User login
Session to Spotlight Key Research Papers
VAM attendees have the opportunity to learn about several medical journal articles of relevance to their vascular surgery practice during a session on Saturday.
Entitled “Beyond the Journal of Vascular Surgery: ‘Top Ten’ Papers Relevant to Vascular Surgery,” the session “serves to inform VAM attendees on important literature outside of our core vascular surgery journals that might be missed in a busy practice,” said session co-moderator Ellen Dillavou, MD, a vascular surgeon in the department of surgery at Duke University Medical Center, Durham, N.C. “Additionally, the articles are discussed by experts in our field, providing a clinical context for interpretation.”
The session’s other co-moderator is Jon S. Matsumura, MD, professor and chairman of the division of vascular surgery at the University of Wisconsin School of Medicine and Public Health, Madison, Wis.
The moderators reported having no financial disclosures.
Saturday, June 3
10:30 a.m. - 12:00 p.m.
SDCC, Room 6 A/B
F2: Beyond the Journal of Vascular Surgery: “Top Ten” Papers Relevant to Vascular Surgery
VAM attendees have the opportunity to learn about several medical journal articles of relevance to their vascular surgery practice during a session on Saturday.
Entitled “Beyond the Journal of Vascular Surgery: ‘Top Ten’ Papers Relevant to Vascular Surgery,” the session “serves to inform VAM attendees on important literature outside of our core vascular surgery journals that might be missed in a busy practice,” said session co-moderator Ellen Dillavou, MD, a vascular surgeon in the department of surgery at Duke University Medical Center, Durham, N.C. “Additionally, the articles are discussed by experts in our field, providing a clinical context for interpretation.”
The session’s other co-moderator is Jon S. Matsumura, MD, professor and chairman of the division of vascular surgery at the University of Wisconsin School of Medicine and Public Health, Madison, Wis.
The moderators reported having no financial disclosures.
Saturday, June 3
10:30 a.m. - 12:00 p.m.
SDCC, Room 6 A/B
F2: Beyond the Journal of Vascular Surgery: “Top Ten” Papers Relevant to Vascular Surgery
VAM attendees have the opportunity to learn about several medical journal articles of relevance to their vascular surgery practice during a session on Saturday.
Entitled “Beyond the Journal of Vascular Surgery: ‘Top Ten’ Papers Relevant to Vascular Surgery,” the session “serves to inform VAM attendees on important literature outside of our core vascular surgery journals that might be missed in a busy practice,” said session co-moderator Ellen Dillavou, MD, a vascular surgeon in the department of surgery at Duke University Medical Center, Durham, N.C. “Additionally, the articles are discussed by experts in our field, providing a clinical context for interpretation.”
The session’s other co-moderator is Jon S. Matsumura, MD, professor and chairman of the division of vascular surgery at the University of Wisconsin School of Medicine and Public Health, Madison, Wis.
The moderators reported having no financial disclosures.
Saturday, June 3
10:30 a.m. - 12:00 p.m.
SDCC, Room 6 A/B
F2: Beyond the Journal of Vascular Surgery: “Top Ten” Papers Relevant to Vascular Surgery
How the Team Approach Can Drive a High-Performance Vascular Practice
On Saturday, June 3, at 10:30 a.m., vascular surgeons and other members of the vascular care team will come together for a session entitled “Building the Vascular Team – Evolving Collaboration of Surgeons and Nurses.”
This session, run jointly by the Society for Vascular Surgery and the Society for Vascular Nursing, will offer attendees “advice and information about how best to value your team, form your team, educate your team, and utilize your team,” said co-moderator Kellie R. Brown, MD, of the Medical College of Wisconsin, Milwaukee.
Yaron Sternbach, MD, and Marie Rossi, RN, BS, both of The Vascular Group, PLLC, in Albany, N. Y., will give the physician and the nursing perspective on “Defining the High-Performing Vascular Practice,” with an emphasis on forming and maintaining a high-performing team, said Dr. Brown.
In turn, Dr. Brown and co-moderator Tiffany K. Street, MSN, ACNP-BC, of Vanderbilt University School of Nursing will give the physician and the advanced practice provider’s perspective on integrating advanced practice providers into a vascular practice.
Dr. Brown said that a vascular surgeon can really benefit from understanding “how best to have the nursing and advanced practice members of your team really work to the top of their licenses.” This, she said, is when a high-performance vascular team really starts working well: “You have a whole team contributing to the care of the patient. The surgeon’s doing surgery, the nurse is doing nursing, and the advanced practice providers are complementing the surgeon’s work in pre- and post-op care.”
Ms. Street agreed. “From a physician’s perspective, we all have unique roles and all have something to contribute toward the care of the patient. How do we get the right people in the right positions, doing the right type of work?” This, she said, will be a key take-away from the session.
Ms. Rossi, also a co-moderator, will speak in more detail about vascular specialty nursing, in a session entitled, “The Case for Vascular Specialty Nursing: What We Know and What Remains to be Clarified.” In another session, attendees will hear from Kathy Rich, PhD, a vascular nurse in Chesterton, Ind. Dr. Rich sits on the editorial board of the Journal of Vascular Nursing; her presentation is entitled “Expanding the Knowledge Base: Training Paradigms in Vascular Nursing.”
The morning’s presentations will be rounded out by Ms. Street, who will give a nuts-and-bolts presentation entitled, “Integrating Nursing Roles into Daily Practice.” Here, she plans to touch on some of the realities of creating and maintaining a high-performing vascular team. These include scope of practice, competencies, compliance, and billing perspectives, all of which can be perceived hurdles to integrating nurse specialists and advanced practice providers into a vascular practice.
Ms. Street will also provide information about potential career paths within vascular nursing in a presentation entitled “Careers in Vascular Nursing: Opportunities for Growth.”
The joint session, said Dr. Brown, represents “an exciting direction” for the Society for Vascular Surgery. “There will be more opportunities for collaboration between individuals in our two career paths,” as the use of advanced practice providers and specialty nurses grows within vascular surgery.
Ms. Street agreed, adding that the team approach doesn’t negate the surgeon’s role. “Surgery can’t be surgery without surgeons. It’s just about using people in the right positions to take the best care of patients,” she said.
Dr. Brown said that the goal of the team approach in vascular surgery is to achieve both high-quality and efficient care; reaching this mark is an especially relevant goal today, since “the need is going to keep rising, and we can’t train vascular surgeons fast enough,” she said. The team approach is a way to have the vascular surgeon care for more patients as demand soars. “In this era of declining reimbursement, we all need to be more efficient,” said Dr. Brown.
Dr. Brown reported being an investigator for the LEOPARD trial. Ms. Street reported no relevant financial relationships.
Saturday, June 3
10:30 a.m. – 12:00 p.m. SDCC, Room 3
C13: Building the Vascular Team
On Saturday, June 3, at 10:30 a.m., vascular surgeons and other members of the vascular care team will come together for a session entitled “Building the Vascular Team – Evolving Collaboration of Surgeons and Nurses.”
This session, run jointly by the Society for Vascular Surgery and the Society for Vascular Nursing, will offer attendees “advice and information about how best to value your team, form your team, educate your team, and utilize your team,” said co-moderator Kellie R. Brown, MD, of the Medical College of Wisconsin, Milwaukee.
Yaron Sternbach, MD, and Marie Rossi, RN, BS, both of The Vascular Group, PLLC, in Albany, N. Y., will give the physician and the nursing perspective on “Defining the High-Performing Vascular Practice,” with an emphasis on forming and maintaining a high-performing team, said Dr. Brown.
In turn, Dr. Brown and co-moderator Tiffany K. Street, MSN, ACNP-BC, of Vanderbilt University School of Nursing will give the physician and the advanced practice provider’s perspective on integrating advanced practice providers into a vascular practice.
Dr. Brown said that a vascular surgeon can really benefit from understanding “how best to have the nursing and advanced practice members of your team really work to the top of their licenses.” This, she said, is when a high-performance vascular team really starts working well: “You have a whole team contributing to the care of the patient. The surgeon’s doing surgery, the nurse is doing nursing, and the advanced practice providers are complementing the surgeon’s work in pre- and post-op care.”
Ms. Street agreed. “From a physician’s perspective, we all have unique roles and all have something to contribute toward the care of the patient. How do we get the right people in the right positions, doing the right type of work?” This, she said, will be a key take-away from the session.
Ms. Rossi, also a co-moderator, will speak in more detail about vascular specialty nursing, in a session entitled, “The Case for Vascular Specialty Nursing: What We Know and What Remains to be Clarified.” In another session, attendees will hear from Kathy Rich, PhD, a vascular nurse in Chesterton, Ind. Dr. Rich sits on the editorial board of the Journal of Vascular Nursing; her presentation is entitled “Expanding the Knowledge Base: Training Paradigms in Vascular Nursing.”
The morning’s presentations will be rounded out by Ms. Street, who will give a nuts-and-bolts presentation entitled, “Integrating Nursing Roles into Daily Practice.” Here, she plans to touch on some of the realities of creating and maintaining a high-performing vascular team. These include scope of practice, competencies, compliance, and billing perspectives, all of which can be perceived hurdles to integrating nurse specialists and advanced practice providers into a vascular practice.
Ms. Street will also provide information about potential career paths within vascular nursing in a presentation entitled “Careers in Vascular Nursing: Opportunities for Growth.”
The joint session, said Dr. Brown, represents “an exciting direction” for the Society for Vascular Surgery. “There will be more opportunities for collaboration between individuals in our two career paths,” as the use of advanced practice providers and specialty nurses grows within vascular surgery.
