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Nicotinamide-containing products gaining interest for aging, dermatologic disorders
NEW YORK – More patients are inquiring about the antiaging claims made for nicotinamide products, according to Christine DeWitt MD, of the department of dermatology, Georgetown University, Washington. She encouraged attendees at the American Academy of Dermatology summer meeting to gain familiarity with the underlying mechanisms and potential uses of nicotinamide for aging skin and prevention of skin cancer as well as for a variety of dermatologic disorders, including atopic dermatitis and bullous pemphigoid.
The ability of nicotinamide to increase oxidized nicotinamide adenine dinucleotide (NAD+) is credited for most of its dermatologic benefits, according to Dr. DeWitt. She explained that NAD+ has a central role in cell metabolism, including serving as a substrate for sirtuins, which help prevent deterioration of telomeres, now thought to be a critical event in aging.
Downstream effects include an improved barrier function to reduce transdermal water loss in patients with atopic dermatitis and anti-inflammatory effects that are relevant to acne and bullous pemphigoid.
The related but unique forms of vitamin B3, nicotinamide riboside and nicotinamide mononucleotide, appear to increase more directly and effectively NAD+ with the potential to provide more potent enzymatic antiaging effects, according to Dr. DeWitt. Not all of the more than 90 active and recruiting trials listed for these compounds on clinicaltrials.gov relate to aging, but many do list this or a related condition, such as frailty or sarcopenia, as the therapeutic target.
The trials are being conducted even as OTC nicotinamide riboside and nicotinamide mononucleotide products are being promoted with terms such as “antiaging DNA repair” and “sirtuins activator.” Dr. DeWitt said that favorable reviews of these products on Internet forums are leading many patients to ask her specifically about their clinical value.
“Patients are starting to look at aging and longevity as an entity to manage and to treat,” Dr. DeWitt explained. Increasingly, patients bring up terms like autophagy and ask about the science behind antiaging products.
The clinical role of nicotinamide-related products, whether to reduce events related to aging or provide other benefits, remains unproven.
Nevertheless, Dr. DeWitt often offers nicotinamide to her patients for such indications as acne and atopic dermatitis. In patients with bullous pemphigoid, nicotinamide is an adjunct to other therapies “in most of my patients.”
When recommending nicotinamide, Dr. DeWitt specifies a brand, not because there is evidence that one brand is better than another but because of a reputation of quality control with branded OTC products.
In general, nicotinamide, which is not generally associated with the flushing that accompanies niacin, is well tolerated. She recommends 500 mg twice daily for most indications.
Dr. DeWitt advised reviewing published studies on nicotinamide in order to respond appropriately to patient inquiries. She noted that many patients come to the clinician’s office already aware of the science behind the potential role of NAD+ to inhibit aging and will be seeking an objective point of view.
Dr. DeWitt reports no conflicts of interest.
NEW YORK – More patients are inquiring about the antiaging claims made for nicotinamide products, according to Christine DeWitt MD, of the department of dermatology, Georgetown University, Washington. She encouraged attendees at the American Academy of Dermatology summer meeting to gain familiarity with the underlying mechanisms and potential uses of nicotinamide for aging skin and prevention of skin cancer as well as for a variety of dermatologic disorders, including atopic dermatitis and bullous pemphigoid.
The ability of nicotinamide to increase oxidized nicotinamide adenine dinucleotide (NAD+) is credited for most of its dermatologic benefits, according to Dr. DeWitt. She explained that NAD+ has a central role in cell metabolism, including serving as a substrate for sirtuins, which help prevent deterioration of telomeres, now thought to be a critical event in aging.
Downstream effects include an improved barrier function to reduce transdermal water loss in patients with atopic dermatitis and anti-inflammatory effects that are relevant to acne and bullous pemphigoid.
The related but unique forms of vitamin B3, nicotinamide riboside and nicotinamide mononucleotide, appear to increase more directly and effectively NAD+ with the potential to provide more potent enzymatic antiaging effects, according to Dr. DeWitt. Not all of the more than 90 active and recruiting trials listed for these compounds on clinicaltrials.gov relate to aging, but many do list this or a related condition, such as frailty or sarcopenia, as the therapeutic target.
The trials are being conducted even as OTC nicotinamide riboside and nicotinamide mononucleotide products are being promoted with terms such as “antiaging DNA repair” and “sirtuins activator.” Dr. DeWitt said that favorable reviews of these products on Internet forums are leading many patients to ask her specifically about their clinical value.
“Patients are starting to look at aging and longevity as an entity to manage and to treat,” Dr. DeWitt explained. Increasingly, patients bring up terms like autophagy and ask about the science behind antiaging products.
The clinical role of nicotinamide-related products, whether to reduce events related to aging or provide other benefits, remains unproven.
Nevertheless, Dr. DeWitt often offers nicotinamide to her patients for such indications as acne and atopic dermatitis. In patients with bullous pemphigoid, nicotinamide is an adjunct to other therapies “in most of my patients.”
When recommending nicotinamide, Dr. DeWitt specifies a brand, not because there is evidence that one brand is better than another but because of a reputation of quality control with branded OTC products.
In general, nicotinamide, which is not generally associated with the flushing that accompanies niacin, is well tolerated. She recommends 500 mg twice daily for most indications.
Dr. DeWitt advised reviewing published studies on nicotinamide in order to respond appropriately to patient inquiries. She noted that many patients come to the clinician’s office already aware of the science behind the potential role of NAD+ to inhibit aging and will be seeking an objective point of view.
Dr. DeWitt reports no conflicts of interest.
NEW YORK – More patients are inquiring about the antiaging claims made for nicotinamide products, according to Christine DeWitt MD, of the department of dermatology, Georgetown University, Washington. She encouraged attendees at the American Academy of Dermatology summer meeting to gain familiarity with the underlying mechanisms and potential uses of nicotinamide for aging skin and prevention of skin cancer as well as for a variety of dermatologic disorders, including atopic dermatitis and bullous pemphigoid.
The ability of nicotinamide to increase oxidized nicotinamide adenine dinucleotide (NAD+) is credited for most of its dermatologic benefits, according to Dr. DeWitt. She explained that NAD+ has a central role in cell metabolism, including serving as a substrate for sirtuins, which help prevent deterioration of telomeres, now thought to be a critical event in aging.
Downstream effects include an improved barrier function to reduce transdermal water loss in patients with atopic dermatitis and anti-inflammatory effects that are relevant to acne and bullous pemphigoid.
The related but unique forms of vitamin B3, nicotinamide riboside and nicotinamide mononucleotide, appear to increase more directly and effectively NAD+ with the potential to provide more potent enzymatic antiaging effects, according to Dr. DeWitt. Not all of the more than 90 active and recruiting trials listed for these compounds on clinicaltrials.gov relate to aging, but many do list this or a related condition, such as frailty or sarcopenia, as the therapeutic target.
The trials are being conducted even as OTC nicotinamide riboside and nicotinamide mononucleotide products are being promoted with terms such as “antiaging DNA repair” and “sirtuins activator.” Dr. DeWitt said that favorable reviews of these products on Internet forums are leading many patients to ask her specifically about their clinical value.
“Patients are starting to look at aging and longevity as an entity to manage and to treat,” Dr. DeWitt explained. Increasingly, patients bring up terms like autophagy and ask about the science behind antiaging products.
The clinical role of nicotinamide-related products, whether to reduce events related to aging or provide other benefits, remains unproven.
Nevertheless, Dr. DeWitt often offers nicotinamide to her patients for such indications as acne and atopic dermatitis. In patients with bullous pemphigoid, nicotinamide is an adjunct to other therapies “in most of my patients.”
When recommending nicotinamide, Dr. DeWitt specifies a brand, not because there is evidence that one brand is better than another but because of a reputation of quality control with branded OTC products.
In general, nicotinamide, which is not generally associated with the flushing that accompanies niacin, is well tolerated. She recommends 500 mg twice daily for most indications.
Dr. DeWitt advised reviewing published studies on nicotinamide in order to respond appropriately to patient inquiries. She noted that many patients come to the clinician’s office already aware of the science behind the potential role of NAD+ to inhibit aging and will be seeking an objective point of view.
Dr. DeWitt reports no conflicts of interest.
EXPERT ANALYSIS FROM SUMMER AAD 2019
Botulinum toxin injections: Err on the side of undercorrecting in first-time users
NEW YORK – In patients receiving first-time botulinum toxin injections for cosmetic enhancements, it is prudent to use a relatively low dose, Gary Goldenberg, MD, advised at the American Academy of Dermatology summer meeting.
Optimal dosing varies by individual, and undertreatment is easier to correct than is excess treatment. “This is a pearl. I always undercorrect, especially if I am injecting a patient for the first time,” said Dr. Goldenberg, an assistant clinical professor of dermatology and pathology at the Icahn School of Medicine at Mount Sinai, New York.
All patients are invited to return 2 weeks after their initial treatments, when the maximum effect is reached. Dr. Goldenberg does not charge for touch-ups administered at that time. “I want the patient to have the best possible experience,” he said.
The demand for botulinum toxin injections is skyrocketing, even among patients in their 20s. Also, men now represent a substantial proportion of those seeking cosmetic botulinum toxin injections.
Botulinum toxin injections are a source of high levels of patient satisfaction, according to Dr. Goldenberg. They are also a good way to get started in performing cosmetic procedures as skills in the injection of botulinum toxin are readily acquired, While some primary care physicians and gynecologists also are offering botulinum toxin injections for cosmetic purposes, dermatologists “are going to do a better job because we know the anatomy the best,” he said.
Dr. Goldenberg said botulinum toxin injections should be offered as a service in promotional efforts for one’s practice, but any mention to patients should be tactful. Patients should be informed that there are solutions for damaged or wrinkled skin, but the topic should be dropped if there is no apparent interest.
“I only suggest. I do not push,” he said. “I never talk about money. If they want to know how much (injections) will cost, they must speak to my office staff.”
With the recent approval of prabotulinumtoxinA (Jeuveau), there are four botulinum toxin injection products available in the United States. These include the original product, onabotulinumtoxinA (Botox), incobotulinumtoxinA (Xeomin), and abobotulinumtoxinA (Dysport). Dr. Goldenberg, who has administered them all, is not so far convinced there are important differences between them in regard to either efficacy or safety.
“There is another product now in clinical trials, so perhaps we will have a fifth product in a year or so,” said Dr. Goldenberg, who noted that the competition has resulted in claims and counterclaims regarding such issues as speed of onset and durability.
For dermatologists new to providing botulinum toxin injections, Dr. Goldenberg suggested restricting initial procedures to the face, particularly glabellar lines for which all of the available products are indicated. The companies that make these products also should offer a broad array of resources for improving skills, he said.
Dr. Goldenberg reports no potential conflicts of interest with companies that make botulinum toxins.
NEW YORK – In patients receiving first-time botulinum toxin injections for cosmetic enhancements, it is prudent to use a relatively low dose, Gary Goldenberg, MD, advised at the American Academy of Dermatology summer meeting.
Optimal dosing varies by individual, and undertreatment is easier to correct than is excess treatment. “This is a pearl. I always undercorrect, especially if I am injecting a patient for the first time,” said Dr. Goldenberg, an assistant clinical professor of dermatology and pathology at the Icahn School of Medicine at Mount Sinai, New York.
All patients are invited to return 2 weeks after their initial treatments, when the maximum effect is reached. Dr. Goldenberg does not charge for touch-ups administered at that time. “I want the patient to have the best possible experience,” he said.
The demand for botulinum toxin injections is skyrocketing, even among patients in their 20s. Also, men now represent a substantial proportion of those seeking cosmetic botulinum toxin injections.
Botulinum toxin injections are a source of high levels of patient satisfaction, according to Dr. Goldenberg. They are also a good way to get started in performing cosmetic procedures as skills in the injection of botulinum toxin are readily acquired, While some primary care physicians and gynecologists also are offering botulinum toxin injections for cosmetic purposes, dermatologists “are going to do a better job because we know the anatomy the best,” he said.
Dr. Goldenberg said botulinum toxin injections should be offered as a service in promotional efforts for one’s practice, but any mention to patients should be tactful. Patients should be informed that there are solutions for damaged or wrinkled skin, but the topic should be dropped if there is no apparent interest.
“I only suggest. I do not push,” he said. “I never talk about money. If they want to know how much (injections) will cost, they must speak to my office staff.”
With the recent approval of prabotulinumtoxinA (Jeuveau), there are four botulinum toxin injection products available in the United States. These include the original product, onabotulinumtoxinA (Botox), incobotulinumtoxinA (Xeomin), and abobotulinumtoxinA (Dysport). Dr. Goldenberg, who has administered them all, is not so far convinced there are important differences between them in regard to either efficacy or safety.
“There is another product now in clinical trials, so perhaps we will have a fifth product in a year or so,” said Dr. Goldenberg, who noted that the competition has resulted in claims and counterclaims regarding such issues as speed of onset and durability.
