Patricia L. Turner, MD, FACS, Director of the American College of Surgeons Division of Member Services, received the 2016 National Medical Association (NMA) Council on Concerns of Women Physicians (CCWP) Service Award. Dr. Turner received the award July 31 at the CCWP Annual Muriel Petioni, MD, Awards Luncheon, which took place during the NMA’s 114th Annual Convention and Scientific Assembly in Los Angeles.

This award honors women physicians who, through research, community service, and activism, strive to eliminate health care disparities, provide people of color with quality health care, and address women’s health and professional issues. The awards program, the most highly attended event of the convention, continues to grow in popularity. This year’s program featured award-winning actress and television director Regina King. Read more about the NMA and the award at http://www.afassanoco.com/nma/ccwpprogram.html.

Patricia L. Turner, MD, FACS, Director of the American College of Surgeons Division of Member Services, received the 2016 National Medical Association (NMA) Council on Concerns of Women Physicians (CCWP) Service Award. Dr. Turner received the award July 31 at the CCWP Annual Muriel Petioni, MD, Awards Luncheon, which took place during the NMA’s 114th Annual Convention and Scientific Assembly in Los Angeles.

This award honors women physicians who, through research, community service, and activism, strive to eliminate health care disparities, provide people of color with quality health care, and address women’s health and professional issues. The awards program, the most highly attended event of the convention, continues to grow in popularity. This year’s program featured award-winning actress and television director Regina King. Read more about the NMA and the award at http://www.afassanoco.com/nma/ccwpprogram.html.

Patricia L. Turner, MD, FACS, Director of the American College of Surgeons Division of Member Services, received the 2016 National Medical Association (NMA) Council on Concerns of Women Physicians (CCWP) Service Award. Dr. Turner received the award July 31 at the CCWP Annual Muriel Petioni, MD, Awards Luncheon, which took place during the NMA’s 114th Annual Convention and Scientific Assembly in Los Angeles.

This award honors women physicians who, through research, community service, and activism, strive to eliminate health care disparities, provide people of color with quality health care, and address women’s health and professional issues. The awards program, the most highly attended event of the convention, continues to grow in popularity. This year’s program featured award-winning actress and television director Regina King. Read more about the NMA and the award at http://www.afassanoco.com/nma/ccwpprogram.html.

SAN FRANCISCO – The patient, a man in his early 50s, smiled as he sang about flatulence. He seemed alert, relaxed, and aware of his wife and the neurologist in the room. Only the length and subject matter of his composition signaled a problem.

Two years later, this same patient was completely nonverbal – a classic case of frontotemporal dementia, said Howard Rosen, MD, a neurologist affiliated with the University of California, San Francisco. He and other experts discussed the disease at the 18th Congress of the International Psychogeriatric Association.

Frontotemporal dementia affects about 15-22 of every 100,000 individuals, and an additional 3-4 will be diagnosed in the next year, according to past studies (Int Rev Psychiatry. 2013 Apr;25[2]:130-7). This and other forms of dementia are often preceded by nondegenerative psychiatric syndromes, such as depression or anxiety, Dr. Rosen noted. “It is often unclear whether patients actually have that psychiatric disorder or symptoms of the disorder that are actually frontotemporal dementia,” he said. “Depression is most common and likely represents a misdiagnosis.”

Frontotemporal dementia also is often misdiagnosed as Alzheimer’s but differs in that about three-quarters of cases begin in midlife. This heightens the need for timely diagnosis and specialized services to support patients and caregivers, who may still have children at home, Dr. Rosen said. Unfortunately, such services are often lacking, he added.

Clinicians who treat patients with frontotemporal dementia encounter several “canonical variants” of the disease, he continued. These include nonfluent and semantic variants of primary progressive aphasia and a third behavioral variant. The nonfluent variant is characterized by frequent grammatical errors (agrammatism), hesitation over individual words, and speech apraxia. In contrast, patients with the semantic variant cannot name common objects, such as a ball or a cup, and only vaguely understand their use. Finally, those with the behavioral variant show “bizarre socioemotional changes,” including disinhibition and antisocial behavior, loss of empathy, “exceedingly poor” judgment, overeating, apathy, and hoarding and other compulsive behaviors, Dr. Rosen said.

Behavioral variant frontotemporal dementia can be especially difficult for family members, other experts said. Jan Oyebode, MD, of the University of Bradford, England, and her colleagues prospectively interviewed seven families and five patients with this form of dementia every 6-9 months to observe how the “lived experience” of the disease changed over time. Family members described struggling to understand emergent and worsening irritability, and lack of empathy in their loved one. “We saw this during the family interviews,” Dr. Oyebode added. “For example, one day a [caregiver with cancer] came back from chemotherapy, and her husband [the patient] turned to her and said something like, ‘you’re late. I’m hungry,’ and did not ask how the chemotherapy had gone. She had tears in her eyes. We had a number of examples like that.”

Another patient with behavioral variant frontotemporal dementia began “going off” on his children, something he had not done before, Dr. Oyebode said. Intellectually, he understood that frontotemporal dementia was causing his behavior, but he struggled to control his rage and could not empathize with his children’s pain, she added. “If you live with behavioral variant frontotemporal dementia, you may be only partially aware of changes in our empathy,” she added. “Because you don’t appreciate the way you have changed, you are puzzled by others’ reactions to you. And because you don’t understand the changes in your own abilities, you tend to attribute them to external factors and blame or avoid others.”

But over time, four of the five patients acknowledged that their families had the most insight into their changing cognition and behavior, and some clearly tried to control their behaviors, Dr. Oyebode said. Nonetheless, it is important to understand that even when patients factually accept their diagnosis, they tend not to “live it from the inside,” she emphasized. “Because you [the patient] feel the same, you may be somewhat bewildered by the changes in your life. But because you do not ‘feel’ the changes, you are able to accept them, even though they are dramatic.”

Such acceptance comes more easily when patients receive calm, direct feedback from family members, she also reported. Family members, too, valued open communication as key to their own process. “For families, there needed to be a [transition] from awareness of the dementia, to empathic understanding, to developing coping processes,” she said. For example, family members learned to help patients plan ahead, step by step, for outings and deconstruct tasks by working them out on a whiteboard, she said.

Studies like this one are important because there is little research on presenile dementia, Dr. Rosen said. “When you’re dealing with young-onset dementia, behavioral variant frontotemporal dementia has to be very prominent in your mind” – particularly because it progresses faster than do the other variants and about twice as fast as does Alzheimer’s disease. It can be easier to understand the symptomatic complexities of frontotemporal dementia by mapping them to specific neuroanatomy, Dr. Rosen added. Imaging is central to diagnosis, and indeed, frontotemporal dementia is the only neurodegenerative disease for which Medicare has approved FDG-PET scans as a diagnostic measure.

“What really differentiates frontotemporal dementia [from other dementias] is involvement of the orbital and medial lobes,” Dr. Rosen emphasized. “Think of Phineas Gage – the rod went right through the part of the brain we’re talking about.”

SAN FRANCISCO – The patient, a man in his early 50s, smiled as he sang about flatulence. He seemed alert, relaxed, and aware of his wife and the neurologist in the room. Only the length and subject matter of his composition signaled a problem.

Two years later, this same patient was completely nonverbal – a classic case of frontotemporal dementia, said Howard Rosen, MD, a neurologist affiliated with the University of California, San Francisco. He and other experts discussed the disease at the 18th Congress of the International Psychogeriatric Association.

Frontotemporal dementia affects about 15-22 of every 100,000 individuals, and an additional 3-4 will be diagnosed in the next year, according to past studies (Int Rev Psychiatry. 2013 Apr;25[2]:130-7). This and other forms of dementia are often preceded by nondegenerative psychiatric syndromes, such as depression or anxiety, Dr. Rosen noted. “It is often unclear whether patients actually have that psychiatric disorder or symptoms of the disorder that are actually frontotemporal dementia,” he said. “Depression is most common and likely represents a misdiagnosis.”

Frontotemporal dementia also is often misdiagnosed as Alzheimer’s but differs in that about three-quarters of cases begin in midlife. This heightens the need for timely diagnosis and specialized services to support patients and caregivers, who may still have children at home, Dr. Rosen said. Unfortunately, such services are often lacking, he added.

Clinicians who treat patients with frontotemporal dementia encounter several “canonical variants” of the disease, he continued. These include nonfluent and semantic variants of primary progressive aphasia and a third behavioral variant. The nonfluent variant is characterized by frequent grammatical errors (agrammatism), hesitation over individual words, and speech apraxia. In contrast, patients with the semantic variant cannot name common objects, such as a ball or a cup, and only vaguely understand their use. Finally, those with the behavioral variant show “bizarre socioemotional changes,” including disinhibition and antisocial behavior, loss of empathy, “exceedingly poor” judgment, overeating, apathy, and hoarding and other compulsive behaviors, Dr. Rosen said.

Behavioral variant frontotemporal dementia can be especially difficult for family members, other experts said. Jan Oyebode, MD, of the University of Bradford, England, and her colleagues prospectively interviewed seven families and five patients with this form of dementia every 6-9 months to observe how the “lived experience” of the disease changed over time. Family members described struggling to understand emergent and worsening irritability, and lack of empathy in their loved one. “We saw this during the family interviews,” Dr. Oyebode added. “For example, one day a [caregiver with cancer] came back from chemotherapy, and her husband [the patient] turned to her and said something like, ‘you’re late. I’m hungry,’ and did not ask how the chemotherapy had gone. She had tears in her eyes. We had a number of examples like that.”

Another patient with behavioral variant frontotemporal dementia began “going off” on his children, something he had not done before, Dr. Oyebode said. Intellectually, he understood that frontotemporal dementia was causing his behavior, but he struggled to control his rage and could not empathize with his children’s pain, she added. “If you live with behavioral variant frontotemporal dementia, you may be only partially aware of changes in our empathy,” she added. “Because you don’t appreciate the way you have changed, you are puzzled by others’ reactions to you. And because you don’t understand the changes in your own abilities, you tend to attribute them to external factors and blame or avoid others.”

But over time, four of the five patients acknowledged that their families had the most insight into their changing cognition and behavior, and some clearly tried to control their behaviors, Dr. Oyebode said. Nonetheless, it is important to understand that even when patients factually accept their diagnosis, they tend not to “live it from the inside,” she emphasized. “Because you [the patient] feel the same, you may be somewhat bewildered by the changes in your life. But because you do not ‘feel’ the changes, you are able to accept them, even though they are dramatic.”

Such acceptance comes more easily when patients receive calm, direct feedback from family members, she also reported. Family members, too, valued open communication as key to their own process. “For families, there needed to be a [transition] from awareness of the dementia, to empathic understanding, to developing coping processes,” she said. For example, family members learned to help patients plan ahead, step by step, for outings and deconstruct tasks by working them out on a whiteboard, she said.

Studies like this one are important because there is little research on presenile dementia, Dr. Rosen said. “When you’re dealing with young-onset dementia, behavioral variant frontotemporal dementia has to be very prominent in your mind” – particularly because it progresses faster than do the other variants and about twice as fast as does Alzheimer’s disease. It can be easier to understand the symptomatic complexities of frontotemporal dementia by mapping them to specific neuroanatomy, Dr. Rosen added. Imaging is central to diagnosis, and indeed, frontotemporal dementia is the only neurodegenerative disease for which Medicare has approved FDG-PET scans as a diagnostic measure.

“What really differentiates frontotemporal dementia [from other dementias] is involvement of the orbital and medial lobes,” Dr. Rosen emphasized. “Think of Phineas Gage – the rod went right through the part of the brain we’re talking about.”

SAN FRANCISCO – The patient, a man in his early 50s, smiled as he sang about flatulence. He seemed alert, relaxed, and aware of his wife and the neurologist in the room. Only the length and subject matter of his composition signaled a problem.

Two years later, this same patient was completely nonverbal – a classic case of frontotemporal dementia, said Howard Rosen, MD, a neurologist affiliated with the University of California, San Francisco. He and other experts discussed the disease at the 18th Congress of the International Psychogeriatric Association.