Ms. Street agreed, adding that the team approach doesn’t negate the surgeon’s role. “Surgery can’t be surgery without surgeons. It’s just about using people in the right positions to take the best care of patients,” she said.
Dr. Brown said that the goal of the team approach in vascular surgery is to achieve both high-quality and efficient care; reaching this mark is an especially relevant goal today, since “the need is going to keep rising, and we can’t train vascular surgeons fast enough,” she said. The team approach is a way to have the vascular surgeon care for more patients as demand soars. “In this era of declining reimbursement, we all need to be more efficient,” said Dr. Brown.
Dr. Brown reported being an investigator for the LEOPARD trial. Ms. Street reported no relevant financial relationships.
Saturday, June 3
10:30 a.m. – 12:00 p.m. SDCC, Room 3
C13: Building the Vascular Team
On Saturday, June 3, at 10:30 a.m., vascular surgeons and other members of the vascular care team will come together for a session entitled “Building the Vascular Team – Evolving Collaboration of Surgeons and Nurses.”
This session, run jointly by the Society for Vascular Surgery and the Society for Vascular Nursing, will offer attendees “advice and information about how best to value your team, form your team, educate your team, and utilize your team,” said co-moderator Kellie R. Brown, MD, of the Medical College of Wisconsin, Milwaukee.
Yaron Sternbach, MD, and Marie Rossi, RN, BS, both of The Vascular Group, PLLC, in Albany, N. Y., will give the physician and the nursing perspective on “Defining the High-Performing Vascular Practice,” with an emphasis on forming and maintaining a high-performing team, said Dr. Brown.
In turn, Dr. Brown and co-moderator Tiffany K. Street, MSN, ACNP-BC, of Vanderbilt University School of Nursing will give the physician and the advanced practice provider’s perspective on integrating advanced practice providers into a vascular practice.
Dr. Brown said that a vascular surgeon can really benefit from understanding “how best to have the nursing and advanced practice members of your team really work to the top of their licenses.” This, she said, is when a high-performance vascular team really starts working well: “You have a whole team contributing to the care of the patient. The surgeon’s doing surgery, the nurse is doing nursing, and the advanced practice providers are complementing the surgeon’s work in pre- and post-op care.”
Ms. Street agreed. “From a physician’s perspective, we all have unique roles and all have something to contribute toward the care of the patient. How do we get the right people in the right positions, doing the right type of work?” This, she said, will be a key take-away from the session.
Ms. Rossi, also a co-moderator, will speak in more detail about vascular specialty nursing, in a session entitled, “The Case for Vascular Specialty Nursing: What We Know and What Remains to be Clarified.” In another session, attendees will hear from Kathy Rich, PhD, a vascular nurse in Chesterton, Ind. Dr. Rich sits on the editorial board of the Journal of Vascular Nursing; her presentation is entitled “Expanding the Knowledge Base: Training Paradigms in Vascular Nursing.”
The morning’s presentations will be rounded out by Ms. Street, who will give a nuts-and-bolts presentation entitled, “Integrating Nursing Roles into Daily Practice.” Here, she plans to touch on some of the realities of creating and maintaining a high-performing vascular team. These include scope of practice, competencies, compliance, and billing perspectives, all of which can be perceived hurdles to integrating nurse specialists and advanced practice providers into a vascular practice.
Ms. Street will also provide information about potential career paths within vascular nursing in a presentation entitled “Careers in Vascular Nursing: Opportunities for Growth.”
The joint session, said Dr. Brown, represents “an exciting direction” for the Society for Vascular Surgery. “There will be more opportunities for collaboration between individuals in our two career paths,” as the use of advanced practice providers and specialty nurses grows within vascular surgery.
Ms. Street agreed, adding that the team approach doesn’t negate the surgeon’s role. “Surgery can’t be surgery without surgeons. It’s just about using people in the right positions to take the best care of patients,” she said.
Dr. Brown said that the goal of the team approach in vascular surgery is to achieve both high-quality and efficient care; reaching this mark is an especially relevant goal today, since “the need is going to keep rising, and we can’t train vascular surgeons fast enough,” she said. The team approach is a way to have the vascular surgeon care for more patients as demand soars. “In this era of declining reimbursement, we all need to be more efficient,” said Dr. Brown.
Dr. Brown reported being an investigator for the LEOPARD trial. Ms. Street reported no relevant financial relationships.
Saturday, June 3
10:30 a.m. – 12:00 p.m. SDCC, Room 3
C13: Building the Vascular Team
Erenumab May Reduce Headache Days in Episodic Migraine
BOSTON—Erenumab reduces the number of migraine days per month in patients with episodic migraine, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology. The treatment also reduces the use of acute migraine medication and improves function.
Erenumab is a fully human monoclonal antibody developed to block the pathway of calcitonin gene-related peptide (CGRP). The treatment showed promise in a phase II study in patients with episodic migraine and in a phase II study of patients with chronic migraine, according to Peter Goadsby, MD, PhD, Professor of Neurology at the University of California, San Francisco School of Medicine. 
A Test of Two Doses
Dr. Goadsby and colleagues conducted a phase III study of 955 participants to examine whether erenumab would be an effective preventive treatment for episodic migraine. Eligible patients had between four and 14 migraine days per month and were allowed to take one concomitant migraine medication. Patients who previously had failed two preventive medications were excluded. After screening, patients underwent a four-week baseline period during which they kept electronic migraine diaries. The investigators then randomized patients in groups of equal size to placebo, 70 mg of subcutaneous erenumab, or 140 mg of subcutaneous erenumab. The treatment period lasted for six months.
As has been the case in many studies of migraine during the past 25 years, the typical patient in this study was a 41-year-old Caucasian woman, said Dr. Goadsby. Slightly more than half of participants had no previous exposure to a preventive therapy. The mean number of migraine days in all treatment groups was eight, and the mean number of headache days was nine. The treatment groups were well balanced.
Treatment Reduced Medication Use
During the last three months of treatment, the mean number of monthly migraine days decreased by 3.2 for patients receiving 70 mg of erenumab and by 3.7 for patients receiving 140 mg of erenumab, compared with 1.8 for patients receiving placebo. The difference between the active and control arms was statistically significant. The rate of participants who had a 50% reduction in migraine attacks was 26.6% for controls, 43% for patients receiving the 70-mg dose, and 50% for patients receiving the 140-mg dose.
The use of acute medicines decreased by 1.1 days for patients receiving 70 mg of erenumab and by 1.6 days for patients receiving 140 mg, compared with a decrease of 0.2 days for patients receiving placebo. Using the Migraine Physical Function Impact Diary, participants in the 70-mg group reported that the impact of migraine on everyday activities decreased by 5.5 points. Participants in the 140-mg group reported a 5.9-point reduction in this end point. Participants in the placebo group reported a 3.3-point reduction. Physical impairment decreased by 4.2 points for the 70-mg group and by 4.8 points for the 140-mg group versus 2.4 points for the placebo group.
Erenumab was well tolerated, and none of the serious adverse events appeared to be related to treatment. The most common adverse event was injection-site reactions. About 6% of the entire cohort developed antibodies to erenumab, including 8% in the 70-mg group and 3.2% in the 140-mg group. One patient receiving 70 mg had a neutralizing antibody, and no patients in the 140-mg group had neutralizing antibodies.
The study results are exciting, said Dr. Goadsby. In the future, treatments that target the CGRP pathway could be provided to migraineurs who do not respond to or cannot tolerate the current therapies, he added.
The trial was sponsored by Amgen, and Dr. Goadsby previously has consulted for the company.
—Erik Greb
BOSTON—Erenumab reduces the number of migraine days per month in patients with episodic migraine, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology. The treatment also reduces the use of acute migraine medication and improves function.
Erenumab is a fully human monoclonal antibody developed to block the pathway of calcitonin gene-related peptide (CGRP). The treatment showed promise in a phase II study in patients with episodic migraine and in a phase II study of patients with chronic migraine, according to Peter Goadsby, MD, PhD, Professor of Neurology at the University of California, San Francisco School of Medicine.
A Test of Two Doses
Dr. Goadsby and colleagues conducted a phase III study of 955 participants to examine whether erenumab would be an effective preventive treatment for episodic migraine. Eligible patients had between four and 14 migraine days per month and were allowed to take one concomitant migraine medication. Patients who previously had failed two preventive medications were excluded. After screening, patients underwent a four-week baseline period during which they kept electronic migraine diaries. The investigators then randomized patients in groups of equal size to placebo, 70 mg of subcutaneous erenumab, or 140 mg of subcutaneous erenumab. The treatment period lasted for six months.
As has been the case in many studies of migraine during the past 25 years, the typical patient in this study was a 41-year-old Caucasian woman, said Dr. Goadsby. Slightly more than half of participants had no previous exposure to a preventive therapy. The mean number of migraine days in all treatment groups was eight, and the mean number of headache days was nine. The treatment groups were well balanced.
Treatment Reduced Medication Use
During the last three months of treatment, the mean number of monthly migraine days decreased by 3.2 for patients receiving 70 mg of erenumab and by 3.7 for patients receiving 140 mg of erenumab, compared with 1.8 for patients receiving placebo. The difference between the active and control arms was statistically significant. The rate of participants who had a 50% reduction in migraine attacks was 26.6% for controls, 43% for patients receiving the 70-mg dose, and 50% for patients receiving the 140-mg dose.
The use of acute medicines decreased by 1.1 days for patients receiving 70 mg of erenumab and by 1.6 days for patients receiving 140 mg, compared with a decrease of 0.2 days for patients receiving placebo. Using the Migraine Physical Function Impact Diary, participants in the 70-mg group reported that the impact of migraine on everyday activities decreased by 5.5 points. Participants in the 140-mg group reported a 5.9-point reduction in this end point. Participants in the placebo group reported a 3.3-point reduction. Physical impairment decreased by 4.2 points for the 70-mg group and by 4.8 points for the 140-mg group versus 2.4 points for the placebo group.
