Richard Mark Kirkner

Almost all patients who develop gastrointestinal side effects from oral immunotherapy for severe food allergies develop some degree of esophageal eosinophilia, but that eventually resolves in most of them after a year of treatment, according to results of a pilot study that was to be presented at the American Academy of Allergy, Asthma & Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

The findings may help identify biomarkers of persistent eosinophilia despite oral immunotherapy.

In January of this year the Food and Drug Administration approved oral immunotherapy (OIT), known as peanut allergen powder-dnfp, or peanut OIT (POIT), for severe food allergies. In an interview, lead study author Benjamin Wright, MD, of the Mayo Clinic, Phoenix, said OIT is a “promising proactive” treatment for food allergies. “But questions regarding the safety of immunotherapy remain,” he said. “About 30% of patients can develop GI side effects, including abdominal pain and vomiting; most concerning is that some patients develop eosinophilic esophagitis (EoE).”

The pilot study was a mechanistic substudy of 20 adult patients with immunoglobulin E–mediated peanut allergies enrolled in the phase 2 Peanut Oral Immunotherapy Safety, Efficacy and Discovery trial (POISED), with 15 randomized to treatment and the remainder to placebo. They had serial gastrointestinal biopsies at baseline (n = 20), 1 year (n = 7 treatment, 3 placebo) and 2 years (n = 7 treatment, 4 placebo) to evaluate eosinophils per high-power field (eos/hpf).

Baseline characteristics between the treatment and placebo groups were similar, with some having signs of preexisting disease. About 14% of them had clinically significant EoE, represented as a measure of more than 15 eos/hpf, Dr. Wright said. “One of the findings that was really fascinating to us was that all of the subjects had evidence of dilated intercellular spaces at baseline,” he said. “This indicates that all the subjects have some degree of epithelial barrier dysfunction before they start OIT.” Dilated intercellular spaces are a marker of inflammation.

Four patients in the treatment group had mild endoscopic findings at weeks 52 and 104, as did one patient on placebo, Dr. Wright said. A plot of eosinophil counts showed a peak at 52 weeks but near resolution at 104 weeks for all but one patient on OIT. “One of the most interesting trends that we noted was that, for most of patients, OIT-induced eosinophilia was transient and not fixed,” he said. “We noted a triangle pattern where tissue eosinophilia peaks and then resolves with the continuation of therapy.” EoE Histologic scoring system results followed a similar pattern in these patients, he added.

Also, results of the comprehensive GI Symptom Questionnaire, which assessed symptoms such as abdominal pain, difficulty swallowing, refusal to eat, and vomiting, showed that patient-reported GI symptoms did not correlate with tissue eosinophilia, Dr. Wright said. “To us, that suggests that perhaps eosinophils are not central to disease pathology or symptom development in these patients,” he said.

However, the findings validate that, in a small number of patients, OIT induces EoE, Dr. Wright said. He used a treadmill analogy to explain how OIT influences epithelial remodeling in some patients. “We’re constantly renewing our esophageal epithelium every 2 weeks, and when you challenge it with an antigen (i.e., OIT), the treadmill speeds up,” he said. “There may be some patients who will fall if the treadmill gets too fast, and they develop disease.”

He added, “Distinguishing someone’s fitness before they get on the treadmill is really going be a key moving forward in determining which subjects are good participants for OIT or how to dose OIT.”

Dr. Wright reported receiving grants from the Arizona Biomedical Research Consortium and Phoenix Children’s Hospital Foundation. Coauthors reported receiving grants from the National Institutes of Health and the Consortium for Food Allergy Research, as well as relationships with Aimmune Therapeutics, Regeneron Pharmaceuticals, Sanofi, Consortium for Food Allergy Research, DBV Technologies, Astellas, AnaptysBio, and Novartis.

SOURCE: Wright B et al. AAAAI, Session 2605, Abstract No. 259.

Almost all patients who develop gastrointestinal side effects from oral immunotherapy for severe food allergies develop some degree of esophageal eosinophilia, but that eventually resolves in most of them after a year of treatment, according to results of a pilot study that was to be presented at the American Academy of Allergy, Asthma & Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

The findings may help identify biomarkers of persistent eosinophilia despite oral immunotherapy.

In January of this year the Food and Drug Administration approved oral immunotherapy (OIT), known as peanut allergen powder-dnfp, or peanut OIT (POIT), for severe food allergies. In an interview, lead study author Benjamin Wright, MD, of the Mayo Clinic, Phoenix, said OIT is a “promising proactive” treatment for food allergies. “But questions regarding the safety of immunotherapy remain,” he said. “About 30% of patients can develop GI side effects, including abdominal pain and vomiting; most concerning is that some patients develop eosinophilic esophagitis (EoE).”

The pilot study was a mechanistic substudy of 20 adult patients with immunoglobulin E–mediated peanut allergies enrolled in the phase 2 Peanut Oral Immunotherapy Safety, Efficacy and Discovery trial (POISED), with 15 randomized to treatment and the remainder to placebo. They had serial gastrointestinal biopsies at baseline (n = 20), 1 year (n = 7 treatment, 3 placebo) and 2 years (n = 7 treatment, 4 placebo) to evaluate eosinophils per high-power field (eos/hpf).

Baseline characteristics between the treatment and placebo groups were similar, with some having signs of preexisting disease. About 14% of them had clinically significant EoE, represented as a measure of more than 15 eos/hpf, Dr. Wright said. “One of the findings that was really fascinating to us was that all of the subjects had evidence of dilated intercellular spaces at baseline,” he said. “This indicates that all the subjects have some degree of epithelial barrier dysfunction before they start OIT.” Dilated intercellular spaces are a marker of inflammation.

Four patients in the treatment group had mild endoscopic findings at weeks 52 and 104, as did one patient on placebo, Dr. Wright said. A plot of eosinophil counts showed a peak at 52 weeks but near resolution at 104 weeks for all but one patient on OIT. “One of the most interesting trends that we noted was that, for most of patients, OIT-induced eosinophilia was transient and not fixed,” he said. “We noted a triangle pattern where tissue eosinophilia peaks and then resolves with the continuation of therapy.” EoE Histologic scoring system results followed a similar pattern in these patients, he added.

Also, results of the comprehensive GI Symptom Questionnaire, which assessed symptoms such as abdominal pain, difficulty swallowing, refusal to eat, and vomiting, showed that patient-reported GI symptoms did not correlate with tissue eosinophilia, Dr. Wright said. “To us, that suggests that perhaps eosinophils are not central to disease pathology or symptom development in these patients,” he said.

However, the findings validate that, in a small number of patients, OIT induces EoE, Dr. Wright said. He used a treadmill analogy to explain how OIT influences epithelial remodeling in some patients. “We’re constantly renewing our esophageal epithelium every 2 weeks, and when you challenge it with an antigen (i.e., OIT), the treadmill speeds up,” he said. “There may be some patients who will fall if the treadmill gets too fast, and they develop disease.”

He added, “Distinguishing someone’s fitness before they get on the treadmill is really going be a key moving forward in determining which subjects are good participants for OIT or how to dose OIT.”

Dr. Wright reported receiving grants from the Arizona Biomedical Research Consortium and Phoenix Children’s Hospital Foundation. Coauthors reported receiving grants from the National Institutes of Health and the Consortium for Food Allergy Research, as well as relationships with Aimmune Therapeutics, Regeneron Pharmaceuticals, Sanofi, Consortium for Food Allergy Research, DBV Technologies, Astellas, AnaptysBio, and Novartis.

SOURCE: Wright B et al. AAAAI, Session 2605, Abstract No. 259.

Almost all patients who develop gastrointestinal side effects from oral immunotherapy for severe food allergies develop some degree of esophageal eosinophilia, but that eventually resolves in most of them after a year of treatment, according to results of a pilot study that was to be presented at the American Academy of Allergy, Asthma & Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

The findings may help identify biomarkers of persistent eosinophilia despite oral immunotherapy.

In January of this year the Food and Drug Administration approved oral immunotherapy (OIT), known as peanut allergen powder-dnfp, or peanut OIT (POIT), for severe food allergies. In an interview, lead study author Benjamin Wright, MD, of the Mayo Clinic, Phoenix, said OIT is a “promising proactive” treatment for food allergies. “But questions regarding the safety of immunotherapy remain,” he said. “About 30% of patients can develop GI side effects, including abdominal pain and vomiting; most concerning is that some patients develop eosinophilic esophagitis (EoE).”

The pilot study was a mechanistic substudy of 20 adult patients with immunoglobulin E–mediated peanut allergies enrolled in the phase 2 Peanut Oral Immunotherapy Safety, Efficacy and Discovery trial (POISED), with 15 randomized to treatment and the remainder to placebo. They had serial gastrointestinal biopsies at baseline (n = 20), 1 year (n = 7 treatment, 3 placebo) and 2 years (n = 7 treatment, 4 placebo) to evaluate eosinophils per high-power field (eos/hpf).

Baseline characteristics between the treatment and placebo groups were similar, with some having signs of preexisting disease. About 14% of them had clinically significant EoE, represented as a measure of more than 15 eos/hpf, Dr. Wright said. “One of the findings that was really fascinating to us was that all of the subjects had evidence of dilated intercellular spaces at baseline,” he said. “This indicates that all the subjects have some degree of epithelial barrier dysfunction before they start OIT.” Dilated intercellular spaces are a marker of inflammation.

Four patients in the treatment group had mild endoscopic findings at weeks 52 and 104, as did one patient on placebo, Dr. Wright said. A plot of eosinophil counts showed a peak at 52 weeks but near resolution at 104 weeks for all but one patient on OIT. “One of the most interesting trends that we noted was that, for most of patients, OIT-induced eosinophilia was transient and not fixed,” he said. “We noted a triangle pattern where tissue eosinophilia peaks and then resolves with the continuation of therapy.” EoE Histologic scoring system results followed a similar pattern in these patients, he added.

Also, results of the comprehensive GI Symptom Questionnaire, which assessed symptoms such as abdominal pain, difficulty swallowing, refusal to eat, and vomiting, showed that patient-reported GI symptoms did not correlate with tissue eosinophilia, Dr. Wright said. “To us, that suggests that perhaps eosinophils are not central to disease pathology or symptom development in these patients,” he said.

However, the findings validate that, in a small number of patients, OIT induces EoE, Dr. Wright said. He used a treadmill analogy to explain how OIT influences epithelial remodeling in some patients. “We’re constantly renewing our esophageal epithelium every 2 weeks, and when you challenge it with an antigen (i.e., OIT), the treadmill speeds up,” he said. “There may be some patients who will fall if the treadmill gets too fast, and they develop disease.”

He added, “Distinguishing someone’s fitness before they get on the treadmill is really going be a key moving forward in determining which subjects are good participants for OIT or how to dose OIT.”

Dr. Wright reported receiving grants from the Arizona Biomedical Research Consortium and Phoenix Children’s Hospital Foundation. Coauthors reported receiving grants from the National Institutes of Health and the Consortium for Food Allergy Research, as well as relationships with Aimmune Therapeutics, Regeneron Pharmaceuticals, Sanofi, Consortium for Food Allergy Research, DBV Technologies, Astellas, AnaptysBio, and Novartis.

SOURCE: Wright B et al. AAAAI, Session 2605, Abstract No. 259.

A small-molecule kinase inhibitor that targets a gene mutation complicit in systemic mastocytosis has been found to reduce symptoms by about 30%, according to early results of a clinical trial scheduled to be presented at the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“This correlates with reduction from very severe to moderate or from moderate to mild category, and all the reductions in symptoms were statistically significant,” Cem Akin, MD, of the University of Michigan, Ann Arbor, said in an interview. He reported on part 1 of the phase 2 PIONEER trial of the kinase inhibitor avapritinib, described as a potent and highly selective inhibitor of the KIT D816V mutation that affects 90% of patients with systemic mastocytosis.

Currently, Dr. Akin noted, patients with indolent or smoldering systemic mastocytosis must rely on over-the-counter antihistamines used for seasonal allergies. “These patients use antihistamines in higher doses because mastocytosis patients have higher counts of mast cells that release histamines that cause a variety of symptoms,” he said. Symptoms, which can occur suddenly, include flushing and reactions that resemble allergic or anaphylactic reactions.

The purpose of the part 1 study was to evaluate three different dosing levels of avapritinib vs. placebo: 25, 50, and 100 mg. Ten patients were in each dosing group and nine were in the placebo group. The primary outcome was reduction in total symptom scores at 16 weeks as measured by the Indolent SM Symptom Assessment Form. “All three dose groups showed significant reductions in total symptom scores as well as specific symptoms that were most bothersome to the patient, whether skin symptoms or GI or neurocognitive symptoms,” Dr. Akin said. “All three doses were effective; the average reduction was about 30% compared to baseline.” Specifically, 25-mg dosing showed an average 30% reduction, 50-mg dosing showed an average 19% reduction, and 100-mg dosing showed an average 35% reduction.

The researchers determined that the 25-mg daily dose was the most effective and safest, with no patients on the dose reporting grade 3 adverse events, Dr. Akin said. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 AEs, according to study results.* The 25-mg daily dose will be evaluated in part 2 of the trial. The trial is estimated to enroll 112 total patients, according to the ClinicalTrials.gov filing. In part 3, patients who complete parts 1 or 2, including those initially randomized to placebo, may participate in a long-term open-label extension, receiving 25 mg avapritinib plus best supportive care.

“This is targeting a population whose symptoms are not controlled by antihistamines, based on a minimum total symptom score according to diaries they fill out, and they have to be on at least two different systemic medications – antihistamine or proton-pump inhibitor and leukotriene inhibitor – and they still have significant symptoms,” Dr. Akin said. He estimated that this describes about two-thirds of his patients with indolent or smoldering systematic mastocytosis.