Frontotemporal dementia affects about 15-22 of every 100,000 individuals, and an additional 3-4 will be diagnosed in the next year, according to past studies (Int Rev Psychiatry. 2013 Apr;25[2]:130-7). This and other forms of dementia are often preceded by nondegenerative psychiatric syndromes, such as depression or anxiety, Dr. Rosen noted. “It is often unclear whether patients actually have that psychiatric disorder or symptoms of the disorder that are actually frontotemporal dementia,” he said. “Depression is most common and likely represents a misdiagnosis.”

Frontotemporal dementia also is often misdiagnosed as Alzheimer’s but differs in that about three-quarters of cases begin in midlife. This heightens the need for timely diagnosis and specialized services to support patients and caregivers, who may still have children at home, Dr. Rosen said. Unfortunately, such services are often lacking, he added.

Clinicians who treat patients with frontotemporal dementia encounter several “canonical variants” of the disease, he continued. These include nonfluent and semantic variants of primary progressive aphasia and a third behavioral variant. The nonfluent variant is characterized by frequent grammatical errors (agrammatism), hesitation over individual words, and speech apraxia. In contrast, patients with the semantic variant cannot name common objects, such as a ball or a cup, and only vaguely understand their use. Finally, those with the behavioral variant show “bizarre socioemotional changes,” including disinhibition and antisocial behavior, loss of empathy, “exceedingly poor” judgment, overeating, apathy, and hoarding and other compulsive behaviors, Dr. Rosen said.

Behavioral variant frontotemporal dementia can be especially difficult for family members, other experts said. Jan Oyebode, MD, of the University of Bradford, England, and her colleagues prospectively interviewed seven families and five patients with this form of dementia every 6-9 months to observe how the “lived experience” of the disease changed over time. Family members described struggling to understand emergent and worsening irritability, and lack of empathy in their loved one. “We saw this during the family interviews,” Dr. Oyebode added. “For example, one day a [caregiver with cancer] came back from chemotherapy, and her husband [the patient] turned to her and said something like, ‘you’re late. I’m hungry,’ and did not ask how the chemotherapy had gone. She had tears in her eyes. We had a number of examples like that.”

Another patient with behavioral variant frontotemporal dementia began “going off” on his children, something he had not done before, Dr. Oyebode said. Intellectually, he understood that frontotemporal dementia was causing his behavior, but he struggled to control his rage and could not empathize with his children’s pain, she added. “If you live with behavioral variant frontotemporal dementia, you may be only partially aware of changes in our empathy,” she added. “Because you don’t appreciate the way you have changed, you are puzzled by others’ reactions to you. And because you don’t understand the changes in your own abilities, you tend to attribute them to external factors and blame or avoid others.”

But over time, four of the five patients acknowledged that their families had the most insight into their changing cognition and behavior, and some clearly tried to control their behaviors, Dr. Oyebode said. Nonetheless, it is important to understand that even when patients factually accept their diagnosis, they tend not to “live it from the inside,” she emphasized. “Because you [the patient] feel the same, you may be somewhat bewildered by the changes in your life. But because you do not ‘feel’ the changes, you are able to accept them, even though they are dramatic.”

Such acceptance comes more easily when patients receive calm, direct feedback from family members, she also reported. Family members, too, valued open communication as key to their own process. “For families, there needed to be a [transition] from awareness of the dementia, to empathic understanding, to developing coping processes,” she said. For example, family members learned to help patients plan ahead, step by step, for outings and deconstruct tasks by working them out on a whiteboard, she said.

Studies like this one are important because there is little research on presenile dementia, Dr. Rosen said. “When you’re dealing with young-onset dementia, behavioral variant frontotemporal dementia has to be very prominent in your mind” – particularly because it progresses faster than do the other variants and about twice as fast as does Alzheimer’s disease. It can be easier to understand the symptomatic complexities of frontotemporal dementia by mapping them to specific neuroanatomy, Dr. Rosen added. Imaging is central to diagnosis, and indeed, frontotemporal dementia is the only neurodegenerative disease for which Medicare has approved FDG-PET scans as a diagnostic measure.

“What really differentiates frontotemporal dementia [from other dementias] is involvement of the orbital and medial lobes,” Dr. Rosen emphasized. “Think of Phineas Gage – the rod went right through the part of the brain we’re talking about.”

Routine thromboembolism risk assessment and use of both pharmacologic and mechanical thromboprophylaxis is an important part of obstetrics care, according to new recommendations from the National Partnership for Maternal Safety.

Although obstetric venous thromboembolism (VTE) remains a common cause of maternal morbidity and mortality, prophylaxis recommendations are varied and nonspecific across obstetric organizations. The new maternity safety bundle from the National Partnership for Maternal Safety (NPMS) aims to eliminate some of the confusion.

©monkeybusinessimages/Thinkstock

“Based on increasing maternal risk of obstetric venous thromboembolism in the United States, the failure of current strategies to decrease venous thromboembolism as a proportionate cause of maternal death, and observational evidence from the United Kingdom that risk factor–based prophylaxis may reduce risk, the NPMS working group has interpreted current epidemiology and clinical research evidence to support routine thromboembolism risk assessment and consideration of more extensive risk factor–based prophylaxis,” the authors wrote (Obstet Gynecol. 2016;128:688-98).

In the recommendations, prophylactic management of obstetric thromboembolism is organized into four categories: readiness, recognition, response, and reporting and systems learning.

The readiness component includes a recommendation to use a standard thromboembolism risk assessment tool at the first prenatal visit, all antepartum admissions, immediately post partum during childbirth hospitalization, and on discharge from the hospital after a birth. The Caprini and Padua scoring systems, which are tools designed for nonobstetric hospitalized patients, can be modified for obstetric patients, according to the recommendations.

The recognition component of the bundle emphasizes the use of education and guidelines to help physicians identify obstetric patients at risk for thromboembolism. The response component proposes a thromboembolism risk assessment at the first prenatal visit, followed by the use of standardized recommendations for mechanical thromboprophylaxis, dosing of prophylactic and therapeutic pharmacologic anticoagulation, and appropriate timing of pharmacologic prophylaxis with neuraxial anesthesia.

The reporting and systems learning component calls for reviews of a sample of a facility’s obstetric population to determine comorbid risk factors for VTE, followed by routine auditing of records to monitor risk assessment programs and patient care.

The NPMS suggests applying the American College of Chest Physicians recommendations for hospitalized, nonsurgical patients to pregnant women and postpartum women who have had a vaginal birth. However, they recommend using the American College of Obstetricians and Gynecologists’ guidelines for pregnant and postpartum women with thrombophilia.

The NPMS also recommends that women receiving pharmacologic VTE prophylaxis plus low-dose aspirin for the prevention of preeclampsia, should discontinue aspirin at 35-36 weeks of gestation.

“Given the wide diversity of birthing facilities, a single national protocol is not recommended; instead, each facility should adapt a single protocol to improve maternal safety based on its patient population and resources,” the NPMS members wrote.

The NPMS is a joint effort including leaders from a range of women’s health care organizations, hospitals, professional societies, and regulators.

The authors reported having no financial disclosures.

Routine thromboembolism risk assessment and use of both pharmacologic and mechanical thromboprophylaxis is an important part of obstetrics care, according to new recommendations from the National Partnership for Maternal Safety.

Although obstetric venous thromboembolism (VTE) remains a common cause of maternal morbidity and mortality, prophylaxis recommendations are varied and nonspecific across obstetric organizations. The new maternity safety bundle from the National Partnership for Maternal Safety (NPMS) aims to eliminate some of the confusion.

©monkeybusinessimages/Thinkstock

“Based on increasing maternal risk of obstetric venous thromboembolism in the United States, the failure of current strategies to decrease venous thromboembolism as a proportionate cause of maternal death, and observational evidence from the United Kingdom that risk factor–based prophylaxis may reduce risk, the NPMS working group has interpreted current epidemiology and clinical research evidence to support routine thromboembolism risk assessment and consideration of more extensive risk factor–based prophylaxis,” the authors wrote (Obstet Gynecol. 2016;128:688-98).

In the recommendations, prophylactic management of obstetric thromboembolism is organized into four categories: readiness, recognition, response, and reporting and systems learning.

The readiness component includes a recommendation to use a standard thromboembolism risk assessment tool at the first prenatal visit, all antepartum admissions, immediately post partum during childbirth hospitalization, and on discharge from the hospital after a birth. The Caprini and Padua scoring systems, which are tools designed for nonobstetric hospitalized patients, can be modified for obstetric patients, according to the recommendations.

The recognition component of the bundle emphasizes the use of education and guidelines to help physicians identify obstetric patients at risk for thromboembolism. The response component proposes a thromboembolism risk assessment at the first prenatal visit, followed by the use of standardized recommendations for mechanical thromboprophylaxis, dosing of prophylactic and therapeutic pharmacologic anticoagulation, and appropriate timing of pharmacologic prophylaxis with neuraxial anesthesia.

The reporting and systems learning component calls for reviews of a sample of a facility’s obstetric population to determine comorbid risk factors for VTE, followed by routine auditing of records to monitor risk assessment programs and patient care.

The NPMS suggests applying the American College of Chest Physicians recommendations for hospitalized, nonsurgical patients to pregnant women and postpartum women who have had a vaginal birth. However, they recommend using the American College of Obstetricians and Gynecologists’ guidelines for pregnant and postpartum women with thrombophilia.

The NPMS also recommends that women receiving pharmacologic VTE prophylaxis plus low-dose aspirin for the prevention of preeclampsia, should discontinue aspirin at 35-36 weeks of gestation.

“Given the wide diversity of birthing facilities, a single national protocol is not recommended; instead, each facility should adapt a single protocol to improve maternal safety based on its patient population and resources,” the NPMS members wrote.

The NPMS is a joint effort including leaders from a range of women’s health care organizations, hospitals, professional societies, and regulators.

The authors reported having no financial disclosures.

Routine thromboembolism risk assessment and use of both pharmacologic and mechanical thromboprophylaxis is an important part of obstetrics care, according to new recommendations from the National Partnership for Maternal Safety.

Although obstetric venous thromboembolism (VTE) remains a common cause of maternal morbidity and mortality, prophylaxis recommendations are varied and nonspecific across obstetric organizations. The new maternity safety bundle from the National Partnership for Maternal Safety (NPMS) aims to eliminate some of the confusion.

©monkeybusinessimages/Thinkstock

“Based on increasing maternal risk of obstetric venous thromboembolism in the United States, the failure of current strategies to decrease venous thromboembolism as a proportionate cause of maternal death, and observational evidence from the United Kingdom that risk factor–based prophylaxis may reduce risk, the NPMS working group has interpreted current epidemiology and clinical research evidence to support routine thromboembolism risk assessment and consideration of more extensive risk factor–based prophylaxis,” the authors wrote (Obstet Gynecol. 2016;128:688-98).

In the recommendations, prophylactic management of obstetric thromboembolism is organized into four categories: readiness, recognition, response, and reporting and systems learning.

The readiness component includes a recommendation to use a standard thromboembolism risk assessment tool at the first prenatal visit, all antepartum admissions, immediately post partum during childbirth hospitalization, and on discharge from the hospital after a birth. The Caprini and Padua scoring systems, which are tools designed for nonobstetric hospitalized patients, can be modified for obstetric patients, according to the recommendations.

The recognition component of the bundle emphasizes the use of education and guidelines to help physicians identify obstetric patients at risk for thromboembolism. The response component proposes a thromboembolism risk assessment at the first prenatal visit, followed by the use of standardized recommendations for mechanical thromboprophylaxis, dosing of prophylactic and therapeutic pharmacologic anticoagulation, and appropriate timing of pharmacologic prophylaxis with neuraxial anesthesia.

The reporting and systems learning component calls for reviews of a sample of a facility’s obstetric population to determine comorbid risk factors for VTE, followed by routine auditing of records to monitor risk assessment programs and patient care.

