” she explained. “We can’t necessarily extrapolate data from a study of people with an average age in the 40s to someone in their 70s.”
But, she emphasized, steroid use for more than 3 months is potentially inappropriate.
“If we have a patient on steroids, we should be saying which steroid-sparing strategy will be incorporated into their regimen when we start them on their course of steroids,” she explained.
Ha said she gets asked frequently whether the man-made steroid budesonide, which is readily available, should be considered an acceptable alternative to prednisone.
“Steroids are not maintenance therapies,” she pointed out. “One could argue that maybe someone who has symptomatic mild Crohn’s disease could be kept on low doses of budesonide. But I would argue whether it is really the budesonide that’s helping them or some other disease process related to polypharmacy.”
There are no long-term safety or efficacy data for budesonide in patients with ulcerative colitis or Crohn’s disease, she added.
Special considerations
Older patients with IBD have a decreased ability to handle disease activity; they have more comorbidities and a susceptibility to falls, said Ha. Early control of the disease is therefore essential.
Sarcopenia, an inherent part of aging when muscle mass decreases over time, is central to physiologic changes, which have implications for older adults with IBD, she said.
“We’re learning that sarcopenia is also prevalent in our patients with moderate to severe inflammatory bowel disease,” she explained. “Sarcopenia is associated with increased risk of infections, hospitalizations, and postoperative complications.”
Other changes occur in the intestines as patients age, Ha reported. “Recent studies have shown that there are changes in the intestinal barrier in terms of the junctions within the mucosal lining that increase intestinal permeability, which may help explain why some patients respond to treatments and others don’t.”
Physical therapy underused
Other treatment options, such as physical therapy, have also been underused in older patients with IBD. For example, there’s often considerable pushback against doing a physical therapy assessment on a hospitalized older patient, said Ha.
Medicare covers up to 80% of those services, but referral wording is key. “They’re not going to cover it for a primary diagnosis of ulcerative colitis or Crohn’s,” she explained. However, “they will cover it for a primary diagnosis of deconditioning with a secondary diagnoses of steroid exposure, anemia, Crohn’s disease, or ulcerative colitis.”
Physical therapy can improve muscle function, decrease muscle pain, potentially decrease analgesics, improve bone mass, and decrease joint pain, stress, fatigue, and debility. Fatigue is prevalent in patients with IBD, Ha explained.
Another underused resource is psychosocial assessment, she added. Although depression is not part of the aging process, it is common in those with chronic conditions.
Visits with licensed psychiatrists and clinical psychologists are covered under Medicare Part B, Ha pointed out, as are psychiatric evaluation and testing and individual and group therapy.
Older patients with IBD are often not receiving the care they need, said Uma Mahadevan, MD, a gastroenterologist at UCSF Health in San Francisco.
The need for awareness of polypharmacy, which Ha also discussed, is a concern in all older patients, but especially those with IBD, Mahadevan said in an interview. Clinicians need to be aware of the cascading effect of pharmacy, in which one drug’s adverse effect leads to the prescription of another drug, with different adverse effects.
Ha gave the example of a patient with IBD who started to have diarrhea as an adverse effect of a medication. A clinician might then prescribe a medication for Clostridium difficile, but that might lead to nausea, leading to the prescription of an antinausea medicine.
A multidisciplinary team is needed to perform medication reconciliation, Ha noted.
Correcting anemia important for IBD
Anemia is also underidentified and undertreated in older patients with IBD, Ha said.
“Across the board with inflammatory bowel disease, we don’t do a great job of being aggressive and correcting anemia. That has implications for fatigue and implications with functional status and circulating volume,” she said.
In older patients, it might be that the decline in hemoglobin over time is more important to outcomes than the number itself, she said. “A hemoglobin of 8 g/dL is one thing, but if it was at 12 g/dL 6 months ago, that’s a different story.”
“For older patients, anemia is associated with a high incidence of cardiovascular disease, cognitive impairment, increased risks of falls and fractures, longer hospitalizations (and thus increased costs of care), increased frailty and dementia, and increased risk of mortality,” Ha said. But, she pointed out, Medicare benefits do cover intravenous iron formulations.
This article originally appeared on Medscape.com.
MAUI, HAWAII – said Christina Ha, MD, from the Inflammatory Bowel Disease Center at Cedars-Sinai in Los Angeles.
Clinicians sometimes fall back on steroids because they are typically inexpensive and because there are fears that the new anti-TNF biologics can cause adverse events in older patients, Ha said at the Gastroenterology Updates, IBD, Liver Disease Conference.
“There are not a lot of safety data for the age group, which is not well represented in clinical trials,” she explained. “We can’t necessarily extrapolate data from a study of people with an average age in the 40s to someone in their 70s.”
But, she emphasized, steroid use for more than 3 months is potentially inappropriate.
“If we have a patient on steroids, we should be saying which steroid-sparing strategy will be incorporated into their regimen when we start them on their course of steroids,” she explained.
Ha said she gets asked frequently whether the man-made steroid budesonide, which is readily available, should be considered an acceptable alternative to prednisone.
“Steroids are not maintenance therapies,” she pointed out. “One could argue that maybe someone who has symptomatic mild Crohn’s disease could be kept on low doses of budesonide. But I would argue whether it is really the budesonide that’s helping them or some other disease process related to polypharmacy.”
There are no long-term safety or efficacy data for budesonide in patients with ulcerative colitis or Crohn’s disease, she added.
Special considerations
Older patients with IBD have a decreased ability to handle disease activity; they have more comorbidities and a susceptibility to falls, said Ha. Early control of the disease is therefore essential.
Sarcopenia, an inherent part of aging when muscle mass decreases over time, is central to physiologic changes, which have implications for older adults with IBD, she said.
“We’re learning that sarcopenia is also prevalent in our patients with moderate to severe inflammatory bowel disease,” she explained. “Sarcopenia is associated with increased risk of infections, hospitalizations, and postoperative complications.”
Other changes occur in the intestines as patients age, Ha reported. “Recent studies have shown that there are changes in the intestinal barrier in terms of the junctions within the mucosal lining that increase intestinal permeability, which may help explain why some patients respond to treatments and others don’t.”
Physical therapy underused
Other treatment options, such as physical therapy, have also been underused in older patients with IBD. For example, there’s often considerable pushback against doing a physical therapy assessment on a hospitalized older patient, said Ha.
Medicare covers up to 80% of those services, but referral wording is key. “They’re not going to cover it for a primary diagnosis of ulcerative colitis or Crohn’s,” she explained. However, “they will cover it for a primary diagnosis of deconditioning with a secondary diagnoses of steroid exposure, anemia, Crohn’s disease, or ulcerative colitis.”
Physical therapy can improve muscle function, decrease muscle pain, potentially decrease analgesics, improve bone mass, and decrease joint pain, stress, fatigue, and debility. Fatigue is prevalent in patients with IBD, Ha explained.
Another underused resource is psychosocial assessment, she added. Although depression is not part of the aging process, it is common in those with chronic conditions.
Visits with licensed psychiatrists and clinical psychologists are covered under Medicare Part B, Ha pointed out, as are psychiatric evaluation and testing and individual and group therapy.
Older patients with IBD are often not receiving the care they need, said Uma Mahadevan, MD, a gastroenterologist at UCSF Health in San Francisco.
The need for awareness of polypharmacy, which Ha also discussed, is a concern in all older patients, but especially those with IBD, Mahadevan said in an interview. Clinicians need to be aware of the cascading effect of pharmacy, in which one drug’s adverse effect leads to the prescription of another drug, with different adverse effects.
Ha gave the example of a patient with IBD who started to have diarrhea as an adverse effect of a medication. A clinician might then prescribe a medication for Clostridium difficile, but that might lead to nausea, leading to the prescription of an antinausea medicine.
A multidisciplinary team is needed to perform medication reconciliation, Ha noted.
Correcting anemia important for IBD
Anemia is also underidentified and undertreated in older patients with IBD, Ha said.
“Across the board with inflammatory bowel disease, we don’t do a great job of being aggressive and correcting anemia. That has implications for fatigue and implications with functional status and circulating volume,” she said.
In older patients, it might be that the decline in hemoglobin over time is more important to outcomes than the number itself, she said. “A hemoglobin of 8 g/dL is one thing, but if it was at 12 g/dL 6 months ago, that’s a different story.”
“For older patients, anemia is associated with a high incidence of cardiovascular disease, cognitive impairment, increased risks of falls and fractures, longer hospitalizations (and thus increased costs of care), increased frailty and dementia, and increased risk of mortality,” Ha said. But, she pointed out, Medicare benefits do cover intravenous iron formulations.
This article originally appeared on Medscape.com.
MAUI, HAWAII – said Christina Ha, MD, from the Inflammatory Bowel Disease Center at Cedars-Sinai in Los Angeles.
Clinicians sometimes fall back on steroids because they are typically inexpensive and because there are fears that the new anti-TNF biologics can cause adverse events in older patients, Ha said at the Gastroenterology Updates, IBD, Liver Disease Conference.