“This is a disease that also takes a psychological toll,” he said. “This is a problem that starts in the bone marrow; it is similar to a hematological stem-cell disorder that affects the mast cell progenitor and it’s caused by a mutation that has not been particularly targeted until this drug,” he said. While most of these patients live with a benign mastocytosis their entire lives, the symptoms can be debilitating to the point where the disease disrupts and restricts social activities and comprises their quality of life, he said.

“This is a groundbreaking therapy that will change the way we think about mastocytosis treatment going forward,” Dr. Akin said. “It’s the first time we are actually targeting the underlying mutation that’s causing the disease, in terms of reducing directly that mutation as opposed to just treating the symptoms in indolent disease.”

Scheduled session moderator Anil Nanda, MD, of the Asthma and Allergy Center in Lewisville, Texas, said the findings are encouraging. “As a practicing allergist and immunologist in the community, it is very exciting to have a potential new treatment option for indolent or smoldering systemic mastocytosis,” he said via email. “Patients appreciate new options in therapy.”

Dr. Akin, the primary investigator, receives funding from and serves as a consultant for Blueprint Medicines, which sponsored the trial. He also disclosed a financial relationship with Novartis.

SOURCE: Akin C et al. AAAAI 2020, Presentation L5.

*Correction, 4/6/2020: An earlier version of this story misstated the percentage of grade 3 adverse events. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 adverse events.  

A small-molecule kinase inhibitor that targets a gene mutation complicit in systemic mastocytosis has been found to reduce symptoms by about 30%, according to early results of a clinical trial scheduled to be presented at the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“This correlates with reduction from very severe to moderate or from moderate to mild category, and all the reductions in symptoms were statistically significant,” Cem Akin, MD, of the University of Michigan, Ann Arbor, said in an interview. He reported on part 1 of the phase 2 PIONEER trial of the kinase inhibitor avapritinib, described as a potent and highly selective inhibitor of the KIT D816V mutation that affects 90% of patients with systemic mastocytosis.

Currently, Dr. Akin noted, patients with indolent or smoldering systemic mastocytosis must rely on over-the-counter antihistamines used for seasonal allergies. “These patients use antihistamines in higher doses because mastocytosis patients have higher counts of mast cells that release histamines that cause a variety of symptoms,” he said. Symptoms, which can occur suddenly, include flushing and reactions that resemble allergic or anaphylactic reactions.

The purpose of the part 1 study was to evaluate three different dosing levels of avapritinib vs. placebo: 25, 50, and 100 mg. Ten patients were in each dosing group and nine were in the placebo group. The primary outcome was reduction in total symptom scores at 16 weeks as measured by the Indolent SM Symptom Assessment Form. “All three dose groups showed significant reductions in total symptom scores as well as specific symptoms that were most bothersome to the patient, whether skin symptoms or GI or neurocognitive symptoms,” Dr. Akin said. “All three doses were effective; the average reduction was about 30% compared to baseline.” Specifically, 25-mg dosing showed an average 30% reduction, 50-mg dosing showed an average 19% reduction, and 100-mg dosing showed an average 35% reduction.

The researchers determined that the 25-mg daily dose was the most effective and safest, with no patients on the dose reporting grade 3 adverse events, Dr. Akin said. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 AEs, according to study results.* The 25-mg daily dose will be evaluated in part 2 of the trial. The trial is estimated to enroll 112 total patients, according to the ClinicalTrials.gov filing. In part 3, patients who complete parts 1 or 2, including those initially randomized to placebo, may participate in a long-term open-label extension, receiving 25 mg avapritinib plus best supportive care.

“This is targeting a population whose symptoms are not controlled by antihistamines, based on a minimum total symptom score according to diaries they fill out, and they have to be on at least two different systemic medications – antihistamine or proton-pump inhibitor and leukotriene inhibitor – and they still have significant symptoms,” Dr. Akin said. He estimated that this describes about two-thirds of his patients with indolent or smoldering systematic mastocytosis.

“This is a disease that also takes a psychological toll,” he said. “This is a problem that starts in the bone marrow; it is similar to a hematological stem-cell disorder that affects the mast cell progenitor and it’s caused by a mutation that has not been particularly targeted until this drug,” he said. While most of these patients live with a benign mastocytosis their entire lives, the symptoms can be debilitating to the point where the disease disrupts and restricts social activities and comprises their quality of life, he said.

“This is a groundbreaking therapy that will change the way we think about mastocytosis treatment going forward,” Dr. Akin said. “It’s the first time we are actually targeting the underlying mutation that’s causing the disease, in terms of reducing directly that mutation as opposed to just treating the symptoms in indolent disease.”

Scheduled session moderator Anil Nanda, MD, of the Asthma and Allergy Center in Lewisville, Texas, said the findings are encouraging. “As a practicing allergist and immunologist in the community, it is very exciting to have a potential new treatment option for indolent or smoldering systemic mastocytosis,” he said via email. “Patients appreciate new options in therapy.”

Dr. Akin, the primary investigator, receives funding from and serves as a consultant for Blueprint Medicines, which sponsored the trial. He also disclosed a financial relationship with Novartis.

SOURCE: Akin C et al. AAAAI 2020, Presentation L5.

*Correction, 4/6/2020: An earlier version of this story misstated the percentage of grade 3 adverse events. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 adverse events.  

A small-molecule kinase inhibitor that targets a gene mutation complicit in systemic mastocytosis has been found to reduce symptoms by about 30%, according to early results of a clinical trial scheduled to be presented at the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“This correlates with reduction from very severe to moderate or from moderate to mild category, and all the reductions in symptoms were statistically significant,” Cem Akin, MD, of the University of Michigan, Ann Arbor, said in an interview. He reported on part 1 of the phase 2 PIONEER trial of the kinase inhibitor avapritinib, described as a potent and highly selective inhibitor of the KIT D816V mutation that affects 90% of patients with systemic mastocytosis.

Currently, Dr. Akin noted, patients with indolent or smoldering systemic mastocytosis must rely on over-the-counter antihistamines used for seasonal allergies. “These patients use antihistamines in higher doses because mastocytosis patients have higher counts of mast cells that release histamines that cause a variety of symptoms,” he said. Symptoms, which can occur suddenly, include flushing and reactions that resemble allergic or anaphylactic reactions.

The purpose of the part 1 study was to evaluate three different dosing levels of avapritinib vs. placebo: 25, 50, and 100 mg. Ten patients were in each dosing group and nine were in the placebo group. The primary outcome was reduction in total symptom scores at 16 weeks as measured by the Indolent SM Symptom Assessment Form. “All three dose groups showed significant reductions in total symptom scores as well as specific symptoms that were most bothersome to the patient, whether skin symptoms or GI or neurocognitive symptoms,” Dr. Akin said. “All three doses were effective; the average reduction was about 30% compared to baseline.” Specifically, 25-mg dosing showed an average 30% reduction, 50-mg dosing showed an average 19% reduction, and 100-mg dosing showed an average 35% reduction.

The researchers determined that the 25-mg daily dose was the most effective and safest, with no patients on the dose reporting grade 3 adverse events, Dr. Akin said. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 AEs, according to study results.* The 25-mg daily dose will be evaluated in part 2 of the trial. The trial is estimated to enroll 112 total patients, according to the ClinicalTrials.gov filing. In part 3, patients who complete parts 1 or 2, including those initially randomized to placebo, may participate in a long-term open-label extension, receiving 25 mg avapritinib plus best supportive care.

“This is targeting a population whose symptoms are not controlled by antihistamines, based on a minimum total symptom score according to diaries they fill out, and they have to be on at least two different systemic medications – antihistamine or proton-pump inhibitor and leukotriene inhibitor – and they still have significant symptoms,” Dr. Akin said. He estimated that this describes about two-thirds of his patients with indolent or smoldering systematic mastocytosis.

“This is a disease that also takes a psychological toll,” he said. “This is a problem that starts in the bone marrow; it is similar to a hematological stem-cell disorder that affects the mast cell progenitor and it’s caused by a mutation that has not been particularly targeted until this drug,” he said. While most of these patients live with a benign mastocytosis their entire lives, the symptoms can be debilitating to the point where the disease disrupts and restricts social activities and comprises their quality of life, he said.

“This is a groundbreaking therapy that will change the way we think about mastocytosis treatment going forward,” Dr. Akin said. “It’s the first time we are actually targeting the underlying mutation that’s causing the disease, in terms of reducing directly that mutation as opposed to just treating the symptoms in indolent disease.”

Scheduled session moderator Anil Nanda, MD, of the Asthma and Allergy Center in Lewisville, Texas, said the findings are encouraging. “As a practicing allergist and immunologist in the community, it is very exciting to have a potential new treatment option for indolent or smoldering systemic mastocytosis,” he said via email. “Patients appreciate new options in therapy.”

Dr. Akin, the primary investigator, receives funding from and serves as a consultant for Blueprint Medicines, which sponsored the trial. He also disclosed a financial relationship with Novartis.

SOURCE: Akin C et al. AAAAI 2020, Presentation L5.

*Correction, 4/6/2020: An earlier version of this story misstated the percentage of grade 3 adverse events. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 adverse events.  

Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.

The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.

He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”

What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.

The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.

For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m². Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.

The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.

Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.

The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.

Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.

Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.

One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.

“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”

Dr. Ishmael has no relevant financial relationships to disclose.

SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.

Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.

The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.

He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”

What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.

The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.

For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m². Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.

The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.

Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.

The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.

Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.

Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.

One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.

“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”

Dr. Ishmael has no relevant financial relationships to disclose.

SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.

Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.

The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.

He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”

What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.

The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.

For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m². Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.

The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.

Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.

The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.

Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.

Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.

One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.

“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”

Dr. Ishmael has no relevant financial relationships to disclose.

SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.

Patients with both type 2 diabetes and asthma who were on glucagonlike peptide receptor–1 (GLP-1R) agonists for glucose control had lower levels of a key biomarker of airway inflammation than similar patients on other types of glucose-control medications, according to results of a study to have been presented at the annual meeting of the American Academy of Asthma, Allergy, and Immunology. The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The findings from this study potentially replicated findings in humans that have been reported in preclinical trials.

“Our work showed that type 2 diabetics with asthma who were treated with GLP-1 receptor agonists had lower levels of periostin, and this provides really one of the first human data to show that these drugs may impact key inflammation pathways in the airway,” Dinah Foer, MD, of Brigham and Women’s Hospital, Boston, said in an interview. She described periostin as “a known critical inducer of airway mucous production and airway responsiveness.”

The study retrospectively evaluated serum samples from the Partners HealthCare Biobank of 161 adults with both asthma and type 2 diabetes, 42 of whom were on GLP-1R agonists and 119 of whom were taking non-GLP-1R agonist diabetes medications. The study used the Partners Healthcare EHR to identify eligible patients.

The study found that periostin levels were significantly decreased in GLP-1R agonist users: 19.1 ng/mL (standard deviation, +8.7) versus 27.4 ng/mL (SD, +14) in the non-GLP-1R agonist group (P = .001), Dr. Foer said. The other known mediators of asthma inflammatory pathways that were measured – interleukin-6, IL-8, sCD163, total IgE, and sST2 (soluble suppression of tumorigenesis–2) – showed no differences between the two groups, Dr. Foer said.

She said that this was the first human study to show similar results to preclinical models of asthma pathways. “What was interesting to us was that our findings were robust even when we controlled for covariates,” she added.

These findings lay the groundwork for further research into the potential therapeutic role GLP-1R agonists in asthma, Dr. Foer said. “This supports using periostin as a biomarker for novel therapeutic use of GLP-1R [agonists] in asthma,” she said. “At this point further study is needed to understand the clinical impact of GPL-1R [agonists] in asthma both for patients with type 2 diabetes and potentially in the future for patients who don’t have type 2 diabetes or metabolic disease.”

She added: “I don’t think we’re there yet; this is just one foot forward.”

The next step for researchers involves analyzing outcomes in asthmatics with type 2 diabetes on GLP-1R agonist therapy using a larger sample size as well as patients with asthma and metabolic disease, Dr. Foer said. The goal would be to identify corresponding biomarkers.

“There’s a terrific conversation in the field about the relationships between metabolism and asthma,” she said. “What our data contributes to that is, it suggests a role for metabolic pathways, specifically as it’s related GLP-1R [agonist] signaling pathways in regulating airway inflammation.”

Mark Moss, MD, associate professor of allergy & immunology at the University of Wisconsin–Madison, who was to serve as the moderator of the session, was positive about the GLP-1R agonist findings. He said in an interview: “This is promising research that provides a possible new target for the treatment of asthma.”

Dr. Foer disclosed that she has no relevant financial relationships.

SOURCE: Foer D et al. AAAAI Session 462, Abstract 784.

Patients with both type 2 diabetes and asthma who were on glucagonlike peptide receptor–1 (GLP-1R) agonists for glucose control had lower levels of a key biomarker of airway inflammation than similar patients on other types of glucose-control medications, according to results of a study to have been presented at the annual meeting of the American Academy of Asthma, Allergy, and Immunology. The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The findings from this study potentially replicated findings in humans that have been reported in preclinical trials.

“Our work showed that type 2 diabetics with asthma who were treated with GLP-1 receptor agonists had lower levels of periostin, and this provides really one of the first human data to show that these drugs may impact key inflammation pathways in the airway,” Dinah Foer, MD, of Brigham and Women’s Hospital, Boston, said in an interview. She described periostin as “a known critical inducer of airway mucous production and airway responsiveness.”

The study retrospectively evaluated serum samples from the Partners HealthCare Biobank of 161 adults with both asthma and type 2 diabetes, 42 of whom were on GLP-1R agonists and 119 of whom were taking non-GLP-1R agonist diabetes medications. The study used the Partners Healthcare EHR to identify eligible patients.

