User login
VIDEO: Painful skin conditions need pain management by dermatologists
Patients with painful skin conditions need pain management that is provided by their dermatologists, Robert G. Micheletti, MD, contended in a presentation at the annual meeting of the American Academy of Dermatology.
Dermatologists are the experts when it comes to treating painful skin conditions like pyoderma gangrenosum, hidradenitis suppurativa, calciphylaxis, and vasculopathies. “We should be willing to treat the pain that goes with (these conditions), at least within our scope of practice,” said Dr. Micheletti, co-director of the Inpatient Dermatology Consult Service at the University of Pennsylvania, Philadelphia. “At the same time, we know opioids should be prescribed only when necessary, at the lowest effective dose, and for the shortest possible duration.”
In our exclusive video interview, Dr. Micheletti outlined the keys to successful care of patients with painful skin disease. He described patient characteristics that influence prescribing choices and tips for accurately assessing pain needs with a preference for a conservative regimen that utilizes non-opioids and avoids over-reliance on narcotics.
Source: Micheletti, R., Session F013
Patients with painful skin conditions need pain management that is provided by their dermatologists, Robert G. Micheletti, MD, contended in a presentation at the annual meeting of the American Academy of Dermatology.
Dermatologists are the experts when it comes to treating painful skin conditions like pyoderma gangrenosum, hidradenitis suppurativa, calciphylaxis, and vasculopathies. “We should be willing to treat the pain that goes with (these conditions), at least within our scope of practice,” said Dr. Micheletti, co-director of the Inpatient Dermatology Consult Service at the University of Pennsylvania, Philadelphia. “At the same time, we know opioids should be prescribed only when necessary, at the lowest effective dose, and for the shortest possible duration.”
In our exclusive video interview, Dr. Micheletti outlined the keys to successful care of patients with painful skin disease. He described patient characteristics that influence prescribing choices and tips for accurately assessing pain needs with a preference for a conservative regimen that utilizes non-opioids and avoids over-reliance on narcotics.
Source: Micheletti, R., Session F013
Patients with painful skin conditions need pain management that is provided by their dermatologists, Robert G. Micheletti, MD, contended in a presentation at the annual meeting of the American Academy of Dermatology.
Dermatologists are the experts when it comes to treating painful skin conditions like pyoderma gangrenosum, hidradenitis suppurativa, calciphylaxis, and vasculopathies. “We should be willing to treat the pain that goes with (these conditions), at least within our scope of practice,” said Dr. Micheletti, co-director of the Inpatient Dermatology Consult Service at the University of Pennsylvania, Philadelphia. “At the same time, we know opioids should be prescribed only when necessary, at the lowest effective dose, and for the shortest possible duration.”
In our exclusive video interview, Dr. Micheletti outlined the keys to successful care of patients with painful skin disease. He described patient characteristics that influence prescribing choices and tips for accurately assessing pain needs with a preference for a conservative regimen that utilizes non-opioids and avoids over-reliance on narcotics.
Source: Micheletti, R., Session F013
VIDEO: Delusional parasitosis? Try these real solutions
SAN DIEGO – The path to successful treatment of patients with imagined skin disorders is paved with compassion, according to John Koo, MD, a dermatologist and psychiatrist with the University of California at San Francisco.
When a patient presents with delusional parasitosis -- horror stories about imagined infestations of parasites or bugs – the key to successful treatment is a positive attitude and validation, not denial, Dr. Koo said in a presentation at the annual meeting of the American Academy of Dermatology.
"I cannot afford to go in (the exam room) with a long face," he said. "If I go in and I’m not looking happy, things can deteriorate quickly. So I make sure I go in with the biggest smile on my face like I'm meeting my favorite Hollywood star."
"When I say something like 'It's like a living hell, isn't it,' patients are really touched, he said. The patient’s response is typically 'You're the first dermatologist to understand what I'm going through.' You cannot endorse their delusion, but you can endorse their suffering."
In our video interview, Dr. Koo delved into techniques for the successful work-up and evaluation of patients with delusional parasitosis, the varying degrees of the condition, medications used for treatment, and the prospects for eventual drug-free relief.
Dr. Koo reports no relevant financial disclosures.
SAN DIEGO – The path to successful treatment of patients with imagined skin disorders is paved with compassion, according to John Koo, MD, a dermatologist and psychiatrist with the University of California at San Francisco.
When a patient presents with delusional parasitosis -- horror stories about imagined infestations of parasites or bugs – the key to successful treatment is a positive attitude and validation, not denial, Dr. Koo said in a presentation at the annual meeting of the American Academy of Dermatology.