Erenumab was well tolerated, and none of the serious adverse events appeared to be related to treatment. The most common adverse event was injection-site reactions. About 6% of the entire cohort developed antibodies to erenumab, including 8% in the 70-mg group and 3.2% in the 140-mg group. One patient receiving 70 mg had a neutralizing antibody, and no patients in the 140-mg group had neutralizing antibodies.
The study results are exciting, said Dr. Goadsby. In the future, treatments that target the CGRP pathway could be provided to migraineurs who do not respond to or cannot tolerate the current therapies, he added.
The trial was sponsored by Amgen, and Dr. Goadsby previously has consulted for the company.
—Erik Greb
BOSTON—Erenumab reduces the number of migraine days per month in patients with episodic migraine, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology. The treatment also reduces the use of acute migraine medication and improves function.
Erenumab is a fully human monoclonal antibody developed to block the pathway of calcitonin gene-related peptide (CGRP). The treatment showed promise in a phase II study in patients with episodic migraine and in a phase II study of patients with chronic migraine, according to Peter Goadsby, MD, PhD, Professor of Neurology at the University of California, San Francisco School of Medicine.
A Test of Two Doses
Dr. Goadsby and colleagues conducted a phase III study of 955 participants to examine whether erenumab would be an effective preventive treatment for episodic migraine. Eligible patients had between four and 14 migraine days per month and were allowed to take one concomitant migraine medication. Patients who previously had failed two preventive medications were excluded. After screening, patients underwent a four-week baseline period during which they kept electronic migraine diaries. The investigators then randomized patients in groups of equal size to placebo, 70 mg of subcutaneous erenumab, or 140 mg of subcutaneous erenumab. The treatment period lasted for six months.
As has been the case in many studies of migraine during the past 25 years, the typical patient in this study was a 41-year-old Caucasian woman, said Dr. Goadsby. Slightly more than half of participants had no previous exposure to a preventive therapy. The mean number of migraine days in all treatment groups was eight, and the mean number of headache days was nine. The treatment groups were well balanced.
Treatment Reduced Medication Use
During the last three months of treatment, the mean number of monthly migraine days decreased by 3.2 for patients receiving 70 mg of erenumab and by 3.7 for patients receiving 140 mg of erenumab, compared with 1.8 for patients receiving placebo. The difference between the active and control arms was statistically significant. The rate of participants who had a 50% reduction in migraine attacks was 26.6% for controls, 43% for patients receiving the 70-mg dose, and 50% for patients receiving the 140-mg dose.
The use of acute medicines decreased by 1.1 days for patients receiving 70 mg of erenumab and by 1.6 days for patients receiving 140 mg, compared with a decrease of 0.2 days for patients receiving placebo. Using the Migraine Physical Function Impact Diary, participants in the 70-mg group reported that the impact of migraine on everyday activities decreased by 5.5 points. Participants in the 140-mg group reported a 5.9-point reduction in this end point. Participants in the placebo group reported a 3.3-point reduction. Physical impairment decreased by 4.2 points for the 70-mg group and by 4.8 points for the 140-mg group versus 2.4 points for the placebo group.
Erenumab was well tolerated, and none of the serious adverse events appeared to be related to treatment. The most common adverse event was injection-site reactions. About 6% of the entire cohort developed antibodies to erenumab, including 8% in the 70-mg group and 3.2% in the 140-mg group. One patient receiving 70 mg had a neutralizing antibody, and no patients in the 140-mg group had neutralizing antibodies.
The study results are exciting, said Dr. Goadsby. In the future, treatments that target the CGRP pathway could be provided to migraineurs who do not respond to or cannot tolerate the current therapies, he added.
The trial was sponsored by Amgen, and Dr. Goadsby previously has consulted for the company.
—Erik Greb
Tips for Recovering From Concussion
Click here to download the PDF. 
Click here to download the PDF.
Click here to download the PDF.
FDA advisory committee supports neratinib approval
of adults with early-stage HER2-positive breast cancer who received prior adjuvant trastuzumab-based therapy.
Members voting during the May 24 meeting expressed concern about the broadness of the indication proposed by the drug’s maker, Puma Biotechnology, but the majority said the risk-benefit profile of the drug is sufficient to support approval, particularly given the unmet need for such an agent. Those voting against approval argued that more data are needed to identify subpopulations of patients who would be most likely to benefit from treatment in order to narrow the indication.
“There are some unknowns that concern me. ... I don’t think I would treat as broadly as the indication describes,” he said, adding that it would be very difficult to decide which patients to treat, and it would be nice to have more data that provide predictive biomarkers to help determine who should be treated. “But at the end of the day I think it’s useful to have this as an option for treating patients.”
Lori M. Minasian, MD, also a temporary voting member from the National Institutes of Health, agreed.
“I think the option should be available,” she said, adding that the analysis was thorough. However, she, too, questioned the proposed indication.
“I remain concerned that the indication is far too broad, and ... I think we need greater understanding of which subsets of patients would be most responsive to this therapy,” she said.
Heidi D. Klepin, MD, of Wake Forest University in Winston-Salem, N.C. said she voted “yes” for similar reasons, despite concerns about the lack of data to help narrow the indication.
“I particularly felt it was important to support this indication because I think this is an unmet need, and I think the primary outcome is an important and relevant outcome for our patients, even though what we’re seeing effect-wise may be modest,” she said.
Patricia A. Spears, a breast cancer survivor and patient representative from Raleigh, N.C., however, voted against approval.
“I think it is important to get drugs out to patients, and I think this will benefit a certain subset of patients. I’m just not sure we know which ones yet. What we do is tend to put a lot of patients at risk to benefit just a few. We do that a lot,” she said.
She expressed concern that the treatment would be “tacked on to the end of trastuzumab” in too many cases without concern for whether the patient is likely to benefit.
Another member who voted no, Courtney J. Preusse, who was a consumer representative on the committee, said she struggled with the decision but ultimately decided that the benefit this drug adds beyond what already exists is “just not compelling.”
Neratinib is a kinase inhibitor that irreversibly binds to epidermal growth factor receptors, HER2, and HER4, and results of the phase III ExteNET trial presented to the committee by representatives of the applicant showed a statistically significant invasive disease-free survival benefit with treatment.
The invasive disease-free survival at 2 years in 1,420 patients with early stage HER2-positive breast cancer after adjuvant treatment with trastuzumab who were randomized to receive neratinib was 94.2%, compared with 91.9% in 1,420 who received placebo (stratified hazard ratio 0.66). Follow-up data from patients who reconsented to participate showed similar outcomes from 2 to 5 years post-randomization.
An exploratory subgroup analysis suggested a possible difference in the magnitude of benefit based on hormone receptor status, with a 51% reduction in recurrence risk among HR-positive patients, compared with a 7% reduction in HR-negative patients (hazard ratios, 0.49 and 0.93, respectively).
Some concern was raised regarding multiple amendments to the protocol during the study, but committee members who spoke about this expressed satisfaction with the way these issues were handled in terms of sensitivity analysis.
As for safety, diarrhea was the most frequently reported adverse reaction, occurring in 95% of treated patients. Grade 3 diarrhea occurred in 40% of treated patients. Additional data were presented showing that antidiarrheal prophylaxis was effective. Several patients who spoke during the public hearing portion of the meeting–some of whom had travel expenses paid by the applicant, said they either had no problem with diarrhea or that it was manageable. Nearly all of those who spoke during the open public hearing, including patients and family members, shared emotional stories about their personal battles with breast cancer and urged the committee to support approval of neratinib to expand the options available to patients.
The FDA will now consider the new drug application for neratinib, and although it is not bound by the advisory committee’s recommendation, it usually follows such recommendations.
The advisory committee members reported having no relevant conflicts of interest.
of adults with early-stage HER2-positive breast cancer who received prior adjuvant trastuzumab-based therapy.
Members voting during the May 24 meeting expressed concern about the broadness of the indication proposed by the drug’s maker, Puma Biotechnology, but the majority said the risk-benefit profile of the drug is sufficient to support approval, particularly given the unmet need for such an agent. Those voting against approval argued that more data are needed to identify subpopulations of patients who would be most likely to benefit from treatment in order to narrow the indication.
“There are some unknowns that concern me. ... I don’t think I would treat as broadly as the indication describes,” he said, adding that it would be very difficult to decide which patients to treat, and it would be nice to have more data that provide predictive biomarkers to help determine who should be treated. “But at the end of the day I think it’s useful to have this as an option for treating patients.”
Lori M. Minasian, MD, also a temporary voting member from the National Institutes of Health, agreed.
“I think the option should be available,” she said, adding that the analysis was thorough. However, she, too, questioned the proposed indication.
“I remain concerned that the indication is far too broad, and ... I think we need greater understanding of which subsets of patients would be most responsive to this therapy,” she said.
Heidi D. Klepin, MD, of Wake Forest University in Winston-Salem, N.C. said she voted “yes” for similar reasons, despite concerns about the lack of data to help narrow the indication.
“I particularly felt it was important to support this indication because I think this is an unmet need, and I think the primary outcome is an important and relevant outcome for our patients, even though what we’re seeing effect-wise may be modest,” she said.
Patricia A. Spears, a breast cancer survivor and patient representative from Raleigh, N.C., however, voted against approval.
“I think it is important to get drugs out to patients, and I think this will benefit a certain subset of patients. I’m just not sure we know which ones yet. What we do is tend to put a lot of patients at risk to benefit just a few. We do that a lot,” she said.