The study found that periostin levels were significantly decreased in GLP-1R agonist users: 19.1 ng/mL (standard deviation, +8.7) versus 27.4 ng/mL (SD, +14) in the non-GLP-1R agonist group (P = .001), Dr. Foer said. The other known mediators of asthma inflammatory pathways that were measured – interleukin-6, IL-8, sCD163, total IgE, and sST2 (soluble suppression of tumorigenesis–2) – showed no differences between the two groups, Dr. Foer said.

She said that this was the first human study to show similar results to preclinical models of asthma pathways. “What was interesting to us was that our findings were robust even when we controlled for covariates,” she added.

These findings lay the groundwork for further research into the potential therapeutic role GLP-1R agonists in asthma, Dr. Foer said. “This supports using periostin as a biomarker for novel therapeutic use of GLP-1R [agonists] in asthma,” she said. “At this point further study is needed to understand the clinical impact of GPL-1R [agonists] in asthma both for patients with type 2 diabetes and potentially in the future for patients who don’t have type 2 diabetes or metabolic disease.”

She added: “I don’t think we’re there yet; this is just one foot forward.”

The next step for researchers involves analyzing outcomes in asthmatics with type 2 diabetes on GLP-1R agonist therapy using a larger sample size as well as patients with asthma and metabolic disease, Dr. Foer said. The goal would be to identify corresponding biomarkers.

“There’s a terrific conversation in the field about the relationships between metabolism and asthma,” she said. “What our data contributes to that is, it suggests a role for metabolic pathways, specifically as it’s related GLP-1R [agonist] signaling pathways in regulating airway inflammation.”

Mark Moss, MD, associate professor of allergy & immunology at the University of Wisconsin–Madison, who was to serve as the moderator of the session, was positive about the GLP-1R agonist findings. He said in an interview: “This is promising research that provides a possible new target for the treatment of asthma.”

Dr. Foer disclosed that she has no relevant financial relationships.

SOURCE: Foer D et al. AAAAI Session 462, Abstract 784.

Patients with both type 2 diabetes and asthma who were on glucagonlike peptide receptor–1 (GLP-1R) agonists for glucose control had lower levels of a key biomarker of airway inflammation than similar patients on other types of glucose-control medications, according to results of a study to have been presented at the annual meeting of the American Academy of Asthma, Allergy, and Immunology. The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The findings from this study potentially replicated findings in humans that have been reported in preclinical trials.

“Our work showed that type 2 diabetics with asthma who were treated with GLP-1 receptor agonists had lower levels of periostin, and this provides really one of the first human data to show that these drugs may impact key inflammation pathways in the airway,” Dinah Foer, MD, of Brigham and Women’s Hospital, Boston, said in an interview. She described periostin as “a known critical inducer of airway mucous production and airway responsiveness.”

The study retrospectively evaluated serum samples from the Partners HealthCare Biobank of 161 adults with both asthma and type 2 diabetes, 42 of whom were on GLP-1R agonists and 119 of whom were taking non-GLP-1R agonist diabetes medications. The study used the Partners Healthcare EHR to identify eligible patients.

The study found that periostin levels were significantly decreased in GLP-1R agonist users: 19.1 ng/mL (standard deviation, +8.7) versus 27.4 ng/mL (SD, +14) in the non-GLP-1R agonist group (P = .001), Dr. Foer said. The other known mediators of asthma inflammatory pathways that were measured – interleukin-6, IL-8, sCD163, total IgE, and sST2 (soluble suppression of tumorigenesis–2) – showed no differences between the two groups, Dr. Foer said.

She said that this was the first human study to show similar results to preclinical models of asthma pathways. “What was interesting to us was that our findings were robust even when we controlled for covariates,” she added.

These findings lay the groundwork for further research into the potential therapeutic role GLP-1R agonists in asthma, Dr. Foer said. “This supports using periostin as a biomarker for novel therapeutic use of GLP-1R [agonists] in asthma,” she said. “At this point further study is needed to understand the clinical impact of GPL-1R [agonists] in asthma both for patients with type 2 diabetes and potentially in the future for patients who don’t have type 2 diabetes or metabolic disease.”

She added: “I don’t think we’re there yet; this is just one foot forward.”

The next step for researchers involves analyzing outcomes in asthmatics with type 2 diabetes on GLP-1R agonist therapy using a larger sample size as well as patients with asthma and metabolic disease, Dr. Foer said. The goal would be to identify corresponding biomarkers.

“There’s a terrific conversation in the field about the relationships between metabolism and asthma,” she said. “What our data contributes to that is, it suggests a role for metabolic pathways, specifically as it’s related GLP-1R [agonist] signaling pathways in regulating airway inflammation.”

Mark Moss, MD, associate professor of allergy & immunology at the University of Wisconsin–Madison, who was to serve as the moderator of the session, was positive about the GLP-1R agonist findings. He said in an interview: “This is promising research that provides a possible new target for the treatment of asthma.”

Dr. Foer disclosed that she has no relevant financial relationships.

SOURCE: Foer D et al. AAAAI Session 462, Abstract 784.

For moderate to severe ulcerative colitis, treatment with any one of the leading biologic agents is superior to no treatment at all. And in treatment-naive patients, infliximab or vedolizumab should be used rather than adalimumab for inducing remission. These are key recommendations from the American Gastroenterological Association guideline for patients with moderate to severe ulcerative colitis (UC), published in Gastroenterology (doi: 10.1053/j.gastro.2020.01.006).

In all, the guideline comprises 11 recommendations for using immunomodulators, biologics, and small-molecule agents to induce and maintain remission in outpatients with moderate to severe UC and to decrease the need for colectomy in hospitalized patients with acute severe UC. The latest guideline follows a guideline for mild to moderate UC published last year (Gastroenterology. 2019;156[3]:748-64). A technical review accompanied the most recent publication (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.007).

An updated guideline was long overdue, lead author Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. “The care of patients with inflammatory bowel disease – both ulcerative colitis and Crohn’s – has become increasingly complicated with many newer drugs becoming available,” he said. “The paradigm of how we are treating the disease is evolving, but we haven’t had updated, evidence-based guidelines.” Dr. Feuerstein is the lead author of this guideline.

The guideline can also aid in influencing payers’ policies that now require step-up therapy – that is, failing with the least costly drug before moving onto newer and more effective but costlier agents – Dr. Feuerstein said. “These guidelines show now that we should be treating people based on the evidence and not based on just an insurance company’s preferred policy,” he said.

The strongest recommendation is to use the tumor necrosis factor–alpha (TNF-alpha) antagonists infliximab, adalimumab, and golimumab, the anti-integrin agent vedolizumab, or the anti-interleukin 12/23 agent ustekinumab — all biologics — or the synthetic JAK inhibitor tofacitinib rather than not treating the UC. This is the only recommendation labeled as “strong,” based on “moderate quality evidence.” The relative risk profiles the committee analyzed all favored the biologics over the JAK inhibitor.

Also based on moderate evidence is the recommendation to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who had taken biologic agents before. The other recommendations are based on evidence listed at “low” or “very low” quality, or citing a “knowledge gap.”

“The quality of the evidence available is variable, and we can only make our recommendations based on the quality of the evidence there, but it doesn’t negate the effects of the guideline itself,” Dr. Feuerstein said. The strong recommendation is based on randomized clinical trials that led to the Food and Drug Administration approvals, said Aline Charabaty-Pishvaian, MD, AGAF, associate professor at Johns Hopkins University, Baltimore, and director of the Inflammatory Bowel Disease Center at Sibley Memorial Hospital, Washington. “For everything else, we do not have randomized controlled trials to help make a decision, and the recommendations are made based on the interpretation of different RCTs [randomized controlled trials], knowing that these trials have different designs, patient populations, and endpoints, as well as on experts’ opinions,” she said in an interview.

The only other recommendation based on moderate quality evidence is to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who haven’t previously used biologic agents. The guideline also recommends using tofacitinib in these patients in the confines of a clinical trial; and using ustekinumab or tofacitinib rather than vedolizumab or adalimumab in patients who’ve already been on infliximab, particularly if they haven’t responded to treatment.

The guideline also recommends against thiopurine monotherapy to induce remission, but, for maintenance of remission, recommends such treatment vs. none. However, the guideline suggests against methotrexate monotherapy to induce or maintain remission. And biologic monotherapy is preferred to thiopurine to induce remission, but the guideline makes no recommendation for biologic vs. thiopurine monotherapy to maintain remission. Likewise, combining vedolizumab or ustekinumab with thiopurines or methotrexate is preferred to monotherapy with either a biologic or thiopurine.

The guideline also addresses step-up therapy. It suggests biologics as a first treatment, either as monotherapy or in combination with an immunomodulator, rather than a step-up after failure with 5-aminosalicylates. Also, it recommends against continuing 5-aminosalicylates to induce or maintain remission after a patient has achieved remission with biologics as monotherapy or in combination with immunomodulators or tofacitinib.

The guideline also offers four recommendations for hospitalized patients with acute severe ulcerative colitis: use of intravenous 40-60 mg/d methylprednisolone rather than higher dose IV corticosteroids, no adjunctive antibiotics in the absence of infection; use of infliximab or cyclosporine when IV corticosteroids fail, and no recommendation on the use of intensive vs. standard infliximab dosing when IV corticosteroids fail and the patient is already on infliximab.

The guideline will be meaningful in closing the evidence gap going forward because it can help direct the design of clinical trials, Dr. Charabaty-Pishvaian said. “The guideline highlights areas of need in terms of randomized clinical trials,” she said. “We need these trials to answer the questions we ask ourselves in our daily practice when managing patients with UC: Which drug to choose as the first-line agent? Which drug is the second-line therapy when the disease doesn’t respond or loses response to the first-line agent? Do we need to use combination therapy with all biologics, or only with anti-TNF-alpha agents? For how long? Can we use vedolizumab or ustekinumab as monotherapy when used as a first-line agent? And is there any advantage in adding an immunomodulator when these agents are used as third- or fourth-line therapy?”

Dr. Feuerstein has no relevant financial relationships to disclose. Guideline author Kim Isaacs, MD, disclosed relationships with AbbVie, Takeda, UCB, Janssen and Hoffmann-Laroche. All other committee members have no relevant disclosures.

*This story was updated on 5/7/2020.

SOURCE: Feuerstein JD et al. on behalf of the AGA Institute Clinical Guidelines Committee. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.006.

For moderate to severe ulcerative colitis, treatment with any one of the leading biologic agents is superior to no treatment at all. And in treatment-naive patients, infliximab or vedolizumab should be used rather than adalimumab for inducing remission. These are key recommendations from the American Gastroenterological Association guideline for patients with moderate to severe ulcerative colitis (UC), published in Gastroenterology (doi: 10.1053/j.gastro.2020.01.006).

In all, the guideline comprises 11 recommendations for using immunomodulators, biologics, and small-molecule agents to induce and maintain remission in outpatients with moderate to severe UC and to decrease the need for colectomy in hospitalized patients with acute severe UC. The latest guideline follows a guideline for mild to moderate UC published last year (Gastroenterology. 2019;156[3]:748-64). A technical review accompanied the most recent publication (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.007).

An updated guideline was long overdue, lead author Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. “The care of patients with inflammatory bowel disease – both ulcerative colitis and Crohn’s – has become increasingly complicated with many newer drugs becoming available,” he said. “The paradigm of how we are treating the disease is evolving, but we haven’t had updated, evidence-based guidelines.” Dr. Feuerstein is the lead author of this guideline.

The guideline can also aid in influencing payers’ policies that now require step-up therapy – that is, failing with the least costly drug before moving onto newer and more effective but costlier agents – Dr. Feuerstein said. “These guidelines show now that we should be treating people based on the evidence and not based on just an insurance company’s preferred policy,” he said.

The strongest recommendation is to use the tumor necrosis factor–alpha (TNF-alpha) antagonists infliximab, adalimumab, and golimumab, the anti-integrin agent vedolizumab, or the anti-interleukin 12/23 agent ustekinumab — all biologics — or the synthetic JAK inhibitor tofacitinib rather than not treating the UC. This is the only recommendation labeled as “strong,” based on “moderate quality evidence.” The relative risk profiles the committee analyzed all favored the biologics over the JAK inhibitor.

Also based on moderate evidence is the recommendation to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who had taken biologic agents before. The other recommendations are based on evidence listed at “low” or “very low” quality, or citing a “knowledge gap.”

“The quality of the evidence available is variable, and we can only make our recommendations based on the quality of the evidence there, but it doesn’t negate the effects of the guideline itself,” Dr. Feuerstein said. The strong recommendation is based on randomized clinical trials that led to the Food and Drug Administration approvals, said Aline Charabaty-Pishvaian, MD, AGAF, associate professor at Johns Hopkins University, Baltimore, and director of the Inflammatory Bowel Disease Center at Sibley Memorial Hospital, Washington. “For everything else, we do not have randomized controlled trials to help make a decision, and the recommendations are made based on the interpretation of different RCTs [randomized controlled trials], knowing that these trials have different designs, patient populations, and endpoints, as well as on experts’ opinions,” she said in an interview.

The only other recommendation based on moderate quality evidence is to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who haven’t previously used biologic agents. The guideline also recommends using tofacitinib in these patients in the confines of a clinical trial; and using ustekinumab or tofacitinib rather than vedolizumab or adalimumab in patients who’ve already been on infliximab, particularly if they haven’t responded to treatment.

The guideline also recommends against thiopurine monotherapy to induce remission, but, for maintenance of remission, recommends such treatment vs. none. However, the guideline suggests against methotrexate monotherapy to induce or maintain remission. And biologic monotherapy is preferred to thiopurine to induce remission, but the guideline makes no recommendation for biologic vs. thiopurine monotherapy to maintain remission. Likewise, combining vedolizumab or ustekinumab with thiopurines or methotrexate is preferred to monotherapy with either a biologic or thiopurine.

The guideline also addresses step-up therapy. It suggests biologics as a first treatment, either as monotherapy or in combination with an immunomodulator, rather than a step-up after failure with 5-aminosalicylates. Also, it recommends against continuing 5-aminosalicylates to induce or maintain remission after a patient has achieved remission with biologics as monotherapy or in combination with immunomodulators or tofacitinib.

