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Inebilizumab benefits patients with NMOSD
WEST PALM BEACH, FLA. – Compared with placebo, inebilizumab reduces the risk of attacks, the risk of disability worsening, the number of hospitalizations, and the number of new MRI lesions in patients with neuromyelitis optica spectrum disorder (NMOSD), according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The drug’s efficacy was sustained for one year in the study, and the treatment had an acceptable safety profile.
“Multiple lines of evidence suggest that NMO is predominantly a B-cell–mediated disorder,” said Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences. Inebilizumab depletes B cells and reduces inflammatory disease activity in NMO potentially by altering immune networks that are dependent on B cells for cytokine production or antigen presentation.” Inebilizumab is an anti-CD19 monoclonal antibody.
Dr. Cree and colleagues conducted a randomized, controlled trial called N-MOmentum to characterize the long-term efficacy and safety of inebilizumab in patients with NMOSD. The investigators randomized patients with NMOSD to inebilizumab or placebo monotherapy in a 3:1 ratio for 6.5 months. The study’s primary outcome was the time to the first adjudicated attack. Patients who had an adjudicated attack or completed the trial could receive inebilizumab in an ongoing open-label extension.
The study was conducted at 99 sites in 25 countries. In all, 230 patients were randomized and dosed (174 received inebilizumab, and 56 received placebo). About 91% of the population was aquaporin-4-IgG–positive (AQP4-IgG+), and 91% was female. The population’s mean age at baseline was 43 years. The population’s median baseline Expanded Disability Status Scale score was approximately 3.5, and the range was from 0 to 8.0. Approximately 50% of participants were white, 20% were Asian, and 9% were of African descent. “The demographic profile is similar to that of many published studies,” said Dr. Cree.
Because of clear evidence of efficacy, the independent data monitoring committee recommended that the study be stopped early. In the randomized, controlled trial, inebilizumab reduced the risk of attack by 77.3% among AQP4-IgG+ patients and by 72.8% in the total population. The number needed to treat for 6.5 months to prevent one attack was 3.2 for the AQP4-IgG+ group and 3.7 for the total population.
Furthermore, inebilizumab significantly reduced the risk of worsening disability, the number of new MRI lesions, and NMOSD-related hospitalizations. After 1 year on inebilizumab, 85% of patients were free of an NMOSD attack. In safety analyses that combined data from the randomized, controlled trial and interim data from the open-label extension, the mean duration of inebilizumab treatment was 1.5 years.
“The rapid effect of inebilizumab on attack prevention is not mediated by decreasing AQP4-IgG, although it is possible that long-term inebilizumab treatment might eventually reduce AQP4-IgG production,” said Dr. Cree.
The most common adverse events (AEs) were urinary tract infection (UTI, 19.6%), nasopharyngitis (12.9%), and infusion-related reactions (IRRs, 11.6%). IRRs were most common with the first infusion. The proportion of inebilizumab-treated patients with IgG levels below the lower limit of normal was 7.5% at 1 year and 13.4% at 2 years. Serious AEs occurred in 12% of patients, and UTI was the most common (2.2%). Two patients died in the open-label extension; one death resulted from NMOSD, and one from new presumed inflammatory brain lesions of undetermined etiology.
“The open-label results show a striking durability of treatment effect,” said Dr. Cree. “Most of the attacks that occurred during the open-label extension occurred early on, suggesting that the risk of attack decreases with duration of B-cell depletion. The open-label study also is important for assessing the longer-term AE profile of inebilizumab treatment. One potentially important observation from the open-label extension is that the extent of B-cell depletion correlates with reduced attack risk. Approximately 95% of participants with deep B-cell depletion were free of attacks. Participants who either incompletely depleted B cells or who began to reconstitute B cells more rapidly were at increased risk of attack. Therefore, by monitoring B-cell counts in inebilizumab-treated patients, it may be possible to further reduce the risk of attack in patients who partially deplete, or replete B cells early, with an extra inebilizumab treatment.”
Viela Bio, which is developing inebilizumab, and MedImmune sponsored the study. Dr. Cree has received compensation for consulting services that he provided to Alexion, Atara, Biogen, EMD Serono, Novartis, and TG Therapeutics.
SOURCE: Cree BA et al. ACTRIMS 2020. Abstract P207.
WEST PALM BEACH, FLA. – Compared with placebo, inebilizumab reduces the risk of attacks, the risk of disability worsening, the number of hospitalizations, and the number of new MRI lesions in patients with neuromyelitis optica spectrum disorder (NMOSD), according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The drug’s efficacy was sustained for one year in the study, and the treatment had an acceptable safety profile.
“Multiple lines of evidence suggest that NMO is predominantly a B-cell–mediated disorder,” said Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences. Inebilizumab depletes B cells and reduces inflammatory disease activity in NMO potentially by altering immune networks that are dependent on B cells for cytokine production or antigen presentation.” Inebilizumab is an anti-CD19 monoclonal antibody.
Dr. Cree and colleagues conducted a randomized, controlled trial called N-MOmentum to characterize the long-term efficacy and safety of inebilizumab in patients with NMOSD. The investigators randomized patients with NMOSD to inebilizumab or placebo monotherapy in a 3:1 ratio for 6.5 months. The study’s primary outcome was the time to the first adjudicated attack. Patients who had an adjudicated attack or completed the trial could receive inebilizumab in an ongoing open-label extension.
The study was conducted at 99 sites in 25 countries. In all, 230 patients were randomized and dosed (174 received inebilizumab, and 56 received placebo). About 91% of the population was aquaporin-4-IgG–positive (AQP4-IgG+), and 91% was female. The population’s mean age at baseline was 43 years. The population’s median baseline Expanded Disability Status Scale score was approximately 3.5, and the range was from 0 to 8.0. Approximately 50% of participants were white, 20% were Asian, and 9% were of African descent. “The demographic profile is similar to that of many published studies,” said Dr. Cree.
Because of clear evidence of efficacy, the independent data monitoring committee recommended that the study be stopped early. In the randomized, controlled trial, inebilizumab reduced the risk of attack by 77.3% among AQP4-IgG+ patients and by 72.8% in the total population. The number needed to treat for 6.5 months to prevent one attack was 3.2 for the AQP4-IgG+ group and 3.7 for the total population.
Furthermore, inebilizumab significantly reduced the risk of worsening disability, the number of new MRI lesions, and NMOSD-related hospitalizations. After 1 year on inebilizumab, 85% of patients were free of an NMOSD attack. In safety analyses that combined data from the randomized, controlled trial and interim data from the open-label extension, the mean duration of inebilizumab treatment was 1.5 years.
“The rapid effect of inebilizumab on attack prevention is not mediated by decreasing AQP4-IgG, although it is possible that long-term inebilizumab treatment might eventually reduce AQP4-IgG production,” said Dr. Cree.
The most common adverse events (AEs) were urinary tract infection (UTI, 19.6%), nasopharyngitis (12.9%), and infusion-related reactions (IRRs, 11.6%). IRRs were most common with the first infusion. The proportion of inebilizumab-treated patients with IgG levels below the lower limit of normal was 7.5% at 1 year and 13.4% at 2 years. Serious AEs occurred in 12% of patients, and UTI was the most common (2.2%). Two patients died in the open-label extension; one death resulted from NMOSD, and one from new presumed inflammatory brain lesions of undetermined etiology.
“The open-label results show a striking durability of treatment effect,” said Dr. Cree. “Most of the attacks that occurred during the open-label extension occurred early on, suggesting that the risk of attack decreases with duration of B-cell depletion. The open-label study also is important for assessing the longer-term AE profile of inebilizumab treatment. One potentially important observation from the open-label extension is that the extent of B-cell depletion correlates with reduced attack risk. Approximately 95% of participants with deep B-cell depletion were free of attacks. Participants who either incompletely depleted B cells or who began to reconstitute B cells more rapidly were at increased risk of attack. Therefore, by monitoring B-cell counts in inebilizumab-treated patients, it may be possible to further reduce the risk of attack in patients who partially deplete, or replete B cells early, with an extra inebilizumab treatment.”
Viela Bio, which is developing inebilizumab, and MedImmune sponsored the study. Dr. Cree has received compensation for consulting services that he provided to Alexion, Atara, Biogen, EMD Serono, Novartis, and TG Therapeutics.
SOURCE: Cree BA et al. ACTRIMS 2020. Abstract P207.
WEST PALM BEACH, FLA. – Compared with placebo, inebilizumab reduces the risk of attacks, the risk of disability worsening, the number of hospitalizations, and the number of new MRI lesions in patients with neuromyelitis optica spectrum disorder (NMOSD), according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The drug’s efficacy was sustained for one year in the study, and the treatment had an acceptable safety profile.
“Multiple lines of evidence suggest that NMO is predominantly a B-cell–mediated disorder,” said Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences. Inebilizumab depletes B cells and reduces inflammatory disease activity in NMO potentially by altering immune networks that are dependent on B cells for cytokine production or antigen presentation.” Inebilizumab is an anti-CD19 monoclonal antibody.