“There are not a lot of safety data for the age group, which is not well represented in clinical trials,” she explained. “We can’t necessarily extrapolate data from a study of people with an average age in the 40s to someone in their 70s.”
But, she emphasized, steroid use for more than 3 months is potentially inappropriate.
“If we have a patient on steroids, we should be saying which steroid-sparing strategy will be incorporated into their regimen when we start them on their course of steroids,” she explained.
Ha said she gets asked frequently whether the man-made steroid budesonide, which is readily available, should be considered an acceptable alternative to prednisone.
“Steroids are not maintenance therapies,” she pointed out. “One could argue that maybe someone who has symptomatic mild Crohn’s disease could be kept on low doses of budesonide. But I would argue whether it is really the budesonide that’s helping them or some other disease process related to polypharmacy.”
There are no long-term safety or efficacy data for budesonide in patients with ulcerative colitis or Crohn’s disease, she added.
Special considerations
Older patients with IBD have a decreased ability to handle disease activity; they have more comorbidities and a susceptibility to falls, said Ha. Early control of the disease is therefore essential.
Sarcopenia, an inherent part of aging when muscle mass decreases over time, is central to physiologic changes, which have implications for older adults with IBD, she said.
“We’re learning that sarcopenia is also prevalent in our patients with moderate to severe inflammatory bowel disease,” she explained. “Sarcopenia is associated with increased risk of infections, hospitalizations, and postoperative complications.”
Other changes occur in the intestines as patients age, Ha reported. “Recent studies have shown that there are changes in the intestinal barrier in terms of the junctions within the mucosal lining that increase intestinal permeability, which may help explain why some patients respond to treatments and others don’t.”
Physical therapy underused
Other treatment options, such as physical therapy, have also been underused in older patients with IBD. For example, there’s often considerable pushback against doing a physical therapy assessment on a hospitalized older patient, said Ha.
Medicare covers up to 80% of those services, but referral wording is key. “They’re not going to cover it for a primary diagnosis of ulcerative colitis or Crohn’s,” she explained. However, “they will cover it for a primary diagnosis of deconditioning with a secondary diagnoses of steroid exposure, anemia, Crohn’s disease, or ulcerative colitis.”
Physical therapy can improve muscle function, decrease muscle pain, potentially decrease analgesics, improve bone mass, and decrease joint pain, stress, fatigue, and debility. Fatigue is prevalent in patients with IBD, Ha explained.
Another underused resource is psychosocial assessment, she added. Although depression is not part of the aging process, it is common in those with chronic conditions.
Visits with licensed psychiatrists and clinical psychologists are covered under Medicare Part B, Ha pointed out, as are psychiatric evaluation and testing and individual and group therapy.
Older patients with IBD are often not receiving the care they need, said Uma Mahadevan, MD, a gastroenterologist at UCSF Health in San Francisco.
The need for awareness of polypharmacy, which Ha also discussed, is a concern in all older patients, but especially those with IBD, Mahadevan said in an interview. Clinicians need to be aware of the cascading effect of pharmacy, in which one drug’s adverse effect leads to the prescription of another drug, with different adverse effects.
Ha gave the example of a patient with IBD who started to have diarrhea as an adverse effect of a medication. A clinician might then prescribe a medication for Clostridium difficile, but that might lead to nausea, leading to the prescription of an antinausea medicine.
A multidisciplinary team is needed to perform medication reconciliation, Ha noted.
Correcting anemia important for IBD
Anemia is also underidentified and undertreated in older patients with IBD, Ha said.
“Across the board with inflammatory bowel disease, we don’t do a great job of being aggressive and correcting anemia. That has implications for fatigue and implications with functional status and circulating volume,” she said.
In older patients, it might be that the decline in hemoglobin over time is more important to outcomes than the number itself, she said. “A hemoglobin of 8 g/dL is one thing, but if it was at 12 g/dL 6 months ago, that’s a different story.”
“For older patients, anemia is associated with a high incidence of cardiovascular disease, cognitive impairment, increased risks of falls and fractures, longer hospitalizations (and thus increased costs of care), increased frailty and dementia, and increased risk of mortality,” Ha said. But, she pointed out, Medicare benefits do cover intravenous iron formulations.
This article originally appeared on Medscape.com.
EXPERT ANALYSIS FROM GUILD 2020
A case is building for proactive anti-TNF monitoring in IBD
MAUI, HAWAII – Gastroenterologists are starting to embrace proactive therapeutic drug monitoring for inflammatory bowel disease patients on tumor necrosis factor inhibitors, according to reports at the Gastroenterology Updates, IBD, and Liver Disease conference.
Proactive therapeutic drug monitoring (TDM) is an alternative to standard combination therapy for inflammatory bowel disease, which involves giving a tumor necrosis factor inhibitor (TNFi) with an immunomodulator, usually azathioprine.
The immunomodulator is meant to prevent antibodies from forming against the TNFi and short-circuiting its effect. Growing evidence suggests that proactive TDM can do the same thing without the second drug and its sometimes fatal adverse events.
Serum TNFi levels are checked during induction, when the risk of antibody formation is highest if levels are too low, and increased upward if they are. Levels are also checked to make sure they aren’t too high, and sometimes followed during maintenance, speakers said at the meeting.
Commercially available serum assays make it easy; the turnaround time is a few days.
Reactive testing is too late
Reactive, instead of proactive, TNFi level testing is standard at the moment, which means levels are checked when people stop responding, but by then it’s often too late. “Why wait until a patient isn’t doing well and potentially has antibodies you can’t overcome before optimizing them? Why not deal with dose optimizing [tumor necrosis factor inhibitors] as opposed to using another drug like a thiopurine? This is common sense,” said gastroenterologist Adam Cheifetz, MD, director of the Center for Inflammatory Bowel Disease at Beth Israel Deaconess Medical Center and professor of medicine at Harvard Medical School, Boston, and a long-time advocate for proactive TDM.
Not too long ago, Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., doubted the approach, but he’s since come around “now that we are starting to see higher level data.” In his own practice, he said he now checks infliximab levels at week 14, before the fourth infusion. Other clinicians check at week 6 before the third infusion.
Whatever the timing, “If we are going to put somebody into remission, it’s going to be in that first 3-month window, so I think early optimization is important. Once you’ve adjusted the dose and optimized it, it might be something you want to check once a year. In my own practice, I’ve been inclined to do more combination therapy, but we’ll see how this goes,” Dr. Loftus said.
The evidence
Both presenters reviewed a recent randomized trial from Israel in pediatric Crohn’s patients induced with adalimumab. Trough levels were checked and adjusted as necessary to concentrations of 5 mcg/mL at weeks 4 and 8, and every 8 weeks thereafter, in 38 children; 40 others were randomized to reactive monitoring, with adjustments to the same trough level. Most of the children in the proactive group had dose intensifications, versus fewer than two-thirds in the reactive group.
At week 72, 31 children (82%) in the proactive group, but only 19 children (48%) in the reactive group, met the study’s primary endpoint, sustained corticosteroid-free clinical remission at all visits (Gastroenterology. 2019 Oct;157[4]:985-96.e2).
In short, “proactive TDM was far superior to reactive testing,” Dr. Cheifetz said.
There’s a question if the results would translate to adults, but, Dr. Loftus said, they beg “the issue of if I should be checking adalimumab trough levels at weeks 4 and 8. It certainly gives you pause to think about doing that.”
Among other reports, Dr. Cheifetz also reviewed a retrospective study of 264 patients – almost two-thirds with Crohn’s disease, the rest with ulcerative colitis - on infliximab maintenance therapy; half had proactive TDM, and the rest reactive monitoring. The target trough concentration was 5-10 mcg/mL; median follow-up was 2.4 years. He was the senior investigator.
On multiple Cox regression analysis, the proactive group had an 84% lower risk of treatment failure, an 84% lower risk of IBD hospitalization, a 75% lower risk of antibody formation, an 83% lower risk of serious infusion reactions, and a 70% lower risk of IBD surgery (Clin Gastroenterol Hepatol. 2017 Oct;15[10]:1580-8.e3).
Dr. Cheifetz said he uses assays from Prometheus Laboratories for proactive TDM, but there are other options. Prometheus turnaround times are a few days. He and his colleagues also have a website – www.bridgeibd.com – where doctors can plug in patient characteristics and get proactive TDM advice.
Dr. Cheifetz is a consultant for Prometheus, as well as Janssen, Abbvie and other companies. He disclosed research funding form Inform Diagnostics. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies.
MAUI, HAWAII – Gastroenterologists are starting to embrace proactive therapeutic drug monitoring for inflammatory bowel disease patients on tumor necrosis factor inhibitors, according to reports at the Gastroenterology Updates, IBD, and Liver Disease conference.