For dermatologists new to providing botulinum toxin injections, Dr. Goldenberg suggested restricting initial procedures to the face, particularly glabellar lines for which all of the available products are indicated. The companies that make these products also should offer a broad array of resources for improving skills, he said.
Dr. Goldenberg reports no potential conflicts of interest with companies that make botulinum toxins.
NEW YORK – In patients receiving first-time botulinum toxin injections for cosmetic enhancements, it is prudent to use a relatively low dose, Gary Goldenberg, MD, advised at the American Academy of Dermatology summer meeting.
Optimal dosing varies by individual, and undertreatment is easier to correct than is excess treatment. “This is a pearl. I always undercorrect, especially if I am injecting a patient for the first time,” said Dr. Goldenberg, an assistant clinical professor of dermatology and pathology at the Icahn School of Medicine at Mount Sinai, New York.
All patients are invited to return 2 weeks after their initial treatments, when the maximum effect is reached. Dr. Goldenberg does not charge for touch-ups administered at that time. “I want the patient to have the best possible experience,” he said.
The demand for botulinum toxin injections is skyrocketing, even among patients in their 20s. Also, men now represent a substantial proportion of those seeking cosmetic botulinum toxin injections.
Botulinum toxin injections are a source of high levels of patient satisfaction, according to Dr. Goldenberg. They are also a good way to get started in performing cosmetic procedures as skills in the injection of botulinum toxin are readily acquired, While some primary care physicians and gynecologists also are offering botulinum toxin injections for cosmetic purposes, dermatologists “are going to do a better job because we know the anatomy the best,” he said.
Dr. Goldenberg said botulinum toxin injections should be offered as a service in promotional efforts for one’s practice, but any mention to patients should be tactful. Patients should be informed that there are solutions for damaged or wrinkled skin, but the topic should be dropped if there is no apparent interest.
“I only suggest. I do not push,” he said. “I never talk about money. If they want to know how much (injections) will cost, they must speak to my office staff.”
With the recent approval of prabotulinumtoxinA (Jeuveau), there are four botulinum toxin injection products available in the United States. These include the original product, onabotulinumtoxinA (Botox), incobotulinumtoxinA (Xeomin), and abobotulinumtoxinA (Dysport). Dr. Goldenberg, who has administered them all, is not so far convinced there are important differences between them in regard to either efficacy or safety.
“There is another product now in clinical trials, so perhaps we will have a fifth product in a year or so,” said Dr. Goldenberg, who noted that the competition has resulted in claims and counterclaims regarding such issues as speed of onset and durability.
For dermatologists new to providing botulinum toxin injections, Dr. Goldenberg suggested restricting initial procedures to the face, particularly glabellar lines for which all of the available products are indicated. The companies that make these products also should offer a broad array of resources for improving skills, he said.
Dr. Goldenberg reports no potential conflicts of interest with companies that make botulinum toxins.
EXPERT ANALYSIS FROM SUMMER AAD 2019
PCPs play role in identifying severe, difficult-to-treat asthma
ORLANDO – Clinicians at the primary care level should learn to distinguish the difference between severe and difficult-to-treat asthma to help facilitate referral to an asthma care specialist, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.
Care providers are seeing patients with severe asthma at their primary care practice, whether they realize it or not, and should therefore learn to recognize and diagnose these patients even if they are not directly treating them for asthma, said Michelle R. Dickens, MSN, RN, FNP-C, AE-C, a nurse practitioner at Ferrell-Duncan Clinic department of allergy, asthma, and immunology in Springfield, Mo., said in her presentation.
“There’s still a lot we can do to get the ball rolling,” Ms. Dickens said. “While you may not be prescribing some of these newer biologics and some of the high-level, $30,000-a-year medications for your asthmatic, you still have a role in this in identifying them and helping us to get to where they need to be.”
Ms. Dickens noted that patients may not even disclose their asthma history with their primary care provider if it is not the reason for the office visit. “Because asthma can be such an episodic disease, it’s not right on the top of their radar,” she said. “They have bigger issues they want to talk about with you, and they forget to mention the asthma part.”
Under Global Initiative for Asthma (GINA) criteria, severe asthma is defined as poorly controlled asthma even after patients demonstrate adherence and good technique. However, before diagnosing a patient with severe asthma, clinicians should first rule out whether the patient has asthma that is difficult to treat, said Ms. Dickens. Difficult-to-treat asthma is characterized by inadequate dosing of medication, noncompliance with medication dose (“spreading out” the medication), poor technique when self-administering the medication, and comorbid conditions. It is also possible that difficult-to-treat asthma is not well controlled because the asthma was misdiagnosed and is actually another condition, she added.
If a patient has difficult-to-treat asthma, ensure they are adhering to the therapy, using proper technique, and that the medicine is being administered at the proper dose. Using Expert Panel Report 3 (EPR-3) and Global Initiative for Asthma (GINA) guidelines, clinicians should maximize the treatment for a patient with severe asthma based on the stepwise approach outlined in the guidelines, and referring out to an asthma specialist for add-on therapy or stepping up therapy when indicated.
Researchers are beginning to explore the genotypes, phenotypes, and endotypes of asthma to learn more about severe asthma and potentially identify asthma subtypes, said Ms. Dickens. “We’re not there yet, but we are learning a little bit about why certain patients have certain types of asthma,” she said.
The Severe Asthma Research Program has found three clusters of likely severe asthma candidates: those with classic childhood asthma onset, those who have asthma with chronic obstructive pulmonary disease (COPD), and patients with both obesity and asthma characterized by “high impairment but mildly abnormal lung function.” Clinicians can use spirometry, complete blood count with differential, total immunoglobulin E, body mass index, allergy testing, and exhaled nitric oxide with these data and biomarkers to gain a better idea of a patient’s asthma situation.
Referrals to an asthma specialist should be considered if a patient experiences a life-threatening exacerbation, is not responding to therapy, has an unusual presentation of asthma symptoms, has comorbid conditions, or needs additional testing or additional education. Patients who are at step 2 or higher in EPR-3 guidelines and ready to move to step 3 and are under 4 years of age, and patients who are 5 years or older at step 4 of therapy or higher should be referred to an asthma specialist. “I think the younger the patient and the more severe the [symptoms], the more likely you should be referring to a specialist,” said Ms. Dickens.
Ms. Dickens reports no relevant financial disclosures. Global Academy for Medical Education and this news organization are owned by the same parent company.
ORLANDO – Clinicians at the primary care level should learn to distinguish the difference between severe and difficult-to-treat asthma to help facilitate referral to an asthma care specialist, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.
Care providers are seeing patients with severe asthma at their primary care practice, whether they realize it or not, and should therefore learn to recognize and diagnose these patients even if they are not directly treating them for asthma, said Michelle R. Dickens, MSN, RN, FNP-C, AE-C, a nurse practitioner at Ferrell-Duncan Clinic department of allergy, asthma, and immunology in Springfield, Mo., said in her presentation.
“There’s still a lot we can do to get the ball rolling,” Ms. Dickens said. “While you may not be prescribing some of these newer biologics and some of the high-level, $30,000-a-year medications for your asthmatic, you still have a role in this in identifying them and helping us to get to where they need to be.”
Ms. Dickens noted that patients may not even disclose their asthma history with their primary care provider if it is not the reason for the office visit. “Because asthma can be such an episodic disease, it’s not right on the top of their radar,” she said. “They have bigger issues they want to talk about with you, and they forget to mention the asthma part.”
Under Global Initiative for Asthma (GINA) criteria, severe asthma is defined as poorly controlled asthma even after patients demonstrate adherence and good technique. However, before diagnosing a patient with severe asthma, clinicians should first rule out whether the patient has asthma that is difficult to treat, said Ms. Dickens. Difficult-to-treat asthma is characterized by inadequate dosing of medication, noncompliance with medication dose (“spreading out” the medication), poor technique when self-administering the medication, and comorbid conditions. It is also possible that difficult-to-treat asthma is not well controlled because the asthma was misdiagnosed and is actually another condition, she added.
If a patient has difficult-to-treat asthma, ensure they are adhering to the therapy, using proper technique, and that the medicine is being administered at the proper dose. Using Expert Panel Report 3 (EPR-3) and Global Initiative for Asthma (GINA) guidelines, clinicians should maximize the treatment for a patient with severe asthma based on the stepwise approach outlined in the guidelines, and referring out to an asthma specialist for add-on therapy or stepping up therapy when indicated.
Researchers are beginning to explore the genotypes, phenotypes, and endotypes of asthma to learn more about severe asthma and potentially identify asthma subtypes, said Ms. Dickens. “We’re not there yet, but we are learning a little bit about why certain patients have certain types of asthma,” she said.
The Severe Asthma Research Program has found three clusters of likely severe asthma candidates: those with classic childhood asthma onset, those who have asthma with chronic obstructive pulmonary disease (COPD), and patients with both obesity and asthma characterized by “high impairment but mildly abnormal lung function.” Clinicians can use spirometry, complete blood count with differential, total immunoglobulin E, body mass index, allergy testing, and exhaled nitric oxide with these data and biomarkers to gain a better idea of a patient’s asthma situation.
Referrals to an asthma specialist should be considered if a patient experiences a life-threatening exacerbation, is not responding to therapy, has an unusual presentation of asthma symptoms, has comorbid conditions, or needs additional testing or additional education. Patients who are at step 2 or higher in EPR-3 guidelines and ready to move to step 3 and are under 4 years of age, and patients who are 5 years or older at step 4 of therapy or higher should be referred to an asthma specialist. “I think the younger the patient and the more severe the [symptoms], the more likely you should be referring to a specialist,” said Ms. Dickens.
Ms. Dickens reports no relevant financial disclosures. Global Academy for Medical Education and this news organization are owned by the same parent company.
ORLANDO – Clinicians at the primary care level should learn to distinguish the difference between severe and difficult-to-treat asthma to help facilitate referral to an asthma care specialist, according to a speaker at the Cardiovascular & Respiratory Summit by Global Academy for Medical Education.
Care providers are seeing patients with severe asthma at their primary care practice, whether they realize it or not, and should therefore learn to recognize and diagnose these patients even if they are not directly treating them for asthma, said Michelle R. Dickens, MSN, RN, FNP-C, AE-C, a nurse practitioner at Ferrell-Duncan Clinic department of allergy, asthma, and immunology in Springfield, Mo., said in her presentation.
“There’s still a lot we can do to get the ball rolling,” Ms. Dickens said. “While you may not be prescribing some of these newer biologics and some of the high-level, $30,000-a-year medications for your asthmatic, you still have a role in this in identifying them and helping us to get to where they need to be.”
Ms. Dickens noted that patients may not even disclose their asthma history with their primary care provider if it is not the reason for the office visit. “Because asthma can be such an episodic disease, it’s not right on the top of their radar,” she said. “They have bigger issues they want to talk about with you, and they forget to mention the asthma part.”
Under Global Initiative for Asthma (GINA) criteria, severe asthma is defined as poorly controlled asthma even after patients demonstrate adherence and good technique. However, before diagnosing a patient with severe asthma, clinicians should first rule out whether the patient has asthma that is difficult to treat, said Ms. Dickens. Difficult-to-treat asthma is characterized by inadequate dosing of medication, noncompliance with medication dose (“spreading out” the medication), poor technique when self-administering the medication, and comorbid conditions. It is also possible that difficult-to-treat asthma is not well controlled because the asthma was misdiagnosed and is actually another condition, she added.
If a patient has difficult-to-treat asthma, ensure they are adhering to the therapy, using proper technique, and that the medicine is being administered at the proper dose. Using Expert Panel Report 3 (EPR-3) and Global Initiative for Asthma (GINA) guidelines, clinicians should maximize the treatment for a patient with severe asthma based on the stepwise approach outlined in the guidelines, and referring out to an asthma specialist for add-on therapy or stepping up therapy when indicated.
Researchers are beginning to explore the genotypes, phenotypes, and endotypes of asthma to learn more about severe asthma and potentially identify asthma subtypes, said Ms. Dickens. “We’re not there yet, but we are learning a little bit about why certain patients have certain types of asthma,” she said.
The Severe Asthma Research Program has found three clusters of likely severe asthma candidates: those with classic childhood asthma onset, those who have asthma with chronic obstructive pulmonary disease (COPD), and patients with both obesity and asthma characterized by “high impairment but mildly abnormal lung function.” Clinicians can use spirometry, complete blood count with differential, total immunoglobulin E, body mass index, allergy testing, and exhaled nitric oxide with these data and biomarkers to gain a better idea of a patient’s asthma situation.
Referrals to an asthma specialist should be considered if a patient experiences a life-threatening exacerbation, is not responding to therapy, has an unusual presentation of asthma symptoms, has comorbid conditions, or needs additional testing or additional education. Patients who are at step 2 or higher in EPR-3 guidelines and ready to move to step 3 and are under 4 years of age, and patients who are 5 years or older at step 4 of therapy or higher should be referred to an asthma specialist. “I think the younger the patient and the more severe the [symptoms], the more likely you should be referring to a specialist,” said Ms. Dickens.