The guideline also offers four recommendations for hospitalized patients with acute severe ulcerative colitis: use of intravenous 40-60 mg/d methylprednisolone rather than higher dose IV corticosteroids, no adjunctive antibiotics in the absence of infection; use of infliximab or cyclosporine when IV corticosteroids fail, and no recommendation on the use of intensive vs. standard infliximab dosing when IV corticosteroids fail and the patient is already on infliximab.

The guideline will be meaningful in closing the evidence gap going forward because it can help direct the design of clinical trials, Dr. Charabaty-Pishvaian said. “The guideline highlights areas of need in terms of randomized clinical trials,” she said. “We need these trials to answer the questions we ask ourselves in our daily practice when managing patients with UC: Which drug to choose as the first-line agent? Which drug is the second-line therapy when the disease doesn’t respond or loses response to the first-line agent? Do we need to use combination therapy with all biologics, or only with anti-TNF-alpha agents? For how long? Can we use vedolizumab or ustekinumab as monotherapy when used as a first-line agent? And is there any advantage in adding an immunomodulator when these agents are used as third- or fourth-line therapy?”

Dr. Feuerstein has no relevant financial relationships to disclose. Guideline author Kim Isaacs, MD, disclosed relationships with AbbVie, Takeda, UCB, Janssen and Hoffmann-Laroche. All other committee members have no relevant disclosures.

*This story was updated on 5/7/2020.

SOURCE: Feuerstein JD et al. on behalf of the AGA Institute Clinical Guidelines Committee. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.006.

For moderate to severe ulcerative colitis, treatment with any one of the leading biologic agents is superior to no treatment at all. And in treatment-naive patients, infliximab or vedolizumab should be used rather than adalimumab for inducing remission. These are key recommendations from the American Gastroenterological Association guideline for patients with moderate to severe ulcerative colitis (UC), published in Gastroenterology (doi: 10.1053/j.gastro.2020.01.006).

In all, the guideline comprises 11 recommendations for using immunomodulators, biologics, and small-molecule agents to induce and maintain remission in outpatients with moderate to severe UC and to decrease the need for colectomy in hospitalized patients with acute severe UC. The latest guideline follows a guideline for mild to moderate UC published last year (Gastroenterology. 2019;156[3]:748-64). A technical review accompanied the most recent publication (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.007).

An updated guideline was long overdue, lead author Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. “The care of patients with inflammatory bowel disease – both ulcerative colitis and Crohn’s – has become increasingly complicated with many newer drugs becoming available,” he said. “The paradigm of how we are treating the disease is evolving, but we haven’t had updated, evidence-based guidelines.” Dr. Feuerstein is the lead author of this guideline.

The guideline can also aid in influencing payers’ policies that now require step-up therapy – that is, failing with the least costly drug before moving onto newer and more effective but costlier agents – Dr. Feuerstein said. “These guidelines show now that we should be treating people based on the evidence and not based on just an insurance company’s preferred policy,” he said.

The strongest recommendation is to use the tumor necrosis factor–alpha (TNF-alpha) antagonists infliximab, adalimumab, and golimumab, the anti-integrin agent vedolizumab, or the anti-interleukin 12/23 agent ustekinumab — all biologics — or the synthetic JAK inhibitor tofacitinib rather than not treating the UC. This is the only recommendation labeled as “strong,” based on “moderate quality evidence.” The relative risk profiles the committee analyzed all favored the biologics over the JAK inhibitor.

Also based on moderate evidence is the recommendation to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who had taken biologic agents before. The other recommendations are based on evidence listed at “low” or “very low” quality, or citing a “knowledge gap.”

“The quality of the evidence available is variable, and we can only make our recommendations based on the quality of the evidence there, but it doesn’t negate the effects of the guideline itself,” Dr. Feuerstein said. The strong recommendation is based on randomized clinical trials that led to the Food and Drug Administration approvals, said Aline Charabaty-Pishvaian, MD, AGAF, associate professor at Johns Hopkins University, Baltimore, and director of the Inflammatory Bowel Disease Center at Sibley Memorial Hospital, Washington. “For everything else, we do not have randomized controlled trials to help make a decision, and the recommendations are made based on the interpretation of different RCTs [randomized controlled trials], knowing that these trials have different designs, patient populations, and endpoints, as well as on experts’ opinions,” she said in an interview.

The only other recommendation based on moderate quality evidence is to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who haven’t previously used biologic agents. The guideline also recommends using tofacitinib in these patients in the confines of a clinical trial; and using ustekinumab or tofacitinib rather than vedolizumab or adalimumab in patients who’ve already been on infliximab, particularly if they haven’t responded to treatment.

The guideline also recommends against thiopurine monotherapy to induce remission, but, for maintenance of remission, recommends such treatment vs. none. However, the guideline suggests against methotrexate monotherapy to induce or maintain remission. And biologic monotherapy is preferred to thiopurine to induce remission, but the guideline makes no recommendation for biologic vs. thiopurine monotherapy to maintain remission. Likewise, combining vedolizumab or ustekinumab with thiopurines or methotrexate is preferred to monotherapy with either a biologic or thiopurine.

The guideline also addresses step-up therapy. It suggests biologics as a first treatment, either as monotherapy or in combination with an immunomodulator, rather than a step-up after failure with 5-aminosalicylates. Also, it recommends against continuing 5-aminosalicylates to induce or maintain remission after a patient has achieved remission with biologics as monotherapy or in combination with immunomodulators or tofacitinib.

The guideline also offers four recommendations for hospitalized patients with acute severe ulcerative colitis: use of intravenous 40-60 mg/d methylprednisolone rather than higher dose IV corticosteroids, no adjunctive antibiotics in the absence of infection; use of infliximab or cyclosporine when IV corticosteroids fail, and no recommendation on the use of intensive vs. standard infliximab dosing when IV corticosteroids fail and the patient is already on infliximab.

The guideline will be meaningful in closing the evidence gap going forward because it can help direct the design of clinical trials, Dr. Charabaty-Pishvaian said. “The guideline highlights areas of need in terms of randomized clinical trials,” she said. “We need these trials to answer the questions we ask ourselves in our daily practice when managing patients with UC: Which drug to choose as the first-line agent? Which drug is the second-line therapy when the disease doesn’t respond or loses response to the first-line agent? Do we need to use combination therapy with all biologics, or only with anti-TNF-alpha agents? For how long? Can we use vedolizumab or ustekinumab as monotherapy when used as a first-line agent? And is there any advantage in adding an immunomodulator when these agents are used as third- or fourth-line therapy?”

Dr. Feuerstein has no relevant financial relationships to disclose. Guideline author Kim Isaacs, MD, disclosed relationships with AbbVie, Takeda, UCB, Janssen and Hoffmann-Laroche. All other committee members have no relevant disclosures.

*This story was updated on 5/7/2020.

SOURCE: Feuerstein JD et al. on behalf of the AGA Institute Clinical Guidelines Committee. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.006.

It’s been 11 years since the American Academy of Dermatology updated its guidelines for using nonbiologic systemic therapies for psoriasis, and now new guidelines recommend oral apremilast monotherapy and suggest a framework for a number of off-label treatments.

The guidelines, issued jointly with the National Psoriasis Foundation (NPF), were published in the Journal of the American Academy of Dermatology.

“I think we are way behind,” Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, and cochair of the guideline writing committee, said in an interview. “Most other countries update their guidelines every 1 or 2 years; we were 10 years behind.” The guidelines for systemic nonbiologic drugs follow up psoriasis guidelines issued by the AAD and the NPF on pediatric patients issued earlier this year, and on phototherapy, biologic treatments, and management of comorbidities issued last year.

“A lot has happened in the last 10 years,” said cochair Craig Elmets, MD, professor of dermatology at the University of Alabama at Birmingham. “While much of the interest is on biologic agents, nonbiologics are still used quite frequently, and the guidelines for their appropriate use have changed. Use of the guidelines provides people in the health profession with the most up to date evidence-based information so they can give their patients the best care.”

The guidelines acknowledge that the medications it covers are still widely used, either by themselves or in combination with biologic agents; readily available; easy to use; and, in the case of older therapies, relatively cheap.

Methotrexate has been available since the 1970s. Given as an injection or taken orally, the guidelines recommend supplementation with folic acid to counteract methotrexate’s side effects, particularly GI upset. The guidelines note that folic acid is less expensive than folinic acid. Combination therapy with methotrexate and tumor necrosis factor (TNF) inhibitors is more effective than methotrexate monotherapy, with a similar side effect profile, the guidelines state.

Methotrexate is more widely used outside the United States, “but it is a very good, quick fix and it’s much safer in children and young people than it is in people with cardiovascular disease,” Dr. Menter noted. “It’s still the most commonly used drug worldwide because it’s cheap, and you do have to worry about the long-term toxicity which is related the liver issues.”

The guidelines say that subcutaneous administration of methotrexate “may be particularly useful” for patients on higher doses, which when taken orally, are associated with a higher risk of GI effects.

Dr. Menter referred to a 2017 study, which reported 41% of patients treated with subcutaneous methotrexate once a week achieved a Psoriasis Area and Severity Index 75 score of 41% after a year of treatment, compared with 10% of those on placebo (Lancet. 2017 Feb 4;389[10068]:528-37).

The guidelines rate strength of recommendation as class A for methotrexate for moderate to severe psoriasis in adults, recommend supplementation with folic or folinic acid to counteract GI complications and liver problems, and note that adalimumab and infliximab are more effective than methotrexate for cutaneous psoriasis. Class B recommendations for methotrexate and psoriasis include statements that patients should begin with a test dose, especially if they have impaired kidney function; methotrexate is effective for peripheral, but not axial, psoriatic arthritis (PsA); and TNF inhibitors are more effective than methotrexate for PsA.

Approved by the FDA in 2014 for psoriasis, apremilast, which inhibits phosphodiesterase-4, is the newest drug in the recommendations. The guidelines recommend its use for moderate to severe psoriasis in adults, with a class A recommendation. Patients should start on a low dose and then build up to the 30-mg, twice-daily dose over 6 days and should be counseled about the risk of depression before starting treatment. Routine laboratory testing can be considered on an individual basis.

The guidelines also lay out three recommendations (and strength of recommendation) for cyclosporine, a drug that’s been around since the 1990s: for severe, recalcitrant cases (class A); for erythrodermic, general pustular, and palmoplantar psoriasis (class B); and as short-term therapy for psoriasis flare in patients already on another drug (class C).

Acitretin is another longstanding therapy used mostly for palmar-plantar psoriasis, but it can also be used as monotherapy for plaque psoriasis as well as erythrodermic and pustular disease. It can also be used in combination with psoralens with UVA for psoriasis and combined with broadband UVB phototherapy for plaque psoriasis. The acitretin recommendations are class B.

The oral Janus kinase (JAK) inhibitor tofacitinib isn’t specifically approved for psoriasis, but it is approved for RA, PsA, and ulcerative colitis. The drug targets the JAK-STAT signaling pathway that causes inflammation. The guidelines state that tofacitinib can be considered for moderate to severe psoriasis, but lists no strength of recommendation. The recommended dose is either 5 or 10 mg orally twice a day, with a caveat that the higher dose carries a higher risk of adverse events. Patients should be evaluated for getting a zoster vaccine before they begin therapy.

“We thought that, because there was probably a small chance that it might get approved for psoriasis, that we would discuss it briefly,” Dr. Menter said of tofacitinib.

Another off-label use the guidelines address is for fumaric and acid esters, also known as fumarates, which are used to in Europe to treat moderate to severe psoriasis. Dimethyl fumarate is approved for relapsing forms of multiple sclerosis in the United States. The guidelines state that fumarates can be used for psoriasis, but offer no strength of recommendation. Side effects include gastrointestinal disturbance and flushing.

Other treatments that are also addressed in the guidelines include a host of systemic immunosuppressants and antimetabolites: azathioprine, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus, none of which are FDA approved for psoriasis. They’re rarely used for psoriasis, but may have value in selected cases, the guidelines state.

Dr. Menter said that apremilast is the only oral drug in the guidelines, but they are the wave of the future for treating psoriasis. “I think there’s a tremendous potential for new oral drugs – TK2 [thymidine kinase], the JAK inhibitors, and other drugs coming down the pipelines. The majority of patients, if you ask them their preference, would like to take an oral drug rather than an injectable drug. And it would be much easier for dermatologists, they wouldn’t have to train patients on how to do the injections.”

Dr. Menter and Dr. Elmets disclosed financial relationships with numerous pharmaceutical companies. Other authors/work group members also had disclosures related to pharmaceutical manufacturers, and several had no disclosures.

SOURCE: Menter A et al. J Am Acad Dermatol. 2020 Feb 28. doi: 10.1016/j.jaad.2020.02.044.

It’s been 11 years since the American Academy of Dermatology updated its guidelines for using nonbiologic systemic therapies for psoriasis, and now new guidelines recommend oral apremilast monotherapy and suggest a framework for a number of off-label treatments.

The guidelines, issued jointly with the National Psoriasis Foundation (NPF), were published in the Journal of the American Academy of Dermatology.

“I think we are way behind,” Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, and cochair of the guideline writing committee, said in an interview. “Most other countries update their guidelines every 1 or 2 years; we were 10 years behind.” The guidelines for systemic nonbiologic drugs follow up psoriasis guidelines issued by the AAD and the NPF on pediatric patients issued earlier this year, and on phototherapy, biologic treatments, and management of comorbidities issued last year.

“A lot has happened in the last 10 years,” said cochair Craig Elmets, MD, professor of dermatology at the University of Alabama at Birmingham. “While much of the interest is on biologic agents, nonbiologics are still used quite frequently, and the guidelines for their appropriate use have changed. Use of the guidelines provides people in the health profession with the most up to date evidence-based information so they can give their patients the best care.”