Proactive therapeutic drug monitoring (TDM) is an alternative to standard combination therapy for inflammatory bowel disease, which involves giving a tumor necrosis factor inhibitor (TNFi) with an immunomodulator, usually azathioprine.
The immunomodulator is meant to prevent antibodies from forming against the TNFi and short-circuiting its effect. Growing evidence suggests that proactive TDM can do the same thing without the second drug and its sometimes fatal adverse events.
Serum TNFi levels are checked during induction, when the risk of antibody formation is highest if levels are too low, and increased upward if they are. Levels are also checked to make sure they aren’t too high, and sometimes followed during maintenance, speakers said at the meeting.
Commercially available serum assays make it easy; the turnaround time is a few days.
Reactive testing is too late
Reactive, instead of proactive, TNFi level testing is standard at the moment, which means levels are checked when people stop responding, but by then it’s often too late. “Why wait until a patient isn’t doing well and potentially has antibodies you can’t overcome before optimizing them? Why not deal with dose optimizing [tumor necrosis factor inhibitors] as opposed to using another drug like a thiopurine? This is common sense,” said gastroenterologist Adam Cheifetz, MD, director of the Center for Inflammatory Bowel Disease at Beth Israel Deaconess Medical Center and professor of medicine at Harvard Medical School, Boston, and a long-time advocate for proactive TDM.
Not too long ago, Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., doubted the approach, but he’s since come around “now that we are starting to see higher level data.” In his own practice, he said he now checks infliximab levels at week 14, before the fourth infusion. Other clinicians check at week 6 before the third infusion.
Whatever the timing, “If we are going to put somebody into remission, it’s going to be in that first 3-month window, so I think early optimization is important. Once you’ve adjusted the dose and optimized it, it might be something you want to check once a year. In my own practice, I’ve been inclined to do more combination therapy, but we’ll see how this goes,” Dr. Loftus said.
The evidence
Both presenters reviewed a recent randomized trial from Israel in pediatric Crohn’s patients induced with adalimumab. Trough levels were checked and adjusted as necessary to concentrations of 5 mcg/mL at weeks 4 and 8, and every 8 weeks thereafter, in 38 children; 40 others were randomized to reactive monitoring, with adjustments to the same trough level. Most of the children in the proactive group had dose intensifications, versus fewer than two-thirds in the reactive group.
At week 72, 31 children (82%) in the proactive group, but only 19 children (48%) in the reactive group, met the study’s primary endpoint, sustained corticosteroid-free clinical remission at all visits (Gastroenterology. 2019 Oct;157[4]:985-96.e2).
In short, “proactive TDM was far superior to reactive testing,” Dr. Cheifetz said.
There’s a question if the results would translate to adults, but, Dr. Loftus said, they beg “the issue of if I should be checking adalimumab trough levels at weeks 4 and 8. It certainly gives you pause to think about doing that.”
Among other reports, Dr. Cheifetz also reviewed a retrospective study of 264 patients – almost two-thirds with Crohn’s disease, the rest with ulcerative colitis - on infliximab maintenance therapy; half had proactive TDM, and the rest reactive monitoring. The target trough concentration was 5-10 mcg/mL; median follow-up was 2.4 years. He was the senior investigator.
On multiple Cox regression analysis, the proactive group had an 84% lower risk of treatment failure, an 84% lower risk of IBD hospitalization, a 75% lower risk of antibody formation, an 83% lower risk of serious infusion reactions, and a 70% lower risk of IBD surgery (Clin Gastroenterol Hepatol. 2017 Oct;15[10]:1580-8.e3).
Dr. Cheifetz said he uses assays from Prometheus Laboratories for proactive TDM, but there are other options. Prometheus turnaround times are a few days. He and his colleagues also have a website – www.bridgeibd.com – where doctors can plug in patient characteristics and get proactive TDM advice.
Dr. Cheifetz is a consultant for Prometheus, as well as Janssen, Abbvie and other companies. He disclosed research funding form Inform Diagnostics. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies.
MAUI, HAWAII – Gastroenterologists are starting to embrace proactive therapeutic drug monitoring for inflammatory bowel disease patients on tumor necrosis factor inhibitors, according to reports at the Gastroenterology Updates, IBD, and Liver Disease conference.
Proactive therapeutic drug monitoring (TDM) is an alternative to standard combination therapy for inflammatory bowel disease, which involves giving a tumor necrosis factor inhibitor (TNFi) with an immunomodulator, usually azathioprine.
The immunomodulator is meant to prevent antibodies from forming against the TNFi and short-circuiting its effect. Growing evidence suggests that proactive TDM can do the same thing without the second drug and its sometimes fatal adverse events.
Serum TNFi levels are checked during induction, when the risk of antibody formation is highest if levels are too low, and increased upward if they are. Levels are also checked to make sure they aren’t too high, and sometimes followed during maintenance, speakers said at the meeting.
Commercially available serum assays make it easy; the turnaround time is a few days.
Reactive testing is too late
Reactive, instead of proactive, TNFi level testing is standard at the moment, which means levels are checked when people stop responding, but by then it’s often too late. “Why wait until a patient isn’t doing well and potentially has antibodies you can’t overcome before optimizing them? Why not deal with dose optimizing [tumor necrosis factor inhibitors] as opposed to using another drug like a thiopurine? This is common sense,” said gastroenterologist Adam Cheifetz, MD, director of the Center for Inflammatory Bowel Disease at Beth Israel Deaconess Medical Center and professor of medicine at Harvard Medical School, Boston, and a long-time advocate for proactive TDM.
Not too long ago, Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., doubted the approach, but he’s since come around “now that we are starting to see higher level data.” In his own practice, he said he now checks infliximab levels at week 14, before the fourth infusion. Other clinicians check at week 6 before the third infusion.
Whatever the timing, “If we are going to put somebody into remission, it’s going to be in that first 3-month window, so I think early optimization is important. Once you’ve adjusted the dose and optimized it, it might be something you want to check once a year. In my own practice, I’ve been inclined to do more combination therapy, but we’ll see how this goes,” Dr. Loftus said.
The evidence
Both presenters reviewed a recent randomized trial from Israel in pediatric Crohn’s patients induced with adalimumab. Trough levels were checked and adjusted as necessary to concentrations of 5 mcg/mL at weeks 4 and 8, and every 8 weeks thereafter, in 38 children; 40 others were randomized to reactive monitoring, with adjustments to the same trough level. Most of the children in the proactive group had dose intensifications, versus fewer than two-thirds in the reactive group.
At week 72, 31 children (82%) in the proactive group, but only 19 children (48%) in the reactive group, met the study’s primary endpoint, sustained corticosteroid-free clinical remission at all visits (Gastroenterology. 2019 Oct;157[4]:985-96.e2).
In short, “proactive TDM was far superior to reactive testing,” Dr. Cheifetz said.
There’s a question if the results would translate to adults, but, Dr. Loftus said, they beg “the issue of if I should be checking adalimumab trough levels at weeks 4 and 8. It certainly gives you pause to think about doing that.”
Among other reports, Dr. Cheifetz also reviewed a retrospective study of 264 patients – almost two-thirds with Crohn’s disease, the rest with ulcerative colitis - on infliximab maintenance therapy; half had proactive TDM, and the rest reactive monitoring. The target trough concentration was 5-10 mcg/mL; median follow-up was 2.4 years. He was the senior investigator.
On multiple Cox regression analysis, the proactive group had an 84% lower risk of treatment failure, an 84% lower risk of IBD hospitalization, a 75% lower risk of antibody formation, an 83% lower risk of serious infusion reactions, and a 70% lower risk of IBD surgery (Clin Gastroenterol Hepatol. 2017 Oct;15[10]:1580-8.e3).
Dr. Cheifetz said he uses assays from Prometheus Laboratories for proactive TDM, but there are other options. Prometheus turnaround times are a few days. He and his colleagues also have a website – www.bridgeibd.com – where doctors can plug in patient characteristics and get proactive TDM advice.
Dr. Cheifetz is a consultant for Prometheus, as well as Janssen, Abbvie and other companies. He disclosed research funding form Inform Diagnostics. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies.
REPORTING FROM GUILD 2020
Rising number of young people dying after heavy drinking
MAUI, HAWAII – Alcohol use and deaths related to alcohol-use disorders are increasing, and young adults might be the group to watch, said Norah Terrault, MD, MPH, professor at the Keck School of Medicine of USC in Los Angeles.
“A lot of young people are drinking large amounts and they don’t know they’re at risk. They may not drink much during the week but then drink 30 drinks on the weekend,” Dr. Terrault told Medscape Medical News.
The largest relative increase in deaths from alcoholic cirrhosis – 10.5% from 2009 to 2016 – was in the 25- to 34-year age group, she reported here at the Gastroenterology Updates IBD Liver Disease Conference 2020.
This highlights the importance of asking for details about alcohol use during primary care visits; not only how much, but also what time of day, for instance, she explained.