The NPMS suggests applying the American College of Chest Physicians recommendations for hospitalized, nonsurgical patients to pregnant women and postpartum women who have had a vaginal birth. However, they recommend using the American College of Obstetricians and Gynecologists’ guidelines for pregnant and postpartum women with thrombophilia.

The NPMS also recommends that women receiving pharmacologic VTE prophylaxis plus low-dose aspirin for the prevention of preeclampsia, should discontinue aspirin at 35-36 weeks of gestation.

“Given the wide diversity of birthing facilities, a single national protocol is not recommended; instead, each facility should adapt a single protocol to improve maternal safety based on its patient population and resources,” the NPMS members wrote.

The NPMS is a joint effort including leaders from a range of women’s health care organizations, hospitals, professional societies, and regulators.

The authors reported having no financial disclosures.

The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.

The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.

The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.

“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.

The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.

In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”

Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.

[email protected]

On Twitter @whitneymcknight

The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.

The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.

The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.

“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.

The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.

In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”

Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.

[email protected]

On Twitter @whitneymcknight

The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.

The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.

The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.

“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.

The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.

In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”

Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.

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On Twitter @whitneymcknight

WASHINGTON – EHR woes may tick up as medical practices begin to move from fee for service to a value-based care model, according to the new federal health IT leader, B. Vindell Washington, MD.

“If you are in an environment where you have, say for example, 20%-25% of your patients that are in an accountable care model and the rest of your entire panel is a fee-for-service model, then you’re really not in a position to really reap the full benefit, and quite frankly you are straddling the fence in terms of both your work flow and patient delivery,” Dr. Washington, National Coordinator for Health Information Technology, said at a Sept. 19 press briefing. That said, “I think that there will be improvements for physicians as we work our way through delivery system reform.”

Gregory Twachtman/Frontline Medical News

The Office of the National Coordinator for Health Information Technology (ONC) is working on regulations that would push EHR vendors to publish app interfaces to foster innovation, create more efficient work-flow applications, and improve EHRs in general, said Dr. Washington, former president and chief medical information officer of the Franciscan Missionaries of Our Lady Health System Medical Group, Baton Rogue, La. “This change is not just a change in the tool that folks are using, it is also a change in the system in which they operate.”

Interoperability also should improve as more clinicians move into value-based care models, he said. For example, in Tulsa, Okla., three competing health systems are participating in the Comprehensive Primary Care Initiative demonstration. The health systems involved in the demonstration are seeing unprecedented levels of information sharing between them because participation in CPC requires it.

“Part of this value proposition comes when you take care of groups of patients and you move into more of the CPC+ or medical home or coordinated care models where the sort of larger, longer view and team-based approach to care become more and more prominent,” Dr. Washington said.

He also talked about the value of documenting efforts related to process measures, and the criticism that clinicians are simply checking boxes rather than focusing on outcomes.

Dr. Washington acknowledged that defining and measuring outcomes is a much more difficult task. He noted that improvement in health is the goal. And while the measure may be difficult, what physicians “need to do in health care to lead to those outcomes, to have people have better, healthier, more enriched lives, you end up with measures around.”

As an example, he pointed to preventing diabetic retinopathy or amputation. “Our best guess at how to do that is to keep their hemoglobin A_1c in a certain range,” he said, adding that while tracking hemoglobin A_1c is the measurement, “what you really want is the [diabetes patient] to have a long life, keep their eyesight, and not lose a limb. It’s that juxtaposition of what you can measure easily versus what the ultimate outcome” is, and physicians will come up with a series of steps in order to achieve the outcome of improved overall health status.

[email protected]

WASHINGTON – EHR woes may tick up as medical practices begin to move from fee for service to a value-based care model, according to the new federal health IT leader, B. Vindell Washington, MD.

“If you are in an environment where you have, say for example, 20%-25% of your patients that are in an accountable care model and the rest of your entire panel is a fee-for-service model, then you’re really not in a position to really reap the full benefit, and quite frankly you are straddling the fence in terms of both your work flow and patient delivery,” Dr. Washington, National Coordinator for Health Information Technology, said at a Sept. 19 press briefing. That said, “I think that there will be improvements for physicians as we work our way through delivery system reform.”

Gregory Twachtman/Frontline Medical News

The Office of the National Coordinator for Health Information Technology (ONC) is working on regulations that would push EHR vendors to publish app interfaces to foster innovation, create more efficient work-flow applications, and improve EHRs in general, said Dr. Washington, former president and chief medical information officer of the Franciscan Missionaries of Our Lady Health System Medical Group, Baton Rogue, La. “This change is not just a change in the tool that folks are using, it is also a change in the system in which they operate.”

Interoperability also should improve as more clinicians move into value-based care models, he said. For example, in Tulsa, Okla., three competing health systems are participating in the Comprehensive Primary Care Initiative demonstration. The health systems involved in the demonstration are seeing unprecedented levels of information sharing between them because participation in CPC requires it.

“Part of this value proposition comes when you take care of groups of patients and you move into more of the CPC+ or medical home or coordinated care models where the sort of larger, longer view and team-based approach to care become more and more prominent,” Dr. Washington said.

He also talked about the value of documenting efforts related to process measures, and the criticism that clinicians are simply checking boxes rather than focusing on outcomes.

Dr. Washington acknowledged that defining and measuring outcomes is a much more difficult task. He noted that improvement in health is the goal. And while the measure may be difficult, what physicians “need to do in health care to lead to those outcomes, to have people have better, healthier, more enriched lives, you end up with measures around.”

As an example, he pointed to preventing diabetic retinopathy or amputation. “Our best guess at how to do that is to keep their hemoglobin A_1c in a certain range,” he said, adding that while tracking hemoglobin A_1c is the measurement, “what you really want is the [diabetes patient] to have a long life, keep their eyesight, and not lose a limb. It’s that juxtaposition of what you can measure easily versus what the ultimate outcome” is, and physicians will come up with a series of steps in order to achieve the outcome of improved overall health status.

[email protected]

WASHINGTON – EHR woes may tick up as medical practices begin to move from fee for service to a value-based care model, according to the new federal health IT leader, B. Vindell Washington, MD.

“If you are in an environment where you have, say for example, 20%-25% of your patients that are in an accountable care model and the rest of your entire panel is a fee-for-service model, then you’re really not in a position to really reap the full benefit, and quite frankly you are straddling the fence in terms of both your work flow and patient delivery,” Dr. Washington, National Coordinator for Health Information Technology, said at a Sept. 19 press briefing. That said, “I think that there will be improvements for physicians as we work our way through delivery system reform.”

Gregory Twachtman/Frontline Medical News

The Office of the National Coordinator for Health Information Technology (ONC) is working on regulations that would push EHR vendors to publish app interfaces to foster innovation, create more efficient work-flow applications, and improve EHRs in general, said Dr. Washington, former president and chief medical information officer of the Franciscan Missionaries of Our Lady Health System Medical Group, Baton Rogue, La. “This change is not just a change in the tool that folks are using, it is also a change in the system in which they operate.”

Interoperability also should improve as more clinicians move into value-based care models, he said. For example, in Tulsa, Okla., three competing health systems are participating in the Comprehensive Primary Care Initiative demonstration. The health systems involved in the demonstration are seeing unprecedented levels of information sharing between them because participation in CPC requires it.

“Part of this value proposition comes when you take care of groups of patients and you move into more of the CPC+ or medical home or coordinated care models where the sort of larger, longer view and team-based approach to care become more and more prominent,” Dr. Washington said.

He also talked about the value of documenting efforts related to process measures, and the criticism that clinicians are simply checking boxes rather than focusing on outcomes.

Dr. Washington acknowledged that defining and measuring outcomes is a much more difficult task. He noted that improvement in health is the goal. And while the measure may be difficult, what physicians “need to do in health care to lead to those outcomes, to have people have better, healthier, more enriched lives, you end up with measures around.”

As an example, he pointed to preventing diabetic retinopathy or amputation. “Our best guess at how to do that is to keep their hemoglobin A_1c in a certain range,” he said, adding that while tracking hemoglobin A_1c is the measurement, “what you really want is the [diabetes patient] to have a long life, keep their eyesight, and not lose a limb. It’s that juxtaposition of what you can measure easily versus what the ultimate outcome” is, and physicians will come up with a series of steps in order to achieve the outcome of improved overall health status.

[email protected]

WAIKOLOA, HAWAII – At the annual meeting of the American Association for the Surgery of Trauma (AAST), Grace S. Rozycki, MD, highlighted findings from a survey of 62 seasoned surgeons who were asked to share their insights, advice, and practical suggestions on how to transmit wisdom to the next generation of surgeons.

Dr. Rozycki is professor of surgery at Indiana University, Indianapolis, and is the current president of the AAST. She reported having no financial disclosures.

[email protected]

WAIKOLOA, HAWAII – At the annual meeting of the American Association for the Surgery of Trauma (AAST), Grace S. Rozycki, MD, highlighted findings from a survey of 62 seasoned surgeons who were asked to share their insights, advice, and practical suggestions on how to transmit wisdom to the next generation of surgeons.

Dr. Rozycki is professor of surgery at Indiana University, Indianapolis, and is the current president of the AAST. She reported having no financial disclosures.

[email protected]

WAIKOLOA, HAWAII – At the annual meeting of the American Association for the Surgery of Trauma (AAST), Grace S. Rozycki, MD, highlighted findings from a survey of 62 seasoned surgeons who were asked to share their insights, advice, and practical suggestions on how to transmit wisdom to the next generation of surgeons.

Dr. Rozycki is professor of surgery at Indiana University, Indianapolis, and is the current president of the AAST. She reported having no financial disclosures.

[email protected]

To the Editor:

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder that causes subepithelial damage and scarring of mucosal surfaces with or without skin involvement.¹ The clinical presentation is highly variable. The oropharynx is the most common site of initial presentation, followed by ocular, nasopharyngeal, anogenital, skin, laryngeal, and esophageal involvement.² Patients often present to a variety of specialists depending on initial symptoms, and due to the diverse clinical manifestations, MMP often is misdiagnosed. Our patient presented an even greater challenge because the disease progressed to tracheal and bronchial involvement.

A 37-year-old man presented to his primary care physician with a chief concern of a sore throat and oral ulcers. The patient was treated with a course of antibiotics followed by a nystatin oral solution. He continued to develop ulcerative lesions on the soft palate, posterior pharynx, and nasal mucosae. He sought treatment from 2 otolaryngologists (ENTs) and a gastroenterologist, and continued to be treated with multiple oral antibiotics, fluconazole, and topical nystatin. Despite treatment, the patient developed pansinusitis and laryngitis and presented to the ENT department at our institution with severe hoarseness and dyspnea on exertion. Examination by the ENT department revealed ulcerative lesions of the nares with stenosis and ulcers along the soft palate. Videolaryngostroboscopy showed remarkable supraglottic edema with thick endolaryngeal mucus. The patient worked as a funeral director and had notable formaldehyde exposure. He also hunted wild game and performed taxidermy regularly.

The patient was admitted and treated with intravenous dexamethasone for a compromised airway. Subsequently, he was taken to the operating room and had biopsies performed of the posterior pharynx. Given his exposure history, the infectious disease department was consulted and he was evaluated for multiple viral, bacterial, and fungal suspects including leishmania and tularemia. Age-appropriate screening, physical examination, and review of systems were negative for an underlying neoplasm. Histopathologic examination revealed a subepithelial vesicular mucositis with a mixed infiltrate of lymphocytes and histiocytes. Direct immunofluorescence microscopy demonstrated strong linear fluorescence along the epithelial-subepithelial junction with IgG and C3. Based on these findings, the diagnosis of MMP was made.

Further testing for bullous pemphigoid antigen 1 (BP230) and bullous pemphigoid antigen 2 (BP180) were negative. On one occasion the patient tested positive for anti-BP230 IgG, but it was at a level judged to be insignificant (7.5 [reference range, <9]). The patient also was negative for autoantibodies against desmoglein 1 and 3. Indirect immunofluorescence using rat bladder epithelium was not performed.