The guidelines acknowledge that the medications it covers are still widely used, either by themselves or in combination with biologic agents; readily available; easy to use; and, in the case of older therapies, relatively cheap.

Methotrexate has been available since the 1970s. Given as an injection or taken orally, the guidelines recommend supplementation with folic acid to counteract methotrexate’s side effects, particularly GI upset. The guidelines note that folic acid is less expensive than folinic acid. Combination therapy with methotrexate and tumor necrosis factor (TNF) inhibitors is more effective than methotrexate monotherapy, with a similar side effect profile, the guidelines state.

Methotrexate is more widely used outside the United States, “but it is a very good, quick fix and it’s much safer in children and young people than it is in people with cardiovascular disease,” Dr. Menter noted. “It’s still the most commonly used drug worldwide because it’s cheap, and you do have to worry about the long-term toxicity which is related the liver issues.”

The guidelines say that subcutaneous administration of methotrexate “may be particularly useful” for patients on higher doses, which when taken orally, are associated with a higher risk of GI effects.

Dr. Menter referred to a 2017 study, which reported 41% of patients treated with subcutaneous methotrexate once a week achieved a Psoriasis Area and Severity Index 75 score of 41% after a year of treatment, compared with 10% of those on placebo (Lancet. 2017 Feb 4;389[10068]:528-37).

The guidelines rate strength of recommendation as class A for methotrexate for moderate to severe psoriasis in adults, recommend supplementation with folic or folinic acid to counteract GI complications and liver problems, and note that adalimumab and infliximab are more effective than methotrexate for cutaneous psoriasis. Class B recommendations for methotrexate and psoriasis include statements that patients should begin with a test dose, especially if they have impaired kidney function; methotrexate is effective for peripheral, but not axial, psoriatic arthritis (PsA); and TNF inhibitors are more effective than methotrexate for PsA.

Approved by the FDA in 2014 for psoriasis, apremilast, which inhibits phosphodiesterase-4, is the newest drug in the recommendations. The guidelines recommend its use for moderate to severe psoriasis in adults, with a class A recommendation. Patients should start on a low dose and then build up to the 30-mg, twice-daily dose over 6 days and should be counseled about the risk of depression before starting treatment. Routine laboratory testing can be considered on an individual basis.

The guidelines also lay out three recommendations (and strength of recommendation) for cyclosporine, a drug that’s been around since the 1990s: for severe, recalcitrant cases (class A); for erythrodermic, general pustular, and palmoplantar psoriasis (class B); and as short-term therapy for psoriasis flare in patients already on another drug (class C).

Acitretin is another longstanding therapy used mostly for palmar-plantar psoriasis, but it can also be used as monotherapy for plaque psoriasis as well as erythrodermic and pustular disease. It can also be used in combination with psoralens with UVA for psoriasis and combined with broadband UVB phototherapy for plaque psoriasis. The acitretin recommendations are class B.

The oral Janus kinase (JAK) inhibitor tofacitinib isn’t specifically approved for psoriasis, but it is approved for RA, PsA, and ulcerative colitis. The drug targets the JAK-STAT signaling pathway that causes inflammation. The guidelines state that tofacitinib can be considered for moderate to severe psoriasis, but lists no strength of recommendation. The recommended dose is either 5 or 10 mg orally twice a day, with a caveat that the higher dose carries a higher risk of adverse events. Patients should be evaluated for getting a zoster vaccine before they begin therapy.

“We thought that, because there was probably a small chance that it might get approved for psoriasis, that we would discuss it briefly,” Dr. Menter said of tofacitinib.

Another off-label use the guidelines address is for fumaric and acid esters, also known as fumarates, which are used to in Europe to treat moderate to severe psoriasis. Dimethyl fumarate is approved for relapsing forms of multiple sclerosis in the United States. The guidelines state that fumarates can be used for psoriasis, but offer no strength of recommendation. Side effects include gastrointestinal disturbance and flushing.

Other treatments that are also addressed in the guidelines include a host of systemic immunosuppressants and antimetabolites: azathioprine, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus, none of which are FDA approved for psoriasis. They’re rarely used for psoriasis, but may have value in selected cases, the guidelines state.

Dr. Menter said that apremilast is the only oral drug in the guidelines, but they are the wave of the future for treating psoriasis. “I think there’s a tremendous potential for new oral drugs – TK2 [thymidine kinase], the JAK inhibitors, and other drugs coming down the pipelines. The majority of patients, if you ask them their preference, would like to take an oral drug rather than an injectable drug. And it would be much easier for dermatologists, they wouldn’t have to train patients on how to do the injections.”

Dr. Menter and Dr. Elmets disclosed financial relationships with numerous pharmaceutical companies. Other authors/work group members also had disclosures related to pharmaceutical manufacturers, and several had no disclosures.

SOURCE: Menter A et al. J Am Acad Dermatol. 2020 Feb 28. doi: 10.1016/j.jaad.2020.02.044.

It’s been 11 years since the American Academy of Dermatology updated its guidelines for using nonbiologic systemic therapies for psoriasis, and now new guidelines recommend oral apremilast monotherapy and suggest a framework for a number of off-label treatments.

The guidelines, issued jointly with the National Psoriasis Foundation (NPF), were published in the Journal of the American Academy of Dermatology.

“I think we are way behind,” Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, and cochair of the guideline writing committee, said in an interview. “Most other countries update their guidelines every 1 or 2 years; we were 10 years behind.” The guidelines for systemic nonbiologic drugs follow up psoriasis guidelines issued by the AAD and the NPF on pediatric patients issued earlier this year, and on phototherapy, biologic treatments, and management of comorbidities issued last year.

“A lot has happened in the last 10 years,” said cochair Craig Elmets, MD, professor of dermatology at the University of Alabama at Birmingham. “While much of the interest is on biologic agents, nonbiologics are still used quite frequently, and the guidelines for their appropriate use have changed. Use of the guidelines provides people in the health profession with the most up to date evidence-based information so they can give their patients the best care.”

The guidelines acknowledge that the medications it covers are still widely used, either by themselves or in combination with biologic agents; readily available; easy to use; and, in the case of older therapies, relatively cheap.

Methotrexate has been available since the 1970s. Given as an injection or taken orally, the guidelines recommend supplementation with folic acid to counteract methotrexate’s side effects, particularly GI upset. The guidelines note that folic acid is less expensive than folinic acid. Combination therapy with methotrexate and tumor necrosis factor (TNF) inhibitors is more effective than methotrexate monotherapy, with a similar side effect profile, the guidelines state.

Methotrexate is more widely used outside the United States, “but it is a very good, quick fix and it’s much safer in children and young people than it is in people with cardiovascular disease,” Dr. Menter noted. “It’s still the most commonly used drug worldwide because it’s cheap, and you do have to worry about the long-term toxicity which is related the liver issues.”

The guidelines say that subcutaneous administration of methotrexate “may be particularly useful” for patients on higher doses, which when taken orally, are associated with a higher risk of GI effects.

Dr. Menter referred to a 2017 study, which reported 41% of patients treated with subcutaneous methotrexate once a week achieved a Psoriasis Area and Severity Index 75 score of 41% after a year of treatment, compared with 10% of those on placebo (Lancet. 2017 Feb 4;389[10068]:528-37).

The guidelines rate strength of recommendation as class A for methotrexate for moderate to severe psoriasis in adults, recommend supplementation with folic or folinic acid to counteract GI complications and liver problems, and note that adalimumab and infliximab are more effective than methotrexate for cutaneous psoriasis. Class B recommendations for methotrexate and psoriasis include statements that patients should begin with a test dose, especially if they have impaired kidney function; methotrexate is effective for peripheral, but not axial, psoriatic arthritis (PsA); and TNF inhibitors are more effective than methotrexate for PsA.

Approved by the FDA in 2014 for psoriasis, apremilast, which inhibits phosphodiesterase-4, is the newest drug in the recommendations. The guidelines recommend its use for moderate to severe psoriasis in adults, with a class A recommendation. Patients should start on a low dose and then build up to the 30-mg, twice-daily dose over 6 days and should be counseled about the risk of depression before starting treatment. Routine laboratory testing can be considered on an individual basis.

The guidelines also lay out three recommendations (and strength of recommendation) for cyclosporine, a drug that’s been around since the 1990s: for severe, recalcitrant cases (class A); for erythrodermic, general pustular, and palmoplantar psoriasis (class B); and as short-term therapy for psoriasis flare in patients already on another drug (class C).

Acitretin is another longstanding therapy used mostly for palmar-plantar psoriasis, but it can also be used as monotherapy for plaque psoriasis as well as erythrodermic and pustular disease. It can also be used in combination with psoralens with UVA for psoriasis and combined with broadband UVB phototherapy for plaque psoriasis. The acitretin recommendations are class B.

The oral Janus kinase (JAK) inhibitor tofacitinib isn’t specifically approved for psoriasis, but it is approved for RA, PsA, and ulcerative colitis. The drug targets the JAK-STAT signaling pathway that causes inflammation. The guidelines state that tofacitinib can be considered for moderate to severe psoriasis, but lists no strength of recommendation. The recommended dose is either 5 or 10 mg orally twice a day, with a caveat that the higher dose carries a higher risk of adverse events. Patients should be evaluated for getting a zoster vaccine before they begin therapy.

“We thought that, because there was probably a small chance that it might get approved for psoriasis, that we would discuss it briefly,” Dr. Menter said of tofacitinib.

Another off-label use the guidelines address is for fumaric and acid esters, also known as fumarates, which are used to in Europe to treat moderate to severe psoriasis. Dimethyl fumarate is approved for relapsing forms of multiple sclerosis in the United States. The guidelines state that fumarates can be used for psoriasis, but offer no strength of recommendation. Side effects include gastrointestinal disturbance and flushing.

Other treatments that are also addressed in the guidelines include a host of systemic immunosuppressants and antimetabolites: azathioprine, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus, none of which are FDA approved for psoriasis. They’re rarely used for psoriasis, but may have value in selected cases, the guidelines state.

Dr. Menter said that apremilast is the only oral drug in the guidelines, but they are the wave of the future for treating psoriasis. “I think there’s a tremendous potential for new oral drugs – TK2 [thymidine kinase], the JAK inhibitors, and other drugs coming down the pipelines. The majority of patients, if you ask them their preference, would like to take an oral drug rather than an injectable drug. And it would be much easier for dermatologists, they wouldn’t have to train patients on how to do the injections.”

Dr. Menter and Dr. Elmets disclosed financial relationships with numerous pharmaceutical companies. Other authors/work group members also had disclosures related to pharmaceutical manufacturers, and several had no disclosures.

SOURCE: Menter A et al. J Am Acad Dermatol. 2020 Feb 28. doi: 10.1016/j.jaad.2020.02.044.

The risk for microvascular complications in adults with latent autoimmune diabetes increases the longer they have the disease, according a post hoc analysis of a large European database.

However, Ernesto Maddaloni, MD, of Sapienza University of Rome and University of Oxford (England), and colleagues noted that the risk is less than half that in patients with type 2 disease during the first several years after diagnosis but that, after 9 years, the risk curves cross over, and patients with latent autoimmune diabetes of adulthood (LADA) matriculate to a 25% greater risk microvascular complications than do their type 2 counterparts.

The results point to a need for tighter glycemic control in patients with latent autoimmune disease and “might have relevant implications for the understanding of the differential risk of complications between type 2 diabetes and autoimmune diabetes in general,” the researchers wrote online in The Lancet Diabetes & Endocrinology. They emphasized that the study represents the largest population of patients with latent autoimmune diabetes with the longest follow-up in a randomized controlled trial so far.

Diabetic microvascular complications are a major cause of end-stage renal disease and blindness in LADA, therefore, “implementing strict glycemic control from the time of diagnosis could reduce the later risk of microvascular complications in [these patients],” the authors wrote.

The researchers analyzed 30 years of data from the United Kingdom Prospective Diabetes Study, focusing on 564 patients with LADA and 4,464 adults with type 2 diabetes. The primary outcome was first occurrence of renal failure, death from renal disease, blindness in one eye, vitreous hemorrhage, or retinal laser treatment.

With a median follow-up of 17.3 years, 21% of all patients (1,041) developed microvascular complications, of which there were 65 renal events and 976 retinopathy events. Secondary outcomes were nephropathy and retinopathy.

The study measured incidence in 1,000 person-years and found that the incidence for the overall primary composite microvascular outcome was 5.3% for LADA and 10% for type 2 diabetes in the first 9 years after diagnosis (P = .0020), but 13.6% and 9.2%, respectively, after that (P less than .0001). That translated into adjusted hazard ratios of 0.45 for LADA, compared with type 2 diabetes, in the first 9 years (P less than .0001) and 1.25 beyond 9 years (P = .047). The incidence of retinopathy events was 5.3% for LADA and 9.6% for type 2 diabetes up to 9 years (P = .003), and 12.5% and 8.6% thereafter (P = .001). Nephropathy rates were similar in both groups at 1.3% or less.

“The lower risk of microvascular complications during the first years after the diagnosis of latent autoimmune diabetes needs further examination,” Dr. Maddaloni and colleagues wrote.

They cautioned that LADA is often misdiagnosed as a form of type 1 diabetes. “Therefore, latent autoimmune diabetes could be the right bench test for studying differences between autoimmune diabetes and type 2 diabetes, because of fewer disparities in age and disease duration than with the comparison of type 1 diabetes and type 2 diabetes,” they wrote.

In an accompanying editorial, Didac Mauricio, MD, of the Autonomous University of Barcelona, credited Dr. Maddaloni and colleagues with presenting evidence “of major relevance” in an adequately powered study that provided “a robust conclusion” about the risk of microvascular complications in latent autoimmune diabetes.