Dr. Terrault’s team at Keck is part of the ACCELERATE-AH consortium, a group of 12 transplant centers looking at patterns of alcohol use before and after liver transplantation.
In their retrospective study of 147 consecutive transplant patients from 2006 to 2018, they found that young age, a history of multiple rehab attempts, and overt encephalopathy at time of transplantation were predictors of alcohol use after the procedure.
Corticosteroids remain the only proven therapy for alcoholic hepatitis. “We have not seen a new therapy in this arena in decades,” said Dr. Terrault. “We really have nothing to offer these patients, yet it’s an incredibly common presentation with a high mortality.”
More treatment options
The good news is that some phase 2 data look promising for new therapies, she reported.
“Some of them are targeting injury and regeneration primarily. Others are looking at the anti-inflammatory and antifibrotic effects. Some are also looking at how gut permeability and the microbiome are influencing outcomes,” she explained.
Transplantation has become very important for patients who do not respond to current therapy, and selection criteria have evolved over the years to take this into account, she pointed out.
In the early 1980s, alcoholic hepatitis was considered an inappropriate indication for liver transplantation. In the early 2000s, the guidance moved to setting 6 months of alcohol abstinence as a criterion for transplantation. The 6-month rule effectively eliminated patients with severe alcoholic hepatitis, who, by the time they needed a new liver, would not have 6 months to live.
Recently, guidelines have added the option of transplantation for patients with alcoholic hepatitis. The option was always there for people who developed alcohol cirrhosis or liver cancer, but now alcoholic hepatitis is recognized as a potential indication for transplantation, Dr. Terrault explained.
Today, transplant centers are moving away from the 6-month rule for two main reasons, she said. One is that few data support the 6-month time period as the duration that makes a difference.
“There is nothing magical about 6 months vs. 3 months or 12 months,” she said, adding that studies have shown that other factors might be better indicators, such as family support and whether the person is employed.
Second, recent studies have shown that rates of 3-year survival are similar in people who did not abstain at all before the procedure and those who undergo transplantation for other reasons.
The ACCELERATE-AH consortium also found that 70% of patients with severe alcoholic hepatitis remained abstinent up to 3 years after transplantation.
Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant.
The selection process remains complicated and controversial, Dr. Terrault acknowledged.
“Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant,” she said.
And there is concern that because patients with severe alcoholic hepatitis present with severe illness, they get moved to the top of the wait list. The rationale for that, she explained, is that it is done that way in other acute situations.
“We transplant individuals who have an acetaminophen overdose, for example. That’s common in many programs,” she said.
“My issue is that some patients with acute alcoholic hepatitis that have a very high severity score, but some of them, just with abstinence, will get better,” said Guadalupe Garcia-Tsao, MD, professor of medicine at Yale University in New Haven, Conn.
There are cases in which acute alcoholic hepatitis will resolve with abstinence, “and patients can return to an entirely compensated state of cirrhosis, in which they are entirely asymptomatic and they can live,” she told Medscape Medical News.
But it’s hard to know without a control group which patients would have that kind of success with just abstinence, she acknowledged.
Terrault said she agreed, and added that “our tools are not that good,” so determining which patients can be “pulled back from the brink” without transplantation is a challenge.
“There’s still a lot to learn about how we do this, and how we do it well,” she said.
Alcoholic hepatitis as an indication for liver transplantation is rare – less than 1% – but growing.
“This is a potential therapy for your patient who is sick in the ICU with a high severity of disease who has failed steroids. We should call out to see if there’s a transplant program that might be willing to evaluate them,” she said.
This article first appeared on Medscape.com.
MAUI, HAWAII – Alcohol use and deaths related to alcohol-use disorders are increasing, and young adults might be the group to watch, said Norah Terrault, MD, MPH, professor at the Keck School of Medicine of USC in Los Angeles.
“A lot of young people are drinking large amounts and they don’t know they’re at risk. They may not drink much during the week but then drink 30 drinks on the weekend,” Dr. Terrault told Medscape Medical News.
The largest relative increase in deaths from alcoholic cirrhosis – 10.5% from 2009 to 2016 – was in the 25- to 34-year age group, she reported here at the Gastroenterology Updates IBD Liver Disease Conference 2020.
This highlights the importance of asking for details about alcohol use during primary care visits; not only how much, but also what time of day, for instance, she explained.
Dr. Terrault’s team at Keck is part of the ACCELERATE-AH consortium, a group of 12 transplant centers looking at patterns of alcohol use before and after liver transplantation.
In their retrospective study of 147 consecutive transplant patients from 2006 to 2018, they found that young age, a history of multiple rehab attempts, and overt encephalopathy at time of transplantation were predictors of alcohol use after the procedure.
Corticosteroids remain the only proven therapy for alcoholic hepatitis. “We have not seen a new therapy in this arena in decades,” said Dr. Terrault. “We really have nothing to offer these patients, yet it’s an incredibly common presentation with a high mortality.”
More treatment options
The good news is that some phase 2 data look promising for new therapies, she reported.
“Some of them are targeting injury and regeneration primarily. Others are looking at the anti-inflammatory and antifibrotic effects. Some are also looking at how gut permeability and the microbiome are influencing outcomes,” she explained.
Transplantation has become very important for patients who do not respond to current therapy, and selection criteria have evolved over the years to take this into account, she pointed out.
In the early 1980s, alcoholic hepatitis was considered an inappropriate indication for liver transplantation. In the early 2000s, the guidance moved to setting 6 months of alcohol abstinence as a criterion for transplantation. The 6-month rule effectively eliminated patients with severe alcoholic hepatitis, who, by the time they needed a new liver, would not have 6 months to live.
Recently, guidelines have added the option of transplantation for patients with alcoholic hepatitis. The option was always there for people who developed alcohol cirrhosis or liver cancer, but now alcoholic hepatitis is recognized as a potential indication for transplantation, Dr. Terrault explained.
Today, transplant centers are moving away from the 6-month rule for two main reasons, she said. One is that few data support the 6-month time period as the duration that makes a difference.
“There is nothing magical about 6 months vs. 3 months or 12 months,” she said, adding that studies have shown that other factors might be better indicators, such as family support and whether the person is employed.
Second, recent studies have shown that rates of 3-year survival are similar in people who did not abstain at all before the procedure and those who undergo transplantation for other reasons.
The ACCELERATE-AH consortium also found that 70% of patients with severe alcoholic hepatitis remained abstinent up to 3 years after transplantation.
Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant.
The selection process remains complicated and controversial, Dr. Terrault acknowledged.
“Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant,” she said.
And there is concern that because patients with severe alcoholic hepatitis present with severe illness, they get moved to the top of the wait list. The rationale for that, she explained, is that it is done that way in other acute situations.
“We transplant individuals who have an acetaminophen overdose, for example. That’s common in many programs,” she said.
“My issue is that some patients with acute alcoholic hepatitis that have a very high severity score, but some of them, just with abstinence, will get better,” said Guadalupe Garcia-Tsao, MD, professor of medicine at Yale University in New Haven, Conn.
There are cases in which acute alcoholic hepatitis will resolve with abstinence, “and patients can return to an entirely compensated state of cirrhosis, in which they are entirely asymptomatic and they can live,” she told Medscape Medical News.
But it’s hard to know without a control group which patients would have that kind of success with just abstinence, she acknowledged.
Terrault said she agreed, and added that “our tools are not that good,” so determining which patients can be “pulled back from the brink” without transplantation is a challenge.
“There’s still a lot to learn about how we do this, and how we do it well,” she said.
Alcoholic hepatitis as an indication for liver transplantation is rare – less than 1% – but growing.
“This is a potential therapy for your patient who is sick in the ICU with a high severity of disease who has failed steroids. We should call out to see if there’s a transplant program that might be willing to evaluate them,” she said.
This article first appeared on Medscape.com.
MAUI, HAWAII – Alcohol use and deaths related to alcohol-use disorders are increasing, and young adults might be the group to watch, said Norah Terrault, MD, MPH, professor at the Keck School of Medicine of USC in Los Angeles.
“A lot of young people are drinking large amounts and they don’t know they’re at risk. They may not drink much during the week but then drink 30 drinks on the weekend,” Dr. Terrault told Medscape Medical News.
The largest relative increase in deaths from alcoholic cirrhosis – 10.5% from 2009 to 2016 – was in the 25- to 34-year age group, she reported here at the Gastroenterology Updates IBD Liver Disease Conference 2020.
This highlights the importance of asking for details about alcohol use during primary care visits; not only how much, but also what time of day, for instance, she explained.
Dr. Terrault’s team at Keck is part of the ACCELERATE-AH consortium, a group of 12 transplant centers looking at patterns of alcohol use before and after liver transplantation.
In their retrospective study of 147 consecutive transplant patients from 2006 to 2018, they found that young age, a history of multiple rehab attempts, and overt encephalopathy at time of transplantation were predictors of alcohol use after the procedure.