Dr. Cree and colleagues conducted a randomized, controlled trial called N-MOmentum to characterize the long-term efficacy and safety of inebilizumab in patients with NMOSD. The investigators randomized patients with NMOSD to inebilizumab or placebo monotherapy in a 3:1 ratio for 6.5 months. The study’s primary outcome was the time to the first adjudicated attack. Patients who had an adjudicated attack or completed the trial could receive inebilizumab in an ongoing open-label extension.
The study was conducted at 99 sites in 25 countries. In all, 230 patients were randomized and dosed (174 received inebilizumab, and 56 received placebo). About 91% of the population was aquaporin-4-IgG–positive (AQP4-IgG+), and 91% was female. The population’s mean age at baseline was 43 years. The population’s median baseline Expanded Disability Status Scale score was approximately 3.5, and the range was from 0 to 8.0. Approximately 50% of participants were white, 20% were Asian, and 9% were of African descent. “The demographic profile is similar to that of many published studies,” said Dr. Cree.
Because of clear evidence of efficacy, the independent data monitoring committee recommended that the study be stopped early. In the randomized, controlled trial, inebilizumab reduced the risk of attack by 77.3% among AQP4-IgG+ patients and by 72.8% in the total population. The number needed to treat for 6.5 months to prevent one attack was 3.2 for the AQP4-IgG+ group and 3.7 for the total population.
Furthermore, inebilizumab significantly reduced the risk of worsening disability, the number of new MRI lesions, and NMOSD-related hospitalizations. After 1 year on inebilizumab, 85% of patients were free of an NMOSD attack. In safety analyses that combined data from the randomized, controlled trial and interim data from the open-label extension, the mean duration of inebilizumab treatment was 1.5 years.
“The rapid effect of inebilizumab on attack prevention is not mediated by decreasing AQP4-IgG, although it is possible that long-term inebilizumab treatment might eventually reduce AQP4-IgG production,” said Dr. Cree.
The most common adverse events (AEs) were urinary tract infection (UTI, 19.6%), nasopharyngitis (12.9%), and infusion-related reactions (IRRs, 11.6%). IRRs were most common with the first infusion. The proportion of inebilizumab-treated patients with IgG levels below the lower limit of normal was 7.5% at 1 year and 13.4% at 2 years. Serious AEs occurred in 12% of patients, and UTI was the most common (2.2%). Two patients died in the open-label extension; one death resulted from NMOSD, and one from new presumed inflammatory brain lesions of undetermined etiology.
“The open-label results show a striking durability of treatment effect,” said Dr. Cree. “Most of the attacks that occurred during the open-label extension occurred early on, suggesting that the risk of attack decreases with duration of B-cell depletion. The open-label study also is important for assessing the longer-term AE profile of inebilizumab treatment. One potentially important observation from the open-label extension is that the extent of B-cell depletion correlates with reduced attack risk. Approximately 95% of participants with deep B-cell depletion were free of attacks. Participants who either incompletely depleted B cells or who began to reconstitute B cells more rapidly were at increased risk of attack. Therefore, by monitoring B-cell counts in inebilizumab-treated patients, it may be possible to further reduce the risk of attack in patients who partially deplete, or replete B cells early, with an extra inebilizumab treatment.”
Viela Bio, which is developing inebilizumab, and MedImmune sponsored the study. Dr. Cree has received compensation for consulting services that he provided to Alexion, Atara, Biogen, EMD Serono, Novartis, and TG Therapeutics.
SOURCE: Cree BA et al. ACTRIMS 2020. Abstract P207.
REPORTING FROM ACTRIMS FORUM 2020
Eculizumab reduces relapse-related hospitalizations in patients with NMOSD
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that eculizumab may have a favorable effect on health-resource utilization.
Many patients with NMOSD, a rare autoimmune inflammatory disease, have relapses that result in hospitalization. Eculizumab (Soliris)is a humanized monoclonal antibody that inhibits the terminal complement protein C5. In the randomized, double-blind, placebo-controlled PREVENT study, Dean M. Wingerchuk, MD, chair of neurology at Mayo Clinic in Phoenix, , and colleagues found that eculizumab was associated with a 94% reduction in the risk of relapse, compared with placebo, in AQP4-IgG-positive patients with NMOSD.
In a new analysis of the PREVENT data, the investigators sought to evaluate rates of relapse-related hospitalization and associated treatment among study participants. The researchers chose time to first adjudicated relapse as their primary endpoint.
In the PREVENT study, Dr. Wingerchuk and colleagues randomized patients with AQP4-IgG-positive NMOSD to eculizumab (1,200 mg/2 weeks) or placebo. The annualized relapse-related hospitalization and treatment rates were calculated as the number of relapses requiring hospitalization or treatment divided by the total number of patient-years during the study.
Approximately 91% of participants were female. Mean age at initial clinical presentation was about 37 years. Participants’ median Expanded Disability Status Scale score at baseline was 4, and their mean annualized relapse rate in the 24 months before screening was 2. In all, 96 patients received eculizumab, and 47 received placebo. The median length of exposure to treatment was 89.4 weeks in the eculizumab group and 41.3 weeks among controls.
The rate of adverse events requiring hospitalization was 29% in the eculizumab group and 53% in the placebo group. The most common events requiring hospitalization were physician-determined relapses. Infections were the next most common events requiring hospitalization.
The overall annualized hospitalization rate was 0.26 in the eculizumab group and 0.78 in the placebo group. The difference between groups was statistically significant. In addition, the annualized relapse-related hospitalization rate was lower in the eculizumab group than in the placebo group (0.04 vs. 0.31, respectively).
The annualized relapse-related use of intravenous methylprednisolone for the eculizumab and placebo groups were 0.07 and 0.42, respectively; for use of plasma exchange, 0.02 and 0.19; and for use of high-dose oral corticosteroids, 0.04 and 0.11. The differences between groups in use of intravenous methylprednisolone and plasma exchange were statistically significant.
Alexion Pharmaceuticals, which markets eculizumab, sponsored the study. Dr. Wingerchuk received grants from Alexion during the study. He also received personal fees from Biogen, BrainStorm Therapeutics, Celgene, MedImmune, Novartis, and ONO Pharmaceutical.
SOURCE: Kim H et al. ACTRIMS 2020. Abstract P197.
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that eculizumab may have a favorable effect on health-resource utilization.
Many patients with NMOSD, a rare autoimmune inflammatory disease, have relapses that result in hospitalization. Eculizumab (Soliris)is a humanized monoclonal antibody that inhibits the terminal complement protein C5. In the randomized, double-blind, placebo-controlled PREVENT study, Dean M. Wingerchuk, MD, chair of neurology at Mayo Clinic in Phoenix, , and colleagues found that eculizumab was associated with a 94% reduction in the risk of relapse, compared with placebo, in AQP4-IgG-positive patients with NMOSD.
In a new analysis of the PREVENT data, the investigators sought to evaluate rates of relapse-related hospitalization and associated treatment among study participants. The researchers chose time to first adjudicated relapse as their primary endpoint.
In the PREVENT study, Dr. Wingerchuk and colleagues randomized patients with AQP4-IgG-positive NMOSD to eculizumab (1,200 mg/2 weeks) or placebo. The annualized relapse-related hospitalization and treatment rates were calculated as the number of relapses requiring hospitalization or treatment divided by the total number of patient-years during the study.
Approximately 91% of participants were female. Mean age at initial clinical presentation was about 37 years. Participants’ median Expanded Disability Status Scale score at baseline was 4, and their mean annualized relapse rate in the 24 months before screening was 2. In all, 96 patients received eculizumab, and 47 received placebo. The median length of exposure to treatment was 89.4 weeks in the eculizumab group and 41.3 weeks among controls.
The rate of adverse events requiring hospitalization was 29% in the eculizumab group and 53% in the placebo group. The most common events requiring hospitalization were physician-determined relapses. Infections were the next most common events requiring hospitalization.
The overall annualized hospitalization rate was 0.26 in the eculizumab group and 0.78 in the placebo group. The difference between groups was statistically significant. In addition, the annualized relapse-related hospitalization rate was lower in the eculizumab group than in the placebo group (0.04 vs. 0.31, respectively).
The annualized relapse-related use of intravenous methylprednisolone for the eculizumab and placebo groups were 0.07 and 0.42, respectively; for use of plasma exchange, 0.02 and 0.19; and for use of high-dose oral corticosteroids, 0.04 and 0.11. The differences between groups in use of intravenous methylprednisolone and plasma exchange were statistically significant.
Alexion Pharmaceuticals, which markets eculizumab, sponsored the study. Dr. Wingerchuk received grants from Alexion during the study. He also received personal fees from Biogen, BrainStorm Therapeutics, Celgene, MedImmune, Novartis, and ONO Pharmaceutical.
SOURCE: Kim H et al. ACTRIMS 2020. Abstract P197.
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that eculizumab may have a favorable effect on health-resource utilization.