"I cannot afford to go in (the exam room) with a long face," he said. "If I go in and I’m not looking happy, things can deteriorate quickly. So I make sure I go in with the biggest smile on my face like I'm meeting my favorite Hollywood star."
"When I say something like 'It's like a living hell, isn't it,' patients are really touched, he said. The patient’s response is typically 'You're the first dermatologist to understand what I'm going through.' You cannot endorse their delusion, but you can endorse their suffering."
In our video interview, Dr. Koo delved into techniques for the successful work-up and evaluation of patients with delusional parasitosis, the varying degrees of the condition, medications used for treatment, and the prospects for eventual drug-free relief.
Dr. Koo reports no relevant financial disclosures.
SAN DIEGO – The path to successful treatment of patients with imagined skin disorders is paved with compassion, according to John Koo, MD, a dermatologist and psychiatrist with the University of California at San Francisco.
When a patient presents with delusional parasitosis -- horror stories about imagined infestations of parasites or bugs – the key to successful treatment is a positive attitude and validation, not denial, Dr. Koo said in a presentation at the annual meeting of the American Academy of Dermatology.
"I cannot afford to go in (the exam room) with a long face," he said. "If I go in and I’m not looking happy, things can deteriorate quickly. So I make sure I go in with the biggest smile on my face like I'm meeting my favorite Hollywood star."
"When I say something like 'It's like a living hell, isn't it,' patients are really touched, he said. The patient’s response is typically 'You're the first dermatologist to understand what I'm going through.' You cannot endorse their delusion, but you can endorse their suffering."
In our video interview, Dr. Koo delved into techniques for the successful work-up and evaluation of patients with delusional parasitosis, the varying degrees of the condition, medications used for treatment, and the prospects for eventual drug-free relief.
Dr. Koo reports no relevant financial disclosures.
REPORTING FROM AAD 18
Biologics gaining traction in children with moderate to severe psoriasis
SAN DIEGO – Systemic therapies are increasingly being used for children with moderate to severe psoriasis; methotrexate is still the mainstay of systemic treatment, but biologics appear to achieve superior results with fewer side effects, Amy S. Paller, MD, said at the annual meeting of the American Academy of Dermatology.
Etanercept was approved in 2016 for children ages 6 and up, and ustekinumab was approved for use in patients aged 12 years or older in October 2017. Ongoing trials are examining adalimumab, apremilast, ustekinumab, and ixekizumab for use in adolescents and younger children. Trials are also being planned for other therapies that inhibit the Th17/IL-23 pathway, said Dr. Paller, the Walter J. Hamlin Professor and chair of dermatology at Northwestern University Feinberg School of Medicine, Chicago.
Further, the study found that biologic agents, primarily etanercept, were used by 27%, acitretin by nearly 15%, cyclosporine by about 8%, and fumaric acid esters by 5%. More than 1 medication was used by 19%, according to the study results.
Adverse events affected the ability to tolerate therapy, and methotrexate and biologic agents were taken for a mean duration that was 2-fold greater than the mean duration for cyclosporine or fumaric acid esters. “A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis,” the authors concluded.
Dr. Paller reported that, in her practice, "we're still primarily using methotrexate. It takes time to see an effect with methotrexate, and you have to let people know this up front.” She pointed to a 2015 single-site prospective study of 25 children that found just 40% achieved Psoriasis Area and Severity Index 50 at 12 weeks, with that number rising to 80% by 36 weeks. (J Derm Treat 2015; 26: 406-12)
Dr. Paller recommends baseline and annual TB testing, updated vaccinations and pregnancy counseling for all patients taking immunosuppressant therapies.
"I don't use a lot of retinoids for plaque psoriasis in kids," Dr. Paller said, "but for pustular psoriasis, I use (them) quite a bit. The beauty of retinoids is that they are not immunosuppressants, and you can start and stop them without loss of efficacy. There are many potential side effects, primarily skin and mucosal dryness."
Cyclosporine "has the greatest potential toxicity, which leaves it lower on the therapeutic ladder," Dr. Paller said. "But it has a pretty good safety record. The nice thing we can say is that (cyclosporine has) been around a long time. We have decades of experience in children, and we're using a low dose."
Benefits of biologics include convenience, infrequent dosing, and, potentially, fewer lab tests, Dr. Paller said. She added that there's no consensus about whether lab tests beyond annual TB tests are a good idea for patients on biologics.
Long-term risks are unclear, however, and drug holidays could spell trouble for efficacy when kids return to the medications.
Dr. Paller noted that biologics can cost tens of thousands of dollars for several weeks of treatment, and insurers may not cover them.