Corticosteroids remain the only proven therapy for alcoholic hepatitis. “We have not seen a new therapy in this arena in decades,” said Dr. Terrault. “We really have nothing to offer these patients, yet it’s an incredibly common presentation with a high mortality.”
More treatment options
The good news is that some phase 2 data look promising for new therapies, she reported.
“Some of them are targeting injury and regeneration primarily. Others are looking at the anti-inflammatory and antifibrotic effects. Some are also looking at how gut permeability and the microbiome are influencing outcomes,” she explained.
Transplantation has become very important for patients who do not respond to current therapy, and selection criteria have evolved over the years to take this into account, she pointed out.
In the early 1980s, alcoholic hepatitis was considered an inappropriate indication for liver transplantation. In the early 2000s, the guidance moved to setting 6 months of alcohol abstinence as a criterion for transplantation. The 6-month rule effectively eliminated patients with severe alcoholic hepatitis, who, by the time they needed a new liver, would not have 6 months to live.
Recently, guidelines have added the option of transplantation for patients with alcoholic hepatitis. The option was always there for people who developed alcohol cirrhosis or liver cancer, but now alcoholic hepatitis is recognized as a potential indication for transplantation, Dr. Terrault explained.
Today, transplant centers are moving away from the 6-month rule for two main reasons, she said. One is that few data support the 6-month time period as the duration that makes a difference.
“There is nothing magical about 6 months vs. 3 months or 12 months,” she said, adding that studies have shown that other factors might be better indicators, such as family support and whether the person is employed.
Second, recent studies have shown that rates of 3-year survival are similar in people who did not abstain at all before the procedure and those who undergo transplantation for other reasons.
The ACCELERATE-AH consortium also found that 70% of patients with severe alcoholic hepatitis remained abstinent up to 3 years after transplantation.
Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant.
The selection process remains complicated and controversial, Dr. Terrault acknowledged.
“Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant,” she said.
And there is concern that because patients with severe alcoholic hepatitis present with severe illness, they get moved to the top of the wait list. The rationale for that, she explained, is that it is done that way in other acute situations.
“We transplant individuals who have an acetaminophen overdose, for example. That’s common in many programs,” she said.
“My issue is that some patients with acute alcoholic hepatitis that have a very high severity score, but some of them, just with abstinence, will get better,” said Guadalupe Garcia-Tsao, MD, professor of medicine at Yale University in New Haven, Conn.
There are cases in which acute alcoholic hepatitis will resolve with abstinence, “and patients can return to an entirely compensated state of cirrhosis, in which they are entirely asymptomatic and they can live,” she told Medscape Medical News.
But it’s hard to know without a control group which patients would have that kind of success with just abstinence, she acknowledged.
Terrault said she agreed, and added that “our tools are not that good,” so determining which patients can be “pulled back from the brink” without transplantation is a challenge.
“There’s still a lot to learn about how we do this, and how we do it well,” she said.
Alcoholic hepatitis as an indication for liver transplantation is rare – less than 1% – but growing.
“This is a potential therapy for your patient who is sick in the ICU with a high severity of disease who has failed steroids. We should call out to see if there’s a transplant program that might be willing to evaluate them,” she said.
This article first appeared on Medscape.com.
EXPERT ANALYSIS FROM GUILD 2020
Osteoporosis, fracture risk higher in patients with IBD
MAUI, HAWAII –
In the general population, those who develop osteoporosis are typically women who are thin and postmenopausal, and family history, smoking status, and alcohol use usually play a role, Long said at the Gastroenterology Updates, IBD, Liver Disease Conference.
But in the population with IBD, the risk for osteoporosis is similar in women and men, age plays a large role, and corticosteroid use seems to be a driving factor in the development of the disease, she explained.
A previous study that looked at fractures in patients with IBD showed that the risk “is 40% greater than in the general population,” Long reported. In patients younger than 40 years, the risk for fracture was 37% higher than in the general population, and this rate increased with age.
Preventing fractures
Fractures to the hip and spine are linked to significant morbidity, including hospitalization, major surgery, and even death, Long noted. But they are one of the preventable downstream effects of IBD, and patients need to understand that there’s something they can do about their elevated risk.
Patients should be educated on the importance of weight-bearing exercise and quitting smoking, she said.
“We need to think of preventive measures for anyone on more than 5 mg of prednisone a day for a time period of about 3 months,” she added. “Unfortunately, most of our patients meet this criterion.”
Patients with IBD should undergo dual-energy x-ray absorptiometry (DXA) to calculate bone density and establish the need for calcium and vitamin D supplementation.
“One of the things I’m starting to do in my practice is check vitamin D levels annually on my patients. I do this in the springtime and try to optimize their levels,” Long said.
Higher risk for herpes zoster
The risk for infection is also elevated in patients with IBD, including the risk for herpes zoster, which is already high, affecting one in three people in the general population.
In fact, the risk for herpes zoster in patients with IBD in their 20s is similar to the risk for people in their 50s in the general population. This is “something we need to be addressing in all of our patients,” said Long.
Physicians should emphasize the need for zoster vaccination in patients at least 50 years of age, and potentially younger patients on certain therapies, she added.
But because the Shingrix shingles vaccine (GlaxoSmithKline) is so much more powerful than the previous live vaccine, some have wondered whether it could stimulate an immune response, causing the IBD to flare after vaccination, she said.
However, a recent study of IBD patients followed for 207 days after shingles vaccination showed that only one of the 67 study participants (1.5%) experienced a flare. But fever is fairly common after the shot.
“I counsel my patients that they may feel pretty wiped out for 24 hours; they may have myalgias,” Long reported. “If you have someone who has to travel for work, you want them to time this vaccination so they can have a day of rest afterward. It’s the real deal.”
Screening for TB
Screening to rule out latent tuberculosis (TB) is also important in IBD.
“We should be looking at whether they’ve had close contact with active TB or people from endemic areas,” said Long. “The reason we really care about this is that the risk of serious infection is doubled with anti-TNF therapy.”
The treatment of latent TB prior to the initiation of an anti-TNF “reduces the incidence of active TB by over 80%. This is why it’s imperative to screen prior to initiation, and then periodically based on risk factors,” she explained.
“It’s profound how much maintenance is required for patients with IBD,” said Christopher Stanke, MD, from the Oregon Medical Group in Eugene.
He said he is particularly struck by the collective risks for younger patients with IBD.
“Young people look to us as their only doctor. They don’t even see their primary care physicians very often. We have to take over a lot of this stuff,” he told Medscape Medical News.
And osteoporosis doesn’t often get the attention it needs in gastroenterologists’ offices, he acknowledged.
“I often check it on people as they get close to 50 or 60,” said Stanke, who added that Long’s presentation is a good reminder that younger patients, especially those who have been on steroids for a while, need more attention.
This article first appeared on Medscape.com.
MAUI, HAWAII –
In the general population, those who develop osteoporosis are typically women who are thin and postmenopausal, and family history, smoking status, and alcohol use usually play a role, Long said at the Gastroenterology Updates, IBD, Liver Disease Conference.
But in the population with IBD, the risk for osteoporosis is similar in women and men, age plays a large role, and corticosteroid use seems to be a driving factor in the development of the disease, she explained.
A previous study that looked at fractures in patients with IBD showed that the risk “is 40% greater than in the general population,” Long reported. In patients younger than 40 years, the risk for fracture was 37% higher than in the general population, and this rate increased with age.
Preventing fractures
Fractures to the hip and spine are linked to significant morbidity, including hospitalization, major surgery, and even death, Long noted. But they are one of the preventable downstream effects of IBD, and patients need to understand that there’s something they can do about their elevated risk.
Patients should be educated on the importance of weight-bearing exercise and quitting smoking, she said.
“We need to think of preventive measures for anyone on more than 5 mg of prednisone a day for a time period of about 3 months,” she added. “Unfortunately, most of our patients meet this criterion.”
Patients with IBD should undergo dual-energy x-ray absorptiometry (DXA) to calculate bone density and establish the need for calcium and vitamin D supplementation.
“One of the things I’m starting to do in my practice is check vitamin D levels annually on my patients. I do this in the springtime and try to optimize their levels,” Long said.
Higher risk for herpes zoster
The risk for infection is also elevated in patients with IBD, including the risk for herpes zoster, which is already high, affecting one in three people in the general population.
In fact, the risk for herpes zoster in patients with IBD in their 20s is similar to the risk for people in their 50s in the general population. This is “something we need to be addressing in all of our patients,” said Long.
Physicians should emphasize the need for zoster vaccination in patients at least 50 years of age, and potentially younger patients on certain therapies, she added.
But because the Shingrix shingles vaccine (GlaxoSmithKline) is so much more powerful than the previous live vaccine, some have wondered whether it could stimulate an immune response, causing the IBD to flare after vaccination, she said.
However, a recent study of IBD patients followed for 207 days after shingles vaccination showed that only one of the 67 study participants (1.5%) experienced a flare. But fever is fairly common after the shot.