Ms. Dickens reports no relevant financial disclosures. Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM CARPS 2019
Keep your staff current – and happy
It goes without saying that as a physician, it’s essential to keep your knowledge and skills current. But too many private practitioners overlook the similar needs of their employees.
Like you, staff members provide better care to patients when they know the latest findings and techniques. They also provide better information: When patients ask questions of your staff, either in the office or over the phone (which happens more often than you probably think), you certainly want their answers to be accurate and up to date.
But there are lots of other good reasons to invest in ongoing staff training. It’s a win-win strategy for you, your staff, and for your practice.
The more your employees know, the more productive they will be. Not only will they complete everyday duties more efficiently, they will be stimulated to learn new tasks and accept more responsibility.
Staffers who have learned new skills are more willing to take on new challenges. And the better their skills and the greater their confidence, the less supervision they need from you, and the more they become involved in their work.
They will also be happier in their jobs. Investing in your employees’ competence makes them feel valued and appreciated. This leads to reduced turnover – which, alone, often pays for the training.
You probably already do some ongoing education: You do your yearly OSHA training because the law requires it, you run HIPAA updates as necessary, and you have everyone recertified periodically in basic or advanced CPR (I hope). But I’m talking about going beyond the basic stuff, which may satisfy legal requirements, but does not motivate your people to loftier goals.
An obvious example is sending your insurance people annually to coding and insurance processing courses – or at the very least, online refreshers – so they are always current on the latest third-party changes. The use of outdated or obsolete codes can cost you thousands of dollars every month. Other opportunities include keyboarding and computer courses for staff who work with your computers, and Excel and QuickBooks updates for your bookkeepers.
Continuing education does not have to be costly, and in some cases it can be free. For example, pharmaceutical representatives will be happy to run an in-service for your staff on a new medication or procedure or instrument, or refresh their memories on an established one. Be sure to make clear to the rep that the presentation must be as objective and impartial as possible, given the obvious potential conflict of interest involved.
Your office manager should join the Association of Dermatology Administrators and Managers. It holds annual meetings at the same time and in the same city as the American Academy of Dermatology winter meetings, with a good selection of refresher courses and lots of opportunities for networking with other managers, both personally or virtually.
Many other venues are available for employee education, in the cloud and in conventional classrooms. Courses are offered in many relevant subjects; a quick Google search turns up an eclectic mix, including medical terminology, record keeping and accounting, laboratory skills, diagnostic tests and procedures, pharmacology and medication administration, patient relations, medical law and ethics, and many others.
By far the most common question I receive on this issue is, “What if I pay for all that training, and then the employees leave?”
My reply: “What if you don’t, and they stay?”
Well-trained employees are vastly preferable to untrained ones. I suppose there is some risk of an occasional staffer accepting training and then moving on; but in 38 years, it has never happened in my office. In my experience, well-trained employees will stay. Education fosters loyalty. Employees who know you care enough about them to advance their skills will sense that they have a stake in the practice, and thus will be less likely to want to leave. Furthermore, continuing education will always be cheaper than training new employees from scratch.
In any case, everyone will benefit from a well-trained staff – you, your employees, your practice, and most importantly your patients.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
It goes without saying that as a physician, it’s essential to keep your knowledge and skills current. But too many private practitioners overlook the similar needs of their employees.
Like you, staff members provide better care to patients when they know the latest findings and techniques. They also provide better information: When patients ask questions of your staff, either in the office or over the phone (which happens more often than you probably think), you certainly want their answers to be accurate and up to date.
But there are lots of other good reasons to invest in ongoing staff training. It’s a win-win strategy for you, your staff, and for your practice.
The more your employees know, the more productive they will be. Not only will they complete everyday duties more efficiently, they will be stimulated to learn new tasks and accept more responsibility.
Staffers who have learned new skills are more willing to take on new challenges. And the better their skills and the greater their confidence, the less supervision they need from you, and the more they become involved in their work.
They will also be happier in their jobs. Investing in your employees’ competence makes them feel valued and appreciated. This leads to reduced turnover – which, alone, often pays for the training.
You probably already do some ongoing education: You do your yearly OSHA training because the law requires it, you run HIPAA updates as necessary, and you have everyone recertified periodically in basic or advanced CPR (I hope). But I’m talking about going beyond the basic stuff, which may satisfy legal requirements, but does not motivate your people to loftier goals.
An obvious example is sending your insurance people annually to coding and insurance processing courses – or at the very least, online refreshers – so they are always current on the latest third-party changes. The use of outdated or obsolete codes can cost you thousands of dollars every month. Other opportunities include keyboarding and computer courses for staff who work with your computers, and Excel and QuickBooks updates for your bookkeepers.
Continuing education does not have to be costly, and in some cases it can be free. For example, pharmaceutical representatives will be happy to run an in-service for your staff on a new medication or procedure or instrument, or refresh their memories on an established one. Be sure to make clear to the rep that the presentation must be as objective and impartial as possible, given the obvious potential conflict of interest involved.
Your office manager should join the Association of Dermatology Administrators and Managers. It holds annual meetings at the same time and in the same city as the American Academy of Dermatology winter meetings, with a good selection of refresher courses and lots of opportunities for networking with other managers, both personally or virtually.
Many other venues are available for employee education, in the cloud and in conventional classrooms. Courses are offered in many relevant subjects; a quick Google search turns up an eclectic mix, including medical terminology, record keeping and accounting, laboratory skills, diagnostic tests and procedures, pharmacology and medication administration, patient relations, medical law and ethics, and many others.
By far the most common question I receive on this issue is, “What if I pay for all that training, and then the employees leave?”
My reply: “What if you don’t, and they stay?”
Well-trained employees are vastly preferable to untrained ones. I suppose there is some risk of an occasional staffer accepting training and then moving on; but in 38 years, it has never happened in my office. In my experience, well-trained employees will stay. Education fosters loyalty. Employees who know you care enough about them to advance their skills will sense that they have a stake in the practice, and thus will be less likely to want to leave. Furthermore, continuing education will always be cheaper than training new employees from scratch.
In any case, everyone will benefit from a well-trained staff – you, your employees, your practice, and most importantly your patients.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
It goes without saying that as a physician, it’s essential to keep your knowledge and skills current. But too many private practitioners overlook the similar needs of their employees.
Like you, staff members provide better care to patients when they know the latest findings and techniques. They also provide better information: When patients ask questions of your staff, either in the office or over the phone (which happens more often than you probably think), you certainly want their answers to be accurate and up to date.
But there are lots of other good reasons to invest in ongoing staff training. It’s a win-win strategy for you, your staff, and for your practice.
The more your employees know, the more productive they will be. Not only will they complete everyday duties more efficiently, they will be stimulated to learn new tasks and accept more responsibility.
Staffers who have learned new skills are more willing to take on new challenges. And the better their skills and the greater their confidence, the less supervision they need from you, and the more they become involved in their work.
They will also be happier in their jobs. Investing in your employees’ competence makes them feel valued and appreciated. This leads to reduced turnover – which, alone, often pays for the training.
You probably already do some ongoing education: You do your yearly OSHA training because the law requires it, you run HIPAA updates as necessary, and you have everyone recertified periodically in basic or advanced CPR (I hope). But I’m talking about going beyond the basic stuff, which may satisfy legal requirements, but does not motivate your people to loftier goals.
An obvious example is sending your insurance people annually to coding and insurance processing courses – or at the very least, online refreshers – so they are always current on the latest third-party changes. The use of outdated or obsolete codes can cost you thousands of dollars every month. Other opportunities include keyboarding and computer courses for staff who work with your computers, and Excel and QuickBooks updates for your bookkeepers.
Continuing education does not have to be costly, and in some cases it can be free. For example, pharmaceutical representatives will be happy to run an in-service for your staff on a new medication or procedure or instrument, or refresh their memories on an established one. Be sure to make clear to the rep that the presentation must be as objective and impartial as possible, given the obvious potential conflict of interest involved.
Your office manager should join the Association of Dermatology Administrators and Managers. It holds annual meetings at the same time and in the same city as the American Academy of Dermatology winter meetings, with a good selection of refresher courses and lots of opportunities for networking with other managers, both personally or virtually.
Many other venues are available for employee education, in the cloud and in conventional classrooms. Courses are offered in many relevant subjects; a quick Google search turns up an eclectic mix, including medical terminology, record keeping and accounting, laboratory skills, diagnostic tests and procedures, pharmacology and medication administration, patient relations, medical law and ethics, and many others.
By far the most common question I receive on this issue is, “What if I pay for all that training, and then the employees leave?”
My reply: “What if you don’t, and they stay?”
Well-trained employees are vastly preferable to untrained ones. I suppose there is some risk of an occasional staffer accepting training and then moving on; but in 38 years, it has never happened in my office. In my experience, well-trained employees will stay. Education fosters loyalty. Employees who know you care enough about them to advance their skills will sense that they have a stake in the practice, and thus will be less likely to want to leave. Furthermore, continuing education will always be cheaper than training new employees from scratch.
In any case, everyone will benefit from a well-trained staff – you, your employees, your practice, and most importantly your patients.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Study: Cardiac biomarkers predicted CV events in CAP
in a recently conducted study.
These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.
“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”
Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.
Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.
With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.
After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO2/FiO2) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.
Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.
This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.
in a recently conducted study.
These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.
“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”
Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.
Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.
With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.
After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO2/FiO2) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.
Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.
This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.
in a recently conducted study.
These biomarkers were also used to predict late cardiovascular events at day 30 of community-acquired pneumonia (CAP) in patients who did not have a history of cardiovascular disease, according to Rosario Menéndez, MD, from the Hospital Universitario y Politécnico La Fe and Instituto de Investigación Sanitaria La Fe in Valencia, Spain, and colleagues.
“Some patients have still high levels of inflammatory and cardiac biomarkers at 30 days, when they are usually referred to primary care without receiving any specific additional recommendations,” Dr. Menéndez and colleagues wrote in CHEST. “Our results suggest that a change in usual practice is needed to reduce current and further cardiovascular CAP complications.”
Dr. Menéndez and colleagues prospectively followed 730 patients for 1 year who were hospitalized for CAP, measuring the cardiac biomarkers proadrenomedullin (proADM), pro b-type natriuretic peptide (proBNP), proendothelin-1, and troponin T, and the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT). The researchers also collected data on age, gender, smoking status, and vaccination history, as well as whether patients had any cardiac, renal, pulmonary, neurological or diabetes-related comorbidities.
Overall, 95 patients experienced early cardiovascular events, 67 patients had long-term cardiovascular events, and 20 patients experienced both early and late events. In hospital, the mortality rate was 4.7%; the 30-day mortality rate was 5.3%, and the 1-year mortality rate was 9.9%.
With regard to biomarkers, patients who experienced both early and late cardiovascular events had significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6. Patients who experienced later events had consistent levels of these biomarkers until day 30, except for a decrease at day 4 or day 5.
After adjustment for age, sepsis, previous cardiac disease, and a partial pressure of oxygen in the alveoli to fractional inspired oxygen ratio (PaO2/FiO2) of less than 250mm Hg, cardiac biomarkers proendothelin-1 (odds ratio, 2.25; 95% confidence interval, 1.34-3.79), proADM (OR, 2.53; 95% CI, 1.53-4.20), proBNP (OR, 2.67; 95% CI, 1.59-4.49), and troponin T (OR, 2.70; 95% CI, 1.62-4.49) significantly predicted early cardiovascular events, while proendothelin-1 (OR, 3.13; 95% CI, 1.41-7.80), proADM (2.29; 95% CI, 1.01-5.19) and proBNP (OR, 2.34; 95% CI, 1.01-5.56) significantly predicted late cardiovascular events. For day 30 results, when researchers added IL-6 levels to proendothelin-1, the odds ratio for late events increased to 3.53, and when they added IL-6 levels to proADM, the odds ratio increased to 2.80.
Researchers noted the limitations of the study included that they did not analyze cardiac biomarkers to predict specific cardiovascular events, did not identify the cause for mortality at 1 year in most patients, and did not include a control group.
This study was supported in part by funding from Instituto de Salud Carlos III, Sociedad Española de Neumología y Cirugía Torácica, and the Center for Biomedical Research Network in Respiratory Diseases. The authors reported no relevant conflicts of interest.
SOURCE: Menéndez R et al. Chest. 2019 Aug 2. doi: 10.1016/j.chest.2019.06.040.
FROM CHEST
Lasmiditan is associated with driving impairment
Philadelphia – according to research presented at the annual meeting of the American Headache Society. This impairment coincides with the time of peak drug concentration and is resolved by 8 hours after dosing.