A 2014 meta-analysis of 48 randomized, controlled trials of 16,696 adult patients with psoriasis put biologics as the most effective therapies, with infliximab at the top (risk difference 76%), followed by adalimumab (RD 61%) and ustekinumab (RD 63%).
“These biologics are more effective than etanercept and all conventional treatments. Head-to-head trials indicate the superiority of adalimumab and infliximab over methotrexate (MTX), the superiority of ustekinumab over etanercept …” the meta-analysis concluded. (Br J Dermatol. 2014 Feb;170(2):274-303)
Dr. Paller disclosed that she is an investigator for Abbvie; Celgene; Eli Lilly, Janssen, Leo Foundation; Novartis. She is a consultant with honorarium for Amgen; Celgene; Eli Lilly; and Novartis.
SOURCE: Paller, A. et al, Session F025 Update on systemic therapies and emerging treatments
SAN DIEGO – Systemic therapies are increasingly being used for children with moderate to severe psoriasis; methotrexate is still the mainstay of systemic treatment, but biologics appear to achieve superior results with fewer side effects, Amy S. Paller, MD, said at the annual meeting of the American Academy of Dermatology.
Etanercept was approved in 2016 for children ages 6 and up, and ustekinumab was approved for use in patients aged 12 years or older in October 2017. Ongoing trials are examining adalimumab, apremilast, ustekinumab, and ixekizumab for use in adolescents and younger children. Trials are also being planned for other therapies that inhibit the Th17/IL-23 pathway, said Dr. Paller, the Walter J. Hamlin Professor and chair of dermatology at Northwestern University Feinberg School of Medicine, Chicago.
Further, the study found that biologic agents, primarily etanercept, were used by 27%, acitretin by nearly 15%, cyclosporine by about 8%, and fumaric acid esters by 5%. More than 1 medication was used by 19%, according to the study results.
Adverse events affected the ability to tolerate therapy, and methotrexate and biologic agents were taken for a mean duration that was 2-fold greater than the mean duration for cyclosporine or fumaric acid esters. “A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis,” the authors concluded.
Dr. Paller reported that, in her practice, "we're still primarily using methotrexate. It takes time to see an effect with methotrexate, and you have to let people know this up front.” She pointed to a 2015 single-site prospective study of 25 children that found just 40% achieved Psoriasis Area and Severity Index 50 at 12 weeks, with that number rising to 80% by 36 weeks. (J Derm Treat 2015; 26: 406-12)
Dr. Paller recommends baseline and annual TB testing, updated vaccinations and pregnancy counseling for all patients taking immunosuppressant therapies.
"I don't use a lot of retinoids for plaque psoriasis in kids," Dr. Paller said, "but for pustular psoriasis, I use (them) quite a bit. The beauty of retinoids is that they are not immunosuppressants, and you can start and stop them without loss of efficacy. There are many potential side effects, primarily skin and mucosal dryness."
Cyclosporine "has the greatest potential toxicity, which leaves it lower on the therapeutic ladder," Dr. Paller said. "But it has a pretty good safety record. The nice thing we can say is that (cyclosporine has) been around a long time. We have decades of experience in children, and we're using a low dose."
Benefits of biologics include convenience, infrequent dosing, and, potentially, fewer lab tests, Dr. Paller said. She added that there's no consensus about whether lab tests beyond annual TB tests are a good idea for patients on biologics.
Long-term risks are unclear, however, and drug holidays could spell trouble for efficacy when kids return to the medications.
Dr. Paller noted that biologics can cost tens of thousands of dollars for several weeks of treatment, and insurers may not cover them.
A 2014 meta-analysis of 48 randomized, controlled trials of 16,696 adult patients with psoriasis put biologics as the most effective therapies, with infliximab at the top (risk difference 76%), followed by adalimumab (RD 61%) and ustekinumab (RD 63%).
“These biologics are more effective than etanercept and all conventional treatments. Head-to-head trials indicate the superiority of adalimumab and infliximab over methotrexate (MTX), the superiority of ustekinumab over etanercept …” the meta-analysis concluded. (Br J Dermatol. 2014 Feb;170(2):274-303)
Dr. Paller disclosed that she is an investigator for Abbvie; Celgene; Eli Lilly, Janssen, Leo Foundation; Novartis. She is a consultant with honorarium for Amgen; Celgene; Eli Lilly; and Novartis.
SOURCE: Paller, A. et al, Session F025 Update on systemic therapies and emerging treatments
SAN DIEGO – Systemic therapies are increasingly being used for children with moderate to severe psoriasis; methotrexate is still the mainstay of systemic treatment, but biologics appear to achieve superior results with fewer side effects, Amy S. Paller, MD, said at the annual meeting of the American Academy of Dermatology.