She expressed concern that the treatment would be “tacked on to the end of trastuzumab” in too many cases without concern for whether the patient is likely to benefit.
Another member who voted no, Courtney J. Preusse, who was a consumer representative on the committee, said she struggled with the decision but ultimately decided that the benefit this drug adds beyond what already exists is “just not compelling.”
Neratinib is a kinase inhibitor that irreversibly binds to epidermal growth factor receptors, HER2, and HER4, and results of the phase III ExteNET trial presented to the committee by representatives of the applicant showed a statistically significant invasive disease-free survival benefit with treatment.
The invasive disease-free survival at 2 years in 1,420 patients with early stage HER2-positive breast cancer after adjuvant treatment with trastuzumab who were randomized to receive neratinib was 94.2%, compared with 91.9% in 1,420 who received placebo (stratified hazard ratio 0.66). Follow-up data from patients who reconsented to participate showed similar outcomes from 2 to 5 years post-randomization.
An exploratory subgroup analysis suggested a possible difference in the magnitude of benefit based on hormone receptor status, with a 51% reduction in recurrence risk among HR-positive patients, compared with a 7% reduction in HR-negative patients (hazard ratios, 0.49 and 0.93, respectively).
Some concern was raised regarding multiple amendments to the protocol during the study, but committee members who spoke about this expressed satisfaction with the way these issues were handled in terms of sensitivity analysis.
As for safety, diarrhea was the most frequently reported adverse reaction, occurring in 95% of treated patients. Grade 3 diarrhea occurred in 40% of treated patients. Additional data were presented showing that antidiarrheal prophylaxis was effective. Several patients who spoke during the public hearing portion of the meeting–some of whom had travel expenses paid by the applicant, said they either had no problem with diarrhea or that it was manageable. Nearly all of those who spoke during the open public hearing, including patients and family members, shared emotional stories about their personal battles with breast cancer and urged the committee to support approval of neratinib to expand the options available to patients.
The FDA will now consider the new drug application for neratinib, and although it is not bound by the advisory committee’s recommendation, it usually follows such recommendations.
The advisory committee members reported having no relevant conflicts of interest.
of adults with early-stage HER2-positive breast cancer who received prior adjuvant trastuzumab-based therapy.
Members voting during the May 24 meeting expressed concern about the broadness of the indication proposed by the drug’s maker, Puma Biotechnology, but the majority said the risk-benefit profile of the drug is sufficient to support approval, particularly given the unmet need for such an agent. Those voting against approval argued that more data are needed to identify subpopulations of patients who would be most likely to benefit from treatment in order to narrow the indication.
“There are some unknowns that concern me. ... I don’t think I would treat as broadly as the indication describes,” he said, adding that it would be very difficult to decide which patients to treat, and it would be nice to have more data that provide predictive biomarkers to help determine who should be treated. “But at the end of the day I think it’s useful to have this as an option for treating patients.”
Lori M. Minasian, MD, also a temporary voting member from the National Institutes of Health, agreed.
“I think the option should be available,” she said, adding that the analysis was thorough. However, she, too, questioned the proposed indication.
“I remain concerned that the indication is far too broad, and ... I think we need greater understanding of which subsets of patients would be most responsive to this therapy,” she said.
Heidi D. Klepin, MD, of Wake Forest University in Winston-Salem, N.C. said she voted “yes” for similar reasons, despite concerns about the lack of data to help narrow the indication.
“I particularly felt it was important to support this indication because I think this is an unmet need, and I think the primary outcome is an important and relevant outcome for our patients, even though what we’re seeing effect-wise may be modest,” she said.
Patricia A. Spears, a breast cancer survivor and patient representative from Raleigh, N.C., however, voted against approval.
“I think it is important to get drugs out to patients, and I think this will benefit a certain subset of patients. I’m just not sure we know which ones yet. What we do is tend to put a lot of patients at risk to benefit just a few. We do that a lot,” she said.
She expressed concern that the treatment would be “tacked on to the end of trastuzumab” in too many cases without concern for whether the patient is likely to benefit.
Another member who voted no, Courtney J. Preusse, who was a consumer representative on the committee, said she struggled with the decision but ultimately decided that the benefit this drug adds beyond what already exists is “just not compelling.”
Neratinib is a kinase inhibitor that irreversibly binds to epidermal growth factor receptors, HER2, and HER4, and results of the phase III ExteNET trial presented to the committee by representatives of the applicant showed a statistically significant invasive disease-free survival benefit with treatment.
The invasive disease-free survival at 2 years in 1,420 patients with early stage HER2-positive breast cancer after adjuvant treatment with trastuzumab who were randomized to receive neratinib was 94.2%, compared with 91.9% in 1,420 who received placebo (stratified hazard ratio 0.66). Follow-up data from patients who reconsented to participate showed similar outcomes from 2 to 5 years post-randomization.
An exploratory subgroup analysis suggested a possible difference in the magnitude of benefit based on hormone receptor status, with a 51% reduction in recurrence risk among HR-positive patients, compared with a 7% reduction in HR-negative patients (hazard ratios, 0.49 and 0.93, respectively).
Some concern was raised regarding multiple amendments to the protocol during the study, but committee members who spoke about this expressed satisfaction with the way these issues were handled in terms of sensitivity analysis.
As for safety, diarrhea was the most frequently reported adverse reaction, occurring in 95% of treated patients. Grade 3 diarrhea occurred in 40% of treated patients. Additional data were presented showing that antidiarrheal prophylaxis was effective. Several patients who spoke during the public hearing portion of the meeting–some of whom had travel expenses paid by the applicant, said they either had no problem with diarrhea or that it was manageable. Nearly all of those who spoke during the open public hearing, including patients and family members, shared emotional stories about their personal battles with breast cancer and urged the committee to support approval of neratinib to expand the options available to patients.
The FDA will now consider the new drug application for neratinib, and although it is not bound by the advisory committee’s recommendation, it usually follows such recommendations.
The advisory committee members reported having no relevant conflicts of interest.
SVS, STS Host Joint Aortic Summit Saturday Afternoon
The surgeons and society leaders involved in this summit want continued collaboration to become a cultural expectation. It is expected that future summits will be held in alternate venues: at the SVS Annual Meeting this year, at the STS Annual Meeting the next time.
“That shows it’s a team effort, that yes, we’re going to care for these complex patients together as a multidisciplinary aortic team, and collaborate nationally to exchange ideas,”according to Dr. Szeto and Dr. Lee.
The summit, “Advances and Controversies in the Management of Complex Thoracoabdominal Aneurysmal Disease and Type B Aortic Dissection,” will take place from 1:30 to 5:15 p.m. Saturday, in SDCC, Room 3. A separate registration fee is required; all members are encouraged to attend this unique discussion with experts from multiple disciplines reviewing the most contemporary treatments for these complex problems, said Jason T. Lee, MD of Stanford University, Calif. He and Wilson Szeto, MD (University of Pennsylvania, Philadelphia) of STS are co-moderating the program.
The 2013 symposium was so “extremely valuable, productive, and popular” that leaders from both societies felt it was time to reinvigorate the collaborative program, said Dr. Szeto. Members of both specialties care for patients with aortic disease, with a great deal of overlap in the management of disease processes and treatments. “It makes sense to continue to foster and embrace this collaboration with the goal of improving patient care,” said Dr. Szeto. “A multidisciplinary approach of an aortic disease team is the ideal paradigm, in our opinion. We prefer to work in teams, not silos.”
With that in mind, Joseph E. Bavaria, MD, immediate past president of STS, and SVS President Ronald M. Fairman, MD, worked to make the vision of a 2017 summit a reality
It will cover the technical aspects of both open and endovascular repair of thoracoabdominal aneurysms, compare and contrast options for preserving spinal cord function, and identify current and future treatment options in the arena of TEVAR focusing on aortic dissection.
“To optimize best delivery of patient-centered care, when it comes to complex aortic disease, collaboration and team management are necessary,” said Dr. Lee. “Institutions that have experts who work together and provide all types of technologies, whether open or endovascular, will be best equipped to provide the level of care necessary for best outcomes. To assemble numerous experts from across the country and world to discuss these issues will make this a very educational and exciting session.”
The summit is broken into several parts. Dr. Lee and Dr. Szeto will moderate the thoracoabdominal section and Matthew Eagleton, MD, of the Cleveland Clinic (SVS) and Michael Fischbein, MD, of Stanford University in California (STS) will moderate the portion on Type B Aortic Dissection.
The summit will conclude with a look to the future in the treatment of aortic disease. Dr. Szeto will discuss how to optimally train future cardiovascular surgeons to manage complex aortic disease while Dr. R. Clement Darling, III, MD, SVS President-elect, will talk about the need for members of both specialties to work together as open and endovascular experts to manage complex aortic disease.
The surgeons and society leaders involved in this summit want continued collaboration to become a cultural expectation. It is expected that future summits will be held in alternate venues: at the SVS Annual Meeting this year, at the STS Annual Meeting the next time.
“That shows it’s a team effort, that yes, we’re going to care for these complex patients together as a multidisciplinary aortic team, and collaborate nationally to exchange ideas,”according to Dr. Szeto and Dr. Lee.
The summit, “Advances and Controversies in the Management of Complex Thoracoabdominal Aneurysmal Disease and Type B Aortic Dissection,” will take place from 1:30 to 5:15 p.m. Saturday, in SDCC, Room 3. A separate registration fee is required; all members are encouraged to attend this unique discussion with experts from multiple disciplines reviewing the most contemporary treatments for these complex problems, said Jason T. Lee, MD of Stanford University, Calif. He and Wilson Szeto, MD (University of Pennsylvania, Philadelphia) of STS are co-moderating the program.