Many patients with NMOSD, a rare autoimmune inflammatory disease, have relapses that result in hospitalization. Eculizumab (Soliris)is a humanized monoclonal antibody that inhibits the terminal complement protein C5. In the randomized, double-blind, placebo-controlled PREVENT study, Dean M. Wingerchuk, MD, chair of neurology at Mayo Clinic in Phoenix, , and colleagues found that eculizumab was associated with a 94% reduction in the risk of relapse, compared with placebo, in AQP4-IgG-positive patients with NMOSD.
In a new analysis of the PREVENT data, the investigators sought to evaluate rates of relapse-related hospitalization and associated treatment among study participants. The researchers chose time to first adjudicated relapse as their primary endpoint.
In the PREVENT study, Dr. Wingerchuk and colleagues randomized patients with AQP4-IgG-positive NMOSD to eculizumab (1,200 mg/2 weeks) or placebo. The annualized relapse-related hospitalization and treatment rates were calculated as the number of relapses requiring hospitalization or treatment divided by the total number of patient-years during the study.
Approximately 91% of participants were female. Mean age at initial clinical presentation was about 37 years. Participants’ median Expanded Disability Status Scale score at baseline was 4, and their mean annualized relapse rate in the 24 months before screening was 2. In all, 96 patients received eculizumab, and 47 received placebo. The median length of exposure to treatment was 89.4 weeks in the eculizumab group and 41.3 weeks among controls.
The rate of adverse events requiring hospitalization was 29% in the eculizumab group and 53% in the placebo group. The most common events requiring hospitalization were physician-determined relapses. Infections were the next most common events requiring hospitalization.
The overall annualized hospitalization rate was 0.26 in the eculizumab group and 0.78 in the placebo group. The difference between groups was statistically significant. In addition, the annualized relapse-related hospitalization rate was lower in the eculizumab group than in the placebo group (0.04 vs. 0.31, respectively).
The annualized relapse-related use of intravenous methylprednisolone for the eculizumab and placebo groups were 0.07 and 0.42, respectively; for use of plasma exchange, 0.02 and 0.19; and for use of high-dose oral corticosteroids, 0.04 and 0.11. The differences between groups in use of intravenous methylprednisolone and plasma exchange were statistically significant.
Alexion Pharmaceuticals, which markets eculizumab, sponsored the study. Dr. Wingerchuk received grants from Alexion during the study. He also received personal fees from Biogen, BrainStorm Therapeutics, Celgene, MedImmune, Novartis, and ONO Pharmaceutical.
SOURCE: Kim H et al. ACTRIMS 2020. Abstract P197.
REPORTING FROM ACTRIMS FORUM 2020
Isotretinoin data provide postmeal absorption guidance
LAHAINA, HAWAII – Recent , Hilary E. Baldwin, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
It is recommended that isotretinoin, which is fat-soluble, be taken with food, preferably high-fat foods. So it has been unclear what the effect would be when taken with lower-fat food, such as low-fat cereal and raspberries, for example, Dr. Baldwin, medical director of the Acne Treatment and Research Center in New York, pointed out.
“We’ve been trying for years to figure out how we’re going to get around this,” and there have not been any relevant data available until recently, other than in the setting of taking isotretinoin on an empty stomach or with a high-fat meal, she commented.
She referred to a open-label, single-dose, randomized crossover study that compared the bioavailability of the lidose formulation of isotretinoin (Absorica) and brand name Accutane, at a dose of 40 mg either on top of a fatty meal (the Food and Drug Administration-stipulated high-fat, high-calorie diet) or after a 10-hour fast; 60 patients did all four arms, with a 21-day washout period between them (J Am Acad Dermatol. 2013 Nov;69[5]:762-7).
In the fed state, both isotretinoin formulations were absorbed to the same extent, “but in the fasting state, there was a considerable difference,” Dr. Baldwin said. Absorption of both dropped in the fasting state, but the drop was more extreme with Accutane, “about a 50% difference between the two, in terms of how much drug was getting into the system,” she noted.
That is important because weight-based dosing is considered with isotretinoin, so at the end of treatment, a patient who has been taking it on an empty stomach may be getting a 60% lower dose than prescribed, “which could lead to a lessening of the effectiveness of the drug and also an increase in relapse over time.”
But how would a low-fat meal, like low-fat cereal and raspberries, affect the absorption, and ultimate efficacy?
This question was addressed in an open-label, single-arm study of 163 patients with acne, who were taking the lidose isotretinoin formulation without food, at the standard dose, for no longer than 20 weeks. Whether they relapsed was evaluated in a 2-year observational phase of the study, Dr. Baldwin said.
At the end of the trial, the drug was considered effective, with improvements in IGA (the 5-point Investigator’s Global Assessment scale). But the change from baseline was maintained at the 2-year posttreatment period, so the benefits of treatment lasted, which indicates that patients can take it “on top of absolutely no food whatsoever ... so if they eat anything, we are headed in the right direction,” including a low-fat meal. During the 2-year period, most patients did not need to be retreated. Of those people who needed treatment, only 4.2% needed treatment with isotretinoin, which is better than the historical relapse rates with isotretinoin, she noted.
Dr. Baldwin’s disclosures included being on the speakers’ bureau, serving as an advisor, and/or an investigator for companies that include Almirall, BioPharmx, Foamix, Galderma, Ortho Dermatologics, Sun Pharmaceuticals, Johnson & Johnson, and La Roche–Posay.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – Recent , Hilary E. Baldwin, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
It is recommended that isotretinoin, which is fat-soluble, be taken with food, preferably high-fat foods. So it has been unclear what the effect would be when taken with lower-fat food, such as low-fat cereal and raspberries, for example, Dr. Baldwin, medical director of the Acne Treatment and Research Center in New York, pointed out.
“We’ve been trying for years to figure out how we’re going to get around this,” and there have not been any relevant data available until recently, other than in the setting of taking isotretinoin on an empty stomach or with a high-fat meal, she commented.
She referred to a open-label, single-dose, randomized crossover study that compared the bioavailability of the lidose formulation of isotretinoin (Absorica) and brand name Accutane, at a dose of 40 mg either on top of a fatty meal (the Food and Drug Administration-stipulated high-fat, high-calorie diet) or after a 10-hour fast; 60 patients did all four arms, with a 21-day washout period between them (J Am Acad Dermatol. 2013 Nov;69[5]:762-7).
In the fed state, both isotretinoin formulations were absorbed to the same extent, “but in the fasting state, there was a considerable difference,” Dr. Baldwin said. Absorption of both dropped in the fasting state, but the drop was more extreme with Accutane, “about a 50% difference between the two, in terms of how much drug was getting into the system,” she noted.
That is important because weight-based dosing is considered with isotretinoin, so at the end of treatment, a patient who has been taking it on an empty stomach may be getting a 60% lower dose than prescribed, “which could lead to a lessening of the effectiveness of the drug and also an increase in relapse over time.”
But how would a low-fat meal, like low-fat cereal and raspberries, affect the absorption, and ultimate efficacy?
This question was addressed in an open-label, single-arm study of 163 patients with acne, who were taking the lidose isotretinoin formulation without food, at the standard dose, for no longer than 20 weeks. Whether they relapsed was evaluated in a 2-year observational phase of the study, Dr. Baldwin said.
At the end of the trial, the drug was considered effective, with improvements in IGA (the 5-point Investigator’s Global Assessment scale). But the change from baseline was maintained at the 2-year posttreatment period, so the benefits of treatment lasted, which indicates that patients can take it “on top of absolutely no food whatsoever ... so if they eat anything, we are headed in the right direction,” including a low-fat meal. During the 2-year period, most patients did not need to be retreated. Of those people who needed treatment, only 4.2% needed treatment with isotretinoin, which is better than the historical relapse rates with isotretinoin, she noted.
Dr. Baldwin’s disclosures included being on the speakers’ bureau, serving as an advisor, and/or an investigator for companies that include Almirall, BioPharmx, Foamix, Galderma, Ortho Dermatologics, Sun Pharmaceuticals, Johnson & Johnson, and La Roche–Posay.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – Recent , Hilary E. Baldwin, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
It is recommended that isotretinoin, which is fat-soluble, be taken with food, preferably high-fat foods. So it has been unclear what the effect would be when taken with lower-fat food, such as low-fat cereal and raspberries, for example, Dr. Baldwin, medical director of the Acne Treatment and Research Center in New York, pointed out.
“We’ve been trying for years to figure out how we’re going to get around this,” and there have not been any relevant data available until recently, other than in the setting of taking isotretinoin on an empty stomach or with a high-fat meal, she commented.
She referred to a open-label, single-dose, randomized crossover study that compared the bioavailability of the lidose formulation of isotretinoin (Absorica) and brand name Accutane, at a dose of 40 mg either on top of a fatty meal (the Food and Drug Administration-stipulated high-fat, high-calorie diet) or after a 10-hour fast; 60 patients did all four arms, with a 21-day washout period between them (J Am Acad Dermatol. 2013 Nov;69[5]:762-7).
In the fed state, both isotretinoin formulations were absorbed to the same extent, “but in the fasting state, there was a considerable difference,” Dr. Baldwin said. Absorption of both dropped in the fasting state, but the drop was more extreme with Accutane, “about a 50% difference between the two, in terms of how much drug was getting into the system,” she noted.