Etanercept was approved in 2016 for children ages 6 and up, and ustekinumab was approved for use in patients aged 12 years or older in October 2017. Ongoing trials are examining adalimumab, apremilast, ustekinumab, and ixekizumab for use in adolescents and younger children. Trials are also being planned for other therapies that inhibit the Th17/IL-23 pathway, said Dr. Paller, the Walter J. Hamlin Professor and chair of dermatology at Northwestern University Feinberg School of Medicine, Chicago.
Further, the study found that biologic agents, primarily etanercept, were used by 27%, acitretin by nearly 15%, cyclosporine by about 8%, and fumaric acid esters by 5%. More than 1 medication was used by 19%, according to the study results.
Adverse events affected the ability to tolerate therapy, and methotrexate and biologic agents were taken for a mean duration that was 2-fold greater than the mean duration for cyclosporine or fumaric acid esters. “A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis,” the authors concluded.
Dr. Paller reported that, in her practice, "we're still primarily using methotrexate. It takes time to see an effect with methotrexate, and you have to let people know this up front.” She pointed to a 2015 single-site prospective study of 25 children that found just 40% achieved Psoriasis Area and Severity Index 50 at 12 weeks, with that number rising to 80% by 36 weeks. (J Derm Treat 2015; 26: 406-12)
Dr. Paller recommends baseline and annual TB testing, updated vaccinations and pregnancy counseling for all patients taking immunosuppressant therapies.
"I don't use a lot of retinoids for plaque psoriasis in kids," Dr. Paller said, "but for pustular psoriasis, I use (them) quite a bit. The beauty of retinoids is that they are not immunosuppressants, and you can start and stop them without loss of efficacy. There are many potential side effects, primarily skin and mucosal dryness."
Cyclosporine "has the greatest potential toxicity, which leaves it lower on the therapeutic ladder," Dr. Paller said. "But it has a pretty good safety record. The nice thing we can say is that (cyclosporine has) been around a long time. We have decades of experience in children, and we're using a low dose."
Benefits of biologics include convenience, infrequent dosing, and, potentially, fewer lab tests, Dr. Paller said. She added that there's no consensus about whether lab tests beyond annual TB tests are a good idea for patients on biologics.
Long-term risks are unclear, however, and drug holidays could spell trouble for efficacy when kids return to the medications.
Dr. Paller noted that biologics can cost tens of thousands of dollars for several weeks of treatment, and insurers may not cover them.
A 2014 meta-analysis of 48 randomized, controlled trials of 16,696 adult patients with psoriasis put biologics as the most effective therapies, with infliximab at the top (risk difference 76%), followed by adalimumab (RD 61%) and ustekinumab (RD 63%).
“These biologics are more effective than etanercept and all conventional treatments. Head-to-head trials indicate the superiority of adalimumab and infliximab over methotrexate (MTX), the superiority of ustekinumab over etanercept …” the meta-analysis concluded. (Br J Dermatol. 2014 Feb;170(2):274-303)
Dr. Paller disclosed that she is an investigator for Abbvie; Celgene; Eli Lilly, Janssen, Leo Foundation; Novartis. She is a consultant with honorarium for Amgen; Celgene; Eli Lilly; and Novartis.
SOURCE: Paller, A. et al, Session F025 Update on systemic therapies and emerging treatments
EXPERT ANALYSIS AT AAD 18
Physicians often bypass cognition, depression screening in MS
SAN DIEGO – A new study finds that physicians at two . Physicians who did perform screening hardly ever used validated tools and often didn’t refer appropriate patients for higher-level care.
In addition, researchers interviewed 13 leading MS specialists from coast to coast and “found that about half reported not using formal screening tools to assess cognitive impairment and depression,” said study coauthor Tamar Sapir, PhD, chief scientific officer with Prime Education, a firm based in Fort Lauderdale, Fla., that provides a variety of health-related services such as training and research.
The study findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Three of the study authors spoke in interviews.
The researchers sought to understand how frequently MS patients are screened for cognitive problems and depression.
“Cognitive impairment is experienced by approximately half of patients with multiple sclerosis, yet many are never screened or treated, which can impact their daily activities, their ability to work, and overall quality of life,” Dr. Sapir said.
Depression, meanwhile, is believed to be much more common in patients with MS than in the general population, with one recent meta-analysis of 58 studies finding that the average prevalence was 31%. Other research suggests depression is underdiagnosed and undertreated in this population (J Neurol Sci. 2017 Jan 15;372:331-41; ISRN Neurology. 2012, Article ID 427102. doi: 10.5402/2012/427102).