Dr. Mauricio noted that the study adds to the literature that different subgroups of type 2 diabetes patients exist and highlights the distinct characteristics of latent autoimmune diabetes. In addition, it builds on a previous study by Dr. Maddaloni and coauthors that found cardiovascular disease outcomes did not differ between latent autoimmune and type 2 diabetes (Diabetes Obes Metab. 2019;21:2115-22), he wrote. The research team’s most recent findings “emphasize the need for early identification of latent autoimmune disease,” he stated.

The findings also raise important questions about screening all patients for antibodies upon diagnosis of diabetes, he said. “I firmly believe that it is time to take action,” first, because antibody testing is likely cost-effective and cost-saving because it facilitates better-informed, more timely decisions early in the disease trajectory, and second, it has already been well documented that patients with latent autoimmune diabetes have a higher glycemic burden.

An alternative to early universal screening for antibodies would be to raise awareness, especially among general practitioners, about the importance of timely diagnosis of LADA, Dr. Mauricio added.

The study received funding from the European Foundation for the Study of Diabetes Mentorship Program, supported by AstraZeneca. Dr. Maddaloni disclosed financial relationships with Sanofi, Eli Lilly, Abbott, and AstraZeneca. Another author disclosed financial relationships with Boehringer Ingelheim, Merck, Bayer, AstraZeneca, Novartis, and Novo Nordisk. All the other authors had no relevant financial relationships to disclose. Dr. Mauricio disclosed financial relationships with AstraZeneca, Eli Lilly, Merck Sharp & Dohme, NovoNordisk, Sanofi, Almirall, Boehringer Ingelheim, Eli Lilly, Ferrer, Janssen, Menarini, and URGO.
 

SOURCE: Maddaloni E et al. Lancet Diabetes Endocrinol. 2020 Feb 4. doi: 0.1016/S2213-8587(20)30003-6.

The risk for microvascular complications in adults with latent autoimmune diabetes increases the longer they have the disease, according a post hoc analysis of a large European database.

However, Ernesto Maddaloni, MD, of Sapienza University of Rome and University of Oxford (England), and colleagues noted that the risk is less than half that in patients with type 2 disease during the first several years after diagnosis but that, after 9 years, the risk curves cross over, and patients with latent autoimmune diabetes of adulthood (LADA) matriculate to a 25% greater risk microvascular complications than do their type 2 counterparts.

The results point to a need for tighter glycemic control in patients with latent autoimmune disease and “might have relevant implications for the understanding of the differential risk of complications between type 2 diabetes and autoimmune diabetes in general,” the researchers wrote online in The Lancet Diabetes & Endocrinology. They emphasized that the study represents the largest population of patients with latent autoimmune diabetes with the longest follow-up in a randomized controlled trial so far.

Diabetic microvascular complications are a major cause of end-stage renal disease and blindness in LADA, therefore, “implementing strict glycemic control from the time of diagnosis could reduce the later risk of microvascular complications in [these patients],” the authors wrote.

The researchers analyzed 30 years of data from the United Kingdom Prospective Diabetes Study, focusing on 564 patients with LADA and 4,464 adults with type 2 diabetes. The primary outcome was first occurrence of renal failure, death from renal disease, blindness in one eye, vitreous hemorrhage, or retinal laser treatment.

With a median follow-up of 17.3 years, 21% of all patients (1,041) developed microvascular complications, of which there were 65 renal events and 976 retinopathy events. Secondary outcomes were nephropathy and retinopathy.

The study measured incidence in 1,000 person-years and found that the incidence for the overall primary composite microvascular outcome was 5.3% for LADA and 10% for type 2 diabetes in the first 9 years after diagnosis (P = .0020), but 13.6% and 9.2%, respectively, after that (P less than .0001). That translated into adjusted hazard ratios of 0.45 for LADA, compared with type 2 diabetes, in the first 9 years (P less than .0001) and 1.25 beyond 9 years (P = .047). The incidence of retinopathy events was 5.3% for LADA and 9.6% for type 2 diabetes up to 9 years (P = .003), and 12.5% and 8.6% thereafter (P = .001). Nephropathy rates were similar in both groups at 1.3% or less.

“The lower risk of microvascular complications during the first years after the diagnosis of latent autoimmune diabetes needs further examination,” Dr. Maddaloni and colleagues wrote.

They cautioned that LADA is often misdiagnosed as a form of type 1 diabetes. “Therefore, latent autoimmune diabetes could be the right bench test for studying differences between autoimmune diabetes and type 2 diabetes, because of fewer disparities in age and disease duration than with the comparison of type 1 diabetes and type 2 diabetes,” they wrote.

In an accompanying editorial, Didac Mauricio, MD, of the Autonomous University of Barcelona, credited Dr. Maddaloni and colleagues with presenting evidence “of major relevance” in an adequately powered study that provided “a robust conclusion” about the risk of microvascular complications in latent autoimmune diabetes.

Dr. Mauricio noted that the study adds to the literature that different subgroups of type 2 diabetes patients exist and highlights the distinct characteristics of latent autoimmune diabetes. In addition, it builds on a previous study by Dr. Maddaloni and coauthors that found cardiovascular disease outcomes did not differ between latent autoimmune and type 2 diabetes (Diabetes Obes Metab. 2019;21:2115-22), he wrote. The research team’s most recent findings “emphasize the need for early identification of latent autoimmune disease,” he stated.

The findings also raise important questions about screening all patients for antibodies upon diagnosis of diabetes, he said. “I firmly believe that it is time to take action,” first, because antibody testing is likely cost-effective and cost-saving because it facilitates better-informed, more timely decisions early in the disease trajectory, and second, it has already been well documented that patients with latent autoimmune diabetes have a higher glycemic burden.

An alternative to early universal screening for antibodies would be to raise awareness, especially among general practitioners, about the importance of timely diagnosis of LADA, Dr. Mauricio added.

The study received funding from the European Foundation for the Study of Diabetes Mentorship Program, supported by AstraZeneca. Dr. Maddaloni disclosed financial relationships with Sanofi, Eli Lilly, Abbott, and AstraZeneca. Another author disclosed financial relationships with Boehringer Ingelheim, Merck, Bayer, AstraZeneca, Novartis, and Novo Nordisk. All the other authors had no relevant financial relationships to disclose. Dr. Mauricio disclosed financial relationships with AstraZeneca, Eli Lilly, Merck Sharp & Dohme, NovoNordisk, Sanofi, Almirall, Boehringer Ingelheim, Eli Lilly, Ferrer, Janssen, Menarini, and URGO.
 

SOURCE: Maddaloni E et al. Lancet Diabetes Endocrinol. 2020 Feb 4. doi: 0.1016/S2213-8587(20)30003-6.

The risk for microvascular complications in adults with latent autoimmune diabetes increases the longer they have the disease, according a post hoc analysis of a large European database.

However, Ernesto Maddaloni, MD, of Sapienza University of Rome and University of Oxford (England), and colleagues noted that the risk is less than half that in patients with type 2 disease during the first several years after diagnosis but that, after 9 years, the risk curves cross over, and patients with latent autoimmune diabetes of adulthood (LADA) matriculate to a 25% greater risk microvascular complications than do their type 2 counterparts.

The results point to a need for tighter glycemic control in patients with latent autoimmune disease and “might have relevant implications for the understanding of the differential risk of complications between type 2 diabetes and autoimmune diabetes in general,” the researchers wrote online in The Lancet Diabetes & Endocrinology. They emphasized that the study represents the largest population of patients with latent autoimmune diabetes with the longest follow-up in a randomized controlled trial so far.

Diabetic microvascular complications are a major cause of end-stage renal disease and blindness in LADA, therefore, “implementing strict glycemic control from the time of diagnosis could reduce the later risk of microvascular complications in [these patients],” the authors wrote.

The researchers analyzed 30 years of data from the United Kingdom Prospective Diabetes Study, focusing on 564 patients with LADA and 4,464 adults with type 2 diabetes. The primary outcome was first occurrence of renal failure, death from renal disease, blindness in one eye, vitreous hemorrhage, or retinal laser treatment.

With a median follow-up of 17.3 years, 21% of all patients (1,041) developed microvascular complications, of which there were 65 renal events and 976 retinopathy events. Secondary outcomes were nephropathy and retinopathy.

The study measured incidence in 1,000 person-years and found that the incidence for the overall primary composite microvascular outcome was 5.3% for LADA and 10% for type 2 diabetes in the first 9 years after diagnosis (P = .0020), but 13.6% and 9.2%, respectively, after that (P less than .0001). That translated into adjusted hazard ratios of 0.45 for LADA, compared with type 2 diabetes, in the first 9 years (P less than .0001) and 1.25 beyond 9 years (P = .047). The incidence of retinopathy events was 5.3% for LADA and 9.6% for type 2 diabetes up to 9 years (P = .003), and 12.5% and 8.6% thereafter (P = .001). Nephropathy rates were similar in both groups at 1.3% or less.

“The lower risk of microvascular complications during the first years after the diagnosis of latent autoimmune diabetes needs further examination,” Dr. Maddaloni and colleagues wrote.

They cautioned that LADA is often misdiagnosed as a form of type 1 diabetes. “Therefore, latent autoimmune diabetes could be the right bench test for studying differences between autoimmune diabetes and type 2 diabetes, because of fewer disparities in age and disease duration than with the comparison of type 1 diabetes and type 2 diabetes,” they wrote.

In an accompanying editorial, Didac Mauricio, MD, of the Autonomous University of Barcelona, credited Dr. Maddaloni and colleagues with presenting evidence “of major relevance” in an adequately powered study that provided “a robust conclusion” about the risk of microvascular complications in latent autoimmune diabetes.

Dr. Mauricio noted that the study adds to the literature that different subgroups of type 2 diabetes patients exist and highlights the distinct characteristics of latent autoimmune diabetes. In addition, it builds on a previous study by Dr. Maddaloni and coauthors that found cardiovascular disease outcomes did not differ between latent autoimmune and type 2 diabetes (Diabetes Obes Metab. 2019;21:2115-22), he wrote. The research team’s most recent findings “emphasize the need for early identification of latent autoimmune disease,” he stated.

The findings also raise important questions about screening all patients for antibodies upon diagnosis of diabetes, he said. “I firmly believe that it is time to take action,” first, because antibody testing is likely cost-effective and cost-saving because it facilitates better-informed, more timely decisions early in the disease trajectory, and second, it has already been well documented that patients with latent autoimmune diabetes have a higher glycemic burden.

An alternative to early universal screening for antibodies would be to raise awareness, especially among general practitioners, about the importance of timely diagnosis of LADA, Dr. Mauricio added.

The study received funding from the European Foundation for the Study of Diabetes Mentorship Program, supported by AstraZeneca. Dr. Maddaloni disclosed financial relationships with Sanofi, Eli Lilly, Abbott, and AstraZeneca. Another author disclosed financial relationships with Boehringer Ingelheim, Merck, Bayer, AstraZeneca, Novartis, and Novo Nordisk. All the other authors had no relevant financial relationships to disclose. Dr. Mauricio disclosed financial relationships with AstraZeneca, Eli Lilly, Merck Sharp & Dohme, NovoNordisk, Sanofi, Almirall, Boehringer Ingelheim, Eli Lilly, Ferrer, Janssen, Menarini, and URGO.
 

SOURCE: Maddaloni E et al. Lancet Diabetes Endocrinol. 2020 Feb 4. doi: 0.1016/S2213-8587(20)30003-6.

Researchers have found three potential gut mechanisms linked to secondary bile acid (SBA) deficiencies implicated in intestinal inflammation in ulcerative colitis (UC), and reported that supplementation may aid in restoring bile acid levels and potentially treating intestinal inflammation, according to a study published in Cell Host & Microbe.

The study identified lower levels of the following gut components in SBA deficiency in colectomy patients with UC, compared with those with familial adenomatous polyposis (FAP): deoxycholic and lithocholic acids (DCA and LCA), the most abundant gut secondary bile acids (SBAs); expression of the genes needed to convert primary bile acids (PBAs) into SBAs; and the number of Ruminococcaceae, one of the few taxa that include bacteria that generate SBAs.

“Our findings confirm that significant changes in bacterial diversity and composition occur in UC versus FAP pouches,” wrote Sidhartha R. Sinha, MD, of Stanford (Calif.) University, and coauthors. “Notably, our finding of decreased Ruminococcaceae in UC, compared to FAP pouch stool, requires further exploration.” They added that this is the first study to identify Ruminococcaceae as a key contributor to the production of LCA or DCA from PBAs.

The study found average DCA counts of 60,957 in FAP versus 1,593 in UC (P = .002), and average LCA counts of 30,644 and 282.9, respectively (P = .001). The study profiled stools from ileal pouches in colectomy patients who had UC (17) or FAP (7), a noninflammatory disease. “Remarkably, our data identify LCA and DCA to be almost undetectable in UC pouch patients,” Dr. Sinha and coauthors wrote. “This striking finding in patients who underwent colectomy suggests that SBAs may play a role in dysregulated metabolism-induced intestinal inflammation.”

The study found that UC pouches demonstrated less bacterial diversity, or alpha-diversity, than FAP pouches, which is in line with previously reported findings (J Inflamm Res. 2017;10:63-73), and had significantly lower expression of bile-acid inducible genes that encode enzymes that transform PBA to SBA.

The researchers also demonstrated that LCA and DCA supplementation reduced intestinal inflammation in mice with UC.

“Our results show that LCA and DCA treatments caused a remarkable and significant decrease in multiple chemokines and cytokines associated with inflammation, including those often increased in intestinal inflammation,” Dr. Sinha and coauthors wrote. However, they found that LCA had no protective effect on dextran sodium sulfate–induced colitis in mice with TGR5-deficient immune cells. The TGR5 bile acid receptor influences the anti-inflammatory effect in SBA supplementation, the study reported.