Lasmiditan, a 5-HT1F receptor agonist, is under regulatory review as an acute treatment of migraine in adults. In two phase 3 trials, a significant proportion of participants who received the treatment were pain-free at 2 hours and free of their most bothersome symptom at 2 hours, compared with controls. The most common treatment-emergent adverse events (dizziness, paresthesia, somnolence, fatigue, and hypoaesthesia) reflected the drug’s penetration of the CNS. Because CNS-related adverse events could affect a patient’s ability to drive, the effects of lasmiditan on simulated driving were studied, consistent with regulatory guidance.
Two studies in healthy participants
Eric Pearlman, MD, PhD, senior medical director for neuroscience, U.S. Medical Affairs, at Eli Lilly, and colleagues conducted two simulated driving studies with crossover designs. In the first study, the researchers randomized 90 healthy subjects (mean age, 34.9 years) to 50 mg, 100 mg, or 200 mg of lasmiditan; 1 mg of alprazolam (an active control); or placebo. After appropriate washout periods, participants received each treatment in random order. At 1.5 hours after each treatment, participants underwent a driving assessment using a driving simulator.
In the second study, Dr. Pearlman and colleagues randomized 68 healthy subjects (mean age, 32.8 years) to 100 mg or 200 mg of lasmiditan, 50 mg of diphenhydramine (an active control), or placebo. Participants underwent driving assessments at 8, 12, and 24 hours after baseline. Participants randomized to lasmiditan received treatment at baseline, but participants randomized to diphenhydramine received treatment 2 hours before each driving assessment. The diphenhydramine arm was intended to test the sensitivity of the driving assessment to impairment, as was the alprazolam arm in the first study.
During the driving assessments, participants were asked to maintain a speed of 100 km/h and to stay in the middle of the lane. The simulated road included gentle curves and hills, and oncoming traffic appeared occasionally. Participants also completed a secondary attention task, mimicking real-world conditions. Each assessment took about 1 hour. The primary endpoint was the standard deviation of lateral position (SDLP), which is known colloquially as weaving. The investigators defined noninferiority to placebo as an SDLP of 4.4 cm or less.
Participants reported that they could drive safely
In the first study, Dr. Pearlman and colleagues reported a dose-related increase in SDLP at 1.5 hours post treatment. All three doses of lasmiditan were inferior to placebo, in terms of their effect on SDLP. In the second study, both doses of lasmiditan were noninferior to placebo at 8 hours, 12 hours, and 24 hours. In both studies, the positive control confirmed the assay’s sensitivity to driving impairment. Secondary endpoints in the second study did not indicate an association between lasmiditan and clinically meaningful driving impairment at 8, 12, and 24 hours after dosing.
Single oral doses of lasmiditan were absorbed rapidly. The median time to peak concentration was approximately 2 hours, and the mean elimination half-life was about 4.25 hours. Exposure to lasmiditan was approximately dose proportional.
Before each driving assessment, investigators asked participants, “Do you feel safe to drive?” Depending on the dose, 55%-80% of participants responded affirmatively, but the majority of participants had clinically meaningful changes in SDLP. “This [result] is consistent with the FDA guidance in the literature that subject perception of safety to drive is faulty and supports the need for formal driving assessments,” said Dr. Pearlman.
Dizziness, somnolence, and headache were the most common adverse events in the study, and this result was similar to those of the phase 3 trials. Most of the adverse events were of mild to moderate severity.
Questions for further study
Among the questions that future research could address is whether the lasmiditan-related effects seen in these studies in healthy subjects are similar to those in patients with migraine when lasmiditan is taken to treat a migraine attack, said Dr. Pearlman. Another open question is whether migraine has ictal and interictal effects on driving performance.
Eli Lilly, which has developed lasmiditan, sponsored the studies. Dr. Pearlman and several of coinvestigators are employees of the company.
SOURCE: Pearlman E et al. AHS 2019, Abstract IOR06.
Philadelphia – according to research presented at the annual meeting of the American Headache Society. This impairment coincides with the time of peak drug concentration and is resolved by 8 hours after dosing.
Lasmiditan, a 5-HT1F receptor agonist, is under regulatory review as an acute treatment of migraine in adults. In two phase 3 trials, a significant proportion of participants who received the treatment were pain-free at 2 hours and free of their most bothersome symptom at 2 hours, compared with controls. The most common treatment-emergent adverse events (dizziness, paresthesia, somnolence, fatigue, and hypoaesthesia) reflected the drug’s penetration of the CNS. Because CNS-related adverse events could affect a patient’s ability to drive, the effects of lasmiditan on simulated driving were studied, consistent with regulatory guidance.
Two studies in healthy participants
Eric Pearlman, MD, PhD, senior medical director for neuroscience, U.S. Medical Affairs, at Eli Lilly, and colleagues conducted two simulated driving studies with crossover designs. In the first study, the researchers randomized 90 healthy subjects (mean age, 34.9 years) to 50 mg, 100 mg, or 200 mg of lasmiditan; 1 mg of alprazolam (an active control); or placebo. After appropriate washout periods, participants received each treatment in random order. At 1.5 hours after each treatment, participants underwent a driving assessment using a driving simulator.
In the second study, Dr. Pearlman and colleagues randomized 68 healthy subjects (mean age, 32.8 years) to 100 mg or 200 mg of lasmiditan, 50 mg of diphenhydramine (an active control), or placebo. Participants underwent driving assessments at 8, 12, and 24 hours after baseline. Participants randomized to lasmiditan received treatment at baseline, but participants randomized to diphenhydramine received treatment 2 hours before each driving assessment. The diphenhydramine arm was intended to test the sensitivity of the driving assessment to impairment, as was the alprazolam arm in the first study.
During the driving assessments, participants were asked to maintain a speed of 100 km/h and to stay in the middle of the lane. The simulated road included gentle curves and hills, and oncoming traffic appeared occasionally. Participants also completed a secondary attention task, mimicking real-world conditions. Each assessment took about 1 hour. The primary endpoint was the standard deviation of lateral position (SDLP), which is known colloquially as weaving. The investigators defined noninferiority to placebo as an SDLP of 4.4 cm or less.
Participants reported that they could drive safely
In the first study, Dr. Pearlman and colleagues reported a dose-related increase in SDLP at 1.5 hours post treatment. All three doses of lasmiditan were inferior to placebo, in terms of their effect on SDLP. In the second study, both doses of lasmiditan were noninferior to placebo at 8 hours, 12 hours, and 24 hours. In both studies, the positive control confirmed the assay’s sensitivity to driving impairment. Secondary endpoints in the second study did not indicate an association between lasmiditan and clinically meaningful driving impairment at 8, 12, and 24 hours after dosing.
Single oral doses of lasmiditan were absorbed rapidly. The median time to peak concentration was approximately 2 hours, and the mean elimination half-life was about 4.25 hours. Exposure to lasmiditan was approximately dose proportional.
Before each driving assessment, investigators asked participants, “Do you feel safe to drive?” Depending on the dose, 55%-80% of participants responded affirmatively, but the majority of participants had clinically meaningful changes in SDLP. “This [result] is consistent with the FDA guidance in the literature that subject perception of safety to drive is faulty and supports the need for formal driving assessments,” said Dr. Pearlman.
Dizziness, somnolence, and headache were the most common adverse events in the study, and this result was similar to those of the phase 3 trials. Most of the adverse events were of mild to moderate severity.
Questions for further study
Among the questions that future research could address is whether the lasmiditan-related effects seen in these studies in healthy subjects are similar to those in patients with migraine when lasmiditan is taken to treat a migraine attack, said Dr. Pearlman. Another open question is whether migraine has ictal and interictal effects on driving performance.
Eli Lilly, which has developed lasmiditan, sponsored the studies. Dr. Pearlman and several of coinvestigators are employees of the company.
SOURCE: Pearlman E et al. AHS 2019, Abstract IOR06.
Philadelphia – according to research presented at the annual meeting of the American Headache Society. This impairment coincides with the time of peak drug concentration and is resolved by 8 hours after dosing.
Lasmiditan, a 5-HT1F receptor agonist, is under regulatory review as an acute treatment of migraine in adults. In two phase 3 trials, a significant proportion of participants who received the treatment were pain-free at 2 hours and free of their most bothersome symptom at 2 hours, compared with controls. The most common treatment-emergent adverse events (dizziness, paresthesia, somnolence, fatigue, and hypoaesthesia) reflected the drug’s penetration of the CNS. Because CNS-related adverse events could affect a patient’s ability to drive, the effects of lasmiditan on simulated driving were studied, consistent with regulatory guidance.
Two studies in healthy participants
Eric Pearlman, MD, PhD, senior medical director for neuroscience, U.S. Medical Affairs, at Eli Lilly, and colleagues conducted two simulated driving studies with crossover designs. In the first study, the researchers randomized 90 healthy subjects (mean age, 34.9 years) to 50 mg, 100 mg, or 200 mg of lasmiditan; 1 mg of alprazolam (an active control); or placebo. After appropriate washout periods, participants received each treatment in random order. At 1.5 hours after each treatment, participants underwent a driving assessment using a driving simulator.
In the second study, Dr. Pearlman and colleagues randomized 68 healthy subjects (mean age, 32.8 years) to 100 mg or 200 mg of lasmiditan, 50 mg of diphenhydramine (an active control), or placebo. Participants underwent driving assessments at 8, 12, and 24 hours after baseline. Participants randomized to lasmiditan received treatment at baseline, but participants randomized to diphenhydramine received treatment 2 hours before each driving assessment. The diphenhydramine arm was intended to test the sensitivity of the driving assessment to impairment, as was the alprazolam arm in the first study.
During the driving assessments, participants were asked to maintain a speed of 100 km/h and to stay in the middle of the lane. The simulated road included gentle curves and hills, and oncoming traffic appeared occasionally. Participants also completed a secondary attention task, mimicking real-world conditions. Each assessment took about 1 hour. The primary endpoint was the standard deviation of lateral position (SDLP), which is known colloquially as weaving. The investigators defined noninferiority to placebo as an SDLP of 4.4 cm or less.
Participants reported that they could drive safely
In the first study, Dr. Pearlman and colleagues reported a dose-related increase in SDLP at 1.5 hours post treatment. All three doses of lasmiditan were inferior to placebo, in terms of their effect on SDLP. In the second study, both doses of lasmiditan were noninferior to placebo at 8 hours, 12 hours, and 24 hours. In both studies, the positive control confirmed the assay’s sensitivity to driving impairment. Secondary endpoints in the second study did not indicate an association between lasmiditan and clinically meaningful driving impairment at 8, 12, and 24 hours after dosing.
Single oral doses of lasmiditan were absorbed rapidly. The median time to peak concentration was approximately 2 hours, and the mean elimination half-life was about 4.25 hours. Exposure to lasmiditan was approximately dose proportional.
Before each driving assessment, investigators asked participants, “Do you feel safe to drive?” Depending on the dose, 55%-80% of participants responded affirmatively, but the majority of participants had clinically meaningful changes in SDLP. “This [result] is consistent with the FDA guidance in the literature that subject perception of safety to drive is faulty and supports the need for formal driving assessments,” said Dr. Pearlman.
Dizziness, somnolence, and headache were the most common adverse events in the study, and this result was similar to those of the phase 3 trials. Most of the adverse events were of mild to moderate severity.
Questions for further study
Among the questions that future research could address is whether the lasmiditan-related effects seen in these studies in healthy subjects are similar to those in patients with migraine when lasmiditan is taken to treat a migraine attack, said Dr. Pearlman. Another open question is whether migraine has ictal and interictal effects on driving performance.
Eli Lilly, which has developed lasmiditan, sponsored the studies. Dr. Pearlman and several of coinvestigators are employees of the company.
SOURCE: Pearlman E et al. AHS 2019, Abstract IOR06.
REPORTING FROM AHS 2019
Medicare’s CAR T-cell coverage decision draws praise, but cost issues linger
Physicians are praising the decision by officials at the Centers for Medicare & Medicaid Services to provide coverage of chimeric antigen receptor T-cell therapy, though they say the planned payment structure will still leave hospitals in the red when treatment is administered.
On Aug. 7, 2019, the agency issued a national coverage determination that outlines Medicare coverage of chimeric antigen receptor (CAR) T-cell therapies when they are provided in health care facilities enrolled in the Food and Drug Administration’s Risk Evaluation and Mitigation Strategies program. Medicare will cover treatments for both FDA-approved indications and off-label uses that are recommended in CMS-approved compendia.
“What you’ve seen in both the [Medicare Inpatient Prospective Payment System] rule, as well as this coverage determination, is recognition by CMS that, with CAR T cells, we are dealing with something different and something extraordinary,” Joseph Alvarnas, MD, vice president of government affairs at City of Hope, Duarte, Calif., said in an interview. “For a lot of patients who suffer with non-Hodgkin’s lymphoma, the consequences of being refractory to standard therapies mean that many patients have few great prospects for moving forward with curative treatments. CAR T cells represent a really innovative set of treatments for patients.”
A proposed national coverage determination, issued in February 2019, would have put in place a coverage with evidence development (CED) requirement for CAR T-cell therapy, covering treatment nationwide if it was offered through CMS-approved registries or clinical studies in which patients were monitored for 2 or more years following treatment.