For the current study, researchers tracked 300 patients at two unidentified MS clinics via their charts over a 2-year period from 2014 to 2016. Their median age was 52 years, 76% were women, and 15 had experienced at least one relapse within the previous 24 months.
“Screening for cognitive impairment and depression was documented for only 52% and 63% of MS patients, respectively, and only about a quarter of patients diagnosed with these conditions were referred to a higher level of care,” said lead author Guy J. Buckle, MD, MPH, of the Andrew C. Carlos MS Institute at Shepherd Center in Atlanta.
Among all 300 patients, just 2% and 4% were screened using a validated tool for cognitive impairment and depression, respectively.
The screening often turned up evidence of the conditions: Physicians saw signs of cognitive impairment in 69% and 78% of those screened aged under 65 years and aged 65 and older, respectively, and they detected depression in 71% and 54% of those screened in those two age groups, respectively.
Researchers also noted several disparities. “Cognitive screening was conducted more frequently in older, employed, or white patients, while the presence of cognitive impairment was documented more often in black, nonworking, and those on Medicare or Medicaid,” Dr. Buckle said. “Depression screening was performed most frequently in older or white patients, yet depression was more common in younger, nonworking patients and those on Medicare/Medicaid.”
In another part of their study, researchers surveyed 13 unidentified “national leaders” in MS research and treatment. Just seven said they used validated tools to screen for cognitive impairment and six said they used them to screen for depression.
“We hear from MS specialists that they want to be measuring for cognition but don’t know how to efficiently work it into their routine, how to approach the patient, and what tools to use,” said study coauthor Derrick S. Robertson, MD, of the University of South Florida, Tampa. “In addition, there is no one tool that is accepted in the MS treatment community.”
MS specialists who didn’t use the screening tests also pointed to factors like lack of reimbursement and lack of integration into electronic medical records. “Doubt very much that neurologists have time to use any of these tests,” one respondent said, referring to cognitive impairment screening.
What’s next? “There are several new exciting developments in clinical trials demonstrating efficacy of disease-modifying therapies in maintaining or improving cognition in patients with relapsing MS,” Dr. Robertson said. “This highlights the urgent need to overcome barriers to use of formal cognitive screening tools in clinical practice to identify patients who need a higher level of care, and perhaps even a change in treatment with the ultimate goal to improve quality of life and overall outcomes.”
Genentech funded the study through an educational grant. Dr. Sapir and three other study authors reported no relevant disclosures. Dr. Buckle and Dr. Robertson reported multiple disclosures, including principle investigator and advisory board/panel member work.
SOURCE: Buckle GJ et al. ACTRIMS Forum 2018, abstract No. P161.
SAN DIEGO – A new study finds that physicians at two . Physicians who did perform screening hardly ever used validated tools and often didn’t refer appropriate patients for higher-level care.
In addition, researchers interviewed 13 leading MS specialists from coast to coast and “found that about half reported not using formal screening tools to assess cognitive impairment and depression,” said study coauthor Tamar Sapir, PhD, chief scientific officer with Prime Education, a firm based in Fort Lauderdale, Fla., that provides a variety of health-related services such as training and research.
The study findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Three of the study authors spoke in interviews.
The researchers sought to understand how frequently MS patients are screened for cognitive problems and depression.
“Cognitive impairment is experienced by approximately half of patients with multiple sclerosis, yet many are never screened or treated, which can impact their daily activities, their ability to work, and overall quality of life,” Dr. Sapir said.
Depression, meanwhile, is believed to be much more common in patients with MS than in the general population, with one recent meta-analysis of 58 studies finding that the average prevalence was 31%. Other research suggests depression is underdiagnosed and undertreated in this population (J Neurol Sci. 2017 Jan 15;372:331-41; ISRN Neurology. 2012, Article ID 427102. doi: 10.5402/2012/427102).
For the current study, researchers tracked 300 patients at two unidentified MS clinics via their charts over a 2-year period from 2014 to 2016. Their median age was 52 years, 76% were women, and 15 had experienced at least one relapse within the previous 24 months.
“Screening for cognitive impairment and depression was documented for only 52% and 63% of MS patients, respectively, and only about a quarter of patients diagnosed with these conditions were referred to a higher level of care,” said lead author Guy J. Buckle, MD, MPH, of the Andrew C. Carlos MS Institute at Shepherd Center in Atlanta.
Among all 300 patients, just 2% and 4% were screened using a validated tool for cognitive impairment and depression, respectively.
The screening often turned up evidence of the conditions: Physicians saw signs of cognitive impairment in 69% and 78% of those screened aged under 65 years and aged 65 and older, respectively, and they detected depression in 71% and 54% of those screened in those two age groups, respectively.