The patient was started on methotrexate and oral prednisone by the rheumatology department, but after 1 week, he presented in respiratory distress and was taken for an emergency tracheostomy. The patient eventually was referred to the dermatology department where methotrexate was discontinued and the patient was started on titrating doses of prednisone and mycophenolate mofetil. Eight weeks later, the patient became completely aphonic and was taken by ENT for dilation of the supraglottic, glottic, and subglottic stenosis with mucosal triamcinolone injections. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily was initiated in addition to mycophenolate mofetil 3 g and prednisone 80 mg, but again the patient developed near-complete tracheal stenosis just proximal to the tracheostomy entry site. At 16 weeks, balloon dilation was repeated with dexamethasone injections and topical mitomycin C. Subsequently, the patient regained some use of his voice. Although the next several laryngoscopes showed improvement in the patient’s epiglottis and glottis, the trachea continued to require debridement and dilation.

Despite maximal medical therapy and surgical interventions, the patient had little improvement in his voice and large clots of blood obstructed his tracheostomy daily. He was unable to sleep in his preferred position on the stomach (prone) due to dyspnea but had less distress sleeping on his back (supine). The patient was referred to the pulmonology department for an endotracheobronchoscopy to further evaluate the airway. It was discovered that the mucosa of the trachea from the level of the tracheostomy to the carina was friable with active erosions and thick bloody secretions (Figure 1). Lesions extended as far as the scope was able to visualize to the left upper lobe takeoff and the right mainstem bronchus (Figure 2). Biopsies of the carinal mucosa showed 3+/3+ linear fluorescence with IgG along the dermoepidermal junction. Salt-split studies were performed, but because the specimen was fragmented, it was not possible to assess if the fluorescence was present at the floor or at the roof of the split.

Given the severity of disease and failure to respond to other aggressive immunosuppressive therapies as well as having been with a tracheostomy for 22 months, the patient was started on 2 doses of intravenous rituximab 1 g 2 weeks apart along with trimethoprim-sulfamethoxazole (3 times weekly) for pneumocystis pneumonia prophylaxis. No complications were observed during infusions. After 2 rituximab infusions, he was weaned off of prednisone and a repeat bronchoscopy showed no airway ulcers beyond the distal trachea or endobronchial obstruction. However, the subglottic space and area above the tracheostomy showed remarkable stenosis with a cobblestone pattern and granulation tissue with continued narrowing of the subglottic area. The ENT performed further dilation and after 34 months, the tracheostomy was removed and a T-tube was placed. The patient required cleaning out of the T-tube approximately every 3 months, and after 2 years the original T-tube was replaced with a new one. At the time of this report, the ENT recommended removing the T-tube, but the patient was reluctant to do so; therefore, a second T-tube replacement is planned. He continues to do well without relapse and has been off all medical therapy for nearly 4 years.

Mucous membrane pemphigoid is an acquired autoimmune subepithelial blistering disease that predominantly affects mucous membranes with or without skin involvement. This condition has been referred to as cicatricial pemphigoid, oral pemphigoid, and ocular cicatricial pemphigoid, among other names. It is characterized by linear deposition of IgG, IgA, or C3 along the epithelial basement membrane zone. According to the international consensus on MMP, the target antigens identified in the epithelial basement membrane zone include bullous pemphigoid antigen 1 (BP230), bullous pemphigoid antigen 2 (BP180), laminin 5 (α3, β3, γ2 chains), laminin 6 (α3 chain), type VII collagen, and integrin β4 subunit.³ Not all patients with MMP will have circulating autoantibodies to the above components, and although our patient did have detectable anti-BP230 IgG, it was not considered clinically significant. Furthermore, the type of autoantibody does not impact decisions regarding therapy selection.³

Although rare, MMP is well-known to dermatologists and ophthalmologists who manage a large majority of MMP patients depending on which mucosa is involved. Mucous membrane pemphigoid is extremely rare in the lower respiratory tract, and when these lesions are discovered, it often is in the face of life-threatening respiratory distress. Mucous membrane pemphigoid is a challenging disease to treat, even more so when the primary specialty physician is unable to visualize the affected areas. Our patient’s disease was limited primarily to the pharynx, larynx, trachea, and bronchi with few oral lesions. According to a PubMed search of articles indexed for MEDLINE using the terms mucous membrane pemphigus, cicatricial pemphigoid, trachea, bronchus, and fatal, 8 reports (7 case reports and 1 prospective study) of MMP involving the lower respiratory tract have been published.^4-11 Of the case reports, each patient also presented with involvement of the eyes or skin.^4,5,7-11 Four of these cases were fatal secondary to cardiopulmonary arrest.^5,7,9,10 In the prospective study, 110 consecutive patients with clinical, histologic, and immunologic criteria of MMP were examined with a flexible nasopharyngolaryngoscope.⁶ Thirty-eight patients had nose or throat symptoms but only 10 had laryngeal involvement and 5 had acute dyspnea. The nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 patients, which was fatal in 3.⁶

Medical treatment should be based on the following factors of the patient’s disease: site, severity, and rapidity of progression.³ High-risk patients can be defined as those who have lesions at any of the following sites: ocular, genital, nasopharyngeal, esophageal, and laryngeal mucosae. As our patient had involvement at several high-risk sites, in particular sites only visualized by various scoping procedures, a team of physicians including dermatologists, ENT physicians, pulmonologists, and oncologists was necessary to facilitate his care. Scarring is the hallmark of MMP and prevention of scarring is the most important aspect of treatment of MMP. Surgical repair of the previously involved mucosa is difficult, as the tissue is prone to re-scarring and difficult to heal. Over the last several years, there has been increasing evidence for the use of rituximab in autoimmune bullous skin diseases including pemphigus vulgaris, epidermolysis bullosa acquisita, and MMP.^12-14 After 2 infusions of rituximab, our patient had clearance of his disease and currently is doing well with a T-tube.

Acknowledgments

We thank Kim Yancey, MD (Dallas, Texas), for providing access to the patient’s diagnostic laboratory immunology and reviewing biopsy specimens; Luis Angel, MD (San Antonio, Texas), for providing bronchoscopy photographs; and C. Blake Simpson, MD (San Antonio, Texas), for co-managing this challenging case.

To the Editor:

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder that causes subepithelial damage and scarring of mucosal surfaces with or without skin involvement.¹ The clinical presentation is highly variable. The oropharynx is the most common site of initial presentation, followed by ocular, nasopharyngeal, anogenital, skin, laryngeal, and esophageal involvement.² Patients often present to a variety of specialists depending on initial symptoms, and due to the diverse clinical manifestations, MMP often is misdiagnosed. Our patient presented an even greater challenge because the disease progressed to tracheal and bronchial involvement.

A 37-year-old man presented to his primary care physician with a chief concern of a sore throat and oral ulcers. The patient was treated with a course of antibiotics followed by a nystatin oral solution. He continued to develop ulcerative lesions on the soft palate, posterior pharynx, and nasal mucosae. He sought treatment from 2 otolaryngologists (ENTs) and a gastroenterologist, and continued to be treated with multiple oral antibiotics, fluconazole, and topical nystatin. Despite treatment, the patient developed pansinusitis and laryngitis and presented to the ENT department at our institution with severe hoarseness and dyspnea on exertion. Examination by the ENT department revealed ulcerative lesions of the nares with stenosis and ulcers along the soft palate. Videolaryngostroboscopy showed remarkable supraglottic edema with thick endolaryngeal mucus. The patient worked as a funeral director and had notable formaldehyde exposure. He also hunted wild game and performed taxidermy regularly.

The patient was admitted and treated with intravenous dexamethasone for a compromised airway. Subsequently, he was taken to the operating room and had biopsies performed of the posterior pharynx. Given his exposure history, the infectious disease department was consulted and he was evaluated for multiple viral, bacterial, and fungal suspects including leishmania and tularemia. Age-appropriate screening, physical examination, and review of systems were negative for an underlying neoplasm. Histopathologic examination revealed a subepithelial vesicular mucositis with a mixed infiltrate of lymphocytes and histiocytes. Direct immunofluorescence microscopy demonstrated strong linear fluorescence along the epithelial-subepithelial junction with IgG and C3. Based on these findings, the diagnosis of MMP was made.

Further testing for bullous pemphigoid antigen 1 (BP230) and bullous pemphigoid antigen 2 (BP180) were negative. On one occasion the patient tested positive for anti-BP230 IgG, but it was at a level judged to be insignificant (7.5 [reference range, <9]). The patient also was negative for autoantibodies against desmoglein 1 and 3. Indirect immunofluorescence using rat bladder epithelium was not performed.

The patient was started on methotrexate and oral prednisone by the rheumatology department, but after 1 week, he presented in respiratory distress and was taken for an emergency tracheostomy. The patient eventually was referred to the dermatology department where methotrexate was discontinued and the patient was started on titrating doses of prednisone and mycophenolate mofetil. Eight weeks later, the patient became completely aphonic and was taken by ENT for dilation of the supraglottic, glottic, and subglottic stenosis with mucosal triamcinolone injections. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily was initiated in addition to mycophenolate mofetil 3 g and prednisone 80 mg, but again the patient developed near-complete tracheal stenosis just proximal to the tracheostomy entry site. At 16 weeks, balloon dilation was repeated with dexamethasone injections and topical mitomycin C. Subsequently, the patient regained some use of his voice. Although the next several laryngoscopes showed improvement in the patient’s epiglottis and glottis, the trachea continued to require debridement and dilation.

Despite maximal medical therapy and surgical interventions, the patient had little improvement in his voice and large clots of blood obstructed his tracheostomy daily. He was unable to sleep in his preferred position on the stomach (prone) due to dyspnea but had less distress sleeping on his back (supine). The patient was referred to the pulmonology department for an endotracheobronchoscopy to further evaluate the airway. It was discovered that the mucosa of the trachea from the level of the tracheostomy to the carina was friable with active erosions and thick bloody secretions (Figure 1). Lesions extended as far as the scope was able to visualize to the left upper lobe takeoff and the right mainstem bronchus (Figure 2). Biopsies of the carinal mucosa showed 3+/3+ linear fluorescence with IgG along the dermoepidermal junction. Salt-split studies were performed, but because the specimen was fragmented, it was not possible to assess if the fluorescence was present at the floor or at the roof of the split.

Given the severity of disease and failure to respond to other aggressive immunosuppressive therapies as well as having been with a tracheostomy for 22 months, the patient was started on 2 doses of intravenous rituximab 1 g 2 weeks apart along with trimethoprim-sulfamethoxazole (3 times weekly) for pneumocystis pneumonia prophylaxis. No complications were observed during infusions. After 2 rituximab infusions, he was weaned off of prednisone and a repeat bronchoscopy showed no airway ulcers beyond the distal trachea or endobronchial obstruction. However, the subglottic space and area above the tracheostomy showed remarkable stenosis with a cobblestone pattern and granulation tissue with continued narrowing of the subglottic area. The ENT performed further dilation and after 34 months, the tracheostomy was removed and a T-tube was placed. The patient required cleaning out of the T-tube approximately every 3 months, and after 2 years the original T-tube was replaced with a new one. At the time of this report, the ENT recommended removing the T-tube, but the patient was reluctant to do so; therefore, a second T-tube replacement is planned. He continues to do well without relapse and has been off all medical therapy for nearly 4 years.