Physicians applauded the decision not to restrict access by imposing the CED requirement.
“I think what CMS has put out is a good thing,” said Navneet Majhail, MD, director of the Cleveland Clinic’s blood and marrow transplant program, and president of the American Society for Transplantation and Cellular Therapy.
“Both at the Cleveland Clinic level and the society level, we have been asking CMS for something similar and we are really glad and excited that CMS did do this. The concern was that CMS might do this in the context of some other regulatory requirements like CED that they sometimes do. I am glad that CMS decided not to put that mechanism into place for the CAR T-cell therapies,” Dr. Majhail said.
Dr. Alvarnas, who also serves as chair of the American Society of Hematology Committee on Practice, agreed. “I see good. I don’t see bad. I have read through this and it strikes me as being written with fairly great clarity.”
Dr. Alvarnas added that he had been worried about potential restrictions, such as CED. “Once you put something under that whole rubric of coverage with evidence development, then what you do is you create a bottleneck around access to therapy because you have to have an accruing clinical trial for patients to, in fact, be able to participate in that form of therapy.”
By not imposing a CED requirement, it opens the door to better understanding the role CAR T cells play in treatment, Dr. Alvarnas noted.
“Over time, the number of patients for whom these therapeutics work, based upon real medical evidence, will escalate and grow at a pace that can far exceed the restrictions placed under a CED model,” he said, adding that the national coverage determination “gives us the license to deliver therapeutics to the right patients based upon medical evidence as it evolves, provided that these things get listed as part of the compendia. I think that is a fantastic recognition that new roles for drugs, agents, therapeutics ... are going to evolve at a pace far faster than what CMS can write rules about.”
While Medicare’s coverage determination garnered positive reviews, the agency’s Inpatient Prospective Payment System final rule – which outlines reimbursement for CAR T-cell therapy and other new technologies – got a more tepid response.
In the final rule, CMS raised the payment it makes to hospitals for administering CAR T-cell therapies through its new technology add-on payment. Payments will rise from 50% of the technology to 65%, an increase from $186,500 to $242,450 for CAR T-cell therapies, beginning on Oct. 1, 2019.
But even the bump up to 65% may not be enough.
“I see the move to 65% as a new technology add-on payment as an incremental step in the correct direction, but what we’ve done to some extent is that we’ve delayed getting to some sort of more wholly conceived system,” Dr. Alvarnas said, noting that a new system will be needed as the new technology add-on payment goes away in 2021.
Abhinav Deol, MD, of the Karmanos Cancer Institute in Detroit said it’s a challenge to cover costs for the treatment. “If you just look at the simple math, it is still going to be an economic challenge. The cells that are approved for lymphoma patients that will probably fall into the Medicare category, the list price of those cells is $373,000. Even with the 65% coverage, it’s about $235,000-$240,000 in reimbursement,” he said. “For a facility to be able to provide the care for patients, you have that delta that is still not covered. It is still going to be an economic challenge for many of the facilities to provide this care.”
Thomas LeBlanc, MD, an associate professor of medicine at Duke University, Durham, N.C., said that, while the coverage determination is a positive step, it’s not clear that it will provide meaningful access to CAR T-cell therapy because of the cost.
“These products are incredibly expensive, and the total cost of providing them is woefully underestimated in only focusing on the sticker price of the product,” he said. “Doing so ignores the significant hospital care, sometimes even critical care, as well as specialized knowledge and high touch supportive care, all of which is required to safely get patients through this revolutionary yet often risky treatment. So when CMS offers to pay just 65% of the sticker price, I suspect that many institutions will still lose six figures for each patient treated.”
Dr. LeBlanc predicted that many centers will decline to provide CAR T-cell therapy despite the increase in the new technology add-on payment, though he added that “I’d love to be wrong about this.”
Dr. Majhail agreed, noting that, even with the bump in the add-on payment, hospitals “won’t be whole in terms of providing care for these patients.”
“The reimbursement piece continues to be a challenge,” he said. “It is better than what it was, but there is still more work to be done. That is something we will have to keep working with the agency on.”
Physicians are praising the decision by officials at the Centers for Medicare & Medicaid Services to provide coverage of chimeric antigen receptor T-cell therapy, though they say the planned payment structure will still leave hospitals in the red when treatment is administered.
On Aug. 7, 2019, the agency issued a national coverage determination that outlines Medicare coverage of chimeric antigen receptor (CAR) T-cell therapies when they are provided in health care facilities enrolled in the Food and Drug Administration’s Risk Evaluation and Mitigation Strategies program. Medicare will cover treatments for both FDA-approved indications and off-label uses that are recommended in CMS-approved compendia.
“What you’ve seen in both the [Medicare Inpatient Prospective Payment System] rule, as well as this coverage determination, is recognition by CMS that, with CAR T cells, we are dealing with something different and something extraordinary,” Joseph Alvarnas, MD, vice president of government affairs at City of Hope, Duarte, Calif., said in an interview. “For a lot of patients who suffer with non-Hodgkin’s lymphoma, the consequences of being refractory to standard therapies mean that many patients have few great prospects for moving forward with curative treatments. CAR T cells represent a really innovative set of treatments for patients.”
A proposed national coverage determination, issued in February 2019, would have put in place a coverage with evidence development (CED) requirement for CAR T-cell therapy, covering treatment nationwide if it was offered through CMS-approved registries or clinical studies in which patients were monitored for 2 or more years following treatment.
Physicians applauded the decision not to restrict access by imposing the CED requirement.
“I think what CMS has put out is a good thing,” said Navneet Majhail, MD, director of the Cleveland Clinic’s blood and marrow transplant program, and president of the American Society for Transplantation and Cellular Therapy.
“Both at the Cleveland Clinic level and the society level, we have been asking CMS for something similar and we are really glad and excited that CMS did do this. The concern was that CMS might do this in the context of some other regulatory requirements like CED that they sometimes do. I am glad that CMS decided not to put that mechanism into place for the CAR T-cell therapies,” Dr. Majhail said.
Dr. Alvarnas, who also serves as chair of the American Society of Hematology Committee on Practice, agreed. “I see good. I don’t see bad. I have read through this and it strikes me as being written with fairly great clarity.”
Dr. Alvarnas added that he had been worried about potential restrictions, such as CED. “Once you put something under that whole rubric of coverage with evidence development, then what you do is you create a bottleneck around access to therapy because you have to have an accruing clinical trial for patients to, in fact, be able to participate in that form of therapy.”
By not imposing a CED requirement, it opens the door to better understanding the role CAR T cells play in treatment, Dr. Alvarnas noted.
“Over time, the number of patients for whom these therapeutics work, based upon real medical evidence, will escalate and grow at a pace that can far exceed the restrictions placed under a CED model,” he said, adding that the national coverage determination “gives us the license to deliver therapeutics to the right patients based upon medical evidence as it evolves, provided that these things get listed as part of the compendia. I think that is a fantastic recognition that new roles for drugs, agents, therapeutics ... are going to evolve at a pace far faster than what CMS can write rules about.”
While Medicare’s coverage determination garnered positive reviews, the agency’s Inpatient Prospective Payment System final rule – which outlines reimbursement for CAR T-cell therapy and other new technologies – got a more tepid response.
In the final rule, CMS raised the payment it makes to hospitals for administering CAR T-cell therapies through its new technology add-on payment. Payments will rise from 50% of the technology to 65%, an increase from $186,500 to $242,450 for CAR T-cell therapies, beginning on Oct. 1, 2019.
But even the bump up to 65% may not be enough.
“I see the move to 65% as a new technology add-on payment as an incremental step in the correct direction, but what we’ve done to some extent is that we’ve delayed getting to some sort of more wholly conceived system,” Dr. Alvarnas said, noting that a new system will be needed as the new technology add-on payment goes away in 2021.
Abhinav Deol, MD, of the Karmanos Cancer Institute in Detroit said it’s a challenge to cover costs for the treatment. “If you just look at the simple math, it is still going to be an economic challenge. The cells that are approved for lymphoma patients that will probably fall into the Medicare category, the list price of those cells is $373,000. Even with the 65% coverage, it’s about $235,000-$240,000 in reimbursement,” he said. “For a facility to be able to provide the care for patients, you have that delta that is still not covered. It is still going to be an economic challenge for many of the facilities to provide this care.”
Thomas LeBlanc, MD, an associate professor of medicine at Duke University, Durham, N.C., said that, while the coverage determination is a positive step, it’s not clear that it will provide meaningful access to CAR T-cell therapy because of the cost.
“These products are incredibly expensive, and the total cost of providing them is woefully underestimated in only focusing on the sticker price of the product,” he said. “Doing so ignores the significant hospital care, sometimes even critical care, as well as specialized knowledge and high touch supportive care, all of which is required to safely get patients through this revolutionary yet often risky treatment. So when CMS offers to pay just 65% of the sticker price, I suspect that many institutions will still lose six figures for each patient treated.”
Dr. LeBlanc predicted that many centers will decline to provide CAR T-cell therapy despite the increase in the new technology add-on payment, though he added that “I’d love to be wrong about this.”
Dr. Majhail agreed, noting that, even with the bump in the add-on payment, hospitals “won’t be whole in terms of providing care for these patients.”
“The reimbursement piece continues to be a challenge,” he said. “It is better than what it was, but there is still more work to be done. That is something we will have to keep working with the agency on.”
Physicians are praising the decision by officials at the Centers for Medicare & Medicaid Services to provide coverage of chimeric antigen receptor T-cell therapy, though they say the planned payment structure will still leave hospitals in the red when treatment is administered.
On Aug. 7, 2019, the agency issued a national coverage determination that outlines Medicare coverage of chimeric antigen receptor (CAR) T-cell therapies when they are provided in health care facilities enrolled in the Food and Drug Administration’s Risk Evaluation and Mitigation Strategies program. Medicare will cover treatments for both FDA-approved indications and off-label uses that are recommended in CMS-approved compendia.
“What you’ve seen in both the [Medicare Inpatient Prospective Payment System] rule, as well as this coverage determination, is recognition by CMS that, with CAR T cells, we are dealing with something different and something extraordinary,” Joseph Alvarnas, MD, vice president of government affairs at City of Hope, Duarte, Calif., said in an interview. “For a lot of patients who suffer with non-Hodgkin’s lymphoma, the consequences of being refractory to standard therapies mean that many patients have few great prospects for moving forward with curative treatments. CAR T cells represent a really innovative set of treatments for patients.”
A proposed national coverage determination, issued in February 2019, would have put in place a coverage with evidence development (CED) requirement for CAR T-cell therapy, covering treatment nationwide if it was offered through CMS-approved registries or clinical studies in which patients were monitored for 2 or more years following treatment.
Physicians applauded the decision not to restrict access by imposing the CED requirement.
“I think what CMS has put out is a good thing,” said Navneet Majhail, MD, director of the Cleveland Clinic’s blood and marrow transplant program, and president of the American Society for Transplantation and Cellular Therapy.
“Both at the Cleveland Clinic level and the society level, we have been asking CMS for something similar and we are really glad and excited that CMS did do this. The concern was that CMS might do this in the context of some other regulatory requirements like CED that they sometimes do. I am glad that CMS decided not to put that mechanism into place for the CAR T-cell therapies,” Dr. Majhail said.
Dr. Alvarnas, who also serves as chair of the American Society of Hematology Committee on Practice, agreed. “I see good. I don’t see bad. I have read through this and it strikes me as being written with fairly great clarity.”
Dr. Alvarnas added that he had been worried about potential restrictions, such as CED. “Once you put something under that whole rubric of coverage with evidence development, then what you do is you create a bottleneck around access to therapy because you have to have an accruing clinical trial for patients to, in fact, be able to participate in that form of therapy.”
By not imposing a CED requirement, it opens the door to better understanding the role CAR T cells play in treatment, Dr. Alvarnas noted.
“Over time, the number of patients for whom these therapeutics work, based upon real medical evidence, will escalate and grow at a pace that can far exceed the restrictions placed under a CED model,” he said, adding that the national coverage determination “gives us the license to deliver therapeutics to the right patients based upon medical evidence as it evolves, provided that these things get listed as part of the compendia. I think that is a fantastic recognition that new roles for drugs, agents, therapeutics ... are going to evolve at a pace far faster than what CMS can write rules about.”
While Medicare’s coverage determination garnered positive reviews, the agency’s Inpatient Prospective Payment System final rule – which outlines reimbursement for CAR T-cell therapy and other new technologies – got a more tepid response.
In the final rule, CMS raised the payment it makes to hospitals for administering CAR T-cell therapies through its new technology add-on payment. Payments will rise from 50% of the technology to 65%, an increase from $186,500 to $242,450 for CAR T-cell therapies, beginning on Oct. 1, 2019.
But even the bump up to 65% may not be enough.