The researchers have initiated a clinical study (NCT03724175) to investigate the role of SBAs in patients with pouchitis that doesn’t respond to antibiotic therapy. “Insights from this study will further inform our understanding of the role of SBAs in intestinal inflammation and hold promise to provide an effective treatment,” Dr. Sinha and coauthors wrote.

Christian Jobin, PhD, of the University of Florida, Gainesville, said in an interview these findings are consistent with a recent paper that found a correlation between production of SBAs such as DCA and disease remission (ISME J. 2020;14:702-13). Dr. Jobin coauthored a 2018 study that similarly found SBAs have a role in intestinal inflammation (Gastroenterology. 2018;154:1751-63).

“For a long time, secondary bile acid, especially DCA was linked to cell injury, toxicity and even cancer,” he said. “It’s time to rehabilitate this important signaling molecule and recognize its important role in regulating host homeostasis.” The 2018 paper he coauthored showed that injection of DCA into germ-free mice did not promote intestinal pathology. “Actually, DCA was critical in preventing Campylobacter jejune–induced colitis,” he added.

Dr. Sinha received funding from the Crohn’s & Colitis Foundation, Stanford Clinical and Translational Science Award, and Kenneth Rainin Foundation Synergy Award. Coauthors received funding from the National Institutes of Health, the Ann and Bill Swindells Charitable Trust, Leslie and Douglas Ballinger, and the Kenneth Rainin Foundation.

SOURCE: Sinha SR et al. Cell Host Microbe. 2020 Feb 25. doi: 10.1016/j.chom.2020.01.021.

Researchers have found three potential gut mechanisms linked to secondary bile acid (SBA) deficiencies implicated in intestinal inflammation in ulcerative colitis (UC), and reported that supplementation may aid in restoring bile acid levels and potentially treating intestinal inflammation, according to a study published in Cell Host & Microbe.

The study identified lower levels of the following gut components in SBA deficiency in colectomy patients with UC, compared with those with familial adenomatous polyposis (FAP): deoxycholic and lithocholic acids (DCA and LCA), the most abundant gut secondary bile acids (SBAs); expression of the genes needed to convert primary bile acids (PBAs) into SBAs; and the number of Ruminococcaceae, one of the few taxa that include bacteria that generate SBAs.

“Our findings confirm that significant changes in bacterial diversity and composition occur in UC versus FAP pouches,” wrote Sidhartha R. Sinha, MD, of Stanford (Calif.) University, and coauthors. “Notably, our finding of decreased Ruminococcaceae in UC, compared to FAP pouch stool, requires further exploration.” They added that this is the first study to identify Ruminococcaceae as a key contributor to the production of LCA or DCA from PBAs.

The study found average DCA counts of 60,957 in FAP versus 1,593 in UC (P = .002), and average LCA counts of 30,644 and 282.9, respectively (P = .001). The study profiled stools from ileal pouches in colectomy patients who had UC (17) or FAP (7), a noninflammatory disease. “Remarkably, our data identify LCA and DCA to be almost undetectable in UC pouch patients,” Dr. Sinha and coauthors wrote. “This striking finding in patients who underwent colectomy suggests that SBAs may play a role in dysregulated metabolism-induced intestinal inflammation.”

The study found that UC pouches demonstrated less bacterial diversity, or alpha-diversity, than FAP pouches, which is in line with previously reported findings (J Inflamm Res. 2017;10:63-73), and had significantly lower expression of bile-acid inducible genes that encode enzymes that transform PBA to SBA.

The researchers also demonstrated that LCA and DCA supplementation reduced intestinal inflammation in mice with UC.

“Our results show that LCA and DCA treatments caused a remarkable and significant decrease in multiple chemokines and cytokines associated with inflammation, including those often increased in intestinal inflammation,” Dr. Sinha and coauthors wrote. However, they found that LCA had no protective effect on dextran sodium sulfate–induced colitis in mice with TGR5-deficient immune cells. The TGR5 bile acid receptor influences the anti-inflammatory effect in SBA supplementation, the study reported.

The researchers have initiated a clinical study (NCT03724175) to investigate the role of SBAs in patients with pouchitis that doesn’t respond to antibiotic therapy. “Insights from this study will further inform our understanding of the role of SBAs in intestinal inflammation and hold promise to provide an effective treatment,” Dr. Sinha and coauthors wrote.

Christian Jobin, PhD, of the University of Florida, Gainesville, said in an interview these findings are consistent with a recent paper that found a correlation between production of SBAs such as DCA and disease remission (ISME J. 2020;14:702-13). Dr. Jobin coauthored a 2018 study that similarly found SBAs have a role in intestinal inflammation (Gastroenterology. 2018;154:1751-63).

“For a long time, secondary bile acid, especially DCA was linked to cell injury, toxicity and even cancer,” he said. “It’s time to rehabilitate this important signaling molecule and recognize its important role in regulating host homeostasis.” The 2018 paper he coauthored showed that injection of DCA into germ-free mice did not promote intestinal pathology. “Actually, DCA was critical in preventing Campylobacter jejune–induced colitis,” he added.

Dr. Sinha received funding from the Crohn’s & Colitis Foundation, Stanford Clinical and Translational Science Award, and Kenneth Rainin Foundation Synergy Award. Coauthors received funding from the National Institutes of Health, the Ann and Bill Swindells Charitable Trust, Leslie and Douglas Ballinger, and the Kenneth Rainin Foundation.

SOURCE: Sinha SR et al. Cell Host Microbe. 2020 Feb 25. doi: 10.1016/j.chom.2020.01.021.

Researchers have found three potential gut mechanisms linked to secondary bile acid (SBA) deficiencies implicated in intestinal inflammation in ulcerative colitis (UC), and reported that supplementation may aid in restoring bile acid levels and potentially treating intestinal inflammation, according to a study published in Cell Host & Microbe.

The study identified lower levels of the following gut components in SBA deficiency in colectomy patients with UC, compared with those with familial adenomatous polyposis (FAP): deoxycholic and lithocholic acids (DCA and LCA), the most abundant gut secondary bile acids (SBAs); expression of the genes needed to convert primary bile acids (PBAs) into SBAs; and the number of Ruminococcaceae, one of the few taxa that include bacteria that generate SBAs.

“Our findings confirm that significant changes in bacterial diversity and composition occur in UC versus FAP pouches,” wrote Sidhartha R. Sinha, MD, of Stanford (Calif.) University, and coauthors. “Notably, our finding of decreased Ruminococcaceae in UC, compared to FAP pouch stool, requires further exploration.” They added that this is the first study to identify Ruminococcaceae as a key contributor to the production of LCA or DCA from PBAs.

The study found average DCA counts of 60,957 in FAP versus 1,593 in UC (P = .002), and average LCA counts of 30,644 and 282.9, respectively (P = .001). The study profiled stools from ileal pouches in colectomy patients who had UC (17) or FAP (7), a noninflammatory disease. “Remarkably, our data identify LCA and DCA to be almost undetectable in UC pouch patients,” Dr. Sinha and coauthors wrote. “This striking finding in patients who underwent colectomy suggests that SBAs may play a role in dysregulated metabolism-induced intestinal inflammation.”

The study found that UC pouches demonstrated less bacterial diversity, or alpha-diversity, than FAP pouches, which is in line with previously reported findings (J Inflamm Res. 2017;10:63-73), and had significantly lower expression of bile-acid inducible genes that encode enzymes that transform PBA to SBA.

The researchers also demonstrated that LCA and DCA supplementation reduced intestinal inflammation in mice with UC.

“Our results show that LCA and DCA treatments caused a remarkable and significant decrease in multiple chemokines and cytokines associated with inflammation, including those often increased in intestinal inflammation,” Dr. Sinha and coauthors wrote. However, they found that LCA had no protective effect on dextran sodium sulfate–induced colitis in mice with TGR5-deficient immune cells. The TGR5 bile acid receptor influences the anti-inflammatory effect in SBA supplementation, the study reported.

The researchers have initiated a clinical study (NCT03724175) to investigate the role of SBAs in patients with pouchitis that doesn’t respond to antibiotic therapy. “Insights from this study will further inform our understanding of the role of SBAs in intestinal inflammation and hold promise to provide an effective treatment,” Dr. Sinha and coauthors wrote.

Christian Jobin, PhD, of the University of Florida, Gainesville, said in an interview these findings are consistent with a recent paper that found a correlation between production of SBAs such as DCA and disease remission (ISME J. 2020;14:702-13). Dr. Jobin coauthored a 2018 study that similarly found SBAs have a role in intestinal inflammation (Gastroenterology. 2018;154:1751-63).

“For a long time, secondary bile acid, especially DCA was linked to cell injury, toxicity and even cancer,” he said. “It’s time to rehabilitate this important signaling molecule and recognize its important role in regulating host homeostasis.” The 2018 paper he coauthored showed that injection of DCA into germ-free mice did not promote intestinal pathology. “Actually, DCA was critical in preventing Campylobacter jejune–induced colitis,” he added.

Dr. Sinha received funding from the Crohn’s & Colitis Foundation, Stanford Clinical and Translational Science Award, and Kenneth Rainin Foundation Synergy Award. Coauthors received funding from the National Institutes of Health, the Ann and Bill Swindells Charitable Trust, Leslie and Douglas Ballinger, and the Kenneth Rainin Foundation.

SOURCE: Sinha SR et al. Cell Host Microbe. 2020 Feb 25. doi: 10.1016/j.chom.2020.01.021.

A unique collection of bacteria in the gut may have a strong association with pulmonary arterial hypertension and could be highly predictive of the disease in undiagnosed patients, according to a study published in the journal Hypertension.

This is the first study to show that people with PAH have a common specific gut microbiota profile, wrote lead study author Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida, Gainesville.

The findings have the potential to change how cardiologists diagnose and treat PAH, he added. “While current PAH treatments focus on the lungs, looking at the lung/gut axis could open the door to new therapies centered in the digestive system,” Dr. Raizada said.

The researchers developed a model that found the specific microbiota profile was 83% accurate in predicting the presence or absence of PAH. If a larger study can validate the findings, the researchers wrote, this could lead to a new test for diagnosing PAH that’s less invasive than cardiac catheterization. It could also lead to new treatments that target the gut microbiome.

Study investigators collected stool samples from 18 PAH patients and 12 people without a history of cardiopulmonary disease. The microbiota DNA from the stool samples were isolated and sequenced. The analysis revealed that PAH patients had reduced richness and evenness of the gut bacteria, known as alpha diversity. They had increased levels of bacteria associated with atherosclerosis, and healthy patients had increased levels of bacteria that produced short-chain fatty acids.

Although recent studies have begun to show potential associations between the gut microbiome and cardiovascular diseases, this research is in its infancy, Mariell Jessup, MD, commented. “Even though the study by Dr. Raizada and colleagues predicted pulmonary arterial hypertension based on an individual’s microbiome with some accuracy, it is an observational study, so it does not prove cause and effect. Many other factors, especially diet, affect the gut microbiome,” added Dr. Jessup, Chief Science and Medical Officer for the American Heart Association.

SOURCE: Raizada MK et al. Hypertension. 2020. doi: 10.1161/HYPERTENSIONAHA.119.14294.

A unique collection of bacteria in the gut may have a strong association with pulmonary arterial hypertension and could be highly predictive of the disease in undiagnosed patients, according to a study published in the journal Hypertension.

This is the first study to show that people with PAH have a common specific gut microbiota profile, wrote lead study author Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida, Gainesville.

The findings have the potential to change how cardiologists diagnose and treat PAH, he added. “While current PAH treatments focus on the lungs, looking at the lung/gut axis could open the door to new therapies centered in the digestive system,” Dr. Raizada said.

The researchers developed a model that found the specific microbiota profile was 83% accurate in predicting the presence or absence of PAH. If a larger study can validate the findings, the researchers wrote, this could lead to a new test for diagnosing PAH that’s less invasive than cardiac catheterization. It could also lead to new treatments that target the gut microbiome.

Study investigators collected stool samples from 18 PAH patients and 12 people without a history of cardiopulmonary disease. The microbiota DNA from the stool samples were isolated and sequenced. The analysis revealed that PAH patients had reduced richness and evenness of the gut bacteria, known as alpha diversity. They had increased levels of bacteria associated with atherosclerosis, and healthy patients had increased levels of bacteria that produced short-chain fatty acids.

Although recent studies have begun to show potential associations between the gut microbiome and cardiovascular diseases, this research is in its infancy, Mariell Jessup, MD, commented. “Even though the study by Dr. Raizada and colleagues predicted pulmonary arterial hypertension based on an individual’s microbiome with some accuracy, it is an observational study, so it does not prove cause and effect. Many other factors, especially diet, affect the gut microbiome,” added Dr. Jessup, Chief Science and Medical Officer for the American Heart Association.

SOURCE: Raizada MK et al. Hypertension. 2020. doi: 10.1161/HYPERTENSIONAHA.119.14294.

A unique collection of bacteria in the gut may have a strong association with pulmonary arterial hypertension and could be highly predictive of the disease in undiagnosed patients, according to a study published in the journal Hypertension.

This is the first study to show that people with PAH have a common specific gut microbiota profile, wrote lead study author Mohan Raizada, PhD, distinguished professor in the department of physiology and functional genomics at the University of Florida, Gainesville.

The findings have the potential to change how cardiologists diagnose and treat PAH, he added. “While current PAH treatments focus on the lungs, looking at the lung/gut axis could open the door to new therapies centered in the digestive system,” Dr. Raizada said.

The researchers developed a model that found the specific microbiota profile was 83% accurate in predicting the presence or absence of PAH. If a larger study can validate the findings, the researchers wrote, this could lead to a new test for diagnosing PAH that’s less invasive than cardiac catheterization. It could also lead to new treatments that target the gut microbiome.

Study investigators collected stool samples from 18 PAH patients and 12 people without a history of cardiopulmonary disease. The microbiota DNA from the stool samples were isolated and sequenced. The analysis revealed that PAH patients had reduced richness and evenness of the gut bacteria, known as alpha diversity. They had increased levels of bacteria associated with atherosclerosis, and healthy patients had increased levels of bacteria that produced short-chain fatty acids.