The 2013 symposium was so “extremely valuable, productive, and popular” that leaders from both societies felt it was time to reinvigorate the collaborative program, said Dr. Szeto. Members of both specialties care for patients with aortic disease, with a great deal of overlap in the management of disease processes and treatments. “It makes sense to continue to foster and embrace this collaboration with the goal of improving patient care,” said Dr. Szeto. “A multidisciplinary approach of an aortic disease team is the ideal paradigm, in our opinion. We prefer to work in teams, not silos.”
With that in mind, Joseph E. Bavaria, MD, immediate past president of STS, and SVS President Ronald M. Fairman, MD, worked to make the vision of a 2017 summit a reality
It will cover the technical aspects of both open and endovascular repair of thoracoabdominal aneurysms, compare and contrast options for preserving spinal cord function, and identify current and future treatment options in the arena of TEVAR focusing on aortic dissection.
“To optimize best delivery of patient-centered care, when it comes to complex aortic disease, collaboration and team management are necessary,” said Dr. Lee. “Institutions that have experts who work together and provide all types of technologies, whether open or endovascular, will be best equipped to provide the level of care necessary for best outcomes. To assemble numerous experts from across the country and world to discuss these issues will make this a very educational and exciting session.”
The summit is broken into several parts. Dr. Lee and Dr. Szeto will moderate the thoracoabdominal section and Matthew Eagleton, MD, of the Cleveland Clinic (SVS) and Michael Fischbein, MD, of Stanford University in California (STS) will moderate the portion on Type B Aortic Dissection.
The summit will conclude with a look to the future in the treatment of aortic disease. Dr. Szeto will discuss how to optimally train future cardiovascular surgeons to manage complex aortic disease while Dr. R. Clement Darling, III, MD, SVS President-elect, will talk about the need for members of both specialties to work together as open and endovascular experts to manage complex aortic disease.
The surgeons and society leaders involved in this summit want continued collaboration to become a cultural expectation. It is expected that future summits will be held in alternate venues: at the SVS Annual Meeting this year, at the STS Annual Meeting the next time.
“That shows it’s a team effort, that yes, we’re going to care for these complex patients together as a multidisciplinary aortic team, and collaborate nationally to exchange ideas,”according to Dr. Szeto and Dr. Lee.
The summit, “Advances and Controversies in the Management of Complex Thoracoabdominal Aneurysmal Disease and Type B Aortic Dissection,” will take place from 1:30 to 5:15 p.m. Saturday, in SDCC, Room 3. A separate registration fee is required; all members are encouraged to attend this unique discussion with experts from multiple disciplines reviewing the most contemporary treatments for these complex problems, said Jason T. Lee, MD of Stanford University, Calif. He and Wilson Szeto, MD (University of Pennsylvania, Philadelphia) of STS are co-moderating the program.
The 2013 symposium was so “extremely valuable, productive, and popular” that leaders from both societies felt it was time to reinvigorate the collaborative program, said Dr. Szeto. Members of both specialties care for patients with aortic disease, with a great deal of overlap in the management of disease processes and treatments. “It makes sense to continue to foster and embrace this collaboration with the goal of improving patient care,” said Dr. Szeto. “A multidisciplinary approach of an aortic disease team is the ideal paradigm, in our opinion. We prefer to work in teams, not silos.”
With that in mind, Joseph E. Bavaria, MD, immediate past president of STS, and SVS President Ronald M. Fairman, MD, worked to make the vision of a 2017 summit a reality
It will cover the technical aspects of both open and endovascular repair of thoracoabdominal aneurysms, compare and contrast options for preserving spinal cord function, and identify current and future treatment options in the arena of TEVAR focusing on aortic dissection.
“To optimize best delivery of patient-centered care, when it comes to complex aortic disease, collaboration and team management are necessary,” said Dr. Lee. “Institutions that have experts who work together and provide all types of technologies, whether open or endovascular, will be best equipped to provide the level of care necessary for best outcomes. To assemble numerous experts from across the country and world to discuss these issues will make this a very educational and exciting session.”
The summit is broken into several parts. Dr. Lee and Dr. Szeto will moderate the thoracoabdominal section and Matthew Eagleton, MD, of the Cleveland Clinic (SVS) and Michael Fischbein, MD, of Stanford University in California (STS) will moderate the portion on Type B Aortic Dissection.
The summit will conclude with a look to the future in the treatment of aortic disease. Dr. Szeto will discuss how to optimally train future cardiovascular surgeons to manage complex aortic disease while Dr. R. Clement Darling, III, MD, SVS President-elect, will talk about the need for members of both specialties to work together as open and endovascular experts to manage complex aortic disease.
Nusinersen for early spinal muscular atrophy: Final findings beat interim results
BOSTON – Last December, the Food and Drug Administration approved nusinersen (Spinraza) as the only treatment for spinal muscular atrophy (SMA) based in part on startling interim results from a study in infants that ended early so all participants could get access to the drug.
Now the final study results are in, and they’re even more impressive: Patients who took the drug were less than half as likely to die as were those in a sham control group, and motor function improved in more than half of infants who took the medication, compared with none in the sham group.
The findings are “incredibly exciting,” said Charlotte J. Sumner, MD, in a discussant presentation at the annual meeting of the American Academy of Neurology. “The data teaches us that this drug is efficacious.”
However, Dr. Sumner, professor of neurology and neuroscience at Johns Hopkins University, Baltimore, cautioned that the drug is tremendously expensive, challenging to administer, and there are several questions about its use that remain unanswered.
SMA is most often caused by mutations in the SMN1 gene, leading to a loss of the protein called survival motor neuron (SMN), which is essential for the survival of motor neurons, except for a small amount produced from the SMN2 gene. The loss of motor neurons in the spinal cord and brainstem leads to weakness and atrophy of muscles used for crawling, walking, sitting up, controlling head movement, and in severe cases, breathing and swallowing. It affects an estimated 1 in 6,000 newborns and is the most common genetic cause of death in infants. Nusinersen is a antisense oligonucleotide that promotes transcription of the full-length SMN protein from the SMN2 gene.
At the AAN meeting, investigators presented the final results of two nusinersen phase III studies as well as interim data from a separate phase II trial.
The ENDEAR trial, a randomized, double-blind, sham-procedure controlled study, assigned 80 patients to 12-mg scaled equivalent doses of nusinersen delivered intrathecally (four doses over 2 months, then one every 4 months) and 41 to a sham procedure (a needle prick in the lower back). The subjects, aged 30-252 days at first dose, underwent 13 months of treatment and follow-up.
Researchers presented an end-of-study analysis of 110 subjects. They found that 51% of those who received the drug were “motor milestone responders” – meaning they had more modified Hammersmith Infant Neurological Examination Section 2 categories with improvement than worsening – compared with 41% at the interim analysis (P less than .0001). None of the sham group patients improved.
The patients treated with nusinersen lived longer: 39% of those in the sham procedure group died, compared with 16% of those in the nusinersen group (hazard ratio, 0.372; P = .0041). Event-free survival (survival without permanent ventilation) was also better in those who received the drugs: 61% in those who took nusinersen, compared with 32% in those who did not (HR, 0.53; P = .0046)
Also, 71% of those treated with the drug were considered responders at day 183 onward based on an improvement of 4 or more points on the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scale, whereas the response rate was only 3% in the sham group (P less than .0001).
The study authors report that nusinersen was well tolerated with adverse events that “were consistent with those expected in the general population of infants with SMA.” No adverse events were linked to the nusinersen treatment.
Researchers also presented the end-of-study results of the phase III CHERISH trial of 126 patients aged 2-12 years with later-onset SMA who could sit up but not walk. All participants were believed to have a life expectancy of at least 2 years.
The trial is a multicenter, randomized, double-blind, sham-procedure controlled study. The 84 subjects who received the drug improved an average of 3.9 points by the end of study (15 months) on the Hammersmith Functional Motor Scale Expanded score, a measurement of motor function in children with SMA (P = .0000001). The 42 children who received the sham treatment (a small needle prick on the lower back) declined by an average of 1.0 point.
Researchers report that children taking the drug had fewer adverse events, and most were not related to the drug itself.
All surviving participants who completed nusinersen investigational studies are being enrolled in the SHINE open-label extension trial.
Also at the AAN meeting, researchers released interim phase II results from the NURTURE trial, an open-label study of nusinersen in patients with diagnosed but presymptomatic SMA. The study, which is expected to be completed in 2022, recruited participants up to the age of 6 weeks.
The 20 enrolled infants were all alive at a median study period of 317.5 days, and none required assistance with respiration.
In terms of motor function and growth, most were making gains “generally consistent with normal development such as head control, independent sitting, standing and walking independently, as measured by validated scales,” according to a statement released by Biogen.
Three patients developed adverse events that may have been drug related, but the events were resolved and they remained in the trial.
In Dr. Sumner’s discussant presentation on the ENDEAR study, she cautioned that it’s still not known how much older patients with SMA will benefit from the drug treatment. It’s possible that younger patients may gain motor function while older patients will maintain what they have, she said.
In addition, it seems that “certain body segments may respond more robustly than some others. It’s possible that an infant may improve limb strength quite robustly but not lumbar strength.”
She pointed out other questions: Can the drug, which is difficult to administer, be stopped at some point? “We do think of SMA as a disease of development,” she said. “Maybe after development is finished we can withdraw the drug.”
Then there’s the issue of cost and whether insurers are willing to cover the drug. As Dr. Sumner pointed out, the drug is $125,000 per dose and $750,000 over the first year, then $325,000 a year.