“I counsel my patients that they may feel pretty wiped out for 24 hours; they may have myalgias,” Long reported. “If you have someone who has to travel for work, you want them to time this vaccination so they can have a day of rest afterward. It’s the real deal.”
Screening for TB
Screening to rule out latent tuberculosis (TB) is also important in IBD.
“We should be looking at whether they’ve had close contact with active TB or people from endemic areas,” said Long. “The reason we really care about this is that the risk of serious infection is doubled with anti-TNF therapy.”
The treatment of latent TB prior to the initiation of an anti-TNF “reduces the incidence of active TB by over 80%. This is why it’s imperative to screen prior to initiation, and then periodically based on risk factors,” she explained.
“It’s profound how much maintenance is required for patients with IBD,” said Christopher Stanke, MD, from the Oregon Medical Group in Eugene.
He said he is particularly struck by the collective risks for younger patients with IBD.
“Young people look to us as their only doctor. They don’t even see their primary care physicians very often. We have to take over a lot of this stuff,” he told Medscape Medical News.
And osteoporosis doesn’t often get the attention it needs in gastroenterologists’ offices, he acknowledged.
“I often check it on people as they get close to 50 or 60,” said Stanke, who added that Long’s presentation is a good reminder that younger patients, especially those who have been on steroids for a while, need more attention.
This article first appeared on Medscape.com.
MAUI, HAWAII –
In the general population, those who develop osteoporosis are typically women who are thin and postmenopausal, and family history, smoking status, and alcohol use usually play a role, Long said at the Gastroenterology Updates, IBD, Liver Disease Conference.
But in the population with IBD, the risk for osteoporosis is similar in women and men, age plays a large role, and corticosteroid use seems to be a driving factor in the development of the disease, she explained.
A previous study that looked at fractures in patients with IBD showed that the risk “is 40% greater than in the general population,” Long reported. In patients younger than 40 years, the risk for fracture was 37% higher than in the general population, and this rate increased with age.
Preventing fractures
Fractures to the hip and spine are linked to significant morbidity, including hospitalization, major surgery, and even death, Long noted. But they are one of the preventable downstream effects of IBD, and patients need to understand that there’s something they can do about their elevated risk.
Patients should be educated on the importance of weight-bearing exercise and quitting smoking, she said.
“We need to think of preventive measures for anyone on more than 5 mg of prednisone a day for a time period of about 3 months,” she added. “Unfortunately, most of our patients meet this criterion.”
Patients with IBD should undergo dual-energy x-ray absorptiometry (DXA) to calculate bone density and establish the need for calcium and vitamin D supplementation.
“One of the things I’m starting to do in my practice is check vitamin D levels annually on my patients. I do this in the springtime and try to optimize their levels,” Long said.
Higher risk for herpes zoster
The risk for infection is also elevated in patients with IBD, including the risk for herpes zoster, which is already high, affecting one in three people in the general population.
In fact, the risk for herpes zoster in patients with IBD in their 20s is similar to the risk for people in their 50s in the general population. This is “something we need to be addressing in all of our patients,” said Long.
Physicians should emphasize the need for zoster vaccination in patients at least 50 years of age, and potentially younger patients on certain therapies, she added.
But because the Shingrix shingles vaccine (GlaxoSmithKline) is so much more powerful than the previous live vaccine, some have wondered whether it could stimulate an immune response, causing the IBD to flare after vaccination, she said.
However, a recent study of IBD patients followed for 207 days after shingles vaccination showed that only one of the 67 study participants (1.5%) experienced a flare. But fever is fairly common after the shot.
“I counsel my patients that they may feel pretty wiped out for 24 hours; they may have myalgias,” Long reported. “If you have someone who has to travel for work, you want them to time this vaccination so they can have a day of rest afterward. It’s the real deal.”
Screening for TB
Screening to rule out latent tuberculosis (TB) is also important in IBD.
“We should be looking at whether they’ve had close contact with active TB or people from endemic areas,” said Long. “The reason we really care about this is that the risk of serious infection is doubled with anti-TNF therapy.”
The treatment of latent TB prior to the initiation of an anti-TNF “reduces the incidence of active TB by over 80%. This is why it’s imperative to screen prior to initiation, and then periodically based on risk factors,” she explained.
“It’s profound how much maintenance is required for patients with IBD,” said Christopher Stanke, MD, from the Oregon Medical Group in Eugene.
He said he is particularly struck by the collective risks for younger patients with IBD.
“Young people look to us as their only doctor. They don’t even see their primary care physicians very often. We have to take over a lot of this stuff,” he told Medscape Medical News.
And osteoporosis doesn’t often get the attention it needs in gastroenterologists’ offices, he acknowledged.
“I often check it on people as they get close to 50 or 60,” said Stanke, who added that Long’s presentation is a good reminder that younger patients, especially those who have been on steroids for a while, need more attention.
This article first appeared on Medscape.com.
REPORTING FROM GUILD 2020
HBV: Rethink the free pass for immune tolerant patients
MAUI, HAWAII – There might well be a cure for hepatitis B in coming years, just like there is now for hepatitis C, according to Norah Terrault, MD, chief of the division of GI and liver at the University of Southern California, Los Angeles.
“We are going to have a laundry list of new drugs” that are in the pipeline now. Phase 2 results “look encouraging. You will hear much more about this in the years ahead,” said Dr. Terrault, lead author of the 2018 American Association for the Study of Liver Diseases (AASLD) hepatitis B guidance.
For now, though, the field is largely limited to the nucleoside analogues tenofovir and entecavir. Treatment is often indefinite because, although hepatitis B virus (HBV) e-antigen is cleared, it usually doesn’t clear the HBV surface antigen, which is linked to liver cancer. “Even with e-antigen–negative patients, we feel that indefinite therapy is really the way to go,” Dr. Terrault said at the Gastroenterology Updates, IBD, Liver Disease Conference.
One of the biggest problems with that strategy is what to do when HBV does not seem to be much of a problem for carriers. Such patients are referred to as immune tolerant.
A newly recognized cancer risk
Immune tolerant patients tend to be young and have extremely high viral loads but no apparent ill effects, with normal ALT levels, normal histology, and no sign of cirrhosis. Although the AASLD recommends not treating these patients until they are 40 years old, waiting makes people nervous. “You have a hammer, you want to hit a nail,” Dr. Terrault said.
A recent review (Gut. 2018 May;67[5]:945-52) suggests that hitting the nail might be the way to go. South Korean investigators found that 413 untreated immune tolerate patients with a mean age of 38 years had more than twice the risk of liver cancer over 10 years than did almost 1,500 treated patients with active disease.
The study investigators concluded that “unnecessary deaths could be prevented through earlier antiviral intervention in select [immune tolerate] patients.”
This finding is one reason “we [AASLD] are rethinking the mantra of not treating the immune tolerant. There is a group that is transitioning” to active disease. “I’m thinking we should really [lower] the age cutoff” to 30 years, as some other groups [European Association for the Study of the Liver and Asian Pacific Association for the Study of the Liver] have done, plus “patients feel really good when they know the virus is controlled, and so do physicians,” Dr. Terrault said.
Entecavir versus tenofovir
Meanwhile, recent studies have raised the question of whether tenofovir is better than entecavir at preventing liver cancer.
A JAMA Oncology (JAMA Oncol. 2019 Jan 1;5[1]:30-6) study of some 25,000 patients in South Korea found a 32% lower risk of liver cancer when they were treated with tenofovir instead of entecavir. “This led to a lot of concern that maybe we should be moving all our patients to tenofovir,” she said.
Another study, a meta-analysis published earlier this year (Hepatol Int. 2020 Jan;14[1]:105-14), confirmed the difference in cancer risk when it combined those findings with other research. After adjustment for potential confounders, including disease stage and length of follow-up, “the difference disappeared” (hazard ration, 0.87; 95% confidence interval, 0.73-1.04), authors of the meta-analysis reported.
Study patients who received entecavir tended to be “treated many years ago and tended to have more severe [baseline] disease,” Dr. Terrault said.
So “while we see this difference, there’s not enough data yet for us to make a recommendation for our patients to switch from” entecavir to tenofovir. “Until a randomized controlled trial is done, this may remain an issue,” she said.
A drug holiday?
Dr. Terrault also reviewed research that suggests nucleoside analogue treatment can be stopped in e-antigen–negative patients after at least 3 years.
“The evidence is increasing that a finite NA [nucleoside analogue] treatment approach leads to higher HBsAg [hepatitis B surface antigen] loss rates, compared with the current long-term NA strategy, and can be considered a rational strategy to induce a functional cure in selected HBeAg-negative patients without cirrhosis who are willing to comply with close follow-up monitoring. ... The current observed functional cure rates” – perhaps about 40% – “would be well worth the effort,” editorialists commenting on the research concluded (Hepatology. 2018 Aug;68[2]:397-400).
It’s an interesting idea, Dr. Terrault said, but the virus will flare 8-12 weeks after treatment withdrawal, which is why it shouldn’t be considered in patients with cirrhosis.