That is important because weight-based dosing is considered with isotretinoin, so at the end of treatment, a patient who has been taking it on an empty stomach may be getting a 60% lower dose than prescribed, “which could lead to a lessening of the effectiveness of the drug and also an increase in relapse over time.”
But how would a low-fat meal, like low-fat cereal and raspberries, affect the absorption, and ultimate efficacy?
This question was addressed in an open-label, single-arm study of 163 patients with acne, who were taking the lidose isotretinoin formulation without food, at the standard dose, for no longer than 20 weeks. Whether they relapsed was evaluated in a 2-year observational phase of the study, Dr. Baldwin said.
At the end of the trial, the drug was considered effective, with improvements in IGA (the 5-point Investigator’s Global Assessment scale). But the change from baseline was maintained at the 2-year posttreatment period, so the benefits of treatment lasted, which indicates that patients can take it “on top of absolutely no food whatsoever ... so if they eat anything, we are headed in the right direction,” including a low-fat meal. During the 2-year period, most patients did not need to be retreated. Of those people who needed treatment, only 4.2% needed treatment with isotretinoin, which is better than the historical relapse rates with isotretinoin, she noted.
Dr. Baldwin’s disclosures included being on the speakers’ bureau, serving as an advisor, and/or an investigator for companies that include Almirall, BioPharmx, Foamix, Galderma, Ortho Dermatologics, Sun Pharmaceuticals, Johnson & Johnson, and La Roche–Posay.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
CDC revises COVID-19 test kits, broadens ‘person under investigation’ definition
In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at .
The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.
Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”
The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”
The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.
Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.
Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.
These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.
As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.
While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.
She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.
In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at .
The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.
Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”
The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”
The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.
Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.
Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.
These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.
As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.
While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.
She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.
In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at .
The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.
Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”
The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”
The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.
Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.
Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.
These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.
As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.
While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.
She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.
REPORTING FROM A CDC BRIEFING
Serum NfL levels may predict 10-year deep gray matter volumes
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Researchers have begun to study longitudinal changes in serum NfL levels as a way to monitor axonal damage in patients with MS and see how they relate to other measures of neuronal loss, such as brain atrophy, and clinical outcomes over the long-term. “Deep gray matter volumes have been shown to correlate with neurological outcomes in MS patients. In particular, thalamic volume has been shown to correlate with measures of cognitive processing speed, such as the Symbol Digit Modalities Test,” said senior author Tanuja Chitnis, MD, professor of neurology at Harvard Medical School in Boston.
She and her colleagues sought to determine whether annual serum NfL measures could predict 10-year deep gray matter atrophy measured by volumetric MRI in patients with MS. They examined patients who were enrolled in the Comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study. Eligible participants were enrolled within 5 years of disease onset and had had annual blood samples drawn for as long as 10 years. In all, 122 patients met these criteria. The investigators measured serum NfL and compared it against deep gray matter volume in the thalamus, caudate, putamen, and globus pallidus from high-resolution 3-T MRI scans taken at year 10. Dr. Chitnis and colleagues assessed correlations between averaged annual NfL and 10-year MRI outcomes using univariate and multivariate linear regression models.
About 96% of participants were white, and about 2% were black. Approximately 73% of participants were female. Average age at the first symptom was 36 years, and average age at the first sample collection was 38 years.
The investigators found several negative associations between averaged NfL values and various MRI volumetric outcomes. Averaged annual serum NfL levels for the first 5 years were significantly and negatively associated with 10-year thalamic volumes in the unadjusted analysis. A 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000272 cm3 in thalamic volume. The association remained significant in an analysis adjusted for age, sex, and disease duration. In this analysis, a 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000259 cm3 in thalamic volume. Analyzing serum NfL levels beyond year 5 did not reveal a stronger association. Serum NfL levels during the first 5 years accounted for about 24% of the variance in 10-year thalamic volumes. Dr. Chitnis and colleagues found similar statistically significant associations between serum NfL levels and caudate, putamen, and globus pallidus volumes. “Therefore, early serum NfL levels contribute to the identification of patients who may require highly effective therapies,” she said.
“We will continue to validate these results. As well, we are exploring other early biomarkers that increase predictive power of long-term outcomes in MS, with the goal of identifying patients most appropriate for high-efficacy treatments.”
The study was supported by funds from the U.S. Department of Defense, Novartis, and the Swiss National Research Foundation. Dr. Chitnis has received personal compensation for consulting and advisory board membership from Biogen, Merck Serono, Novartis, and Sanofi.
SOURCE: Lokhande H et al. ACTRIMS Forum 2020, Abstract P018.
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Researchers have begun to study longitudinal changes in serum NfL levels as a way to monitor axonal damage in patients with MS and see how they relate to other measures of neuronal loss, such as brain atrophy, and clinical outcomes over the long-term. “Deep gray matter volumes have been shown to correlate with neurological outcomes in MS patients. In particular, thalamic volume has been shown to correlate with measures of cognitive processing speed, such as the Symbol Digit Modalities Test,” said senior author Tanuja Chitnis, MD, professor of neurology at Harvard Medical School in Boston.
She and her colleagues sought to determine whether annual serum NfL measures could predict 10-year deep gray matter atrophy measured by volumetric MRI in patients with MS. They examined patients who were enrolled in the Comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study. Eligible participants were enrolled within 5 years of disease onset and had had annual blood samples drawn for as long as 10 years. In all, 122 patients met these criteria. The investigators measured serum NfL and compared it against deep gray matter volume in the thalamus, caudate, putamen, and globus pallidus from high-resolution 3-T MRI scans taken at year 10. Dr. Chitnis and colleagues assessed correlations between averaged annual NfL and 10-year MRI outcomes using univariate and multivariate linear regression models.
About 96% of participants were white, and about 2% were black. Approximately 73% of participants were female. Average age at the first symptom was 36 years, and average age at the first sample collection was 38 years.
The investigators found several negative associations between averaged NfL values and various MRI volumetric outcomes. Averaged annual serum NfL levels for the first 5 years were significantly and negatively associated with 10-year thalamic volumes in the unadjusted analysis. A 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000272 cm3 in thalamic volume. The association remained significant in an analysis adjusted for age, sex, and disease duration. In this analysis, a 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000259 cm3 in thalamic volume. Analyzing serum NfL levels beyond year 5 did not reveal a stronger association. Serum NfL levels during the first 5 years accounted for about 24% of the variance in 10-year thalamic volumes. Dr. Chitnis and colleagues found similar statistically significant associations between serum NfL levels and caudate, putamen, and globus pallidus volumes. “Therefore, early serum NfL levels contribute to the identification of patients who may require highly effective therapies,” she said.
“We will continue to validate these results. As well, we are exploring other early biomarkers that increase predictive power of long-term outcomes in MS, with the goal of identifying patients most appropriate for high-efficacy treatments.”
The study was supported by funds from the U.S. Department of Defense, Novartis, and the Swiss National Research Foundation. Dr. Chitnis has received personal compensation for consulting and advisory board membership from Biogen, Merck Serono, Novartis, and Sanofi.
SOURCE: Lokhande H et al. ACTRIMS Forum 2020, Abstract P018.
WEST PALM BEACH, FLA. – , according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Researchers have begun to study longitudinal changes in serum NfL levels as a way to monitor axonal damage in patients with MS and see how they relate to other measures of neuronal loss, such as brain atrophy, and clinical outcomes over the long-term. “Deep gray matter volumes have been shown to correlate with neurological outcomes in MS patients. In particular, thalamic volume has been shown to correlate with measures of cognitive processing speed, such as the Symbol Digit Modalities Test,” said senior author Tanuja Chitnis, MD, professor of neurology at Harvard Medical School in Boston.
She and her colleagues sought to determine whether annual serum NfL measures could predict 10-year deep gray matter atrophy measured by volumetric MRI in patients with MS. They examined patients who were enrolled in the Comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study. Eligible participants were enrolled within 5 years of disease onset and had had annual blood samples drawn for as long as 10 years. In all, 122 patients met these criteria. The investigators measured serum NfL and compared it against deep gray matter volume in the thalamus, caudate, putamen, and globus pallidus from high-resolution 3-T MRI scans taken at year 10. Dr. Chitnis and colleagues assessed correlations between averaged annual NfL and 10-year MRI outcomes using univariate and multivariate linear regression models.
About 96% of participants were white, and about 2% were black. Approximately 73% of participants were female. Average age at the first symptom was 36 years, and average age at the first sample collection was 38 years.
The investigators found several negative associations between averaged NfL values and various MRI volumetric outcomes. Averaged annual serum NfL levels for the first 5 years were significantly and negatively associated with 10-year thalamic volumes in the unadjusted analysis. A 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000272 cm3 in thalamic volume. The association remained significant in an analysis adjusted for age, sex, and disease duration. In this analysis, a 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000259 cm3 in thalamic volume. Analyzing serum NfL levels beyond year 5 did not reveal a stronger association. Serum NfL levels during the first 5 years accounted for about 24% of the variance in 10-year thalamic volumes. Dr. Chitnis and colleagues found similar statistically significant associations between serum NfL levels and caudate, putamen, and globus pallidus volumes. “Therefore, early serum NfL levels contribute to the identification of patients who may require highly effective therapies,” she said.