It is clear, however, that “the early and efficient diagnosis of SMA is really important, particularly for infantile SMA,” she said. “Time is motor function.”
The studies were funded by Ionis Pharmaceuticals and Biogen. Dr. Sumner reports serving as a consultant for Biogen, Ionis, Avexis, and Roche. She has served on scientific advisory boards for the Cure SMA, SMA Foundation, and Muscular Dystrophy Association nonprofit foundations.
BOSTON – Last December, the Food and Drug Administration approved nusinersen (Spinraza) as the only treatment for spinal muscular atrophy (SMA) based in part on startling interim results from a study in infants that ended early so all participants could get access to the drug.
Now the final study results are in, and they’re even more impressive: Patients who took the drug were less than half as likely to die as were those in a sham control group, and motor function improved in more than half of infants who took the medication, compared with none in the sham group.
The findings are “incredibly exciting,” said Charlotte J. Sumner, MD, in a discussant presentation at the annual meeting of the American Academy of Neurology. “The data teaches us that this drug is efficacious.”
However, Dr. Sumner, professor of neurology and neuroscience at Johns Hopkins University, Baltimore, cautioned that the drug is tremendously expensive, challenging to administer, and there are several questions about its use that remain unanswered.
SMA is most often caused by mutations in the SMN1 gene, leading to a loss of the protein called survival motor neuron (SMN), which is essential for the survival of motor neurons, except for a small amount produced from the SMN2 gene. The loss of motor neurons in the spinal cord and brainstem leads to weakness and atrophy of muscles used for crawling, walking, sitting up, controlling head movement, and in severe cases, breathing and swallowing. It affects an estimated 1 in 6,000 newborns and is the most common genetic cause of death in infants. Nusinersen is a antisense oligonucleotide that promotes transcription of the full-length SMN protein from the SMN2 gene.
At the AAN meeting, investigators presented the final results of two nusinersen phase III studies as well as interim data from a separate phase II trial.
The ENDEAR trial, a randomized, double-blind, sham-procedure controlled study, assigned 80 patients to 12-mg scaled equivalent doses of nusinersen delivered intrathecally (four doses over 2 months, then one every 4 months) and 41 to a sham procedure (a needle prick in the lower back). The subjects, aged 30-252 days at first dose, underwent 13 months of treatment and follow-up.
Researchers presented an end-of-study analysis of 110 subjects. They found that 51% of those who received the drug were “motor milestone responders” – meaning they had more modified Hammersmith Infant Neurological Examination Section 2 categories with improvement than worsening – compared with 41% at the interim analysis (P less than .0001). None of the sham group patients improved.
The patients treated with nusinersen lived longer: 39% of those in the sham procedure group died, compared with 16% of those in the nusinersen group (hazard ratio, 0.372; P = .0041). Event-free survival (survival without permanent ventilation) was also better in those who received the drugs: 61% in those who took nusinersen, compared with 32% in those who did not (HR, 0.53; P = .0046)
Also, 71% of those treated with the drug were considered responders at day 183 onward based on an improvement of 4 or more points on the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scale, whereas the response rate was only 3% in the sham group (P less than .0001).
The study authors report that nusinersen was well tolerated with adverse events that “were consistent with those expected in the general population of infants with SMA.” No adverse events were linked to the nusinersen treatment.
Researchers also presented the end-of-study results of the phase III CHERISH trial of 126 patients aged 2-12 years with later-onset SMA who could sit up but not walk. All participants were believed to have a life expectancy of at least 2 years.
The trial is a multicenter, randomized, double-blind, sham-procedure controlled study. The 84 subjects who received the drug improved an average of 3.9 points by the end of study (15 months) on the Hammersmith Functional Motor Scale Expanded score, a measurement of motor function in children with SMA (P = .0000001). The 42 children who received the sham treatment (a small needle prick on the lower back) declined by an average of 1.0 point.
Researchers report that children taking the drug had fewer adverse events, and most were not related to the drug itself.
All surviving participants who completed nusinersen investigational studies are being enrolled in the SHINE open-label extension trial.
Also at the AAN meeting, researchers released interim phase II results from the NURTURE trial, an open-label study of nusinersen in patients with diagnosed but presymptomatic SMA. The study, which is expected to be completed in 2022, recruited participants up to the age of 6 weeks.
The 20 enrolled infants were all alive at a median study period of 317.5 days, and none required assistance with respiration.
In terms of motor function and growth, most were making gains “generally consistent with normal development such as head control, independent sitting, standing and walking independently, as measured by validated scales,” according to a statement released by Biogen.
Three patients developed adverse events that may have been drug related, but the events were resolved and they remained in the trial.
In Dr. Sumner’s discussant presentation on the ENDEAR study, she cautioned that it’s still not known how much older patients with SMA will benefit from the drug treatment. It’s possible that younger patients may gain motor function while older patients will maintain what they have, she said.
In addition, it seems that “certain body segments may respond more robustly than some others. It’s possible that an infant may improve limb strength quite robustly but not lumbar strength.”
She pointed out other questions: Can the drug, which is difficult to administer, be stopped at some point? “We do think of SMA as a disease of development,” she said. “Maybe after development is finished we can withdraw the drug.”
Then there’s the issue of cost and whether insurers are willing to cover the drug. As Dr. Sumner pointed out, the drug is $125,000 per dose and $750,000 over the first year, then $325,000 a year.
It is clear, however, that “the early and efficient diagnosis of SMA is really important, particularly for infantile SMA,” she said. “Time is motor function.”
The studies were funded by Ionis Pharmaceuticals and Biogen. Dr. Sumner reports serving as a consultant for Biogen, Ionis, Avexis, and Roche. She has served on scientific advisory boards for the Cure SMA, SMA Foundation, and Muscular Dystrophy Association nonprofit foundations.
BOSTON – Last December, the Food and Drug Administration approved nusinersen (Spinraza) as the only treatment for spinal muscular atrophy (SMA) based in part on startling interim results from a study in infants that ended early so all participants could get access to the drug.
Now the final study results are in, and they’re even more impressive: Patients who took the drug were less than half as likely to die as were those in a sham control group, and motor function improved in more than half of infants who took the medication, compared with none in the sham group.
The findings are “incredibly exciting,” said Charlotte J. Sumner, MD, in a discussant presentation at the annual meeting of the American Academy of Neurology. “The data teaches us that this drug is efficacious.”
However, Dr. Sumner, professor of neurology and neuroscience at Johns Hopkins University, Baltimore, cautioned that the drug is tremendously expensive, challenging to administer, and there are several questions about its use that remain unanswered.
SMA is most often caused by mutations in the SMN1 gene, leading to a loss of the protein called survival motor neuron (SMN), which is essential for the survival of motor neurons, except for a small amount produced from the SMN2 gene. The loss of motor neurons in the spinal cord and brainstem leads to weakness and atrophy of muscles used for crawling, walking, sitting up, controlling head movement, and in severe cases, breathing and swallowing. It affects an estimated 1 in 6,000 newborns and is the most common genetic cause of death in infants. Nusinersen is a antisense oligonucleotide that promotes transcription of the full-length SMN protein from the SMN2 gene.
At the AAN meeting, investigators presented the final results of two nusinersen phase III studies as well as interim data from a separate phase II trial.
The ENDEAR trial, a randomized, double-blind, sham-procedure controlled study, assigned 80 patients to 12-mg scaled equivalent doses of nusinersen delivered intrathecally (four doses over 2 months, then one every 4 months) and 41 to a sham procedure (a needle prick in the lower back). The subjects, aged 30-252 days at first dose, underwent 13 months of treatment and follow-up.
Researchers presented an end-of-study analysis of 110 subjects. They found that 51% of those who received the drug were “motor milestone responders” – meaning they had more modified Hammersmith Infant Neurological Examination Section 2 categories with improvement than worsening – compared with 41% at the interim analysis (P less than .0001). None of the sham group patients improved.
The patients treated with nusinersen lived longer: 39% of those in the sham procedure group died, compared with 16% of those in the nusinersen group (hazard ratio, 0.372; P = .0041). Event-free survival (survival without permanent ventilation) was also better in those who received the drugs: 61% in those who took nusinersen, compared with 32% in those who did not (HR, 0.53; P = .0046)
Also, 71% of those treated with the drug were considered responders at day 183 onward based on an improvement of 4 or more points on the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scale, whereas the response rate was only 3% in the sham group (P less than .0001).
The study authors report that nusinersen was well tolerated with adverse events that “were consistent with those expected in the general population of infants with SMA.” No adverse events were linked to the nusinersen treatment.
Researchers also presented the end-of-study results of the phase III CHERISH trial of 126 patients aged 2-12 years with later-onset SMA who could sit up but not walk. All participants were believed to have a life expectancy of at least 2 years.
The trial is a multicenter, randomized, double-blind, sham-procedure controlled study. The 84 subjects who received the drug improved an average of 3.9 points by the end of study (15 months) on the Hammersmith Functional Motor Scale Expanded score, a measurement of motor function in children with SMA (P = .0000001). The 42 children who received the sham treatment (a small needle prick on the lower back) declined by an average of 1.0 point.
Researchers report that children taking the drug had fewer adverse events, and most were not related to the drug itself.
All surviving participants who completed nusinersen investigational studies are being enrolled in the SHINE open-label extension trial.
Also at the AAN meeting, researchers released interim phase II results from the NURTURE trial, an open-label study of nusinersen in patients with diagnosed but presymptomatic SMA. The study, which is expected to be completed in 2022, recruited participants up to the age of 6 weeks.