Dr. Terrault is a consultant for AbbVie, Merck, Gilead, and other companies and disclosed grants from those companies and others.
MAUI, HAWAII – There might well be a cure for hepatitis B in coming years, just like there is now for hepatitis C, according to Norah Terrault, MD, chief of the division of GI and liver at the University of Southern California, Los Angeles.
“We are going to have a laundry list of new drugs” that are in the pipeline now. Phase 2 results “look encouraging. You will hear much more about this in the years ahead,” said Dr. Terrault, lead author of the 2018 American Association for the Study of Liver Diseases (AASLD) hepatitis B guidance.
For now, though, the field is largely limited to the nucleoside analogues tenofovir and entecavir. Treatment is often indefinite because, although hepatitis B virus (HBV) e-antigen is cleared, it usually doesn’t clear the HBV surface antigen, which is linked to liver cancer. “Even with e-antigen–negative patients, we feel that indefinite therapy is really the way to go,” Dr. Terrault said at the Gastroenterology Updates, IBD, Liver Disease Conference.
One of the biggest problems with that strategy is what to do when HBV does not seem to be much of a problem for carriers. Such patients are referred to as immune tolerant.
A newly recognized cancer risk
Immune tolerant patients tend to be young and have extremely high viral loads but no apparent ill effects, with normal ALT levels, normal histology, and no sign of cirrhosis. Although the AASLD recommends not treating these patients until they are 40 years old, waiting makes people nervous. “You have a hammer, you want to hit a nail,” Dr. Terrault said.
A recent review (Gut. 2018 May;67[5]:945-52) suggests that hitting the nail might be the way to go. South Korean investigators found that 413 untreated immune tolerate patients with a mean age of 38 years had more than twice the risk of liver cancer over 10 years than did almost 1,500 treated patients with active disease.
The study investigators concluded that “unnecessary deaths could be prevented through earlier antiviral intervention in select [immune tolerate] patients.”
This finding is one reason “we [AASLD] are rethinking the mantra of not treating the immune tolerant. There is a group that is transitioning” to active disease. “I’m thinking we should really [lower] the age cutoff” to 30 years, as some other groups [European Association for the Study of the Liver and Asian Pacific Association for the Study of the Liver] have done, plus “patients feel really good when they know the virus is controlled, and so do physicians,” Dr. Terrault said.
Entecavir versus tenofovir
Meanwhile, recent studies have raised the question of whether tenofovir is better than entecavir at preventing liver cancer.
A JAMA Oncology (JAMA Oncol. 2019 Jan 1;5[1]:30-6) study of some 25,000 patients in South Korea found a 32% lower risk of liver cancer when they were treated with tenofovir instead of entecavir. “This led to a lot of concern that maybe we should be moving all our patients to tenofovir,” she said.
Another study, a meta-analysis published earlier this year (Hepatol Int. 2020 Jan;14[1]:105-14), confirmed the difference in cancer risk when it combined those findings with other research. After adjustment for potential confounders, including disease stage and length of follow-up, “the difference disappeared” (hazard ration, 0.87; 95% confidence interval, 0.73-1.04), authors of the meta-analysis reported.
Study patients who received entecavir tended to be “treated many years ago and tended to have more severe [baseline] disease,” Dr. Terrault said.
So “while we see this difference, there’s not enough data yet for us to make a recommendation for our patients to switch from” entecavir to tenofovir. “Until a randomized controlled trial is done, this may remain an issue,” she said.
A drug holiday?
Dr. Terrault also reviewed research that suggests nucleoside analogue treatment can be stopped in e-antigen–negative patients after at least 3 years.
“The evidence is increasing that a finite NA [nucleoside analogue] treatment approach leads to higher HBsAg [hepatitis B surface antigen] loss rates, compared with the current long-term NA strategy, and can be considered a rational strategy to induce a functional cure in selected HBeAg-negative patients without cirrhosis who are willing to comply with close follow-up monitoring. ... The current observed functional cure rates” – perhaps about 40% – “would be well worth the effort,” editorialists commenting on the research concluded (Hepatology. 2018 Aug;68[2]:397-400).
It’s an interesting idea, Dr. Terrault said, but the virus will flare 8-12 weeks after treatment withdrawal, which is why it shouldn’t be considered in patients with cirrhosis.
Dr. Terrault is a consultant for AbbVie, Merck, Gilead, and other companies and disclosed grants from those companies and others.
MAUI, HAWAII – There might well be a cure for hepatitis B in coming years, just like there is now for hepatitis C, according to Norah Terrault, MD, chief of the division of GI and liver at the University of Southern California, Los Angeles.
“We are going to have a laundry list of new drugs” that are in the pipeline now. Phase 2 results “look encouraging. You will hear much more about this in the years ahead,” said Dr. Terrault, lead author of the 2018 American Association for the Study of Liver Diseases (AASLD) hepatitis B guidance.
For now, though, the field is largely limited to the nucleoside analogues tenofovir and entecavir. Treatment is often indefinite because, although hepatitis B virus (HBV) e-antigen is cleared, it usually doesn’t clear the HBV surface antigen, which is linked to liver cancer. “Even with e-antigen–negative patients, we feel that indefinite therapy is really the way to go,” Dr. Terrault said at the Gastroenterology Updates, IBD, Liver Disease Conference.
One of the biggest problems with that strategy is what to do when HBV does not seem to be much of a problem for carriers. Such patients are referred to as immune tolerant.
A newly recognized cancer risk
Immune tolerant patients tend to be young and have extremely high viral loads but no apparent ill effects, with normal ALT levels, normal histology, and no sign of cirrhosis. Although the AASLD recommends not treating these patients until they are 40 years old, waiting makes people nervous. “You have a hammer, you want to hit a nail,” Dr. Terrault said.
A recent review (Gut. 2018 May;67[5]:945-52) suggests that hitting the nail might be the way to go. South Korean investigators found that 413 untreated immune tolerate patients with a mean age of 38 years had more than twice the risk of liver cancer over 10 years than did almost 1,500 treated patients with active disease.
The study investigators concluded that “unnecessary deaths could be prevented through earlier antiviral intervention in select [immune tolerate] patients.”
This finding is one reason “we [AASLD] are rethinking the mantra of not treating the immune tolerant. There is a group that is transitioning” to active disease. “I’m thinking we should really [lower] the age cutoff” to 30 years, as some other groups [European Association for the Study of the Liver and Asian Pacific Association for the Study of the Liver] have done, plus “patients feel really good when they know the virus is controlled, and so do physicians,” Dr. Terrault said.
Entecavir versus tenofovir
Meanwhile, recent studies have raised the question of whether tenofovir is better than entecavir at preventing liver cancer.
A JAMA Oncology (JAMA Oncol. 2019 Jan 1;5[1]:30-6) study of some 25,000 patients in South Korea found a 32% lower risk of liver cancer when they were treated with tenofovir instead of entecavir. “This led to a lot of concern that maybe we should be moving all our patients to tenofovir,” she said.
Another study, a meta-analysis published earlier this year (Hepatol Int. 2020 Jan;14[1]:105-14), confirmed the difference in cancer risk when it combined those findings with other research. After adjustment for potential confounders, including disease stage and length of follow-up, “the difference disappeared” (hazard ration, 0.87; 95% confidence interval, 0.73-1.04), authors of the meta-analysis reported.
Study patients who received entecavir tended to be “treated many years ago and tended to have more severe [baseline] disease,” Dr. Terrault said.
So “while we see this difference, there’s not enough data yet for us to make a recommendation for our patients to switch from” entecavir to tenofovir. “Until a randomized controlled trial is done, this may remain an issue,” she said.
A drug holiday?
Dr. Terrault also reviewed research that suggests nucleoside analogue treatment can be stopped in e-antigen–negative patients after at least 3 years.
“The evidence is increasing that a finite NA [nucleoside analogue] treatment approach leads to higher HBsAg [hepatitis B surface antigen] loss rates, compared with the current long-term NA strategy, and can be considered a rational strategy to induce a functional cure in selected HBeAg-negative patients without cirrhosis who are willing to comply with close follow-up monitoring. ... The current observed functional cure rates” – perhaps about 40% – “would be well worth the effort,” editorialists commenting on the research concluded (Hepatology. 2018 Aug;68[2]:397-400).
It’s an interesting idea, Dr. Terrault said, but the virus will flare 8-12 weeks after treatment withdrawal, which is why it shouldn’t be considered in patients with cirrhosis.
Dr. Terrault is a consultant for AbbVie, Merck, Gilead, and other companies and disclosed grants from those companies and others.
EXPERT ANALYSIS FROM GUILD 2020
Sometimes medication is enough for a Crohn’s abscess
MAUI, HAWAII – If an intra-abdominal abscess in a recently diagnosed Crohn’s disease patient is less than 6 cm across with no downstream stenosis, involves only a short segment of bowel, and the patient has no perianal disease, then infliximab and azathioprine after drainage and antibiotics might be enough to heal it, according to Miguel Regueiro, MD, chair of the department of gastroenterology, hepatology, and nutrition at the Cleveland Clinic.