Mucous membrane pemphigoid is an acquired autoimmune subepithelial blistering disease that predominantly affects mucous membranes with or without skin involvement. This condition has been referred to as cicatricial pemphigoid, oral pemphigoid, and ocular cicatricial pemphigoid, among other names. It is characterized by linear deposition of IgG, IgA, or C3 along the epithelial basement membrane zone. According to the international consensus on MMP, the target antigens identified in the epithelial basement membrane zone include bullous pemphigoid antigen 1 (BP230), bullous pemphigoid antigen 2 (BP180), laminin 5 (α3, β3, γ2 chains), laminin 6 (α3 chain), type VII collagen, and integrin β4 subunit.³ Not all patients with MMP will have circulating autoantibodies to the above components, and although our patient did have detectable anti-BP230 IgG, it was not considered clinically significant. Furthermore, the type of autoantibody does not impact decisions regarding therapy selection.³

Although rare, MMP is well-known to dermatologists and ophthalmologists who manage a large majority of MMP patients depending on which mucosa is involved. Mucous membrane pemphigoid is extremely rare in the lower respiratory tract, and when these lesions are discovered, it often is in the face of life-threatening respiratory distress. Mucous membrane pemphigoid is a challenging disease to treat, even more so when the primary specialty physician is unable to visualize the affected areas. Our patient’s disease was limited primarily to the pharynx, larynx, trachea, and bronchi with few oral lesions. According to a PubMed search of articles indexed for MEDLINE using the terms mucous membrane pemphigus, cicatricial pemphigoid, trachea, bronchus, and fatal, 8 reports (7 case reports and 1 prospective study) of MMP involving the lower respiratory tract have been published.^4-11 Of the case reports, each patient also presented with involvement of the eyes or skin.^4,5,7-11 Four of these cases were fatal secondary to cardiopulmonary arrest.^5,7,9,10 In the prospective study, 110 consecutive patients with clinical, histologic, and immunologic criteria of MMP were examined with a flexible nasopharyngolaryngoscope.⁶ Thirty-eight patients had nose or throat symptoms but only 10 had laryngeal involvement and 5 had acute dyspnea. The nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 patients, which was fatal in 3.⁶

Medical treatment should be based on the following factors of the patient’s disease: site, severity, and rapidity of progression.³ High-risk patients can be defined as those who have lesions at any of the following sites: ocular, genital, nasopharyngeal, esophageal, and laryngeal mucosae. As our patient had involvement at several high-risk sites, in particular sites only visualized by various scoping procedures, a team of physicians including dermatologists, ENT physicians, pulmonologists, and oncologists was necessary to facilitate his care. Scarring is the hallmark of MMP and prevention of scarring is the most important aspect of treatment of MMP. Surgical repair of the previously involved mucosa is difficult, as the tissue is prone to re-scarring and difficult to heal. Over the last several years, there has been increasing evidence for the use of rituximab in autoimmune bullous skin diseases including pemphigus vulgaris, epidermolysis bullosa acquisita, and MMP.^12-14 After 2 infusions of rituximab, our patient had clearance of his disease and currently is doing well with a T-tube.

Acknowledgments

We thank Kim Yancey, MD (Dallas, Texas), for providing access to the patient’s diagnostic laboratory immunology and reviewing biopsy specimens; Luis Angel, MD (San Antonio, Texas), for providing bronchoscopy photographs; and C. Blake Simpson, MD (San Antonio, Texas), for co-managing this challenging case.

To the Editor:

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder that causes subepithelial damage and scarring of mucosal surfaces with or without skin involvement.¹ The clinical presentation is highly variable. The oropharynx is the most common site of initial presentation, followed by ocular, nasopharyngeal, anogenital, skin, laryngeal, and esophageal involvement.² Patients often present to a variety of specialists depending on initial symptoms, and due to the diverse clinical manifestations, MMP often is misdiagnosed. Our patient presented an even greater challenge because the disease progressed to tracheal and bronchial involvement.

A 37-year-old man presented to his primary care physician with a chief concern of a sore throat and oral ulcers. The patient was treated with a course of antibiotics followed by a nystatin oral solution. He continued to develop ulcerative lesions on the soft palate, posterior pharynx, and nasal mucosae. He sought treatment from 2 otolaryngologists (ENTs) and a gastroenterologist, and continued to be treated with multiple oral antibiotics, fluconazole, and topical nystatin. Despite treatment, the patient developed pansinusitis and laryngitis and presented to the ENT department at our institution with severe hoarseness and dyspnea on exertion. Examination by the ENT department revealed ulcerative lesions of the nares with stenosis and ulcers along the soft palate. Videolaryngostroboscopy showed remarkable supraglottic edema with thick endolaryngeal mucus. The patient worked as a funeral director and had notable formaldehyde exposure. He also hunted wild game and performed taxidermy regularly.

The patient was admitted and treated with intravenous dexamethasone for a compromised airway. Subsequently, he was taken to the operating room and had biopsies performed of the posterior pharynx. Given his exposure history, the infectious disease department was consulted and he was evaluated for multiple viral, bacterial, and fungal suspects including leishmania and tularemia. Age-appropriate screening, physical examination, and review of systems were negative for an underlying neoplasm. Histopathologic examination revealed a subepithelial vesicular mucositis with a mixed infiltrate of lymphocytes and histiocytes. Direct immunofluorescence microscopy demonstrated strong linear fluorescence along the epithelial-subepithelial junction with IgG and C3. Based on these findings, the diagnosis of MMP was made.

Further testing for bullous pemphigoid antigen 1 (BP230) and bullous pemphigoid antigen 2 (BP180) were negative. On one occasion the patient tested positive for anti-BP230 IgG, but it was at a level judged to be insignificant (7.5 [reference range, <9]). The patient also was negative for autoantibodies against desmoglein 1 and 3. Indirect immunofluorescence using rat bladder epithelium was not performed.

The patient was started on methotrexate and oral prednisone by the rheumatology department, but after 1 week, he presented in respiratory distress and was taken for an emergency tracheostomy. The patient eventually was referred to the dermatology department where methotrexate was discontinued and the patient was started on titrating doses of prednisone and mycophenolate mofetil. Eight weeks later, the patient became completely aphonic and was taken by ENT for dilation of the supraglottic, glottic, and subglottic stenosis with mucosal triamcinolone injections. Doxycycline 100 mg twice daily and nicotinamide 500 mg twice daily was initiated in addition to mycophenolate mofetil 3 g and prednisone 80 mg, but again the patient developed near-complete tracheal stenosis just proximal to the tracheostomy entry site. At 16 weeks, balloon dilation was repeated with dexamethasone injections and topical mitomycin C. Subsequently, the patient regained some use of his voice. Although the next several laryngoscopes showed improvement in the patient’s epiglottis and glottis, the trachea continued to require debridement and dilation.

Despite maximal medical therapy and surgical interventions, the patient had little improvement in his voice and large clots of blood obstructed his tracheostomy daily. He was unable to sleep in his preferred position on the stomach (prone) due to dyspnea but had less distress sleeping on his back (supine). The patient was referred to the pulmonology department for an endotracheobronchoscopy to further evaluate the airway. It was discovered that the mucosa of the trachea from the level of the tracheostomy to the carina was friable with active erosions and thick bloody secretions (Figure 1). Lesions extended as far as the scope was able to visualize to the left upper lobe takeoff and the right mainstem bronchus (Figure 2). Biopsies of the carinal mucosa showed 3+/3+ linear fluorescence with IgG along the dermoepidermal junction. Salt-split studies were performed, but because the specimen was fragmented, it was not possible to assess if the fluorescence was present at the floor or at the roof of the split.

Given the severity of disease and failure to respond to other aggressive immunosuppressive therapies as well as having been with a tracheostomy for 22 months, the patient was started on 2 doses of intravenous rituximab 1 g 2 weeks apart along with trimethoprim-sulfamethoxazole (3 times weekly) for pneumocystis pneumonia prophylaxis. No complications were observed during infusions. After 2 rituximab infusions, he was weaned off of prednisone and a repeat bronchoscopy showed no airway ulcers beyond the distal trachea or endobronchial obstruction. However, the subglottic space and area above the tracheostomy showed remarkable stenosis with a cobblestone pattern and granulation tissue with continued narrowing of the subglottic area. The ENT performed further dilation and after 34 months, the tracheostomy was removed and a T-tube was placed. The patient required cleaning out of the T-tube approximately every 3 months, and after 2 years the original T-tube was replaced with a new one. At the time of this report, the ENT recommended removing the T-tube, but the patient was reluctant to do so; therefore, a second T-tube replacement is planned. He continues to do well without relapse and has been off all medical therapy for nearly 4 years.

Mucous membrane pemphigoid is an acquired autoimmune subepithelial blistering disease that predominantly affects mucous membranes with or without skin involvement. This condition has been referred to as cicatricial pemphigoid, oral pemphigoid, and ocular cicatricial pemphigoid, among other names. It is characterized by linear deposition of IgG, IgA, or C3 along the epithelial basement membrane zone. According to the international consensus on MMP, the target antigens identified in the epithelial basement membrane zone include bullous pemphigoid antigen 1 (BP230), bullous pemphigoid antigen 2 (BP180), laminin 5 (α3, β3, γ2 chains), laminin 6 (α3 chain), type VII collagen, and integrin β4 subunit.³ Not all patients with MMP will have circulating autoantibodies to the above components, and although our patient did have detectable anti-BP230 IgG, it was not considered clinically significant. Furthermore, the type of autoantibody does not impact decisions regarding therapy selection.³

Although rare, MMP is well-known to dermatologists and ophthalmologists who manage a large majority of MMP patients depending on which mucosa is involved. Mucous membrane pemphigoid is extremely rare in the lower respiratory tract, and when these lesions are discovered, it often is in the face of life-threatening respiratory distress. Mucous membrane pemphigoid is a challenging disease to treat, even more so when the primary specialty physician is unable to visualize the affected areas. Our patient’s disease was limited primarily to the pharynx, larynx, trachea, and bronchi with few oral lesions. According to a PubMed search of articles indexed for MEDLINE using the terms mucous membrane pemphigus, cicatricial pemphigoid, trachea, bronchus, and fatal, 8 reports (7 case reports and 1 prospective study) of MMP involving the lower respiratory tract have been published.^4-11 Of the case reports, each patient also presented with involvement of the eyes or skin.^4,5,7-11 Four of these cases were fatal secondary to cardiopulmonary arrest.^5,7,9,10 In the prospective study, 110 consecutive patients with clinical, histologic, and immunologic criteria of MMP were examined with a flexible nasopharyngolaryngoscope.⁶ Thirty-eight patients had nose or throat symptoms but only 10 had laryngeal involvement and 5 had acute dyspnea. The nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 patients, which was fatal in 3.⁶

Medical treatment should be based on the following factors of the patient’s disease: site, severity, and rapidity of progression.³ High-risk patients can be defined as those who have lesions at any of the following sites: ocular, genital, nasopharyngeal, esophageal, and laryngeal mucosae. As our patient had involvement at several high-risk sites, in particular sites only visualized by various scoping procedures, a team of physicians including dermatologists, ENT physicians, pulmonologists, and oncologists was necessary to facilitate his care. Scarring is the hallmark of MMP and prevention of scarring is the most important aspect of treatment of MMP. Surgical repair of the previously involved mucosa is difficult, as the tissue is prone to re-scarring and difficult to heal. Over the last several years, there has been increasing evidence for the use of rituximab in autoimmune bullous skin diseases including pemphigus vulgaris, epidermolysis bullosa acquisita, and MMP.^12-14 After 2 infusions of rituximab, our patient had clearance of his disease and currently is doing well with a T-tube.

Acknowledgments

We thank Kim Yancey, MD (Dallas, Texas), for providing access to the patient’s diagnostic laboratory immunology and reviewing biopsy specimens; Luis Angel, MD (San Antonio, Texas), for providing bronchoscopy photographs; and C. Blake Simpson, MD (San Antonio, Texas), for co-managing this challenging case.

The 2001 American Society of Clinical Oncology clinical practice guideline on postmastectomy radiotherapy has been updated to help clinicians and patients decide which cases of T1-T2 breast cancer with one-three positive axillary lymph nodes will not benefit from the treatment. Recent evidence suggests that some subsets of this patient group are likely to have such a low risk of locoregional recurrence that the potential adverse effects of radiotherapy would outweigh its benefit.