“We will continue to validate these results. As well, we are exploring other early biomarkers that increase predictive power of long-term outcomes in MS, with the goal of identifying patients most appropriate for high-efficacy treatments.”
The study was supported by funds from the U.S. Department of Defense, Novartis, and the Swiss National Research Foundation. Dr. Chitnis has received personal compensation for consulting and advisory board membership from Biogen, Merck Serono, Novartis, and Sanofi.
SOURCE: Lokhande H et al. ACTRIMS Forum 2020, Abstract P018.
REPORTING FROM ACTRIMS FORUM 2020
DDSEP® 9 Quick Quiz Question 2
Q2. Correct answer: D
Rationale
This patient has tropical sprue based on her travel to an endemic country, negative celiac serologies, labs revealing a macrocytic anemia and low albumin and characteristic histology (villous blunting, increased intraepithelial lymphocytes). Treatment is with tetracycline and folate. Diagnosis of tropical sprue is ultimately confirmed by a response to treatment. A gluten-free diet is not appropriate, as the patient does not have celiac disease, confirmed by normal celiac serologies. Ceftriaxone IV followed by Bactrim PO is the correct treatment for Whipple's disease. A diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) is beneficial treatment in some patients with IBS with abdominal bloating or pain. Rifaximin is the correct treatment for small intestine bacterial overgrowth or IBS-D.
References
1. Brown IS, Bettington A, Bettington M, Rosty C. Tropical sprue: revisiting an underrecognized disease. Am J Surg Pathol. 2014;38:666.
2. Shah VH, Rotterdam H, Kotler DP, et al. All that scallops is not celiac disease. Gastrointest Endosc. 2000;51:717.
ginews@gastro.org
Q2. Correct answer: D
Rationale
This patient has tropical sprue based on her travel to an endemic country, negative celiac serologies, labs revealing a macrocytic anemia and low albumin and characteristic histology (villous blunting, increased intraepithelial lymphocytes). Treatment is with tetracycline and folate. Diagnosis of tropical sprue is ultimately confirmed by a response to treatment. A gluten-free diet is not appropriate, as the patient does not have celiac disease, confirmed by normal celiac serologies. Ceftriaxone IV followed by Bactrim PO is the correct treatment for Whipple's disease. A diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) is beneficial treatment in some patients with IBS with abdominal bloating or pain. Rifaximin is the correct treatment for small intestine bacterial overgrowth or IBS-D.
References
1. Brown IS, Bettington A, Bettington M, Rosty C. Tropical sprue: revisiting an underrecognized disease. Am J Surg Pathol. 2014;38:666.
2. Shah VH, Rotterdam H, Kotler DP, et al. All that scallops is not celiac disease. Gastrointest Endosc. 2000;51:717.
ginews@gastro.org
Q2. Correct answer: D
Rationale
This patient has tropical sprue based on her travel to an endemic country, negative celiac serologies, labs revealing a macrocytic anemia and low albumin and characteristic histology (villous blunting, increased intraepithelial lymphocytes). Treatment is with tetracycline and folate. Diagnosis of tropical sprue is ultimately confirmed by a response to treatment. A gluten-free diet is not appropriate, as the patient does not have celiac disease, confirmed by normal celiac serologies. Ceftriaxone IV followed by Bactrim PO is the correct treatment for Whipple's disease. A diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) is beneficial treatment in some patients with IBS with abdominal bloating or pain. Rifaximin is the correct treatment for small intestine bacterial overgrowth or IBS-D.
References
1. Brown IS, Bettington A, Bettington M, Rosty C. Tropical sprue: revisiting an underrecognized disease. Am J Surg Pathol. 2014;38:666.
2. Shah VH, Rotterdam H, Kotler DP, et al. All that scallops is not celiac disease. Gastrointest Endosc. 2000;51:717.
ginews@gastro.org
An 18-year-old woman presents for evaluation of chronic diarrhea, fatigue, and abdominal cramping. She was recently in Puerto Rico for 6 months visiting family and returned a few weeks ago. Her labs are significant for a hemoglobin of 11 g/L with an MCV of 109 fL. Her albumin is 3.6 g/dL. She had stool studies which ruled out infection, including parasites. TtG IgA and total IgA were within normal limits. EGD with multiple duodenal biopsies showed villous blunting with increased intraepithelial lymphocytes.
March 2020 - Question 1
Correct answer: C
Rationale
This patient has been exposed to HBV in the past and has cleared the virus. The HBVcore total Ab is indicative of prior exposure while the HBV surface Ab is detectable and gives immunity against reinfection under most routine clinical scenarios. Patients who have been exposed to HBV still have HBV ccc DNA within their hepatocytes that is dormant, but under extreme combined B and T cell immunosuppression, the patients are at risk for reverse seroconversion where they can lose HBV surface Ab and manifest HBV surface antigen and present as an acute HBV infection. Prophylaxis is required during therapy and for at least 12-18 months after therapy due to the long-lasting effects of anti-B cell monoclonal antibodies like rituximab. Reactivation of HCV in HCV Ab–positive, RNA-negative patients has not been reported.
Reference
1. Pauly MP, Tucker LY, Szpakowski JL, et al. Incidence of hepatitis B virus reactivation and hepatotoxicity in patients receiving long-term treatment with tumor necrosis factor antagonists. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j. cgh.2018.04.033.
ginews@gastro.org
Correct answer: C
Rationale
This patient has been exposed to HBV in the past and has cleared the virus. The HBVcore total Ab is indicative of prior exposure while the HBV surface Ab is detectable and gives immunity against reinfection under most routine clinical scenarios. Patients who have been exposed to HBV still have HBV ccc DNA within their hepatocytes that is dormant, but under extreme combined B and T cell immunosuppression, the patients are at risk for reverse seroconversion where they can lose HBV surface Ab and manifest HBV surface antigen and present as an acute HBV infection. Prophylaxis is required during therapy and for at least 12-18 months after therapy due to the long-lasting effects of anti-B cell monoclonal antibodies like rituximab. Reactivation of HCV in HCV Ab–positive, RNA-negative patients has not been reported.
Reference
1. Pauly MP, Tucker LY, Szpakowski JL, et al. Incidence of hepatitis B virus reactivation and hepatotoxicity in patients receiving long-term treatment with tumor necrosis factor antagonists. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j. cgh.2018.04.033.
ginews@gastro.org
Correct answer: C
Rationale
This patient has been exposed to HBV in the past and has cleared the virus. The HBVcore total Ab is indicative of prior exposure while the HBV surface Ab is detectable and gives immunity against reinfection under most routine clinical scenarios. Patients who have been exposed to HBV still have HBV ccc DNA within their hepatocytes that is dormant, but under extreme combined B and T cell immunosuppression, the patients are at risk for reverse seroconversion where they can lose HBV surface Ab and manifest HBV surface antigen and present as an acute HBV infection. Prophylaxis is required during therapy and for at least 12-18 months after therapy due to the long-lasting effects of anti-B cell monoclonal antibodies like rituximab. Reactivation of HCV in HCV Ab–positive, RNA-negative patients has not been reported.
Reference
1. Pauly MP, Tucker LY, Szpakowski JL, et al. Incidence of hepatitis B virus reactivation and hepatotoxicity in patients receiving long-term treatment with tumor necrosis factor antagonists. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j. cgh.2018.04.033.
ginews@gastro.org
Q1. A 45-year-old man has recently been diagnosed with leukemia. The chemotherapeutic regimen will include rituximab and high-dose steroids. He is a former IV drug user but has been sober for 20 years. His lab work is as follows: ALT 25 U/L, HAV total antibody positive, HBs antibody positive, HBs antigen negative, HBc total positive, HCV antibody positive, HCV RNA undetected.
What is your diagnosis? - March 2020
Squamous metaplasia
Weight regain can accompany re-emergence of obesity-related comorbidities and, thus, early intervention is important. Although diet, exercise, and behavior modifications are fundamental, they can have limited efficacy. Thus, endoscopic management is important, with specific evaluation for gastrogastric fistulae, pouch dilation, and GJA dilation, all of which can be successfully intervened upon endoscopically. For GJA dilation in particular, APC has been used with promising results.1
In the normal GI tract, the esophagus is lined with squamous epithelium, and the stomach is lined with columnar epithelium. One of the most well-known and well-documented scenarios in which the typical mucosal lining is replaced by abnormal mucosa is Barrett’s esophagus (BE). BE is defined by the replacement of the normal distal squamous epithelial lining with columnar epithelium with a minimum length of 1 cm (tongues or circumferential) containing specialized intestinal metaplasia on histopathologic examination. It is well-documented that treatment of BE with thermal ablation and acid suppression therapy results in re-epithelialization of the esophagus with neosquamous mucosa.2 In contrast with this, in our patients, after we burned the gastric columnar mucosa with APC to treat their dilated GJA, the gastric pouch mucosa has been replaced with squamous epithelium, which we have termed “reverse BE.” To our knowledge, there are no reports of this condition in the literature, nor do we know the precise cause. There is a series of patients without a history of bariatric surgery who developed squamous metaplasia in the proximal gastric cardia.3 The authors hypothesized that this condition may be due to chronic mucosal injury owing to hiatal hernia, reflux, caustic ingestion, chronic gastritis, or pyloric stenosis. We suggest two potential mechanisms for this condition in our patients: 1) extending the ablation to the Z-line on the medial aspect of the pouch may allow for the distal extension of squamous mucosa during the healing process; and 2) acid suppression therapy with proton pump inhibitors after the procedure, in combination with a postoperative decrease in acid production, allows for a shift in the cell proliferation and differentiation in the pouch. Notably, although there are well-defined guidelines for surveillance of BE, owing to the risk of progression to esophageal adenocarcinoma,2 it is unclear what clinical significance this reverse BE may have in the future. It is important to continue to monitor these patients and clarify the natural history of this finding.