“I see the move to 65% as a new technology add-on payment as an incremental step in the correct direction, but what we’ve done to some extent is that we’ve delayed getting to some sort of more wholly conceived system,” Dr. Alvarnas said, noting that a new system will be needed as the new technology add-on payment goes away in 2021.
Abhinav Deol, MD, of the Karmanos Cancer Institute in Detroit said it’s a challenge to cover costs for the treatment. “If you just look at the simple math, it is still going to be an economic challenge. The cells that are approved for lymphoma patients that will probably fall into the Medicare category, the list price of those cells is $373,000. Even with the 65% coverage, it’s about $235,000-$240,000 in reimbursement,” he said. “For a facility to be able to provide the care for patients, you have that delta that is still not covered. It is still going to be an economic challenge for many of the facilities to provide this care.”
Thomas LeBlanc, MD, an associate professor of medicine at Duke University, Durham, N.C., said that, while the coverage determination is a positive step, it’s not clear that it will provide meaningful access to CAR T-cell therapy because of the cost.
“These products are incredibly expensive, and the total cost of providing them is woefully underestimated in only focusing on the sticker price of the product,” he said. “Doing so ignores the significant hospital care, sometimes even critical care, as well as specialized knowledge and high touch supportive care, all of which is required to safely get patients through this revolutionary yet often risky treatment. So when CMS offers to pay just 65% of the sticker price, I suspect that many institutions will still lose six figures for each patient treated.”
Dr. LeBlanc predicted that many centers will decline to provide CAR T-cell therapy despite the increase in the new technology add-on payment, though he added that “I’d love to be wrong about this.”
Dr. Majhail agreed, noting that, even with the bump in the add-on payment, hospitals “won’t be whole in terms of providing care for these patients.”
“The reimbursement piece continues to be a challenge,” he said. “It is better than what it was, but there is still more work to be done. That is something we will have to keep working with the agency on.”
Treatment of episodic cluster headache deviates from recommendations
PHILADELPHIA – , according to an analysis presented at the annual meeting of the American Headache Society.
Although consensus treatment guidelines do not exist for episodic cluster headache, treatment of this disorder did not follow many established recommendations that call for the use of preventive medications (e.g., MacGregor et al., 2010; Sarchielli et al., 2012; and May et al., 2006). Additional preventive medication options may be needed.
Patients with episodic cluster headache have several unilateral headache attacks per day. Little information is available to guide the selection of treatments for this population, and little is known about how available treatments are used in routine practice.
Analyzing cross-sectional survey data
To address this paucity of evidence, Jeffrey Scott Andrews, PharmD, a senior research scientist at Eli Lilly in Indianapolis, and colleagues examined data from the Adelphi 2017 Cluster Headache Disease Specific Programme, a large, international, cross-sectional survey. Physicians and patients in Germany, the United Kingdom, and the United States responded to the survey. Eligible physicians consulted with at least four patients with cluster headache per month, and eligible patients had a diagnosis of episodic cluster headache that was consistent with ICHD-3 beta criteria. Additional data were collected from all participants through questionnaires.
The analysis included 309 patients in Germany, 328 in the United Kingdom, and 375 in the United States. The average age of the patients was 40 years, and most of the patients were male. Less than 70% of patients reported working full time, which may indicate “the impact of this condition on work status,” said Dr. Andrews. Patients’ average number of attacks per day within an active period was 2.4. The two most commonly reported comorbidities were anxiety and depression. About 40% of cases of depression were reported to have occurred after the receipt of a diagnosis of cluster headache.
Use of inhaled oxygen was low
Most patients received acute treatments. The proportion of patients who received acute therapy only was 53% in Germany, 48% in the United Kingdom, and 43% in the United States. Approximately 34% of patients in Germany received a combination of acute and preventive therapy, compared with 37% in the United Kingdom and 42% in the United States. The proportion of patients who received preventive therapy only was 10% in Germany, 8% in the United Kingdom, and 12% in the United States.
The most commonly prescribed acute treatment, regardless of formulation, was sumatriptan. About 60% of patients received this medication. Less than one-third of patients used inhaled oxygen. Oxygen was prescribed more often in Germany (45%) and the United Kingdom (33%), compared with the United States (19%). U.S. patients face well-known obstacles in getting access to, and reimbursement for, oxygen, said Dr. Andrews. “That’s an area that deserves increased attention.” Zolmitriptan was the third most commonly prescribed acute medication.
Among prescriptions for sumatriptan, oral and injectable formulations were approximately equally common. Recommendations, however, indicate formulations with potentially fast onset of action. “The average duration of one of these attacks is between 15 and 180 minutes, so that certainly suggests that a formulation that gives you a faster onset of action might improve outcomes,” said Dr. Andrews. The use of injectable sumatriptan was lowest in the United States and highest in the United Kingdom.
“The most common decision regarding preventive treatment was [to give] no preventive treatment,” said Dr. Andrews. Verapamil was the most commonly prescribed preventive therapy (34% in Germany, 29% in the United States, and 25% in the United Kingdom), followed by topiramate, lithium, and valproate.
Nonadherence and noncompliance was common
Fewer U.K. patients (32%) reported taking their preventive therapy as advised, compared with German patients (60%) and U.S. patients (80%). Common reasons for noncompliance, regardless of location, were forgetfulness, the belief that a dose was not needed, and side effects. Most patients in the United Kingdom (60%) and the United States (54%) reported the need to take an extra dose of their acute medication to relieve pain symptoms, compared with 30% in Germany. Furthermore, 13% of U.S. patients indicated that they took extra doses all the time or nearly all the time, compared with 2% in Germany and 7% in the United Kingdom. Among patients who had discontinued a preventive treatment in the past, the most common reasons for discontinuation were lack of efficacy and problems with tolerability.
One limitation of the study was that the survey was not designed to represent the general cluster headache or treating physician populations fully. The data may reflect selection bias in favor of physicians who treat high volumes of patients and in favor of patients who frequently seek health care. In addition, the data were based on self-reports.
“Increased awareness and educational efforts that aim at promoting the need and benefit of the preventive treatment for these patients is warranted,” Dr. Andrews concluded.
Dr. Andrews is an employee of Eli Lilly, which funded the study.
SOURCE: Nichols R et al. AHS 2019. Abstract OR04.
PHILADELPHIA – , according to an analysis presented at the annual meeting of the American Headache Society.
Although consensus treatment guidelines do not exist for episodic cluster headache, treatment of this disorder did not follow many established recommendations that call for the use of preventive medications (e.g., MacGregor et al., 2010; Sarchielli et al., 2012; and May et al., 2006). Additional preventive medication options may be needed.
Patients with episodic cluster headache have several unilateral headache attacks per day. Little information is available to guide the selection of treatments for this population, and little is known about how available treatments are used in routine practice.
Analyzing cross-sectional survey data
To address this paucity of evidence, Jeffrey Scott Andrews, PharmD, a senior research scientist at Eli Lilly in Indianapolis, and colleagues examined data from the Adelphi 2017 Cluster Headache Disease Specific Programme, a large, international, cross-sectional survey. Physicians and patients in Germany, the United Kingdom, and the United States responded to the survey. Eligible physicians consulted with at least four patients with cluster headache per month, and eligible patients had a diagnosis of episodic cluster headache that was consistent with ICHD-3 beta criteria. Additional data were collected from all participants through questionnaires.
The analysis included 309 patients in Germany, 328 in the United Kingdom, and 375 in the United States. The average age of the patients was 40 years, and most of the patients were male. Less than 70% of patients reported working full time, which may indicate “the impact of this condition on work status,” said Dr. Andrews. Patients’ average number of attacks per day within an active period was 2.4. The two most commonly reported comorbidities were anxiety and depression. About 40% of cases of depression were reported to have occurred after the receipt of a diagnosis of cluster headache.
Use of inhaled oxygen was low
Most patients received acute treatments. The proportion of patients who received acute therapy only was 53% in Germany, 48% in the United Kingdom, and 43% in the United States. Approximately 34% of patients in Germany received a combination of acute and preventive therapy, compared with 37% in the United Kingdom and 42% in the United States. The proportion of patients who received preventive therapy only was 10% in Germany, 8% in the United Kingdom, and 12% in the United States.
The most commonly prescribed acute treatment, regardless of formulation, was sumatriptan. About 60% of patients received this medication. Less than one-third of patients used inhaled oxygen. Oxygen was prescribed more often in Germany (45%) and the United Kingdom (33%), compared with the United States (19%). U.S. patients face well-known obstacles in getting access to, and reimbursement for, oxygen, said Dr. Andrews. “That’s an area that deserves increased attention.” Zolmitriptan was the third most commonly prescribed acute medication.
Among prescriptions for sumatriptan, oral and injectable formulations were approximately equally common. Recommendations, however, indicate formulations with potentially fast onset of action. “The average duration of one of these attacks is between 15 and 180 minutes, so that certainly suggests that a formulation that gives you a faster onset of action might improve outcomes,” said Dr. Andrews. The use of injectable sumatriptan was lowest in the United States and highest in the United Kingdom.
“The most common decision regarding preventive treatment was [to give] no preventive treatment,” said Dr. Andrews. Verapamil was the most commonly prescribed preventive therapy (34% in Germany, 29% in the United States, and 25% in the United Kingdom), followed by topiramate, lithium, and valproate.
Nonadherence and noncompliance was common
Fewer U.K. patients (32%) reported taking their preventive therapy as advised, compared with German patients (60%) and U.S. patients (80%). Common reasons for noncompliance, regardless of location, were forgetfulness, the belief that a dose was not needed, and side effects. Most patients in the United Kingdom (60%) and the United States (54%) reported the need to take an extra dose of their acute medication to relieve pain symptoms, compared with 30% in Germany. Furthermore, 13% of U.S. patients indicated that they took extra doses all the time or nearly all the time, compared with 2% in Germany and 7% in the United Kingdom. Among patients who had discontinued a preventive treatment in the past, the most common reasons for discontinuation were lack of efficacy and problems with tolerability.
One limitation of the study was that the survey was not designed to represent the general cluster headache or treating physician populations fully. The data may reflect selection bias in favor of physicians who treat high volumes of patients and in favor of patients who frequently seek health care. In addition, the data were based on self-reports.
“Increased awareness and educational efforts that aim at promoting the need and benefit of the preventive treatment for these patients is warranted,” Dr. Andrews concluded.
Dr. Andrews is an employee of Eli Lilly, which funded the study.
SOURCE: Nichols R et al. AHS 2019. Abstract OR04.
PHILADELPHIA – , according to an analysis presented at the annual meeting of the American Headache Society.
Although consensus treatment guidelines do not exist for episodic cluster headache, treatment of this disorder did not follow many established recommendations that call for the use of preventive medications (e.g., MacGregor et al., 2010; Sarchielli et al., 2012; and May et al., 2006). Additional preventive medication options may be needed.
Patients with episodic cluster headache have several unilateral headache attacks per day. Little information is available to guide the selection of treatments for this population, and little is known about how available treatments are used in routine practice.
Analyzing cross-sectional survey data
To address this paucity of evidence, Jeffrey Scott Andrews, PharmD, a senior research scientist at Eli Lilly in Indianapolis, and colleagues examined data from the Adelphi 2017 Cluster Headache Disease Specific Programme, a large, international, cross-sectional survey. Physicians and patients in Germany, the United Kingdom, and the United States responded to the survey. Eligible physicians consulted with at least four patients with cluster headache per month, and eligible patients had a diagnosis of episodic cluster headache that was consistent with ICHD-3 beta criteria. Additional data were collected from all participants through questionnaires.
The analysis included 309 patients in Germany, 328 in the United Kingdom, and 375 in the United States. The average age of the patients was 40 years, and most of the patients were male. Less than 70% of patients reported working full time, which may indicate “the impact of this condition on work status,” said Dr. Andrews. Patients’ average number of attacks per day within an active period was 2.4. The two most commonly reported comorbidities were anxiety and depression. About 40% of cases of depression were reported to have occurred after the receipt of a diagnosis of cluster headache.
Use of inhaled oxygen was low
Most patients received acute treatments. The proportion of patients who received acute therapy only was 53% in Germany, 48% in the United Kingdom, and 43% in the United States. Approximately 34% of patients in Germany received a combination of acute and preventive therapy, compared with 37% in the United Kingdom and 42% in the United States. The proportion of patients who received preventive therapy only was 10% in Germany, 8% in the United Kingdom, and 12% in the United States.
The most commonly prescribed acute treatment, regardless of formulation, was sumatriptan. About 60% of patients received this medication. Less than one-third of patients used inhaled oxygen. Oxygen was prescribed more often in Germany (45%) and the United Kingdom (33%), compared with the United States (19%). U.S. patients face well-known obstacles in getting access to, and reimbursement for, oxygen, said Dr. Andrews. “That’s an area that deserves increased attention.” Zolmitriptan was the third most commonly prescribed acute medication.