The 20 enrolled infants were all alive at a median study period of 317.5 days, and none required assistance with respiration.
In terms of motor function and growth, most were making gains “generally consistent with normal development such as head control, independent sitting, standing and walking independently, as measured by validated scales,” according to a statement released by Biogen.
Three patients developed adverse events that may have been drug related, but the events were resolved and they remained in the trial.
In Dr. Sumner’s discussant presentation on the ENDEAR study, she cautioned that it’s still not known how much older patients with SMA will benefit from the drug treatment. It’s possible that younger patients may gain motor function while older patients will maintain what they have, she said.
In addition, it seems that “certain body segments may respond more robustly than some others. It’s possible that an infant may improve limb strength quite robustly but not lumbar strength.”
She pointed out other questions: Can the drug, which is difficult to administer, be stopped at some point? “We do think of SMA as a disease of development,” she said. “Maybe after development is finished we can withdraw the drug.”
Then there’s the issue of cost and whether insurers are willing to cover the drug. As Dr. Sumner pointed out, the drug is $125,000 per dose and $750,000 over the first year, then $325,000 a year.
It is clear, however, that “the early and efficient diagnosis of SMA is really important, particularly for infantile SMA,” she said. “Time is motor function.”
The studies were funded by Ionis Pharmaceuticals and Biogen. Dr. Sumner reports serving as a consultant for Biogen, Ionis, Avexis, and Roche. She has served on scientific advisory boards for the Cure SMA, SMA Foundation, and Muscular Dystrophy Association nonprofit foundations.
AT AAN 2017
Key clinical point:
Major finding: 51% of subjects who took the drug were judged to be “motor milestone responders”; none in the sham group improved (P less than .0001).
Data source: Randomized, double-blind, sham-controlled, 13-month study of 110 subjects with infantile-onset SMA aged 30-252 days at first dose. They received 12-mg scaled equivalent doses of nusinersen delivered intrathecally (four doses over 2 months then one every 4 months) or a sham procedure (needle prick).
Disclosures: The studies were funded by Ionis Pharmaceuticals and Biogen.
FDA approves generic Strattera for pediatric, adult ADHD patients
The Food and Drug Administration has approved the first generic versions of Strattera (atomoxetine) for the treatment of attention-deficit/hyperactivity disorder, the agency announced May 30.
Apotex, Teva Pharmaceuticals USA, Aurobindo Pharma, and Glenmark Pharmaceuticals all gained approval to market generic atomoxetine at various strengths. All versions must be sold with a patient medication guide describing the uses and risks of atomoxetine and must also include a boxed warning detailing the potential for increased risk of suicidal ideation in children and adolescents.
“Today’s approvals mark an important step forward in bringing consumers additional treatments that have met the FDA’s rigorous standards. Quickly bringing generics to market so patients have more options to treat their conditions is a top priority for the FDA,” Kathleen Uhl, MD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research, said in a press release.
Find the full press release on the FDA website.
The Food and Drug Administration has approved the first generic versions of Strattera (atomoxetine) for the treatment of attention-deficit/hyperactivity disorder, the agency announced May 30.
Apotex, Teva Pharmaceuticals USA, Aurobindo Pharma, and Glenmark Pharmaceuticals all gained approval to market generic atomoxetine at various strengths. All versions must be sold with a patient medication guide describing the uses and risks of atomoxetine and must also include a boxed warning detailing the potential for increased risk of suicidal ideation in children and adolescents.
“Today’s approvals mark an important step forward in bringing consumers additional treatments that have met the FDA’s rigorous standards. Quickly bringing generics to market so patients have more options to treat their conditions is a top priority for the FDA,” Kathleen Uhl, MD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research, said in a press release.
Find the full press release on the FDA website.
The Food and Drug Administration has approved the first generic versions of Strattera (atomoxetine) for the treatment of attention-deficit/hyperactivity disorder, the agency announced May 30.
Apotex, Teva Pharmaceuticals USA, Aurobindo Pharma, and Glenmark Pharmaceuticals all gained approval to market generic atomoxetine at various strengths. All versions must be sold with a patient medication guide describing the uses and risks of atomoxetine and must also include a boxed warning detailing the potential for increased risk of suicidal ideation in children and adolescents.
“Today’s approvals mark an important step forward in bringing consumers additional treatments that have met the FDA’s rigorous standards. Quickly bringing generics to market so patients have more options to treat their conditions is a top priority for the FDA,” Kathleen Uhl, MD, director of the Office of Generic Drugs in the FDA’s Center for Drug Evaluation and Research, said in a press release.
Find the full press release on the FDA website.
Alemtuzumab May Prevent MRI Lesions for Six Years in Patients With Highly Active Disease
NEW ORLEANS—Most patients with relapsing-remitting multiple sclerosis (MS) with highly active disease remain free of new MRI activity for six years after receiving alemtuzumab, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. The durable effects may result from the distinct pattern of lymphocyte repopulation following treatment with alemtuzumab, which may lead to a rebalancing of the immune system, said Anthony Traboulsee, MD, Associate Professor of Neurology at the University of British Columbia in Vancouver. Additional mechanistic studies are needed to establish this hypothesis, the authors said. 
To evaluate six-year MRI and brain volume loss outcomes in a subset of patient with highly active disease at baseline who were treated with alemtuzumab, Dr. Traboulsee and colleagues analyzed data from the CARE-MS I trial. In that trial, researchers randomized patients with active relapsing-remitting MS who were drug-naïve at baseline to alemtuzumab or interferon beta-1a. After two years, patients who received alemtuzumab had improved clinical and MRI outcomes, including brain loss volume, compared with patients who received interferon beta-1a. In addition, significantly more of these patients had no evidence of disease activity, compared with patients treated with interferon beta1-a.
In an extension study, patients could receive additional treatment with alemtuzumab (12 mg/day on three consecutive days one year or more after the most recent course) as needed for relapse or radiologic activity. During the extension, patients also could receive treatment with other licensed disease-modifying therapies at an investigator’s discretion. Retreatment criteria included one or more relapse, two or more new or enlarging T2 hyperintense lesions, or new gadolinium-enhancing T1 brain or spinal cord lesions on MRI. Researchers defined highly active disease as two or more relapses a year prior to randomization and one or more gadolinium-enhancing T1 lesion at core study baseline.
The researchers obtained MRI scans at baseline and yearly thereafter. Experts masked to patients’ original treatment group assignment analyzed the MRI scans. Investigators assessed the proportion of patients free of MRI disease activity (ie, no new or enlarging T2 hyperintense lesions or new gadolinium-enhancing T1 lesions) and the proportion of patients free of new non-enhancing T1 lesions. Brain volume loss was derived by brain parenchymal fraction change.
Of 376 patients who received alemtuzumab in the CARE-MS I trial, 105 met the criteria for highly active disease at core study baseline. Of these 105 patients, 99 remained in the study through Year 6. Through six years, 63% of patients did not receive additional treatment with alemtuzumab or another disease-modifying therapy. In each year through Year 6, a majority of patients were free of MRI disease activity (61 % at Year 6), free of new gadolinium-enhancing T1 lesions (83% at Year 6), and free of new or enlarging T2 hyperintense lesions (62% at Year 6). The investigators also observed that annually in Years 2 through 6, high proportions of patients had no new non-enhancing T1 hypointense lesions.
“These findings, along with long-term clinical efficacy, suggest that alemtuzumab may provide a unique treatment approach for relapsing-remitting MS patients with highly active disease, offering durable efficacy in the absence of continuous treatment,” said Dr. Traboulsee and colleagues.
NEW ORLEANS—Most patients with relapsing-remitting multiple sclerosis (MS) with highly active disease remain free of new MRI activity for six years after receiving alemtuzumab, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. The durable effects may result from the distinct pattern of lymphocyte repopulation following treatment with alemtuzumab, which may lead to a rebalancing of the immune system, said Anthony Traboulsee, MD, Associate Professor of Neurology at the University of British Columbia in Vancouver. Additional mechanistic studies are needed to establish this hypothesis, the authors said.
To evaluate six-year MRI and brain volume loss outcomes in a subset of patient with highly active disease at baseline who were treated with alemtuzumab, Dr. Traboulsee and colleagues analyzed data from the CARE-MS I trial. In that trial, researchers randomized patients with active relapsing-remitting MS who were drug-naïve at baseline to alemtuzumab or interferon beta-1a. After two years, patients who received alemtuzumab had improved clinical and MRI outcomes, including brain loss volume, compared with patients who received interferon beta-1a. In addition, significantly more of these patients had no evidence of disease activity, compared with patients treated with interferon beta1-a.
In an extension study, patients could receive additional treatment with alemtuzumab (12 mg/day on three consecutive days one year or more after the most recent course) as needed for relapse or radiologic activity. During the extension, patients also could receive treatment with other licensed disease-modifying therapies at an investigator’s discretion. Retreatment criteria included one or more relapse, two or more new or enlarging T2 hyperintense lesions, or new gadolinium-enhancing T1 brain or spinal cord lesions on MRI. Researchers defined highly active disease as two or more relapses a year prior to randomization and one or more gadolinium-enhancing T1 lesion at core study baseline.
The researchers obtained MRI scans at baseline and yearly thereafter. Experts masked to patients’ original treatment group assignment analyzed the MRI scans. Investigators assessed the proportion of patients free of MRI disease activity (ie, no new or enlarging T2 hyperintense lesions or new gadolinium-enhancing T1 lesions) and the proportion of patients free of new non-enhancing T1 lesions. Brain volume loss was derived by brain parenchymal fraction change.