References
1. Brunaldi VO, Jirapinyo P, de Moura DTH et al. Endoscopic treatment of weight regain following Roux-en-Y gastric bypass: a systematic review and meta-analysis. Obes Surg. 2018;28:266-76.
2. Weusten B, Bisschops R, Coron E et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2017;49:191-8.
3. Fass R, Sampliner RE. Extension of squamous epithelium into the proximal stomach: a newly recognized mucosal abnormality. Endoscopy. 2000;32:27-32.
Christopher C. Thompson is a consultant for Boston Scientific and Medtronic, a consultant for and has institutional grants from USGI Medical, Olympus, and Apollo Endosurgery.
ginews@gastro.org
Squamous metaplasia
Weight regain can accompany re-emergence of obesity-related comorbidities and, thus, early intervention is important. Although diet, exercise, and behavior modifications are fundamental, they can have limited efficacy. Thus, endoscopic management is important, with specific evaluation for gastrogastric fistulae, pouch dilation, and GJA dilation, all of which can be successfully intervened upon endoscopically. For GJA dilation in particular, APC has been used with promising results.1
In the normal GI tract, the esophagus is lined with squamous epithelium, and the stomach is lined with columnar epithelium. One of the most well-known and well-documented scenarios in which the typical mucosal lining is replaced by abnormal mucosa is Barrett’s esophagus (BE). BE is defined by the replacement of the normal distal squamous epithelial lining with columnar epithelium with a minimum length of 1 cm (tongues or circumferential) containing specialized intestinal metaplasia on histopathologic examination. It is well-documented that treatment of BE with thermal ablation and acid suppression therapy results in re-epithelialization of the esophagus with neosquamous mucosa.2 In contrast with this, in our patients, after we burned the gastric columnar mucosa with APC to treat their dilated GJA, the gastric pouch mucosa has been replaced with squamous epithelium, which we have termed “reverse BE.” To our knowledge, there are no reports of this condition in the literature, nor do we know the precise cause. There is a series of patients without a history of bariatric surgery who developed squamous metaplasia in the proximal gastric cardia.3 The authors hypothesized that this condition may be due to chronic mucosal injury owing to hiatal hernia, reflux, caustic ingestion, chronic gastritis, or pyloric stenosis. We suggest two potential mechanisms for this condition in our patients: 1) extending the ablation to the Z-line on the medial aspect of the pouch may allow for the distal extension of squamous mucosa during the healing process; and 2) acid suppression therapy with proton pump inhibitors after the procedure, in combination with a postoperative decrease in acid production, allows for a shift in the cell proliferation and differentiation in the pouch. Notably, although there are well-defined guidelines for surveillance of BE, owing to the risk of progression to esophageal adenocarcinoma,2 it is unclear what clinical significance this reverse BE may have in the future. It is important to continue to monitor these patients and clarify the natural history of this finding.
References
1. Brunaldi VO, Jirapinyo P, de Moura DTH et al. Endoscopic treatment of weight regain following Roux-en-Y gastric bypass: a systematic review and meta-analysis. Obes Surg. 2018;28:266-76.
2. Weusten B, Bisschops R, Coron E et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2017;49:191-8.
3. Fass R, Sampliner RE. Extension of squamous epithelium into the proximal stomach: a newly recognized mucosal abnormality. Endoscopy. 2000;32:27-32.
Christopher C. Thompson is a consultant for Boston Scientific and Medtronic, a consultant for and has institutional grants from USGI Medical, Olympus, and Apollo Endosurgery.
ginews@gastro.org
Squamous metaplasia
Weight regain can accompany re-emergence of obesity-related comorbidities and, thus, early intervention is important. Although diet, exercise, and behavior modifications are fundamental, they can have limited efficacy. Thus, endoscopic management is important, with specific evaluation for gastrogastric fistulae, pouch dilation, and GJA dilation, all of which can be successfully intervened upon endoscopically. For GJA dilation in particular, APC has been used with promising results.1
In the normal GI tract, the esophagus is lined with squamous epithelium, and the stomach is lined with columnar epithelium. One of the most well-known and well-documented scenarios in which the typical mucosal lining is replaced by abnormal mucosa is Barrett’s esophagus (BE). BE is defined by the replacement of the normal distal squamous epithelial lining with columnar epithelium with a minimum length of 1 cm (tongues or circumferential) containing specialized intestinal metaplasia on histopathologic examination. It is well-documented that treatment of BE with thermal ablation and acid suppression therapy results in re-epithelialization of the esophagus with neosquamous mucosa.2 In contrast with this, in our patients, after we burned the gastric columnar mucosa with APC to treat their dilated GJA, the gastric pouch mucosa has been replaced with squamous epithelium, which we have termed “reverse BE.” To our knowledge, there are no reports of this condition in the literature, nor do we know the precise cause. There is a series of patients without a history of bariatric surgery who developed squamous metaplasia in the proximal gastric cardia.3 The authors hypothesized that this condition may be due to chronic mucosal injury owing to hiatal hernia, reflux, caustic ingestion, chronic gastritis, or pyloric stenosis. We suggest two potential mechanisms for this condition in our patients: 1) extending the ablation to the Z-line on the medial aspect of the pouch may allow for the distal extension of squamous mucosa during the healing process; and 2) acid suppression therapy with proton pump inhibitors after the procedure, in combination with a postoperative decrease in acid production, allows for a shift in the cell proliferation and differentiation in the pouch. Notably, although there are well-defined guidelines for surveillance of BE, owing to the risk of progression to esophageal adenocarcinoma,2 it is unclear what clinical significance this reverse BE may have in the future. It is important to continue to monitor these patients and clarify the natural history of this finding.
References
1. Brunaldi VO, Jirapinyo P, de Moura DTH et al. Endoscopic treatment of weight regain following Roux-en-Y gastric bypass: a systematic review and meta-analysis. Obes Surg. 2018;28:266-76.
2. Weusten B, Bisschops R, Coron E et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2017;49:191-8.
3. Fass R, Sampliner RE. Extension of squamous epithelium into the proximal stomach: a newly recognized mucosal abnormality. Endoscopy. 2000;32:27-32.
Christopher C. Thompson is a consultant for Boston Scientific and Medtronic, a consultant for and has institutional grants from USGI Medical, Olympus, and Apollo Endosurgery.
ginews@gastro.org
We describe three unique presentations of patients with a prior history of Roux-en-Y gastric bypass who were referred for endoscopic treatment of weight regain. All of the patients had failed prior attempts at lifestyle modifications and pharmacologic weight loss treatment. On physical examination, their body mass indices ranged from 27 to 30 kg/m2, but examination and complete laboratory evaluation, including thyroid-stimulating hormone, were otherwise normal. During the first upper gastrointestinal esophagogastroduodenoscopies, the pouch and the gastrojejunal anastomosis (GJA) were characterized by healthy appearing mucosa. In all three cases, the pouch size measured between 3 and 5 cm and the GJA was dilated, with diameters of more than 20 mm (Figure A). Laser resurfacing of the stoma by argon plasma coagulation (APC) at 0.8 L/min and 70 watts was successfully performed in a 1-cm concentric ring fashion around the gastric side of the GJA (Figure B). Three months after the initial APC, the patients returned for reevaluation. The pouch mucosa again seemed to be normal, but there was persistent, albeit improved, dilation of the GJA. Repeat APC sessions were performed without any adverse events.
On their next follow-up esophagogastroduodenoscopies, all patients were noted to have an abnormal color of approximately 25% of their gastric pouch epithelium, which seemed to be more similar to the esophageal epithelium (Figure C). The GJAs remained dilated, measuring more than 14 mm, and their third APC sessions were performed (Figure D). The patients did well after the procedures, with significant weight loss. A 1-year follow-up endoscopy showed a 10-mm GJA, but the gastric pouch was now approximately 80%-100% covered with this abnormal epithelium (Figure E). A forceps biopsy was performed for histologic evaluation (Figure F).
What is the histopathologic diagnosis of this finding?