Among prescriptions for sumatriptan, oral and injectable formulations were approximately equally common. Recommendations, however, indicate formulations with potentially fast onset of action. “The average duration of one of these attacks is between 15 and 180 minutes, so that certainly suggests that a formulation that gives you a faster onset of action might improve outcomes,” said Dr. Andrews. The use of injectable sumatriptan was lowest in the United States and highest in the United Kingdom.
“The most common decision regarding preventive treatment was [to give] no preventive treatment,” said Dr. Andrews. Verapamil was the most commonly prescribed preventive therapy (34% in Germany, 29% in the United States, and 25% in the United Kingdom), followed by topiramate, lithium, and valproate.
Nonadherence and noncompliance was common
Fewer U.K. patients (32%) reported taking their preventive therapy as advised, compared with German patients (60%) and U.S. patients (80%). Common reasons for noncompliance, regardless of location, were forgetfulness, the belief that a dose was not needed, and side effects. Most patients in the United Kingdom (60%) and the United States (54%) reported the need to take an extra dose of their acute medication to relieve pain symptoms, compared with 30% in Germany. Furthermore, 13% of U.S. patients indicated that they took extra doses all the time or nearly all the time, compared with 2% in Germany and 7% in the United Kingdom. Among patients who had discontinued a preventive treatment in the past, the most common reasons for discontinuation were lack of efficacy and problems with tolerability.
One limitation of the study was that the survey was not designed to represent the general cluster headache or treating physician populations fully. The data may reflect selection bias in favor of physicians who treat high volumes of patients and in favor of patients who frequently seek health care. In addition, the data were based on self-reports.
“Increased awareness and educational efforts that aim at promoting the need and benefit of the preventive treatment for these patients is warranted,” Dr. Andrews concluded.
Dr. Andrews is an employee of Eli Lilly, which funded the study.
SOURCE: Nichols R et al. AHS 2019. Abstract OR04.
REPORTING FROM AHS 2019
What is the future of celiac disease management?
CHICAGO – according to a lecture delivered at the 2019 James W. Freston Conference: Food at the Intersection of Gut Health and Disease.
Home testing services and portable gluten-detection devices enable patients to diagnose and manage themselves without medical supervision, but these strategies raise concerns about accuracy and efficacy, said Benjamin Lebwohl, MD, director of clinical research at the Celiac Disease Center at Columbia University in New York.
Potential treatments on the horizon
The gluten-free diet is the only treatment proven effective for celiac disease, but it can be expensive or unpalatable for some patients. The diet also entails risks of bowel irregularity and weight gain. “The gluten-free diet remains an inadequate treatment for many people with celiac disease,” said Dr. Lebwohl.
Tennyson et al. found that 66% of patients with biopsy-proven celiac disease are interested in nondietary therapy (Therap Adv Gastroenterol. 2013;6[5]:358-64.). Such patients are more likely to be male and older than 50 years.
Latiglutenase, a gluten enzyme derived from bacteria and cereal, is among the pharmacotherapies being investigated as a treatment for nonresponsive celiac disease. It reduces or eliminates the toxicity of gluten. In a recent phase 2b trial, however, the treatment did not achieve the primary outcome measure of histologic improvement (Gastroenterology. 2017;152[4]:787-98.). Compared with placebo, the drug was not associated with significant improvements in histologic and symptom scores.
Another drug in development is the tight-junction modulator larazotide acetate. Studies of zonula occludens toxin and its mammalian analogue zonulin led to the development of larazotide acetate. Leffler et al. found that a 0.5-mg dose of the drug reduced symptoms of nonresponsive celiac disease in patients who were following a gluten-free diet, compared with patients treated with the diet alone (Gastroenterology. 2015;148[7]:1311-9.). Innovate Pharmaceuticals plans to study the drug in phase 3 trials, said Dr. Lebwohl.
ImmunosanT has studied Nexvax2, which promotes gluten peptide desensitization. A phase 2 study examined the drug’s efficacy in reducing symptoms during a masked food challenge. The company discontinued this study when an interim analysis showed that the drug provided no more protection from gluten exposure than placebo. Nexvax2 was safe and well tolerated, and the study revealed no new safety signals.
In addition to newly developed therapies, researchers are studying whether drugs marketed for other indications could be effective treatments for celiac disease. For example, budesonide, a treatment for asthma and chronic obstructive pulmonary disease, is being investigated for nonresponsive celiac disease and refractory celiac disease. Other research is examining whether budesonide could provide effective protection after inadvertent gluten exposure. Systemic steroids, immunosuppressants such as azathioprine, chemotherapeutics such as cladribine, and mesalamine, which is a treatment for inflammatory bowel disease, also are under investigation.
But several questions related to drug development for celiac disease remain unanswered. For example, whether researchers should choose clinical or histologic endpoints for their trials is a subject of debate. “Probably, we’re going to be looking for two endpoints,” said Dr. Lebwohl. No consensus has been established about whether trials should include patients for whom diagnosis is based on a test other than a biopsy. Also, the effect of nondietary therapy on adherence to the gluten-free diet remains to be clarified.
Self-management of celiac disease
“We’re in a new era” of self-monitoring and direct-to-consumer advertising aimed at patients with celiac disease, said Dr. Lebwohl. Products and services that enable patients to diagnose and manage themselves independently are broadly available. For example, 23andMe provides at-home testing for HLA-DQ2.5 and HLA-DQ8, which could support a diagnosis of celiac disease. The service does not, however, test for HLA-DQ2.2, which is present in about 5% of patients with celiac disease. This testing consequently has high negative-predictive value, but poor positive-predictive value, said Dr. Lebwohl.
Similarly, ImAware provides blood tests that patients can take at home and send to the company for results. The tests look for antibodies such as tissue transglutaminase immunoglobulin A/immunoglobulin G and deamidated gliadin peptide IgA/IgG. The company advises patients to share their results with a health care professional.
Furthermore, portable devices such as Nima are marketed as gluten detectors. One study of the device included 804 users from all 50 states. The device found gluten in 32% of all restaurant food tested advertised as gluten-free. The interpretation of these results should take into account the fact that the device may detect gluten levels lower than 20 ppm, which generally are safe for patients with celiac disease. Furthermore, the data were uploaded voluntarily by users, and thus are not a random sample (Am J Gastroenterol. 2019;114[5]:792-7.). The device cannot detect certain forms of gluten such as barley malt. Because of limitations like these, the Nima device has “vocal critics,” said Dr. Lebwohl.
A profusion of books that offer dietary advice for patients with celiac disease also has become available. Data from Google Trends indicate that the popularity of the gluten-free diet spread from small pockets of the country in 2006 to most of the states in 2015.
Yet this “do-it-yourself” approach to celiac disease raises several concerns, said Dr. Lebwohl. Patients are at risk of interpreting their test results incorrectly, for example. Failing to consult a dietitian or physician, each of whom could have expertise in the field, entails risks as well. “Knowledgeable and empathetic care-giving is more important than ever,” Dr. Lebwohl concluded.
Dr. Lebwohl is on the medical advisory board of Innovate Biopharmaceuticals, a consultant for Takeda, and an unpaid advisor for the Nima Sensor.
CHICAGO – according to a lecture delivered at the 2019 James W. Freston Conference: Food at the Intersection of Gut Health and Disease.
Home testing services and portable gluten-detection devices enable patients to diagnose and manage themselves without medical supervision, but these strategies raise concerns about accuracy and efficacy, said Benjamin Lebwohl, MD, director of clinical research at the Celiac Disease Center at Columbia University in New York.
Potential treatments on the horizon
The gluten-free diet is the only treatment proven effective for celiac disease, but it can be expensive or unpalatable for some patients. The diet also entails risks of bowel irregularity and weight gain. “The gluten-free diet remains an inadequate treatment for many people with celiac disease,” said Dr. Lebwohl.
Tennyson et al. found that 66% of patients with biopsy-proven celiac disease are interested in nondietary therapy (Therap Adv Gastroenterol. 2013;6[5]:358-64.). Such patients are more likely to be male and older than 50 years.
Latiglutenase, a gluten enzyme derived from bacteria and cereal, is among the pharmacotherapies being investigated as a treatment for nonresponsive celiac disease. It reduces or eliminates the toxicity of gluten. In a recent phase 2b trial, however, the treatment did not achieve the primary outcome measure of histologic improvement (Gastroenterology. 2017;152[4]:787-98.). Compared with placebo, the drug was not associated with significant improvements in histologic and symptom scores.
Another drug in development is the tight-junction modulator larazotide acetate. Studies of zonula occludens toxin and its mammalian analogue zonulin led to the development of larazotide acetate. Leffler et al. found that a 0.5-mg dose of the drug reduced symptoms of nonresponsive celiac disease in patients who were following a gluten-free diet, compared with patients treated with the diet alone (Gastroenterology. 2015;148[7]:1311-9.). Innovate Pharmaceuticals plans to study the drug in phase 3 trials, said Dr. Lebwohl.
ImmunosanT has studied Nexvax2, which promotes gluten peptide desensitization. A phase 2 study examined the drug’s efficacy in reducing symptoms during a masked food challenge. The company discontinued this study when an interim analysis showed that the drug provided no more protection from gluten exposure than placebo. Nexvax2 was safe and well tolerated, and the study revealed no new safety signals.
In addition to newly developed therapies, researchers are studying whether drugs marketed for other indications could be effective treatments for celiac disease. For example, budesonide, a treatment for asthma and chronic obstructive pulmonary disease, is being investigated for nonresponsive celiac disease and refractory celiac disease. Other research is examining whether budesonide could provide effective protection after inadvertent gluten exposure. Systemic steroids, immunosuppressants such as azathioprine, chemotherapeutics such as cladribine, and mesalamine, which is a treatment for inflammatory bowel disease, also are under investigation.
But several questions related to drug development for celiac disease remain unanswered. For example, whether researchers should choose clinical or histologic endpoints for their trials is a subject of debate. “Probably, we’re going to be looking for two endpoints,” said Dr. Lebwohl. No consensus has been established about whether trials should include patients for whom diagnosis is based on a test other than a biopsy. Also, the effect of nondietary therapy on adherence to the gluten-free diet remains to be clarified.
Self-management of celiac disease
“We’re in a new era” of self-monitoring and direct-to-consumer advertising aimed at patients with celiac disease, said Dr. Lebwohl. Products and services that enable patients to diagnose and manage themselves independently are broadly available. For example, 23andMe provides at-home testing for HLA-DQ2.5 and HLA-DQ8, which could support a diagnosis of celiac disease. The service does not, however, test for HLA-DQ2.2, which is present in about 5% of patients with celiac disease. This testing consequently has high negative-predictive value, but poor positive-predictive value, said Dr. Lebwohl.
Similarly, ImAware provides blood tests that patients can take at home and send to the company for results. The tests look for antibodies such as tissue transglutaminase immunoglobulin A/immunoglobulin G and deamidated gliadin peptide IgA/IgG. The company advises patients to share their results with a health care professional.
Furthermore, portable devices such as Nima are marketed as gluten detectors. One study of the device included 804 users from all 50 states. The device found gluten in 32% of all restaurant food tested advertised as gluten-free. The interpretation of these results should take into account the fact that the device may detect gluten levels lower than 20 ppm, which generally are safe for patients with celiac disease. Furthermore, the data were uploaded voluntarily by users, and thus are not a random sample (Am J Gastroenterol. 2019;114[5]:792-7.). The device cannot detect certain forms of gluten such as barley malt. Because of limitations like these, the Nima device has “vocal critics,” said Dr. Lebwohl.
A profusion of books that offer dietary advice for patients with celiac disease also has become available. Data from Google Trends indicate that the popularity of the gluten-free diet spread from small pockets of the country in 2006 to most of the states in 2015.
Yet this “do-it-yourself” approach to celiac disease raises several concerns, said Dr. Lebwohl. Patients are at risk of interpreting their test results incorrectly, for example. Failing to consult a dietitian or physician, each of whom could have expertise in the field, entails risks as well. “Knowledgeable and empathetic care-giving is more important than ever,” Dr. Lebwohl concluded.
Dr. Lebwohl is on the medical advisory board of Innovate Biopharmaceuticals, a consultant for Takeda, and an unpaid advisor for the Nima Sensor.
CHICAGO – according to a lecture delivered at the 2019 James W. Freston Conference: Food at the Intersection of Gut Health and Disease.
Home testing services and portable gluten-detection devices enable patients to diagnose and manage themselves without medical supervision, but these strategies raise concerns about accuracy and efficacy, said Benjamin Lebwohl, MD, director of clinical research at the Celiac Disease Center at Columbia University in New York.
Potential treatments on the horizon
The gluten-free diet is the only treatment proven effective for celiac disease, but it can be expensive or unpalatable for some patients. The diet also entails risks of bowel irregularity and weight gain. “The gluten-free diet remains an inadequate treatment for many people with celiac disease,” said Dr. Lebwohl.
Tennyson et al. found that 66% of patients with biopsy-proven celiac disease are interested in nondietary therapy (Therap Adv Gastroenterol. 2013;6[5]:358-64.). Such patients are more likely to be male and older than 50 years.