Researchers also noted several disparities. “Cognitive screening was conducted more frequently in older, employed, or white patients, while the presence of cognitive impairment was documented more often in black, nonworking, and those on Medicare or Medicaid,” Dr. Buckle said. “Depression screening was performed most frequently in older or white patients, yet depression was more common in younger, nonworking patients and those on Medicare/Medicaid.”
In another part of their study, researchers surveyed 13 unidentified “national leaders” in MS research and treatment. Just seven said they used validated tools to screen for cognitive impairment and six said they used them to screen for depression.
“We hear from MS specialists that they want to be measuring for cognition but don’t know how to efficiently work it into their routine, how to approach the patient, and what tools to use,” said study coauthor Derrick S. Robertson, MD, of the University of South Florida, Tampa. “In addition, there is no one tool that is accepted in the MS treatment community.”
MS specialists who didn’t use the screening tests also pointed to factors like lack of reimbursement and lack of integration into electronic medical records. “Doubt very much that neurologists have time to use any of these tests,” one respondent said, referring to cognitive impairment screening.
What’s next? “There are several new exciting developments in clinical trials demonstrating efficacy of disease-modifying therapies in maintaining or improving cognition in patients with relapsing MS,” Dr. Robertson said. “This highlights the urgent need to overcome barriers to use of formal cognitive screening tools in clinical practice to identify patients who need a higher level of care, and perhaps even a change in treatment with the ultimate goal to improve quality of life and overall outcomes.”
Genentech funded the study through an educational grant. Dr. Sapir and three other study authors reported no relevant disclosures. Dr. Buckle and Dr. Robertson reported multiple disclosures, including principle investigator and advisory board/panel member work.
SOURCE: Buckle GJ et al. ACTRIMS Forum 2018, abstract No. P161.
SAN DIEGO – A new study finds that physicians at two . Physicians who did perform screening hardly ever used validated tools and often didn’t refer appropriate patients for higher-level care.
In addition, researchers interviewed 13 leading MS specialists from coast to coast and “found that about half reported not using formal screening tools to assess cognitive impairment and depression,” said study coauthor Tamar Sapir, PhD, chief scientific officer with Prime Education, a firm based in Fort Lauderdale, Fla., that provides a variety of health-related services such as training and research.
The study findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Three of the study authors spoke in interviews.
The researchers sought to understand how frequently MS patients are screened for cognitive problems and depression.
“Cognitive impairment is experienced by approximately half of patients with multiple sclerosis, yet many are never screened or treated, which can impact their daily activities, their ability to work, and overall quality of life,” Dr. Sapir said.
Depression, meanwhile, is believed to be much more common in patients with MS than in the general population, with one recent meta-analysis of 58 studies finding that the average prevalence was 31%. Other research suggests depression is underdiagnosed and undertreated in this population (J Neurol Sci. 2017 Jan 15;372:331-41; ISRN Neurology. 2012, Article ID 427102. doi: 10.5402/2012/427102).
For the current study, researchers tracked 300 patients at two unidentified MS clinics via their charts over a 2-year period from 2014 to 2016. Their median age was 52 years, 76% were women, and 15 had experienced at least one relapse within the previous 24 months.
“Screening for cognitive impairment and depression was documented for only 52% and 63% of MS patients, respectively, and only about a quarter of patients diagnosed with these conditions were referred to a higher level of care,” said lead author Guy J. Buckle, MD, MPH, of the Andrew C. Carlos MS Institute at Shepherd Center in Atlanta.
Among all 300 patients, just 2% and 4% were screened using a validated tool for cognitive impairment and depression, respectively.
The screening often turned up evidence of the conditions: Physicians saw signs of cognitive impairment in 69% and 78% of those screened aged under 65 years and aged 65 and older, respectively, and they detected depression in 71% and 54% of those screened in those two age groups, respectively.
Researchers also noted several disparities. “Cognitive screening was conducted more frequently in older, employed, or white patients, while the presence of cognitive impairment was documented more often in black, nonworking, and those on Medicare or Medicaid,” Dr. Buckle said. “Depression screening was performed most frequently in older or white patients, yet depression was more common in younger, nonworking patients and those on Medicare/Medicaid.”
In another part of their study, researchers surveyed 13 unidentified “national leaders” in MS research and treatment. Just seven said they used validated tools to screen for cognitive impairment and six said they used them to screen for depression.
“We hear from MS specialists that they want to be measuring for cognition but don’t know how to efficiently work it into their routine, how to approach the patient, and what tools to use,” said study coauthor Derrick S. Robertson, MD, of the University of South Florida, Tampa. “In addition, there is no one tool that is accepted in the MS treatment community.”