“We still don’t have a single, validated formula that can determine who needs postmastectomy radiotherapy, but we hope that the research evidence summarized in this guideline update will help doctors and patients make more informed decisions,” Abram Recht, MD, cochair of the expert panel that developed the update, said in a press statement.

“Thanks to advances in systemic therapy, fewer women need radiation therapy after a mastectomy. This means we can be more selective when recommending this treatment to our patients,” said Dr. Recht of Beth Israel Deaconess Medical Center, Boston.

ASCO, in collaboration with the American Society for Radiation Oncology and the Society of Surgical Oncology, reviewed the literature since 2001, including a meta-analysis of 22 clinical trials involving 8,135 patients who were randomly assigned to receive or not receive postmastectomy radiotherapy. “Our panel focused on the results for the 3,786 women who underwent axillary dissection.” The 10-year rate of locoregional treatment failure was only 4.3% with irradiation, compared with 21.0% without irradiation. The 10-year rate of local or distant treatment failure was 33.8% with irradiation and 45.5% without it, and the 20-year rates of breast cancer mortality were 41.5% and 49.4%, respectively.

“The panel unanimously agreed that the available evidence shows that postmastectomy radiotherapy reduces the risks of locoregional failure, any recurrence, and breast cancer mortality for patients with T1-T2 breast cancer and one-three positive lymph nodes,” according to the guideline.

However, clinicians and patients “should consider factors that may decrease the risk of locoregional failure, attenuate the benefit of reduced breast cancer–specific mortality, and/or increase the risk of complications.” These include older patient age, limited life expectancy, coexisting conditions that affect the risk of complications, small tumor size, absence of lymphovascular invasion, small nodal metastases, substantial response to neoadjuvant systemic therapy, low tumor grade, or strong tumor sensitivity to hormonal therapy, Dr. Recht and his associates said (J Clin Oncol. 2016 Sep 19. doi: 10.1200/JCO.2016.69.1188).

The guideline also addressed other areas of controversy.

Some clinicians now omit performing axillary lymph node dissection if one-two sentinel nodes are positive, “primarily based on extrapolation of data from randomized trials of patients treated exclusively or predominantly with breast-conserving surgery.” In such cases, the updated guideline “recommends that these patients receive postmastectomy radiotherapy only if there is already sufficient information to justify its use without needing to know that additional axillary nodes are involved.”

Many clinicians are uncertain whether to pursue postmastectomy radiotherapy in patients who have received neoadjuvant systemic therapy, because observational studies suggest the risk of locoregional recurrence is low for those who either have clinically negative nodes before undergoing the treatment or have a complete pathologic response to it in the lymph nodes. The panel decided that current evidence is insufficient to recommend whether radiotherapy should be administered or can be omitted in these groups.

The guideline also recommends that regional nodal irradiation generally should target both the internal mammary and the supraclavicular-axillary apical nodes, in addition to the chest wall or reconstructed breast. “There may be subgroups that will experience limited, if any, benefits from treating both these nodal areas, compared with treating only one or perhaps treating only the chest wall or reconstructed breast. [However,] there is insufficient evidence at this time to define such subgroups in detail.”

Copies of the updated guideline, as well as additional information such as details regarding the panel’s methodology, evidence tables, and clinical tools, are avail at www.asco.org/pmrt-guideline and www.asco.org/guidelineswiki.

This work was supported by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. Dr. Recht reported serving as a consultant or advisor to CareCore and U.S. Oncology and receiving research funding from Genomic Health; his associates reported ties to numerous industry sources.

[email protected]

The 2001 American Society of Clinical Oncology clinical practice guideline on postmastectomy radiotherapy has been updated to help clinicians and patients decide which cases of T1-T2 breast cancer with one-three positive axillary lymph nodes will not benefit from the treatment. Recent evidence suggests that some subsets of this patient group are likely to have such a low risk of locoregional recurrence that the potential adverse effects of radiotherapy would outweigh its benefit.

“We still don’t have a single, validated formula that can determine who needs postmastectomy radiotherapy, but we hope that the research evidence summarized in this guideline update will help doctors and patients make more informed decisions,” Abram Recht, MD, cochair of the expert panel that developed the update, said in a press statement.

“Thanks to advances in systemic therapy, fewer women need radiation therapy after a mastectomy. This means we can be more selective when recommending this treatment to our patients,” said Dr. Recht of Beth Israel Deaconess Medical Center, Boston.

ASCO, in collaboration with the American Society for Radiation Oncology and the Society of Surgical Oncology, reviewed the literature since 2001, including a meta-analysis of 22 clinical trials involving 8,135 patients who were randomly assigned to receive or not receive postmastectomy radiotherapy. “Our panel focused on the results for the 3,786 women who underwent axillary dissection.” The 10-year rate of locoregional treatment failure was only 4.3% with irradiation, compared with 21.0% without irradiation. The 10-year rate of local or distant treatment failure was 33.8% with irradiation and 45.5% without it, and the 20-year rates of breast cancer mortality were 41.5% and 49.4%, respectively.

“The panel unanimously agreed that the available evidence shows that postmastectomy radiotherapy reduces the risks of locoregional failure, any recurrence, and breast cancer mortality for patients with T1-T2 breast cancer and one-three positive lymph nodes,” according to the guideline.

However, clinicians and patients “should consider factors that may decrease the risk of locoregional failure, attenuate the benefit of reduced breast cancer–specific mortality, and/or increase the risk of complications.” These include older patient age, limited life expectancy, coexisting conditions that affect the risk of complications, small tumor size, absence of lymphovascular invasion, small nodal metastases, substantial response to neoadjuvant systemic therapy, low tumor grade, or strong tumor sensitivity to hormonal therapy, Dr. Recht and his associates said (J Clin Oncol. 2016 Sep 19. doi: 10.1200/JCO.2016.69.1188).

The guideline also addressed other areas of controversy.

Some clinicians now omit performing axillary lymph node dissection if one-two sentinel nodes are positive, “primarily based on extrapolation of data from randomized trials of patients treated exclusively or predominantly with breast-conserving surgery.” In such cases, the updated guideline “recommends that these patients receive postmastectomy radiotherapy only if there is already sufficient information to justify its use without needing to know that additional axillary nodes are involved.”

Many clinicians are uncertain whether to pursue postmastectomy radiotherapy in patients who have received neoadjuvant systemic therapy, because observational studies suggest the risk of locoregional recurrence is low for those who either have clinically negative nodes before undergoing the treatment or have a complete pathologic response to it in the lymph nodes. The panel decided that current evidence is insufficient to recommend whether radiotherapy should be administered or can be omitted in these groups.

The guideline also recommends that regional nodal irradiation generally should target both the internal mammary and the supraclavicular-axillary apical nodes, in addition to the chest wall or reconstructed breast. “There may be subgroups that will experience limited, if any, benefits from treating both these nodal areas, compared with treating only one or perhaps treating only the chest wall or reconstructed breast. [However,] there is insufficient evidence at this time to define such subgroups in detail.”

Copies of the updated guideline, as well as additional information such as details regarding the panel’s methodology, evidence tables, and clinical tools, are avail at www.asco.org/pmrt-guideline and www.asco.org/guidelineswiki.

This work was supported by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. Dr. Recht reported serving as a consultant or advisor to CareCore and U.S. Oncology and receiving research funding from Genomic Health; his associates reported ties to numerous industry sources.

[email protected]

The 2001 American Society of Clinical Oncology clinical practice guideline on postmastectomy radiotherapy has been updated to help clinicians and patients decide which cases of T1-T2 breast cancer with one-three positive axillary lymph nodes will not benefit from the treatment. Recent evidence suggests that some subsets of this patient group are likely to have such a low risk of locoregional recurrence that the potential adverse effects of radiotherapy would outweigh its benefit.

“We still don’t have a single, validated formula that can determine who needs postmastectomy radiotherapy, but we hope that the research evidence summarized in this guideline update will help doctors and patients make more informed decisions,” Abram Recht, MD, cochair of the expert panel that developed the update, said in a press statement.

“Thanks to advances in systemic therapy, fewer women need radiation therapy after a mastectomy. This means we can be more selective when recommending this treatment to our patients,” said Dr. Recht of Beth Israel Deaconess Medical Center, Boston.

ASCO, in collaboration with the American Society for Radiation Oncology and the Society of Surgical Oncology, reviewed the literature since 2001, including a meta-analysis of 22 clinical trials involving 8,135 patients who were randomly assigned to receive or not receive postmastectomy radiotherapy. “Our panel focused on the results for the 3,786 women who underwent axillary dissection.” The 10-year rate of locoregional treatment failure was only 4.3% with irradiation, compared with 21.0% without irradiation. The 10-year rate of local or distant treatment failure was 33.8% with irradiation and 45.5% without it, and the 20-year rates of breast cancer mortality were 41.5% and 49.4%, respectively.

“The panel unanimously agreed that the available evidence shows that postmastectomy radiotherapy reduces the risks of locoregional failure, any recurrence, and breast cancer mortality for patients with T1-T2 breast cancer and one-three positive lymph nodes,” according to the guideline.

However, clinicians and patients “should consider factors that may decrease the risk of locoregional failure, attenuate the benefit of reduced breast cancer–specific mortality, and/or increase the risk of complications.” These include older patient age, limited life expectancy, coexisting conditions that affect the risk of complications, small tumor size, absence of lymphovascular invasion, small nodal metastases, substantial response to neoadjuvant systemic therapy, low tumor grade, or strong tumor sensitivity to hormonal therapy, Dr. Recht and his associates said (J Clin Oncol. 2016 Sep 19. doi: 10.1200/JCO.2016.69.1188).

The guideline also addressed other areas of controversy.

Some clinicians now omit performing axillary lymph node dissection if one-two sentinel nodes are positive, “primarily based on extrapolation of data from randomized trials of patients treated exclusively or predominantly with breast-conserving surgery.” In such cases, the updated guideline “recommends that these patients receive postmastectomy radiotherapy only if there is already sufficient information to justify its use without needing to know that additional axillary nodes are involved.”

Many clinicians are uncertain whether to pursue postmastectomy radiotherapy in patients who have received neoadjuvant systemic therapy, because observational studies suggest the risk of locoregional recurrence is low for those who either have clinically negative nodes before undergoing the treatment or have a complete pathologic response to it in the lymph nodes. The panel decided that current evidence is insufficient to recommend whether radiotherapy should be administered or can be omitted in these groups.

The guideline also recommends that regional nodal irradiation generally should target both the internal mammary and the supraclavicular-axillary apical nodes, in addition to the chest wall or reconstructed breast. “There may be subgroups that will experience limited, if any, benefits from treating both these nodal areas, compared with treating only one or perhaps treating only the chest wall or reconstructed breast. [However,] there is insufficient evidence at this time to define such subgroups in detail.”

Copies of the updated guideline, as well as additional information such as details regarding the panel’s methodology, evidence tables, and clinical tools, are avail at www.asco.org/pmrt-guideline and www.asco.org/guidelineswiki.

This work was supported by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. Dr. Recht reported serving as a consultant or advisor to CareCore and U.S. Oncology and receiving research funding from Genomic Health; his associates reported ties to numerous industry sources.

[email protected]

I had my first child during my third year of medical school, and I remember being embarrassed to tell my attending and residents that I needed to pump. I was at the bottom of the training hierarchy and I didn’t want to ask for “special accommodations.” I remember racing to a separate wing of the hospital to pump during my lunch break (if not taken up by lectures), while devouring a sandwich. It quickly became overwhelming, and by the time my daughter was 3 months old, I started supplementing.

I am currently breastfeeding my second child now as a third year pediatric resident. The experience has been much better. My son is 6 months old and is still breastfed! As a resident, I felt more comfortable making everyone aware of my need to pump periodically during work hours. My coresidents and faculty have been very supportive. In fact, I remember my first month back from maternity leave working in the pediatric ICU. I quickly discovered that nearly every floor of the hospital has a lactation room, including the ICU. One time I was in the middle of pumping when my attending paged me with a nonurgent issue. Once finished, I called back and apologized, explaining the reason for my late response. In return, I received an even bigger apology from my attending, who felt bad for disturbing my pumping session. I was moved.