DoD and VA Release Updated List of Agent Orange Locations
The VA has released an updated list of locations outside of Vietnam where tactical herbicides have been used, tested, or stored by the US military. The list, which includes the “rainbow” herbicides (Agents Orange, Pink, Green, Purple, Blue, and White), comes from the DoD, after a “thorough review” of research, reports, and government publications in response to a November 2018 US Government Accountability Office (GAO) report.
The GAO made 6 recommendations, including that the DoD develop a process for updating the list, and that the DoD and the VA develop a process for coordinating the communication of the information. The DoD concurred with 4 recommendations.
The VA, responding to the GAO report, said it was “concerned that the report conflates the terms commercial herbicides with tactical herbicides, which are distinct from one another.” Certain testing and storage locations (eg, Kelly Air Force Base), it noted, are added to the list based on the presence of commercial herbicides or “mere components” of Agent Orange or other rainbow agents.
The distinction is important for veterans applying for disability benefits. The impetus for creating the list of testing and storage sites, the VA says, was to carry out the administration of providing disability benefits in accordance with the applicable Agent Orange statute and regulations. Exposure to tactical herbicides (herbicides intended for military operations in Vietnam) is required for the VA to grant benefits on a presumptive basis for Agent Orange conditions outside of Vietnam. Thus, the VA concludes in its response, unless the commercial herbicides were the “same composition, forms, and mixtures” as the estimated 20 million gallons of rainbow agents specifically produced for operations in Vietnam, the “discussion is misleading.”
The VA also did not concur with the recommendation that it take the lead on developing “clear and transparent criteria” for what constitutes a location to be included on the list.
The DoD and VA did agree with the recommendation that the DoD should be the lead agency for producing and updating the list, while the VA will be the lead agency in providing information to veterans. The list will be updated as verifiable information becomes available, said Defense Secretary Mark Esper.
The full list of locations is available at https://www.publichealth.va.gov/docs/agentorange/dod_herbicides_outside_vietnam.pdf.
The GAO report is available at https://www.gao.gov/assets/gao-19-24.pdf.
The VA has released an updated list of locations outside of Vietnam where tactical herbicides have been used, tested, or stored by the US military. The list, which includes the “rainbow” herbicides (Agents Orange, Pink, Green, Purple, Blue, and White), comes from the DoD, after a “thorough review” of research, reports, and government publications in response to a November 2018 US Government Accountability Office (GAO) report.
The GAO made 6 recommendations, including that the DoD develop a process for updating the list, and that the DoD and the VA develop a process for coordinating the communication of the information. The DoD concurred with 4 recommendations.
The VA, responding to the GAO report, said it was “concerned that the report conflates the terms commercial herbicides with tactical herbicides, which are distinct from one another.” Certain testing and storage locations (eg, Kelly Air Force Base), it noted, are added to the list based on the presence of commercial herbicides or “mere components” of Agent Orange or other rainbow agents.
The distinction is important for veterans applying for disability benefits. The impetus for creating the list of testing and storage sites, the VA says, was to carry out the administration of providing disability benefits in accordance with the applicable Agent Orange statute and regulations. Exposure to tactical herbicides (herbicides intended for military operations in Vietnam) is required for the VA to grant benefits on a presumptive basis for Agent Orange conditions outside of Vietnam. Thus, the VA concludes in its response, unless the commercial herbicides were the “same composition, forms, and mixtures” as the estimated 20 million gallons of rainbow agents specifically produced for operations in Vietnam, the “discussion is misleading.”
The VA also did not concur with the recommendation that it take the lead on developing “clear and transparent criteria” for what constitutes a location to be included on the list.
The DoD and VA did agree with the recommendation that the DoD should be the lead agency for producing and updating the list, while the VA will be the lead agency in providing information to veterans. The list will be updated as verifiable information becomes available, said Defense Secretary Mark Esper.
The full list of locations is available at https://www.publichealth.va.gov/docs/agentorange/dod_herbicides_outside_vietnam.pdf.
The GAO report is available at https://www.gao.gov/assets/gao-19-24.pdf.
The VA has released an updated list of locations outside of Vietnam where tactical herbicides have been used, tested, or stored by the US military. The list, which includes the “rainbow” herbicides (Agents Orange, Pink, Green, Purple, Blue, and White), comes from the DoD, after a “thorough review” of research, reports, and government publications in response to a November 2018 US Government Accountability Office (GAO) report.
The GAO made 6 recommendations, including that the DoD develop a process for updating the list, and that the DoD and the VA develop a process for coordinating the communication of the information. The DoD concurred with 4 recommendations.
The VA, responding to the GAO report, said it was “concerned that the report conflates the terms commercial herbicides with tactical herbicides, which are distinct from one another.” Certain testing and storage locations (eg, Kelly Air Force Base), it noted, are added to the list based on the presence of commercial herbicides or “mere components” of Agent Orange or other rainbow agents.
The distinction is important for veterans applying for disability benefits. The impetus for creating the list of testing and storage sites, the VA says, was to carry out the administration of providing disability benefits in accordance with the applicable Agent Orange statute and regulations. Exposure to tactical herbicides (herbicides intended for military operations in Vietnam) is required for the VA to grant benefits on a presumptive basis for Agent Orange conditions outside of Vietnam. Thus, the VA concludes in its response, unless the commercial herbicides were the “same composition, forms, and mixtures” as the estimated 20 million gallons of rainbow agents specifically produced for operations in Vietnam, the “discussion is misleading.”
The VA also did not concur with the recommendation that it take the lead on developing “clear and transparent criteria” for what constitutes a location to be included on the list.
The DoD and VA did agree with the recommendation that the DoD should be the lead agency for producing and updating the list, while the VA will be the lead agency in providing information to veterans. The list will be updated as verifiable information becomes available, said Defense Secretary Mark Esper.
The full list of locations is available at https://www.publichealth.va.gov/docs/agentorange/dod_herbicides_outside_vietnam.pdf.
The GAO report is available at https://www.gao.gov/assets/gao-19-24.pdf.
Team approach greatly reduces inappropriate PPI use
A multidisciplinary, patient-centered approach can dramatically reduce inappropriate use of proton pump inhibitors (PPI), based on the success of a quality improvement study conducted at an academic, primary care clinic in New York.
In 1 year, the program reduced inappropriate PPI use from 80% to 30%, reported lead author Naren Nallapeta, MD, an internal medicine resident at the State University of New York at Buffalo, and colleagues.
According to the investigators, inappropriate use of PPIs is a common and growing concern. Recent patent expirations have led to wider availability of generic and over-the-counter options; and the consequences of unnecessary usage can be serious.
“PPI intake has been found to have a significant association with community-acquired pneumonia, Clostridium difficile associated diarrhea, impaired B12 absorption, hypomagnesemia, hip fractures, acute and chronic kidney disease, and spontaneous bacterial peritonitis in patients with cirrhotic ascites,” the investigators wrote in the Journal of Clinical Gastroenterology.
In 2017, the American Gastroenterological Association released guidelines that include indications for PPIs. But these guidelines often go unheeded, the investigators noted. Multiple studies have documented rates of inappropriate PPI use ranging from 54.1% to 82%. Previous studies have yielded mixed results: Simple physician education alone was found insufficient to reduce inappropriate prescriptions in a primary care setting, whereas studies involving pharmacy personnel have had positive results in various treatment centers.
In a survey of their own clinic, the Erie County Medical Center, an internal medicine service located in a tertiary care safety net hospital at the University at Buffalo, the investigators found that 80% of PPI prescriptions were inappropriate. This prompted a goal to reduce inappropriate use to less than 60% within 1 year.
To achieve this goal, the investigators started a quality improvement project based on the Plan-Do-Study-Act Cycle (PDSA) Model of health care improvement. The quality improvement team included internal medicine attending physicians and physician residents, gastroenterologists, patients, nurses, administrative and information technology staff, and a social worker.
After identifying root causes, the team deployed a variety of strategies to cut down on inappropriate PPI use. First, a new prompt in the electronic medical record reminded physicians to discuss PPI use with patients. Physicians were also given additional training concerning appropriate indications for PPIs, as well as a pocket guide and brochures that could be used for patient education. These efforts were supplemented by an enhanced nursing workflow, as well as continuous reinforcement with positive feedback for health care workers involved.
One year later, results exceeded expectations. Based on data from 180 patients, inappropriate use decreased from 80% to 30%, with a mean discontinuation rate of approximately 50%, an average that was maintained for 6 months beyond the end of the study. The annual, direct cost savings of the program totaled $13,992.
When indicated, patients on long-term PPIs were referred to the gastroenterology service for esophagogastroduodenoscopy. About half of the referred patients (49.8%) completed this procedure, which exceeded the baseline completion rate of less than 30%.
According to principal author Smita Bakhai, MD, of the department of internal medicine at the University at Buffalo, and a physician with UBMB Internal Medicine, the strategies used in this study are broadly applicable.
“The multidisciplinary approach, including patient engagement, would work well in any setting, even with limited resources and without the use of pharmacy personnel,” Dr. Bakhai said in an interview. “We used a patient-centered approach and physicians used shared decision making with patients to taper and discontinue PPIs or switch them to an H2-blocking agent when [patients] did not need to be on chronic PPIs.”