MS specialists who didn’t use the screening tests also pointed to factors like lack of reimbursement and lack of integration into electronic medical records. “Doubt very much that neurologists have time to use any of these tests,” one respondent said, referring to cognitive impairment screening.
What’s next? “There are several new exciting developments in clinical trials demonstrating efficacy of disease-modifying therapies in maintaining or improving cognition in patients with relapsing MS,” Dr. Robertson said. “This highlights the urgent need to overcome barriers to use of formal cognitive screening tools in clinical practice to identify patients who need a higher level of care, and perhaps even a change in treatment with the ultimate goal to improve quality of life and overall outcomes.”
Genentech funded the study through an educational grant. Dr. Sapir and three other study authors reported no relevant disclosures. Dr. Buckle and Dr. Robertson reported multiple disclosures, including principle investigator and advisory board/panel member work.
SOURCE: Buckle GJ et al. ACTRIMS Forum 2018, abstract No. P161.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point: Screening often turns up signs of trouble, but many MS patients are not screened annually for depression and cognitive impairment.
Major finding: 52% and 63% of patients with MS were screened for cognitive impairment and depression, respectively, over a 1-year period. Study details: 2-year analysis of medical records from two MS clinics in the Southeast.
Disclosures: Genentech funded the study through an educational grant. Some of the study authors reported various disclosures.
Source: Buckle GJ et al. ACTRIMS Forum 2018, abstract No. P161.
Nearly half of MS patients treated by primary docs miss out on meds
SAN DIEGO – than are those treated by neurologists, even though they have more symptoms.
Nearly 85% of those treated at MS centers by neurologists received the drugs, compared with just 51% of those treated at primary care offices, according to results of a study reported at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Halpern spoke in an interview at the ACTRIMS Forum.
The researchers analyzed data from the Sonya Slifka Longitudinal Multiple Sclerosis Study and focused on MS patients who received care at MS centers (376 patients, all treated by neurologists), neurology practices (552 patients), and primary care practices (55 patients).
In the three groups, most of the patients were female (77%-82%). To a statistically significant degree, those who were treated at primary care practices, compared with those at MS centers, were more likely to be white (98% vs. 82%), to have less than a college education (69% vs. 42%), and to have Medicaid/veteran coverage or be uninsured (22% vs. 11%).
In terms of rates of patients receiving disease-modifying therapies, there was a small difference between MS centers (84%) and neurology practices (79%); P less than .05.
However, the gap between these patients and those treated by primary care doctors was wide: Only 51% in the latter group received disease-modifying therapies, even though they reported more symptoms in areas such as vision, walking, bowel, speech, and numbness, compared with those in the other groups (P less than .05).
There was no statistically significant difference among the groups in reported symptoms of tremor, headache, pain, fatigue, cognition, swallowing, depression, mood, and anxiety.
The study doesn’t explain why the MS patients treated by primary care physicians are missing out on care, and it is not known whether the absence of treatment makes their conditions worse.
However, “it’s been well documented that the disease-modifying therapies can reduce the disease progression and the likelihood of experiencing relapses,” Dr. Halpern said. “Individuals with MS who are not being appropriately treated are more likely to experience symptoms, relapses, and faster disability.”
He speculated that primary care doctors may be falling behind on the treatment front because they lack the training and expertise to properly prescribe the MS medications, which are “difficult and complex drugs.”
Whatever the case, he said, there’s a clear need for more collaboration between MS subspecialists and primary care doctors.
The study was funded by the National MS Society. Dr. Halpern reported no relevant disclosures.
SOURCE: Halpern MT et al. ACTRIMS Forum 2018 Abstract P226.
SAN DIEGO – than are those treated by neurologists, even though they have more symptoms.
Nearly 85% of those treated at MS centers by neurologists received the drugs, compared with just 51% of those treated at primary care offices, according to results of a study reported at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Halpern spoke in an interview at the ACTRIMS Forum.
The researchers analyzed data from the Sonya Slifka Longitudinal Multiple Sclerosis Study and focused on MS patients who received care at MS centers (376 patients, all treated by neurologists), neurology practices (552 patients), and primary care practices (55 patients).
In the three groups, most of the patients were female (77%-82%). To a statistically significant degree, those who were treated at primary care practices, compared with those at MS centers, were more likely to be white (98% vs. 82%), to have less than a college education (69% vs. 42%), and to have Medicaid/veteran coverage or be uninsured (22% vs. 11%).
In terms of rates of patients receiving disease-modifying therapies, there was a small difference between MS centers (84%) and neurology practices (79%); P less than .05.