Although recent studies have begun to show potential associations between the gut microbiome and cardiovascular diseases, this research is in its infancy, Mariell Jessup, MD, commented. “Even though the study by Dr. Raizada and colleagues predicted pulmonary arterial hypertension based on an individual’s microbiome with some accuracy, it is an observational study, so it does not prove cause and effect. Many other factors, especially diet, affect the gut microbiome,” added Dr. Jessup, Chief Science and Medical Officer for the American Heart Association.

SOURCE: Raizada MK et al. Hypertension. 2020. doi: 10.1161/HYPERTENSIONAHA.119.14294.

AUSTIN, TEX. – A program of frequent monitoring in Crohn’s disease and ulcerative colitis that includes fecal calprotectin (FC) and C-reactive protein (CRP) testing may be cost effective to significantly reduce disease recurrence and hospitalization rates, according to a review of published studies presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Some data show that calprotectin levels rise months before the onset of symptoms, so it’s my practice that every 3-4 months patients should undergo CRP and calprotectin testing, if they’re willing to do so, while they’re on biologic therapy,” Frank I. Scott, MD, MSCE, of the University of Colorado in Aurora, Denver, said in an interview after the presentation.

Regular monitoring of the two levels makes sense as the practice of tight control of IBD symptoms and treating to target has emerged over the past decade, Dr. Scott said. He noted the 2015 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) guidelines called for using CRP and FC as adjunctive targets only in symptom assessment (Am J Gastroenterol. 2015:110[9]:1324-58). “I argue that we’ve had a growing body of literature that we should be using these tests regularly as well,” he said.

STRIDE calls for endoscopic assessment 6-9 months after therapy change and consideration of cross-sectional imaging if the small bowel is involved, with assessment every 3 months until symptoms improve and then every 6-12 months thereafter.

However, Dr. Scott noted potential drawbacks to these follow-up steps. “They currently focus on clinical symptoms in the short-term follow-up, and we know from looking at our disease activity indices, such as the CDAI [Crohn’s disease activity index] or Harvey-Bradshaw index, that they don’t always perfectly correlate with actual mucosal healing or resolution of inflammation in Crohn’s or [ulcerative colitis],” he said, pointing to a 2014 study that found CDAI had an area under the curve of 0.57, “which is pretty poor correlation” (Gut. 2014;63[1]:88-95).

Whereas a study of 2,499 patients that showed CRP had an area under the curve of 0.72 and FC of 0.89 (Am J Gastroentrol. 2015;110[6]:802-19). “CRP is a really attractive potential noninvasive marker of inflammation,” he said. “It’s relatively inexpensive, it’s widely available, and the cutoff ranges are well defined.”

He noted four potential drawbacks of CRP: the false-positive rate is relatively high; as a marker of systemic inflammation it’s not specific to the GI tract; false negatives have been well described, with up to 15% of patients not registering a response; and levels can depend on disease location. “Those with isolated ileal disease, for instance, may have relatively low CRP elevations when their disease is active,” Dr. Scott said.

Stool-based FC “represents a potentially more attractive option,” Dr. Scott said. Along with an area under the curve superior to CRP, FC has a documented sensitivity and specificity of 88% and 73%, respectively, versus 49% and 92% for CRP. Drawbacks of fecal calprotectin are that it’s specific to the GI tract but not inflammatory bowel disease, it costs more, and insurance coverage is not as universal as it is for CRP, although more carriers are covering the test, he said.

“However, we do know that through clinical trial data that the use of CRP and FC, in addition to clinical symptom monitoring, does appear to improve care,” Dr. Scott said, noting that the CALM trial of tight disease control through the frequent use of biochemical markers of inflammation with anti–tumor necrosis therapy bore this out (Lancet. 2018;390[10114]:2779-89). “This trial was able to demonstrate at 48 weeks that mucosal healing rates were improved in those receiving CRP and FC monitoring, compared to symptom monitoring alone, with higher rates of steroid-free remission at each visit, which persisted over the follow-up time.”

Dr. Scott also cited a post hoc analysis of CALM trial data that validated CRP and FC monitoring to improve steroid-free remission rates and other outcomes (Gut. 2019 Jul 8. doi: 10.1136/gutjnl-2019-318256). That trial reported steroid-free remission rates of 39.3% with clinical management and 59.8% with tight control, a 34% overall difference (P less than .001). “And it was cost effective to incorporate this monitoring at a cost of about $24,300 per quality-adjusted life-year, well below the typically used $50,000 willingness-to-pay threshold when considering new tests,” Dr. Scott said.

Dr. Scott acknowledged that FC testing may pose some inconvenience to patients when collecting their stool samples, but accuracy has improved. “Laboratories are becoming more reliable in terms of what the values are, and the cutoffs are becoming more defined as far as what’s positive and what’s negative, so it’s good way to monitor whether or not patients are at increased risk of a future flare,” he said.

Dr. Scott reported financial relationships with Takeda, Janssen, Merck and PRIME.

SOURCE: Scott FI et al. Crohn’s & Colitis Congress 2020, Session Sp125.

AUSTIN, TEX. – A program of frequent monitoring in Crohn’s disease and ulcerative colitis that includes fecal calprotectin (FC) and C-reactive protein (CRP) testing may be cost effective to significantly reduce disease recurrence and hospitalization rates, according to a review of published studies presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Some data show that calprotectin levels rise months before the onset of symptoms, so it’s my practice that every 3-4 months patients should undergo CRP and calprotectin testing, if they’re willing to do so, while they’re on biologic therapy,” Frank I. Scott, MD, MSCE, of the University of Colorado in Aurora, Denver, said in an interview after the presentation.

Regular monitoring of the two levels makes sense as the practice of tight control of IBD symptoms and treating to target has emerged over the past decade, Dr. Scott said. He noted the 2015 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) guidelines called for using CRP and FC as adjunctive targets only in symptom assessment (Am J Gastroenterol. 2015:110[9]:1324-58). “I argue that we’ve had a growing body of literature that we should be using these tests regularly as well,” he said.

STRIDE calls for endoscopic assessment 6-9 months after therapy change and consideration of cross-sectional imaging if the small bowel is involved, with assessment every 3 months until symptoms improve and then every 6-12 months thereafter.

However, Dr. Scott noted potential drawbacks to these follow-up steps. “They currently focus on clinical symptoms in the short-term follow-up, and we know from looking at our disease activity indices, such as the CDAI [Crohn’s disease activity index] or Harvey-Bradshaw index, that they don’t always perfectly correlate with actual mucosal healing or resolution of inflammation in Crohn’s or [ulcerative colitis],” he said, pointing to a 2014 study that found CDAI had an area under the curve of 0.57, “which is pretty poor correlation” (Gut. 2014;63[1]:88-95).

Whereas a study of 2,499 patients that showed CRP had an area under the curve of 0.72 and FC of 0.89 (Am J Gastroentrol. 2015;110[6]:802-19). “CRP is a really attractive potential noninvasive marker of inflammation,” he said. “It’s relatively inexpensive, it’s widely available, and the cutoff ranges are well defined.”

He noted four potential drawbacks of CRP: the false-positive rate is relatively high; as a marker of systemic inflammation it’s not specific to the GI tract; false negatives have been well described, with up to 15% of patients not registering a response; and levels can depend on disease location. “Those with isolated ileal disease, for instance, may have relatively low CRP elevations when their disease is active,” Dr. Scott said.

Stool-based FC “represents a potentially more attractive option,” Dr. Scott said. Along with an area under the curve superior to CRP, FC has a documented sensitivity and specificity of 88% and 73%, respectively, versus 49% and 92% for CRP. Drawbacks of fecal calprotectin are that it’s specific to the GI tract but not inflammatory bowel disease, it costs more, and insurance coverage is not as universal as it is for CRP, although more carriers are covering the test, he said.

“However, we do know that through clinical trial data that the use of CRP and FC, in addition to clinical symptom monitoring, does appear to improve care,” Dr. Scott said, noting that the CALM trial of tight disease control through the frequent use of biochemical markers of inflammation with anti–tumor necrosis therapy bore this out (Lancet. 2018;390[10114]:2779-89). “This trial was able to demonstrate at 48 weeks that mucosal healing rates were improved in those receiving CRP and FC monitoring, compared to symptom monitoring alone, with higher rates of steroid-free remission at each visit, which persisted over the follow-up time.”

Dr. Scott also cited a post hoc analysis of CALM trial data that validated CRP and FC monitoring to improve steroid-free remission rates and other outcomes (Gut. 2019 Jul 8. doi: 10.1136/gutjnl-2019-318256). That trial reported steroid-free remission rates of 39.3% with clinical management and 59.8% with tight control, a 34% overall difference (P less than .001). “And it was cost effective to incorporate this monitoring at a cost of about $24,300 per quality-adjusted life-year, well below the typically used $50,000 willingness-to-pay threshold when considering new tests,” Dr. Scott said.

Dr. Scott acknowledged that FC testing may pose some inconvenience to patients when collecting their stool samples, but accuracy has improved. “Laboratories are becoming more reliable in terms of what the values are, and the cutoffs are becoming more defined as far as what’s positive and what’s negative, so it’s good way to monitor whether or not patients are at increased risk of a future flare,” he said.

Dr. Scott reported financial relationships with Takeda, Janssen, Merck and PRIME.

SOURCE: Scott FI et al. Crohn’s & Colitis Congress 2020, Session Sp125.

AUSTIN, TEX. – A program of frequent monitoring in Crohn’s disease and ulcerative colitis that includes fecal calprotectin (FC) and C-reactive protein (CRP) testing may be cost effective to significantly reduce disease recurrence and hospitalization rates, according to a review of published studies presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Some data show that calprotectin levels rise months before the onset of symptoms, so it’s my practice that every 3-4 months patients should undergo CRP and calprotectin testing, if they’re willing to do so, while they’re on biologic therapy,” Frank I. Scott, MD, MSCE, of the University of Colorado in Aurora, Denver, said in an interview after the presentation.

Regular monitoring of the two levels makes sense as the practice of tight control of IBD symptoms and treating to target has emerged over the past decade, Dr. Scott said. He noted the 2015 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) guidelines called for using CRP and FC as adjunctive targets only in symptom assessment (Am J Gastroenterol. 2015:110[9]:1324-58). “I argue that we’ve had a growing body of literature that we should be using these tests regularly as well,” he said.

STRIDE calls for endoscopic assessment 6-9 months after therapy change and consideration of cross-sectional imaging if the small bowel is involved, with assessment every 3 months until symptoms improve and then every 6-12 months thereafter.

However, Dr. Scott noted potential drawbacks to these follow-up steps. “They currently focus on clinical symptoms in the short-term follow-up, and we know from looking at our disease activity indices, such as the CDAI [Crohn’s disease activity index] or Harvey-Bradshaw index, that they don’t always perfectly correlate with actual mucosal healing or resolution of inflammation in Crohn’s or [ulcerative colitis],” he said, pointing to a 2014 study that found CDAI had an area under the curve of 0.57, “which is pretty poor correlation” (Gut. 2014;63[1]:88-95).

Whereas a study of 2,499 patients that showed CRP had an area under the curve of 0.72 and FC of 0.89 (Am J Gastroentrol. 2015;110[6]:802-19). “CRP is a really attractive potential noninvasive marker of inflammation,” he said. “It’s relatively inexpensive, it’s widely available, and the cutoff ranges are well defined.”

He noted four potential drawbacks of CRP: the false-positive rate is relatively high; as a marker of systemic inflammation it’s not specific to the GI tract; false negatives have been well described, with up to 15% of patients not registering a response; and levels can depend on disease location. “Those with isolated ileal disease, for instance, may have relatively low CRP elevations when their disease is active,” Dr. Scott said.

Stool-based FC “represents a potentially more attractive option,” Dr. Scott said. Along with an area under the curve superior to CRP, FC has a documented sensitivity and specificity of 88% and 73%, respectively, versus 49% and 92% for CRP. Drawbacks of fecal calprotectin are that it’s specific to the GI tract but not inflammatory bowel disease, it costs more, and insurance coverage is not as universal as it is for CRP, although more carriers are covering the test, he said.

“However, we do know that through clinical trial data that the use of CRP and FC, in addition to clinical symptom monitoring, does appear to improve care,” Dr. Scott said, noting that the CALM trial of tight disease control through the frequent use of biochemical markers of inflammation with anti–tumor necrosis therapy bore this out (Lancet. 2018;390[10114]:2779-89). “This trial was able to demonstrate at 48 weeks that mucosal healing rates were improved in those receiving CRP and FC monitoring, compared to symptom monitoring alone, with higher rates of steroid-free remission at each visit, which persisted over the follow-up time.”

Dr. Scott also cited a post hoc analysis of CALM trial data that validated CRP and FC monitoring to improve steroid-free remission rates and other outcomes (Gut. 2019 Jul 8. doi: 10.1136/gutjnl-2019-318256). That trial reported steroid-free remission rates of 39.3% with clinical management and 59.8% with tight control, a 34% overall difference (P less than .001). “And it was cost effective to incorporate this monitoring at a cost of about $24,300 per quality-adjusted life-year, well below the typically used $50,000 willingness-to-pay threshold when considering new tests,” Dr. Scott said.

Dr. Scott acknowledged that FC testing may pose some inconvenience to patients when collecting their stool samples, but accuracy has improved. “Laboratories are becoming more reliable in terms of what the values are, and the cutoffs are becoming more defined as far as what’s positive and what’s negative, so it’s good way to monitor whether or not patients are at increased risk of a future flare,” he said.

Dr. Scott reported financial relationships with Takeda, Janssen, Merck and PRIME.

SOURCE: Scott FI et al. Crohn’s & Colitis Congress 2020, Session Sp125.