Dr. Bakhai went on to highlight the importance of working with multiple stakeholders.
“This project is unique because it was a resident-led project,” she said. “As academicians, we should always engage the fellows and the residents in any quality improvement work that we do, because they are the doctors of the future.”
Beyond care providers and patients, Dr. Bakhai emphasized the need to involve administrative leadership who can guarantee long-term resources and cultivate the right culture.
“Without the resources, you can’t sustain the project,” Dr. Bakhai said. “You have to have allocated resources, and a culture of safety and quality in the environment that you are doing the project. It has to be a supportive environment. We had all of those things, and that’s why we succeeded.”
The study was funded by the National Institutes of Health. The investigators reported no conflicts of interest.
SOURCE: Nallapeta N et al. J Clin Gastroenterol. 2020 Feb 14. doi: 10.1097/MCG.0000000000001317.
A multidisciplinary, patient-centered approach can dramatically reduce inappropriate use of proton pump inhibitors (PPI), based on the success of a quality improvement study conducted at an academic, primary care clinic in New York.
In 1 year, the program reduced inappropriate PPI use from 80% to 30%, reported lead author Naren Nallapeta, MD, an internal medicine resident at the State University of New York at Buffalo, and colleagues.
According to the investigators, inappropriate use of PPIs is a common and growing concern. Recent patent expirations have led to wider availability of generic and over-the-counter options; and the consequences of unnecessary usage can be serious.
“PPI intake has been found to have a significant association with community-acquired pneumonia, Clostridium difficile associated diarrhea, impaired B12 absorption, hypomagnesemia, hip fractures, acute and chronic kidney disease, and spontaneous bacterial peritonitis in patients with cirrhotic ascites,” the investigators wrote in the Journal of Clinical Gastroenterology.
In 2017, the American Gastroenterological Association released guidelines that include indications for PPIs. But these guidelines often go unheeded, the investigators noted. Multiple studies have documented rates of inappropriate PPI use ranging from 54.1% to 82%. Previous studies have yielded mixed results: Simple physician education alone was found insufficient to reduce inappropriate prescriptions in a primary care setting, whereas studies involving pharmacy personnel have had positive results in various treatment centers.
In a survey of their own clinic, the Erie County Medical Center, an internal medicine service located in a tertiary care safety net hospital at the University at Buffalo, the investigators found that 80% of PPI prescriptions were inappropriate. This prompted a goal to reduce inappropriate use to less than 60% within 1 year.
To achieve this goal, the investigators started a quality improvement project based on the Plan-Do-Study-Act Cycle (PDSA) Model of health care improvement. The quality improvement team included internal medicine attending physicians and physician residents, gastroenterologists, patients, nurses, administrative and information technology staff, and a social worker.
After identifying root causes, the team deployed a variety of strategies to cut down on inappropriate PPI use. First, a new prompt in the electronic medical record reminded physicians to discuss PPI use with patients. Physicians were also given additional training concerning appropriate indications for PPIs, as well as a pocket guide and brochures that could be used for patient education. These efforts were supplemented by an enhanced nursing workflow, as well as continuous reinforcement with positive feedback for health care workers involved.
One year later, results exceeded expectations. Based on data from 180 patients, inappropriate use decreased from 80% to 30%, with a mean discontinuation rate of approximately 50%, an average that was maintained for 6 months beyond the end of the study. The annual, direct cost savings of the program totaled $13,992.
When indicated, patients on long-term PPIs were referred to the gastroenterology service for esophagogastroduodenoscopy. About half of the referred patients (49.8%) completed this procedure, which exceeded the baseline completion rate of less than 30%.
According to principal author Smita Bakhai, MD, of the department of internal medicine at the University at Buffalo, and a physician with UBMB Internal Medicine, the strategies used in this study are broadly applicable.
“The multidisciplinary approach, including patient engagement, would work well in any setting, even with limited resources and without the use of pharmacy personnel,” Dr. Bakhai said in an interview. “We used a patient-centered approach and physicians used shared decision making with patients to taper and discontinue PPIs or switch them to an H2-blocking agent when [patients] did not need to be on chronic PPIs.”
Dr. Bakhai went on to highlight the importance of working with multiple stakeholders.
“This project is unique because it was a resident-led project,” she said. “As academicians, we should always engage the fellows and the residents in any quality improvement work that we do, because they are the doctors of the future.”
Beyond care providers and patients, Dr. Bakhai emphasized the need to involve administrative leadership who can guarantee long-term resources and cultivate the right culture.
“Without the resources, you can’t sustain the project,” Dr. Bakhai said. “You have to have allocated resources, and a culture of safety and quality in the environment that you are doing the project. It has to be a supportive environment. We had all of those things, and that’s why we succeeded.”
The study was funded by the National Institutes of Health. The investigators reported no conflicts of interest.
SOURCE: Nallapeta N et al. J Clin Gastroenterol. 2020 Feb 14. doi: 10.1097/MCG.0000000000001317.
A multidisciplinary, patient-centered approach can dramatically reduce inappropriate use of proton pump inhibitors (PPI), based on the success of a quality improvement study conducted at an academic, primary care clinic in New York.
In 1 year, the program reduced inappropriate PPI use from 80% to 30%, reported lead author Naren Nallapeta, MD, an internal medicine resident at the State University of New York at Buffalo, and colleagues.
According to the investigators, inappropriate use of PPIs is a common and growing concern. Recent patent expirations have led to wider availability of generic and over-the-counter options; and the consequences of unnecessary usage can be serious.
“PPI intake has been found to have a significant association with community-acquired pneumonia, Clostridium difficile associated diarrhea, impaired B12 absorption, hypomagnesemia, hip fractures, acute and chronic kidney disease, and spontaneous bacterial peritonitis in patients with cirrhotic ascites,” the investigators wrote in the Journal of Clinical Gastroenterology.
In 2017, the American Gastroenterological Association released guidelines that include indications for PPIs. But these guidelines often go unheeded, the investigators noted. Multiple studies have documented rates of inappropriate PPI use ranging from 54.1% to 82%. Previous studies have yielded mixed results: Simple physician education alone was found insufficient to reduce inappropriate prescriptions in a primary care setting, whereas studies involving pharmacy personnel have had positive results in various treatment centers.
In a survey of their own clinic, the Erie County Medical Center, an internal medicine service located in a tertiary care safety net hospital at the University at Buffalo, the investigators found that 80% of PPI prescriptions were inappropriate. This prompted a goal to reduce inappropriate use to less than 60% within 1 year.
To achieve this goal, the investigators started a quality improvement project based on the Plan-Do-Study-Act Cycle (PDSA) Model of health care improvement. The quality improvement team included internal medicine attending physicians and physician residents, gastroenterologists, patients, nurses, administrative and information technology staff, and a social worker.
After identifying root causes, the team deployed a variety of strategies to cut down on inappropriate PPI use. First, a new prompt in the electronic medical record reminded physicians to discuss PPI use with patients. Physicians were also given additional training concerning appropriate indications for PPIs, as well as a pocket guide and brochures that could be used for patient education. These efforts were supplemented by an enhanced nursing workflow, as well as continuous reinforcement with positive feedback for health care workers involved.
One year later, results exceeded expectations. Based on data from 180 patients, inappropriate use decreased from 80% to 30%, with a mean discontinuation rate of approximately 50%, an average that was maintained for 6 months beyond the end of the study. The annual, direct cost savings of the program totaled $13,992.
When indicated, patients on long-term PPIs were referred to the gastroenterology service for esophagogastroduodenoscopy. About half of the referred patients (49.8%) completed this procedure, which exceeded the baseline completion rate of less than 30%.
According to principal author Smita Bakhai, MD, of the department of internal medicine at the University at Buffalo, and a physician with UBMB Internal Medicine, the strategies used in this study are broadly applicable.
“The multidisciplinary approach, including patient engagement, would work well in any setting, even with limited resources and without the use of pharmacy personnel,” Dr. Bakhai said in an interview. “We used a patient-centered approach and physicians used shared decision making with patients to taper and discontinue PPIs or switch them to an H2-blocking agent when [patients] did not need to be on chronic PPIs.”
Dr. Bakhai went on to highlight the importance of working with multiple stakeholders.
“This project is unique because it was a resident-led project,” she said. “As academicians, we should always engage the fellows and the residents in any quality improvement work that we do, because they are the doctors of the future.”
Beyond care providers and patients, Dr. Bakhai emphasized the need to involve administrative leadership who can guarantee long-term resources and cultivate the right culture.
“Without the resources, you can’t sustain the project,” Dr. Bakhai said. “You have to have allocated resources, and a culture of safety and quality in the environment that you are doing the project. It has to be a supportive environment. We had all of those things, and that’s why we succeeded.”
The study was funded by the National Institutes of Health. The investigators reported no conflicts of interest.
SOURCE: Nallapeta N et al. J Clin Gastroenterol. 2020 Feb 14. doi: 10.1097/MCG.0000000000001317.
FROM JOURNAL OF CLINICAL GASTROENTEROLGOY