The American Academy of Pediatrics recommends exclusive breastfeeding of healthy term infants for about 6 months.¹ Healthy People 2020 set goals of 82% breastfeeding at birth and 61% at 6 months.² How do we as trainees do? A study published in 1996 looked at 60 female residents who delivered a child during residency. They found that even though 80% initiated breastfeeding, only 15% were still breastfeeding at 6 months. Only 54% of these residents who were breastfeeding after returning to work felt supported by their attending, and 67% felt supported by their colleagues.³ A more recent study published in 2013 looked at breastfeeding during obstetrics residency. Of 89 female residents who had personal experience with breastfeeding, 73% felt supported by their program directors and faculty; and 84% felt supported by colleagues. The rate of breastfeeding at 6 months was now 52%.⁴

Compared with 1996, breastfeeding practices during residency appear to have improved with much higher rates at 6 months. However, we are slightly below the Healthy People 2020 goals. For the most part, residents feel supported by their attendings and colleagues. With continued support and attention, these goals are well within reach. When it comes to breastfeeding during training, be your own advocate!

References

1. Pediatrics. 2012 Mar;129(3):e827-41.

2. Office of Disease Prevention and Health Promotion, U.S. Department of Health and Human Services. Healthy People 2020. Goal MICH 21.

3. Pediatrics. 1996 Sep;98(3 Pt 1):434-7.

4. Breastfeed Med. 2013 Aug;8(4):394-400.

Dr. Burek is a third-year pediatric resident at the Medical College of Wisconsin and the Children’s Hospital of Wisconsin, both in Milwaukee.

I had my first child during my third year of medical school, and I remember being embarrassed to tell my attending and residents that I needed to pump. I was at the bottom of the training hierarchy and I didn’t want to ask for “special accommodations.” I remember racing to a separate wing of the hospital to pump during my lunch break (if not taken up by lectures), while devouring a sandwich. It quickly became overwhelming, and by the time my daughter was 3 months old, I started supplementing.

I am currently breastfeeding my second child now as a third year pediatric resident. The experience has been much better. My son is 6 months old and is still breastfed! As a resident, I felt more comfortable making everyone aware of my need to pump periodically during work hours. My coresidents and faculty have been very supportive. In fact, I remember my first month back from maternity leave working in the pediatric ICU. I quickly discovered that nearly every floor of the hospital has a lactation room, including the ICU. One time I was in the middle of pumping when my attending paged me with a nonurgent issue. Once finished, I called back and apologized, explaining the reason for my late response. In return, I received an even bigger apology from my attending, who felt bad for disturbing my pumping session. I was moved.

The American Academy of Pediatrics recommends exclusive breastfeeding of healthy term infants for about 6 months.¹ Healthy People 2020 set goals of 82% breastfeeding at birth and 61% at 6 months.² How do we as trainees do? A study published in 1996 looked at 60 female residents who delivered a child during residency. They found that even though 80% initiated breastfeeding, only 15% were still breastfeeding at 6 months. Only 54% of these residents who were breastfeeding after returning to work felt supported by their attending, and 67% felt supported by their colleagues.³ A more recent study published in 2013 looked at breastfeeding during obstetrics residency. Of 89 female residents who had personal experience with breastfeeding, 73% felt supported by their program directors and faculty; and 84% felt supported by colleagues. The rate of breastfeeding at 6 months was now 52%.⁴

Compared with 1996, breastfeeding practices during residency appear to have improved with much higher rates at 6 months. However, we are slightly below the Healthy People 2020 goals. For the most part, residents feel supported by their attendings and colleagues. With continued support and attention, these goals are well within reach. When it comes to breastfeeding during training, be your own advocate!

References

1. Pediatrics. 2012 Mar;129(3):e827-41.

2. Office of Disease Prevention and Health Promotion, U.S. Department of Health and Human Services. Healthy People 2020. Goal MICH 21.

3. Pediatrics. 1996 Sep;98(3 Pt 1):434-7.

4. Breastfeed Med. 2013 Aug;8(4):394-400.

Dr. Burek is a third-year pediatric resident at the Medical College of Wisconsin and the Children’s Hospital of Wisconsin, both in Milwaukee.

I had my first child during my third year of medical school, and I remember being embarrassed to tell my attending and residents that I needed to pump. I was at the bottom of the training hierarchy and I didn’t want to ask for “special accommodations.” I remember racing to a separate wing of the hospital to pump during my lunch break (if not taken up by lectures), while devouring a sandwich. It quickly became overwhelming, and by the time my daughter was 3 months old, I started supplementing.

I am currently breastfeeding my second child now as a third year pediatric resident. The experience has been much better. My son is 6 months old and is still breastfed! As a resident, I felt more comfortable making everyone aware of my need to pump periodically during work hours. My coresidents and faculty have been very supportive. In fact, I remember my first month back from maternity leave working in the pediatric ICU. I quickly discovered that nearly every floor of the hospital has a lactation room, including the ICU. One time I was in the middle of pumping when my attending paged me with a nonurgent issue. Once finished, I called back and apologized, explaining the reason for my late response. In return, I received an even bigger apology from my attending, who felt bad for disturbing my pumping session. I was moved.

The American Academy of Pediatrics recommends exclusive breastfeeding of healthy term infants for about 6 months.¹ Healthy People 2020 set goals of 82% breastfeeding at birth and 61% at 6 months.² How do we as trainees do? A study published in 1996 looked at 60 female residents who delivered a child during residency. They found that even though 80% initiated breastfeeding, only 15% were still breastfeeding at 6 months. Only 54% of these residents who were breastfeeding after returning to work felt supported by their attending, and 67% felt supported by their colleagues.³ A more recent study published in 2013 looked at breastfeeding during obstetrics residency. Of 89 female residents who had personal experience with breastfeeding, 73% felt supported by their program directors and faculty; and 84% felt supported by colleagues. The rate of breastfeeding at 6 months was now 52%.⁴

Compared with 1996, breastfeeding practices during residency appear to have improved with much higher rates at 6 months. However, we are slightly below the Healthy People 2020 goals. For the most part, residents feel supported by their attendings and colleagues. With continued support and attention, these goals are well within reach. When it comes to breastfeeding during training, be your own advocate!

References

1. Pediatrics. 2012 Mar;129(3):e827-41.

2. Office of Disease Prevention and Health Promotion, U.S. Department of Health and Human Services. Healthy People 2020. Goal MICH 21.

3. Pediatrics. 1996 Sep;98(3 Pt 1):434-7.

4. Breastfeed Med. 2013 Aug;8(4):394-400.

Dr. Burek is a third-year pediatric resident at the Medical College of Wisconsin and the Children’s Hospital of Wisconsin, both in Milwaukee.

LONDON – New European guidelines on the pharmacologic treatment of multiple sclerosis consider all types of adult patients, including those with clinically isolated syndrome.

In addition to advocating early treatment in clinically isolated syndrome (CIS), the guidelines look at the treatment of relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS), and give recommendations on monitoring therapy, what to do if a treatment needs to be stopped or switched, and how to treat in special situations such as pregnancy.

Developed jointly by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN), the guidelines are the first to formalize how best to use new disease-modifying drugs and strategies in Europe, based on current evidence.

“With several new drugs available in the past years, and others soon to come, this poses a major challenge to advice on a specific treatment for a specific patient,” said Susana Otero-Romero, MD, of the Centre d’Esclerosi Múltiple de Catalunya (CEMCAT) at Vall d’Hebron University Hospital in Barcelona.

Dr. Otero-Romero, who presented some general recommendations from the draft guidelines at the ECTRIMS annual congress, added that evidence-based guidance was needed and so ECTRIMS and EAN convened an expert panel in 2015 to review available data. The focus was on disease-modifying therapies approved by the European Medicines Agency.

The expert panel was chaired by the president of ECTRIMS, Xavier Montalbán, MD, of CEMCAT, and Ralf Gold, MD, of Ruhr-Universität Bochum in Germany, on behalf of the EAN, and included MS experts from across Europe, as well as patient representatives from groups such as the Multiple Sclerosis International Federation and the European Multiple Sclerosis Platform.

The panel followed the EAN’s recently issued framework for developing guidelines (Eur J Neurol. 2015 Dec;22[12]:1505-10) and Dr. Otero-Romero emphasized that the guidelines were built on the evidence base, using GRADE (Grading of Recommendations Assessment, Development Evaluation) methodology, to rate the quality and strength of each recommendation. Where no evidence was found, expert consensus was used.

Dr. Otero-Romero noted that an overall recommendation was that “the entire spectrum of disease-modifying drugs should only be prescribed in centers where there was the infrastructure to provide the proper monitoring of patients, comprehensive assessment, and detection of side effects and how to address them.”

That doesn’t mean patients need to be treated in specialist centers, Dr. Montalbán was keen to point out during discussions. It means that centers who prescribe the expanding range of MS drugs need to have a process to enable them to take good care of patients, monitor them, be aware of side effects, and have the expertise to be able to manage patients if side effects do occur.

“We looked specifically at the subpopulation of patients with CIS,” Dr. Otero-Romero noted, and said the panel decided that treatment with interferon or glatiramer acetate was the best option for CIS patients with an abnormal MRI scan who do not fulfill MS diagnostic criteria.

During discussion, a delegate queried why only injectable drugs were recommended when patients in this early phase of disease would probably be asking for oral treatment. Dr. Otero-Romero responded that this recommendation was based purely on the evidence available. “For now, this would only support starting on interferon or glatiramer acetate,” she said.

For patients with RRMS, defined as multiple relapses, MRI activity, or both, the recommendation is to offer early treatment with disease-modifying drugs. Which drug should be used is not specified, although the guidelines provide general advice on factors to consider when choosing a drug, including patient characteristics and comorbidities, disease severity and activity, the drug’s safety profile, and accessibility to the drug.

“There have not really been any head-to-head comparisons between drugs, so we do not have enough evidence to recommend one over another,” Dr. Otero-Romero said. “If you do not have good evidence you cannot really stratify the drugs and say ‘this one goes first, this one goes second,’ so we still need more evidence.”

For monitoring, consider MRI together with clinical measures. A reference brain MRI, taken within 6 months of starting disease-modifying treatment, is advocated, with a follow-up brain scan at 1 year, although the timing will need to be adjusted based on the drug treatment being used and the level of disease activity.

If there is a poor response to interferon or glatiramer acetate therapy or there is evidence of disease activity, the recommendation is to offer a more efficacious drug. If a highly efficacious drug then needs to be stopped for any reason, another highly efficacious drug should be considered. Factors to consider when switching include the degree of disease activity, which dictates how quickly the switch needs to be made, drugs’ respective half-lives and biological activity, and the potential for rebounding disease activity, particularly with natalizumab (Tysabri).

Although the expert panel has included a recommendation on the use of ocrelizumab for PPMS based on available phase III trial data, this is only if the drug is licensed for use by the EMA by the time the guidelines are published.

“We have agreed on our first set of recommendations. We will probably still work to refine some of these, and we expect to publish at the beginning of next year,” Dr. Otero-Romero said.

Providing independent comment in an interview, Samuel F. Hunter, MD, of the Advanced Neurosciences Institute in Nashville, Tenn., said that the European guidelines were of interest as there were no up-to-date guidelines on drug therapy for MS available in the United States.

While the American Academy of Neurology has produced practice guidelines on the use of disease-modifying therapies in MS (Neurology. 2002;58[2]:169-78) and issued specific guidance on natalizumab (Neurology. 2008;71[10]:766–73), these documents were published years ago. Five new therapies have appeared since then, Dr. Hunter said.

“Guidance is so far behind the advancement of therapy for MS, such that we don’t have any accepted guidelines. The current opinion from various groups is that all therapies should be available for all patients, according to physician advice,” Dr. Hunter said.