Of 376 patients who received alemtuzumab in the CARE-MS I trial, 105 met the criteria for highly active disease at core study baseline. Of these 105 patients, 99 remained in the study through Year 6. Through six years, 63% of patients did not receive additional treatment with alemtuzumab or another disease-modifying therapy. In each year through Year 6, a majority of patients were free of MRI disease activity (61 % at Year 6), free of new gadolinium-enhancing T1 lesions (83% at Year 6), and free of new or enlarging T2 hyperintense lesions (62% at Year 6). The investigators also observed that annually in Years 2 through 6, high proportions of patients had no new non-enhancing T1 hypointense lesions.
“These findings, along with long-term clinical efficacy, suggest that alemtuzumab may provide a unique treatment approach for relapsing-remitting MS patients with highly active disease, offering durable efficacy in the absence of continuous treatment,” said Dr. Traboulsee and colleagues.
NEW ORLEANS—Most patients with relapsing-remitting multiple sclerosis (MS) with highly active disease remain free of new MRI activity for six years after receiving alemtuzumab, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. The durable effects may result from the distinct pattern of lymphocyte repopulation following treatment with alemtuzumab, which may lead to a rebalancing of the immune system, said Anthony Traboulsee, MD, Associate Professor of Neurology at the University of British Columbia in Vancouver. Additional mechanistic studies are needed to establish this hypothesis, the authors said.
To evaluate six-year MRI and brain volume loss outcomes in a subset of patient with highly active disease at baseline who were treated with alemtuzumab, Dr. Traboulsee and colleagues analyzed data from the CARE-MS I trial. In that trial, researchers randomized patients with active relapsing-remitting MS who were drug-naïve at baseline to alemtuzumab or interferon beta-1a. After two years, patients who received alemtuzumab had improved clinical and MRI outcomes, including brain loss volume, compared with patients who received interferon beta-1a. In addition, significantly more of these patients had no evidence of disease activity, compared with patients treated with interferon beta1-a.
In an extension study, patients could receive additional treatment with alemtuzumab (12 mg/day on three consecutive days one year or more after the most recent course) as needed for relapse or radiologic activity. During the extension, patients also could receive treatment with other licensed disease-modifying therapies at an investigator’s discretion. Retreatment criteria included one or more relapse, two or more new or enlarging T2 hyperintense lesions, or new gadolinium-enhancing T1 brain or spinal cord lesions on MRI. Researchers defined highly active disease as two or more relapses a year prior to randomization and one or more gadolinium-enhancing T1 lesion at core study baseline.
The researchers obtained MRI scans at baseline and yearly thereafter. Experts masked to patients’ original treatment group assignment analyzed the MRI scans. Investigators assessed the proportion of patients free of MRI disease activity (ie, no new or enlarging T2 hyperintense lesions or new gadolinium-enhancing T1 lesions) and the proportion of patients free of new non-enhancing T1 lesions. Brain volume loss was derived by brain parenchymal fraction change.
Of 376 patients who received alemtuzumab in the CARE-MS I trial, 105 met the criteria for highly active disease at core study baseline. Of these 105 patients, 99 remained in the study through Year 6. Through six years, 63% of patients did not receive additional treatment with alemtuzumab or another disease-modifying therapy. In each year through Year 6, a majority of patients were free of MRI disease activity (61 % at Year 6), free of new gadolinium-enhancing T1 lesions (83% at Year 6), and free of new or enlarging T2 hyperintense lesions (62% at Year 6). The investigators also observed that annually in Years 2 through 6, high proportions of patients had no new non-enhancing T1 hypointense lesions.
“These findings, along with long-term clinical efficacy, suggest that alemtuzumab may provide a unique treatment approach for relapsing-remitting MS patients with highly active disease, offering durable efficacy in the absence of continuous treatment,” said Dr. Traboulsee and colleagues.
Can Stress Accelerate Progression of Parkinson’s Disease?
BOSTON―Stress may be a modifiable risk factor for Parkinson’s disease progression, according to research presented at the 69th Annual Meeting of the American Academy of Neurology. In a study of more than 4,000 patients, a stress proxy score predicted mortality and was associated with worsening mobility. The findings suggest that stress reduction may be an effective intervention in Parkinson’s disease, said Amie Hiller, MD, Assistant Professor of Neurology at the Oregon Health and Science University in Portland. 
“Potentially, stress reduction is something we could think about to slow Parkinson’s disease progression,” said Dr. Hiller. “Our goal is to not only treat symptoms of Parkinson’s disease, but to slow progression of the disease.”
Research suggests that stressful life events may increase the risk of Parkinson’s disease. In addition, animal studies indicate that stress damages dopamine cells, resulting in more severe parkinsonian symptoms. In humans, acute stress can worsen motor symptoms, including bradykinesia, freezing, and tremor.
To examine the relationship between psychological stress and Parkinson’s disease progression, Dr. Hiller and colleagues analyzed data from the National Parkinson’s Foundation Quality Improvement Initiative. All 4,155 participants in the study were able to walk unassisted at baseline.
For each patient, investigators calculated a stress proxy score derived from the 39-item Parkinson’s Disease Questionnaire (PDQ-39) and the Multidimensional Caregiver Strain Index. They also calculated a mobility proxy score derived from the PDQ-39 and the Instrumented Timed Up and Go, and an overall health score derived from the PDQ-39, falls score, hospital admissions, and cognitive score.
Researchers also calculated patients’ levels of excess stress (ie, emotional stress above typical stress resulting from disease severity and overall health).
The stress proxy score predicted mortality, but the excess stress score did not. High baseline stress proxy scores and high levels of excess stress predicted worsening mobility.
“We need better data, as these were not data that we collected specifically to look at stress,” Dr. Hiller said. In addition, researchers need to conduct intervention studies to see if stress reduction benefits patients with Parkinson’s disease, she said.
—Erica Tricarico
BOSTON―Stress may be a modifiable risk factor for Parkinson’s disease progression, according to research presented at the 69th Annual Meeting of the American Academy of Neurology. In a study of more than 4,000 patients, a stress proxy score predicted mortality and was associated with worsening mobility. The findings suggest that stress reduction may be an effective intervention in Parkinson’s disease, said Amie Hiller, MD, Assistant Professor of Neurology at the Oregon Health and Science University in Portland.
“Potentially, stress reduction is something we could think about to slow Parkinson’s disease progression,” said Dr. Hiller. “Our goal is to not only treat symptoms of Parkinson’s disease, but to slow progression of the disease.”
Research suggests that stressful life events may increase the risk of Parkinson’s disease. In addition, animal studies indicate that stress damages dopamine cells, resulting in more severe parkinsonian symptoms. In humans, acute stress can worsen motor symptoms, including bradykinesia, freezing, and tremor.
To examine the relationship between psychological stress and Parkinson’s disease progression, Dr. Hiller and colleagues analyzed data from the National Parkinson’s Foundation Quality Improvement Initiative. All 4,155 participants in the study were able to walk unassisted at baseline.
For each patient, investigators calculated a stress proxy score derived from the 39-item Parkinson’s Disease Questionnaire (PDQ-39) and the Multidimensional Caregiver Strain Index. They also calculated a mobility proxy score derived from the PDQ-39 and the Instrumented Timed Up and Go, and an overall health score derived from the PDQ-39, falls score, hospital admissions, and cognitive score.
Researchers also calculated patients’ levels of excess stress (ie, emotional stress above typical stress resulting from disease severity and overall health).
The stress proxy score predicted mortality, but the excess stress score did not. High baseline stress proxy scores and high levels of excess stress predicted worsening mobility.
“We need better data, as these were not data that we collected specifically to look at stress,” Dr. Hiller said. In addition, researchers need to conduct intervention studies to see if stress reduction benefits patients with Parkinson’s disease, she said.
—Erica Tricarico
BOSTON―Stress may be a modifiable risk factor for Parkinson’s disease progression, according to research presented at the 69th Annual Meeting of the American Academy of Neurology. In a study of more than 4,000 patients, a stress proxy score predicted mortality and was associated with worsening mobility. The findings suggest that stress reduction may be an effective intervention in Parkinson’s disease, said Amie Hiller, MD, Assistant Professor of Neurology at the Oregon Health and Science University in Portland.
“Potentially, stress reduction is something we could think about to slow Parkinson’s disease progression,” said Dr. Hiller. “Our goal is to not only treat symptoms of Parkinson’s disease, but to slow progression of the disease.”
Research suggests that stressful life events may increase the risk of Parkinson’s disease. In addition, animal studies indicate that stress damages dopamine cells, resulting in more severe parkinsonian symptoms. In humans, acute stress can worsen motor symptoms, including bradykinesia, freezing, and tremor.
To examine the relationship between psychological stress and Parkinson’s disease progression, Dr. Hiller and colleagues analyzed data from the National Parkinson’s Foundation Quality Improvement Initiative. All 4,155 participants in the study were able to walk unassisted at baseline.
For each patient, investigators calculated a stress proxy score derived from the 39-item Parkinson’s Disease Questionnaire (PDQ-39) and the Multidimensional Caregiver Strain Index. They also calculated a mobility proxy score derived from the PDQ-39 and the Instrumented Timed Up and Go, and an overall health score derived from the PDQ-39, falls score, hospital admissions, and cognitive score.
Researchers also calculated patients’ levels of excess stress (ie, emotional stress above typical stress resulting from disease severity and overall health).
The stress proxy score predicted mortality, but the excess stress score did not. High baseline stress proxy scores and high levels of excess stress predicted worsening mobility.
“We need better data, as these were not data that we collected specifically to look at stress,” Dr. Hiller said. In addition, researchers need to conduct intervention studies to see if stress reduction benefits patients with Parkinson’s disease, she said.
—Erica Tricarico