Latiglutenase, a gluten enzyme derived from bacteria and cereal, is among the pharmacotherapies being investigated as a treatment for nonresponsive celiac disease. It reduces or eliminates the toxicity of gluten. In a recent phase 2b trial, however, the treatment did not achieve the primary outcome measure of histologic improvement (Gastroenterology. 2017;152[4]:787-98.). Compared with placebo, the drug was not associated with significant improvements in histologic and symptom scores.
Another drug in development is the tight-junction modulator larazotide acetate. Studies of zonula occludens toxin and its mammalian analogue zonulin led to the development of larazotide acetate. Leffler et al. found that a 0.5-mg dose of the drug reduced symptoms of nonresponsive celiac disease in patients who were following a gluten-free diet, compared with patients treated with the diet alone (Gastroenterology. 2015;148[7]:1311-9.). Innovate Pharmaceuticals plans to study the drug in phase 3 trials, said Dr. Lebwohl.
ImmunosanT has studied Nexvax2, which promotes gluten peptide desensitization. A phase 2 study examined the drug’s efficacy in reducing symptoms during a masked food challenge. The company discontinued this study when an interim analysis showed that the drug provided no more protection from gluten exposure than placebo. Nexvax2 was safe and well tolerated, and the study revealed no new safety signals.
In addition to newly developed therapies, researchers are studying whether drugs marketed for other indications could be effective treatments for celiac disease. For example, budesonide, a treatment for asthma and chronic obstructive pulmonary disease, is being investigated for nonresponsive celiac disease and refractory celiac disease. Other research is examining whether budesonide could provide effective protection after inadvertent gluten exposure. Systemic steroids, immunosuppressants such as azathioprine, chemotherapeutics such as cladribine, and mesalamine, which is a treatment for inflammatory bowel disease, also are under investigation.
But several questions related to drug development for celiac disease remain unanswered. For example, whether researchers should choose clinical or histologic endpoints for their trials is a subject of debate. “Probably, we’re going to be looking for two endpoints,” said Dr. Lebwohl. No consensus has been established about whether trials should include patients for whom diagnosis is based on a test other than a biopsy. Also, the effect of nondietary therapy on adherence to the gluten-free diet remains to be clarified.
Self-management of celiac disease
“We’re in a new era” of self-monitoring and direct-to-consumer advertising aimed at patients with celiac disease, said Dr. Lebwohl. Products and services that enable patients to diagnose and manage themselves independently are broadly available. For example, 23andMe provides at-home testing for HLA-DQ2.5 and HLA-DQ8, which could support a diagnosis of celiac disease. The service does not, however, test for HLA-DQ2.2, which is present in about 5% of patients with celiac disease. This testing consequently has high negative-predictive value, but poor positive-predictive value, said Dr. Lebwohl.
Similarly, ImAware provides blood tests that patients can take at home and send to the company for results. The tests look for antibodies such as tissue transglutaminase immunoglobulin A/immunoglobulin G and deamidated gliadin peptide IgA/IgG. The company advises patients to share their results with a health care professional.
Furthermore, portable devices such as Nima are marketed as gluten detectors. One study of the device included 804 users from all 50 states. The device found gluten in 32% of all restaurant food tested advertised as gluten-free. The interpretation of these results should take into account the fact that the device may detect gluten levels lower than 20 ppm, which generally are safe for patients with celiac disease. Furthermore, the data were uploaded voluntarily by users, and thus are not a random sample (Am J Gastroenterol. 2019;114[5]:792-7.). The device cannot detect certain forms of gluten such as barley malt. Because of limitations like these, the Nima device has “vocal critics,” said Dr. Lebwohl.
A profusion of books that offer dietary advice for patients with celiac disease also has become available. Data from Google Trends indicate that the popularity of the gluten-free diet spread from small pockets of the country in 2006 to most of the states in 2015.
Yet this “do-it-yourself” approach to celiac disease raises several concerns, said Dr. Lebwohl. Patients are at risk of interpreting their test results incorrectly, for example. Failing to consult a dietitian or physician, each of whom could have expertise in the field, entails risks as well. “Knowledgeable and empathetic care-giving is more important than ever,” Dr. Lebwohl concluded.
Dr. Lebwohl is on the medical advisory board of Innovate Biopharmaceuticals, a consultant for Takeda, and an unpaid advisor for the Nima Sensor.
EXPERT ANALYSIS FROM THE 2019 FRESTON CONFERENCE
Are rigid HPV vaccination schedules really necessary?
LJUBLJANA, SLOVENIA – Vladimir Gilca, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This novel observation from a post hoc analysis of two clinical trials conducted by the same research team has important potential implications for both clinical practice and public health, according to Dr. Gilca of the Quebec National Institute of Public Health and Laval University, Quebec City.
“A less rigid immunization schedule might facilitate the coadministration of HPV vaccine with other vaccines, such as meningococcal or Tdap, and reduce the number of vaccination visits. Also, our data support the decision to offer only one dose in cases of vaccine shortage, like we have presently in many countries around the world, with the possibility of giving the second dose several years later when the shortage is resolved,” he said.
He presented a comparison of anti-HPV geometric mean IgG antibody titers and their distribution in two clinical trials with serologic assays performed in the same lab using the same enzyme-linked immunosorbent assay procedures. In the first study, 173 boys and girls aged 9-10 years received two doses of a 9-valent HPV vaccine 6 months apart. In the second trial, 31 girls were vaccinated with one dose of a quadrivalent HPV vaccine at age 9-14 years and then received a dose of the 9-valent vaccine at a mean of 5.4 years and maximum of 8 years later. Blood samples were obtained before and 1 month after the second dose in both trials.
Despite the enormous differences in the time between the first and second doses in the two studies, 100% of subjects in both trials were seropositive to HPV 6, 11, 16, and 18, with similar geometric mean titers and titer distributions before dose number two. Moreover, 1 month after the second dose, the geometric mean titers jumped 40-91 times in study participants with a 6-month dosing interval, and similarly by 60-82 times in those with the far lengthier interval. Titer distributions after the second dose were equivalent in the two studies.
Dr. Gilca and coinvestigators looked at subgroups who received their second dose 3-4 years, 6, or 7-8 years after the first. The time difference didn’t affect the distribution of antibodies.
“We conclude that delayed administration of the second dose has no negative impact on the magnitude of the immune response,” he declared.
There are abundant precedents for this phenomenon of high immunogenicity of delayed doses of vaccine. Rabies, anthrax, hepatitis A and B, and tick-borne encephalitis vaccines have all been shown to elicit at least a similar magnitude of immune response after delayed administration of a second or third dose, compared with dosing at the guideline-recommended intervals, he noted.
Asked about the possible approach of giving just one dose of HPV vaccine, as was supported based upon retrospective data in a high-profile presentation earlier at ESPID 2019, Dr. Gilca replied, “The data we’ve seen so far show clinical noninferiority between one, two, and three doses. An approach that might be used by at least some countries is to give, for example, one dose of HPV vaccine in grade 4 and to then wait for confirmatory data about the efficacy of one dose, which we expect in the next 4-5 years. At least five or six clinical trials are ongoing on one dose versus two or three doses.”
He reported having no financial conflicts of interest regarding his presentation.
SOURCE: Gilca V et al. ESPID 2019, Abstract.
LJUBLJANA, SLOVENIA – Vladimir Gilca, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This novel observation from a post hoc analysis of two clinical trials conducted by the same research team has important potential implications for both clinical practice and public health, according to Dr. Gilca of the Quebec National Institute of Public Health and Laval University, Quebec City.
“A less rigid immunization schedule might facilitate the coadministration of HPV vaccine with other vaccines, such as meningococcal or Tdap, and reduce the number of vaccination visits. Also, our data support the decision to offer only one dose in cases of vaccine shortage, like we have presently in many countries around the world, with the possibility of giving the second dose several years later when the shortage is resolved,” he said.
He presented a comparison of anti-HPV geometric mean IgG antibody titers and their distribution in two clinical trials with serologic assays performed in the same lab using the same enzyme-linked immunosorbent assay procedures. In the first study, 173 boys and girls aged 9-10 years received two doses of a 9-valent HPV vaccine 6 months apart. In the second trial, 31 girls were vaccinated with one dose of a quadrivalent HPV vaccine at age 9-14 years and then received a dose of the 9-valent vaccine at a mean of 5.4 years and maximum of 8 years later. Blood samples were obtained before and 1 month after the second dose in both trials.
Despite the enormous differences in the time between the first and second doses in the two studies, 100% of subjects in both trials were seropositive to HPV 6, 11, 16, and 18, with similar geometric mean titers and titer distributions before dose number two. Moreover, 1 month after the second dose, the geometric mean titers jumped 40-91 times in study participants with a 6-month dosing interval, and similarly by 60-82 times in those with the far lengthier interval. Titer distributions after the second dose were equivalent in the two studies.
Dr. Gilca and coinvestigators looked at subgroups who received their second dose 3-4 years, 6, or 7-8 years after the first. The time difference didn’t affect the distribution of antibodies.
“We conclude that delayed administration of the second dose has no negative impact on the magnitude of the immune response,” he declared.
There are abundant precedents for this phenomenon of high immunogenicity of delayed doses of vaccine. Rabies, anthrax, hepatitis A and B, and tick-borne encephalitis vaccines have all been shown to elicit at least a similar magnitude of immune response after delayed administration of a second or third dose, compared with dosing at the guideline-recommended intervals, he noted.
Asked about the possible approach of giving just one dose of HPV vaccine, as was supported based upon retrospective data in a high-profile presentation earlier at ESPID 2019, Dr. Gilca replied, “The data we’ve seen so far show clinical noninferiority between one, two, and three doses. An approach that might be used by at least some countries is to give, for example, one dose of HPV vaccine in grade 4 and to then wait for confirmatory data about the efficacy of one dose, which we expect in the next 4-5 years. At least five or six clinical trials are ongoing on one dose versus two or three doses.”
He reported having no financial conflicts of interest regarding his presentation.
SOURCE: Gilca V et al. ESPID 2019, Abstract.
LJUBLJANA, SLOVENIA – Vladimir Gilca, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This novel observation from a post hoc analysis of two clinical trials conducted by the same research team has important potential implications for both clinical practice and public health, according to Dr. Gilca of the Quebec National Institute of Public Health and Laval University, Quebec City.
“A less rigid immunization schedule might facilitate the coadministration of HPV vaccine with other vaccines, such as meningococcal or Tdap, and reduce the number of vaccination visits. Also, our data support the decision to offer only one dose in cases of vaccine shortage, like we have presently in many countries around the world, with the possibility of giving the second dose several years later when the shortage is resolved,” he said.
He presented a comparison of anti-HPV geometric mean IgG antibody titers and their distribution in two clinical trials with serologic assays performed in the same lab using the same enzyme-linked immunosorbent assay procedures. In the first study, 173 boys and girls aged 9-10 years received two doses of a 9-valent HPV vaccine 6 months apart. In the second trial, 31 girls were vaccinated with one dose of a quadrivalent HPV vaccine at age 9-14 years and then received a dose of the 9-valent vaccine at a mean of 5.4 years and maximum of 8 years later. Blood samples were obtained before and 1 month after the second dose in both trials.
Despite the enormous differences in the time between the first and second doses in the two studies, 100% of subjects in both trials were seropositive to HPV 6, 11, 16, and 18, with similar geometric mean titers and titer distributions before dose number two. Moreover, 1 month after the second dose, the geometric mean titers jumped 40-91 times in study participants with a 6-month dosing interval, and similarly by 60-82 times in those with the far lengthier interval. Titer distributions after the second dose were equivalent in the two studies.
Dr. Gilca and coinvestigators looked at subgroups who received their second dose 3-4 years, 6, or 7-8 years after the first. The time difference didn’t affect the distribution of antibodies.
“We conclude that delayed administration of the second dose has no negative impact on the magnitude of the immune response,” he declared.
There are abundant precedents for this phenomenon of high immunogenicity of delayed doses of vaccine. Rabies, anthrax, hepatitis A and B, and tick-borne encephalitis vaccines have all been shown to elicit at least a similar magnitude of immune response after delayed administration of a second or third dose, compared with dosing at the guideline-recommended intervals, he noted.
Asked about the possible approach of giving just one dose of HPV vaccine, as was supported based upon retrospective data in a high-profile presentation earlier at ESPID 2019, Dr. Gilca replied, “The data we’ve seen so far show clinical noninferiority between one, two, and three doses. An approach that might be used by at least some countries is to give, for example, one dose of HPV vaccine in grade 4 and to then wait for confirmatory data about the efficacy of one dose, which we expect in the next 4-5 years. At least five or six clinical trials are ongoing on one dose versus two or three doses.”
He reported having no financial conflicts of interest regarding his presentation.
SOURCE: Gilca V et al. ESPID 2019, Abstract.
REPORTING FROM ESPID 2019