That will work in about 30% of patients who hit the mark; the rest will eventually need surgery, said Dr. Regueiro, a clinical researcher who has worked extensively with surgical GI patients and is also a coauthor on the American College of Gastroenterology 2018 Crohn’s disease guidelines (Am J Gastroenterol. 2018 Apr;113[4]:481-517).
Intra-abdominal abscesses are common in Crohn’s, usually from an inflammation-induced fistula or sinus in the small intestines that spills luminal contents into the abdominal cavity. Drainage and antibiotics are first line, but then there’s the question of who needs to go to the operating room and who doesn’t.
It has to do with “how much the hole in the intestines is actually reversible. Evidence of a stricture is of paramount importance. If you have a stricture below a fistula and prestenotic dilatation, that’s a high-pressure zone.” It’s a “fixed complication that, in my opinion, no medication is ever going to treat,” he said at the Gastroenterology Updates, IBD, Liver Disease Conference.
“Infliximab is still probably the best medicine for fistulizing disease,” so Dr. Regueiro opts for that if patients haven’t been on it before, in combination with an immunomodulator, generally azathioprine at half the standard dose, to prevent patients from forming antibodies to the infliximab.
When patients do go to the operating room, there is a good chance they will end up with a temporary ostomy, and definitely so if the abscess can’t be drained completely to prevent spillage. The risk of dehiscence and other complications is too great for primary anastomosis.
“I mentally prepare my patients for that; I tell them up front. I never guarantee that they are not going to have an ostomy bag,” Dr. Regueiro said.
He also said abscess formation isn’t necessarily a sign the biologic patients were on before has failed, especially if they were only on it for 6 months or so. More likely, “the disease was too far gone at that point” for short-term treatment to have much of an effect.
So he’s often likely to continue patients on the same biologic after surgery. “We’ve done a lot of study on” this and have “actually found that” patients do well with the approach. He will switch treatment, however, if they otherwise no longer seem to respond to a biologic they have been taking a while, despite adequate serum levels.
There’s no need to delay surgery for patients on biologics. “If they get a biologic the day before, they can still go to the [operating room]. We are not seeing increased postop complications, infections, or wound dehiscence,” he said.
Dr. Regueiro generally restarts biologics 2-4 weeks after surgery, which is enough time to know if there is going to be a surgical complication but not so long that patients will have a Crohn’s relapse. He restarts the maintenance dose, as “it’s not necessary to reinduct patients after such a short break,” he said.
He also noted that opioids and steroids should be avoided with Crohn’s abscesses. Opioids increase the risk of ileus, and steroids the risk of sepsis.
Dr. Regueiro reported no relevant disclosures.
MAUI, HAWAII – If an intra-abdominal abscess in a recently diagnosed Crohn’s disease patient is less than 6 cm across with no downstream stenosis, involves only a short segment of bowel, and the patient has no perianal disease, then infliximab and azathioprine after drainage and antibiotics might be enough to heal it, according to Miguel Regueiro, MD, chair of the department of gastroenterology, hepatology, and nutrition at the Cleveland Clinic.
That will work in about 30% of patients who hit the mark; the rest will eventually need surgery, said Dr. Regueiro, a clinical researcher who has worked extensively with surgical GI patients and is also a coauthor on the American College of Gastroenterology 2018 Crohn’s disease guidelines (Am J Gastroenterol. 2018 Apr;113[4]:481-517).
Intra-abdominal abscesses are common in Crohn’s, usually from an inflammation-induced fistula or sinus in the small intestines that spills luminal contents into the abdominal cavity. Drainage and antibiotics are first line, but then there’s the question of who needs to go to the operating room and who doesn’t.
It has to do with “how much the hole in the intestines is actually reversible. Evidence of a stricture is of paramount importance. If you have a stricture below a fistula and prestenotic dilatation, that’s a high-pressure zone.” It’s a “fixed complication that, in my opinion, no medication is ever going to treat,” he said at the Gastroenterology Updates, IBD, Liver Disease Conference.
“Infliximab is still probably the best medicine for fistulizing disease,” so Dr. Regueiro opts for that if patients haven’t been on it before, in combination with an immunomodulator, generally azathioprine at half the standard dose, to prevent patients from forming antibodies to the infliximab.
When patients do go to the operating room, there is a good chance they will end up with a temporary ostomy, and definitely so if the abscess can’t be drained completely to prevent spillage. The risk of dehiscence and other complications is too great for primary anastomosis.
“I mentally prepare my patients for that; I tell them up front. I never guarantee that they are not going to have an ostomy bag,” Dr. Regueiro said.
He also said abscess formation isn’t necessarily a sign the biologic patients were on before has failed, especially if they were only on it for 6 months or so. More likely, “the disease was too far gone at that point” for short-term treatment to have much of an effect.
So he’s often likely to continue patients on the same biologic after surgery. “We’ve done a lot of study on” this and have “actually found that” patients do well with the approach. He will switch treatment, however, if they otherwise no longer seem to respond to a biologic they have been taking a while, despite adequate serum levels.
There’s no need to delay surgery for patients on biologics. “If they get a biologic the day before, they can still go to the [operating room]. We are not seeing increased postop complications, infections, or wound dehiscence,” he said.
Dr. Regueiro generally restarts biologics 2-4 weeks after surgery, which is enough time to know if there is going to be a surgical complication but not so long that patients will have a Crohn’s relapse. He restarts the maintenance dose, as “it’s not necessary to reinduct patients after such a short break,” he said.
He also noted that opioids and steroids should be avoided with Crohn’s abscesses. Opioids increase the risk of ileus, and steroids the risk of sepsis.
Dr. Regueiro reported no relevant disclosures.
MAUI, HAWAII – If an intra-abdominal abscess in a recently diagnosed Crohn’s disease patient is less than 6 cm across with no downstream stenosis, involves only a short segment of bowel, and the patient has no perianal disease, then infliximab and azathioprine after drainage and antibiotics might be enough to heal it, according to Miguel Regueiro, MD, chair of the department of gastroenterology, hepatology, and nutrition at the Cleveland Clinic.
That will work in about 30% of patients who hit the mark; the rest will eventually need surgery, said Dr. Regueiro, a clinical researcher who has worked extensively with surgical GI patients and is also a coauthor on the American College of Gastroenterology 2018 Crohn’s disease guidelines (Am J Gastroenterol. 2018 Apr;113[4]:481-517).
Intra-abdominal abscesses are common in Crohn’s, usually from an inflammation-induced fistula or sinus in the small intestines that spills luminal contents into the abdominal cavity. Drainage and antibiotics are first line, but then there’s the question of who needs to go to the operating room and who doesn’t.
It has to do with “how much the hole in the intestines is actually reversible. Evidence of a stricture is of paramount importance. If you have a stricture below a fistula and prestenotic dilatation, that’s a high-pressure zone.” It’s a “fixed complication that, in my opinion, no medication is ever going to treat,” he said at the Gastroenterology Updates, IBD, Liver Disease Conference.
“Infliximab is still probably the best medicine for fistulizing disease,” so Dr. Regueiro opts for that if patients haven’t been on it before, in combination with an immunomodulator, generally azathioprine at half the standard dose, to prevent patients from forming antibodies to the infliximab.
When patients do go to the operating room, there is a good chance they will end up with a temporary ostomy, and definitely so if the abscess can’t be drained completely to prevent spillage. The risk of dehiscence and other complications is too great for primary anastomosis.
“I mentally prepare my patients for that; I tell them up front. I never guarantee that they are not going to have an ostomy bag,” Dr. Regueiro said.
He also said abscess formation isn’t necessarily a sign the biologic patients were on before has failed, especially if they were only on it for 6 months or so. More likely, “the disease was too far gone at that point” for short-term treatment to have much of an effect.
So he’s often likely to continue patients on the same biologic after surgery. “We’ve done a lot of study on” this and have “actually found that” patients do well with the approach. He will switch treatment, however, if they otherwise no longer seem to respond to a biologic they have been taking a while, despite adequate serum levels.
There’s no need to delay surgery for patients on biologics. “If they get a biologic the day before, they can still go to the [operating room]. We are not seeing increased postop complications, infections, or wound dehiscence,” he said.
Dr. Regueiro generally restarts biologics 2-4 weeks after surgery, which is enough time to know if there is going to be a surgical complication but not so long that patients will have a Crohn’s relapse. He restarts the maintenance dose, as “it’s not necessary to reinduct patients after such a short break,” he said.
He also noted that opioids and steroids should be avoided with Crohn’s abscesses. Opioids increase the risk of ileus, and steroids the risk of sepsis.
Dr. Regueiro reported no relevant disclosures.
EXPERT ANALYSIS FROM GUILD 2020