“People predominantly follow individual escalation of therapy efficacy guideline for the majority of patients, and people with very severe, fulminant relapses are relegated to higher-efficacy therapies,” he added.

The new European guidelines will influence what is happening in the United States, Dr. Hunter said, but there is such a diversity of interests among the large managed care organizations, the government, payers, pharmaceutical companies, and different academic centers, for example, that reaching a consensus will be difficult.

Dr. Otero-Romero did not declare any specific disclosures in relation to her presentation of the guidelines. Dr. Hunter did not have any disclosure relevant to his comments.

LONDON – New European guidelines on the pharmacologic treatment of multiple sclerosis consider all types of adult patients, including those with clinically isolated syndrome.

In addition to advocating early treatment in clinically isolated syndrome (CIS), the guidelines look at the treatment of relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS), and give recommendations on monitoring therapy, what to do if a treatment needs to be stopped or switched, and how to treat in special situations such as pregnancy.

Developed jointly by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN), the guidelines are the first to formalize how best to use new disease-modifying drugs and strategies in Europe, based on current evidence.

“With several new drugs available in the past years, and others soon to come, this poses a major challenge to advice on a specific treatment for a specific patient,” said Susana Otero-Romero, MD, of the Centre d’Esclerosi Múltiple de Catalunya (CEMCAT) at Vall d’Hebron University Hospital in Barcelona.

Dr. Otero-Romero, who presented some general recommendations from the draft guidelines at the ECTRIMS annual congress, added that evidence-based guidance was needed and so ECTRIMS and EAN convened an expert panel in 2015 to review available data. The focus was on disease-modifying therapies approved by the European Medicines Agency.

The expert panel was chaired by the president of ECTRIMS, Xavier Montalbán, MD, of CEMCAT, and Ralf Gold, MD, of Ruhr-Universität Bochum in Germany, on behalf of the EAN, and included MS experts from across Europe, as well as patient representatives from groups such as the Multiple Sclerosis International Federation and the European Multiple Sclerosis Platform.

The panel followed the EAN’s recently issued framework for developing guidelines (Eur J Neurol. 2015 Dec;22[12]:1505-10) and Dr. Otero-Romero emphasized that the guidelines were built on the evidence base, using GRADE (Grading of Recommendations Assessment, Development Evaluation) methodology, to rate the quality and strength of each recommendation. Where no evidence was found, expert consensus was used.

Dr. Otero-Romero noted that an overall recommendation was that “the entire spectrum of disease-modifying drugs should only be prescribed in centers where there was the infrastructure to provide the proper monitoring of patients, comprehensive assessment, and detection of side effects and how to address them.”

That doesn’t mean patients need to be treated in specialist centers, Dr. Montalbán was keen to point out during discussions. It means that centers who prescribe the expanding range of MS drugs need to have a process to enable them to take good care of patients, monitor them, be aware of side effects, and have the expertise to be able to manage patients if side effects do occur.

“We looked specifically at the subpopulation of patients with CIS,” Dr. Otero-Romero noted, and said the panel decided that treatment with interferon or glatiramer acetate was the best option for CIS patients with an abnormal MRI scan who do not fulfill MS diagnostic criteria.

During discussion, a delegate queried why only injectable drugs were recommended when patients in this early phase of disease would probably be asking for oral treatment. Dr. Otero-Romero responded that this recommendation was based purely on the evidence available. “For now, this would only support starting on interferon or glatiramer acetate,” she said.

For patients with RRMS, defined as multiple relapses, MRI activity, or both, the recommendation is to offer early treatment with disease-modifying drugs. Which drug should be used is not specified, although the guidelines provide general advice on factors to consider when choosing a drug, including patient characteristics and comorbidities, disease severity and activity, the drug’s safety profile, and accessibility to the drug.

“There have not really been any head-to-head comparisons between drugs, so we do not have enough evidence to recommend one over another,” Dr. Otero-Romero said. “If you do not have good evidence you cannot really stratify the drugs and say ‘this one goes first, this one goes second,’ so we still need more evidence.”

For monitoring, consider MRI together with clinical measures. A reference brain MRI, taken within 6 months of starting disease-modifying treatment, is advocated, with a follow-up brain scan at 1 year, although the timing will need to be adjusted based on the drug treatment being used and the level of disease activity.

If there is a poor response to interferon or glatiramer acetate therapy or there is evidence of disease activity, the recommendation is to offer a more efficacious drug. If a highly efficacious drug then needs to be stopped for any reason, another highly efficacious drug should be considered. Factors to consider when switching include the degree of disease activity, which dictates how quickly the switch needs to be made, drugs’ respective half-lives and biological activity, and the potential for rebounding disease activity, particularly with natalizumab (Tysabri).

Although the expert panel has included a recommendation on the use of ocrelizumab for PPMS based on available phase III trial data, this is only if the drug is licensed for use by the EMA by the time the guidelines are published.

“We have agreed on our first set of recommendations. We will probably still work to refine some of these, and we expect to publish at the beginning of next year,” Dr. Otero-Romero said.

Providing independent comment in an interview, Samuel F. Hunter, MD, of the Advanced Neurosciences Institute in Nashville, Tenn., said that the European guidelines were of interest as there were no up-to-date guidelines on drug therapy for MS available in the United States.

While the American Academy of Neurology has produced practice guidelines on the use of disease-modifying therapies in MS (Neurology. 2002;58[2]:169-78) and issued specific guidance on natalizumab (Neurology. 2008;71[10]:766–73), these documents were published years ago. Five new therapies have appeared since then, Dr. Hunter said.

“Guidance is so far behind the advancement of therapy for MS, such that we don’t have any accepted guidelines. The current opinion from various groups is that all therapies should be available for all patients, according to physician advice,” Dr. Hunter said.

“People predominantly follow individual escalation of therapy efficacy guideline for the majority of patients, and people with very severe, fulminant relapses are relegated to higher-efficacy therapies,” he added.

The new European guidelines will influence what is happening in the United States, Dr. Hunter said, but there is such a diversity of interests among the large managed care organizations, the government, payers, pharmaceutical companies, and different academic centers, for example, that reaching a consensus will be difficult.

Dr. Otero-Romero did not declare any specific disclosures in relation to her presentation of the guidelines. Dr. Hunter did not have any disclosure relevant to his comments.

LONDON – New European guidelines on the pharmacologic treatment of multiple sclerosis consider all types of adult patients, including those with clinically isolated syndrome.

In addition to advocating early treatment in clinically isolated syndrome (CIS), the guidelines look at the treatment of relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS), and give recommendations on monitoring therapy, what to do if a treatment needs to be stopped or switched, and how to treat in special situations such as pregnancy.

Developed jointly by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN), the guidelines are the first to formalize how best to use new disease-modifying drugs and strategies in Europe, based on current evidence.

“With several new drugs available in the past years, and others soon to come, this poses a major challenge to advice on a specific treatment for a specific patient,” said Susana Otero-Romero, MD, of the Centre d’Esclerosi Múltiple de Catalunya (CEMCAT) at Vall d’Hebron University Hospital in Barcelona.

Dr. Otero-Romero, who presented some general recommendations from the draft guidelines at the ECTRIMS annual congress, added that evidence-based guidance was needed and so ECTRIMS and EAN convened an expert panel in 2015 to review available data. The focus was on disease-modifying therapies approved by the European Medicines Agency.

The expert panel was chaired by the president of ECTRIMS, Xavier Montalbán, MD, of CEMCAT, and Ralf Gold, MD, of Ruhr-Universität Bochum in Germany, on behalf of the EAN, and included MS experts from across Europe, as well as patient representatives from groups such as the Multiple Sclerosis International Federation and the European Multiple Sclerosis Platform.

The panel followed the EAN’s recently issued framework for developing guidelines (Eur J Neurol. 2015 Dec;22[12]:1505-10) and Dr. Otero-Romero emphasized that the guidelines were built on the evidence base, using GRADE (Grading of Recommendations Assessment, Development Evaluation) methodology, to rate the quality and strength of each recommendation. Where no evidence was found, expert consensus was used.

Dr. Otero-Romero noted that an overall recommendation was that “the entire spectrum of disease-modifying drugs should only be prescribed in centers where there was the infrastructure to provide the proper monitoring of patients, comprehensive assessment, and detection of side effects and how to address them.”

That doesn’t mean patients need to be treated in specialist centers, Dr. Montalbán was keen to point out during discussions. It means that centers who prescribe the expanding range of MS drugs need to have a process to enable them to take good care of patients, monitor them, be aware of side effects, and have the expertise to be able to manage patients if side effects do occur.

“We looked specifically at the subpopulation of patients with CIS,” Dr. Otero-Romero noted, and said the panel decided that treatment with interferon or glatiramer acetate was the best option for CIS patients with an abnormal MRI scan who do not fulfill MS diagnostic criteria.

During discussion, a delegate queried why only injectable drugs were recommended when patients in this early phase of disease would probably be asking for oral treatment. Dr. Otero-Romero responded that this recommendation was based purely on the evidence available. “For now, this would only support starting on interferon or glatiramer acetate,” she said.

For patients with RRMS, defined as multiple relapses, MRI activity, or both, the recommendation is to offer early treatment with disease-modifying drugs. Which drug should be used is not specified, although the guidelines provide general advice on factors to consider when choosing a drug, including patient characteristics and comorbidities, disease severity and activity, the drug’s safety profile, and accessibility to the drug.

“There have not really been any head-to-head comparisons between drugs, so we do not have enough evidence to recommend one over another,” Dr. Otero-Romero said. “If you do not have good evidence you cannot really stratify the drugs and say ‘this one goes first, this one goes second,’ so we still need more evidence.”

For monitoring, consider MRI together with clinical measures. A reference brain MRI, taken within 6 months of starting disease-modifying treatment, is advocated, with a follow-up brain scan at 1 year, although the timing will need to be adjusted based on the drug treatment being used and the level of disease activity.

If there is a poor response to interferon or glatiramer acetate therapy or there is evidence of disease activity, the recommendation is to offer a more efficacious drug. If a highly efficacious drug then needs to be stopped for any reason, another highly efficacious drug should be considered. Factors to consider when switching include the degree of disease activity, which dictates how quickly the switch needs to be made, drugs’ respective half-lives and biological activity, and the potential for rebounding disease activity, particularly with natalizumab (Tysabri).

Although the expert panel has included a recommendation on the use of ocrelizumab for PPMS based on available phase III trial data, this is only if the drug is licensed for use by the EMA by the time the guidelines are published.

“We have agreed on our first set of recommendations. We will probably still work to refine some of these, and we expect to publish at the beginning of next year,” Dr. Otero-Romero said.

Providing independent comment in an interview, Samuel F. Hunter, MD, of the Advanced Neurosciences Institute in Nashville, Tenn., said that the European guidelines were of interest as there were no up-to-date guidelines on drug therapy for MS available in the United States.

While the American Academy of Neurology has produced practice guidelines on the use of disease-modifying therapies in MS (Neurology. 2002;58[2]:169-78) and issued specific guidance on natalizumab (Neurology. 2008;71[10]:766–73), these documents were published years ago. Five new therapies have appeared since then, Dr. Hunter said.

“Guidance is so far behind the advancement of therapy for MS, such that we don’t have any accepted guidelines. The current opinion from various groups is that all therapies should be available for all patients, according to physician advice,” Dr. Hunter said.

“People predominantly follow individual escalation of therapy efficacy guideline for the majority of patients, and people with very severe, fulminant relapses are relegated to higher-efficacy therapies,” he added.

The new European guidelines will influence what is happening in the United States, Dr. Hunter said, but there is such a diversity of interests among the large managed care organizations, the government, payers, pharmaceutical companies, and different academic centers, for example, that reaching a consensus will be difficult.

Dr. Otero-Romero did not declare any specific disclosures in relation to her presentation of the guidelines. Dr. Hunter did not have any disclosure relevant to his comments.