However, the gap between these patients and those treated by primary care doctors was wide: Only 51% in the latter group received disease-modifying therapies, even though they reported more symptoms in areas such as vision, walking, bowel, speech, and numbness, compared with those in the other groups (P less than .05).
There was no statistically significant difference among the groups in reported symptoms of tremor, headache, pain, fatigue, cognition, swallowing, depression, mood, and anxiety.
The study doesn’t explain why the MS patients treated by primary care physicians are missing out on care, and it is not known whether the absence of treatment makes their conditions worse.
However, “it’s been well documented that the disease-modifying therapies can reduce the disease progression and the likelihood of experiencing relapses,” Dr. Halpern said. “Individuals with MS who are not being appropriately treated are more likely to experience symptoms, relapses, and faster disability.”
He speculated that primary care doctors may be falling behind on the treatment front because they lack the training and expertise to properly prescribe the MS medications, which are “difficult and complex drugs.”
Whatever the case, he said, there’s a clear need for more collaboration between MS subspecialists and primary care doctors.
The study was funded by the National MS Society. Dr. Halpern reported no relevant disclosures.
SOURCE: Halpern MT et al. ACTRIMS Forum 2018 Abstract P226.
SAN DIEGO – than are those treated by neurologists, even though they have more symptoms.
Nearly 85% of those treated at MS centers by neurologists received the drugs, compared with just 51% of those treated at primary care offices, according to results of a study reported at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dr. Halpern spoke in an interview at the ACTRIMS Forum.
The researchers analyzed data from the Sonya Slifka Longitudinal Multiple Sclerosis Study and focused on MS patients who received care at MS centers (376 patients, all treated by neurologists), neurology practices (552 patients), and primary care practices (55 patients).
In the three groups, most of the patients were female (77%-82%). To a statistically significant degree, those who were treated at primary care practices, compared with those at MS centers, were more likely to be white (98% vs. 82%), to have less than a college education (69% vs. 42%), and to have Medicaid/veteran coverage or be uninsured (22% vs. 11%).
In terms of rates of patients receiving disease-modifying therapies, there was a small difference between MS centers (84%) and neurology practices (79%); P less than .05.
However, the gap between these patients and those treated by primary care doctors was wide: Only 51% in the latter group received disease-modifying therapies, even though they reported more symptoms in areas such as vision, walking, bowel, speech, and numbness, compared with those in the other groups (P less than .05).
There was no statistically significant difference among the groups in reported symptoms of tremor, headache, pain, fatigue, cognition, swallowing, depression, mood, and anxiety.
The study doesn’t explain why the MS patients treated by primary care physicians are missing out on care, and it is not known whether the absence of treatment makes their conditions worse.
However, “it’s been well documented that the disease-modifying therapies can reduce the disease progression and the likelihood of experiencing relapses,” Dr. Halpern said. “Individuals with MS who are not being appropriately treated are more likely to experience symptoms, relapses, and faster disability.”
He speculated that primary care doctors may be falling behind on the treatment front because they lack the training and expertise to properly prescribe the MS medications, which are “difficult and complex drugs.”
Whatever the case, he said, there’s a clear need for more collaboration between MS subspecialists and primary care doctors.
The study was funded by the National MS Society. Dr. Halpern reported no relevant disclosures.
SOURCE: Halpern MT et al. ACTRIMS Forum 2018 Abstract P226.
REPORTING FROM ACTRIMS FORUM 2018
VIDEO: Teriflunomide and dimethyl fumarate are comparable in relapsing-remitting MS
SAN DIEGO – New industry-funded research finds that
“The fundamental conclusion is that there’s little to separate them. If you look at efficacy, safety, and MRI scanning, there were no differences between the two medications that matter. ... Both drugs can be used with equal confidence,” said Stanley Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore.
Dr. Cohan spoke in a video interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
The researchers analyzed retrospective data collected in the phase 4 Teri-RADAR study, which tracked two groups of 50 patients each at MS centers in the United States as they took 14 mg of teriflunomide (Aubagio) daily or 240 mg of delayed-release dimethyl fumarate (Tecfidera) twice daily.
In both groups, participants had an average age of about 49 years, about three-quarters were women, and about 93% were white. Twenty-two percent of those in the teriflunomide group had relapses in the 18 months before the index date, compared with 10% of the dimethyl fumarate group.
The study – funded by Sanofi, maker of teriflunomide – followed up with patients at a mean of 15-16 months.
Mean annualized percentage of brain volume change (PBVC) was lower in teriflunomide-treated patients, compared with those treated with dimethyl fumarate (–0.2% vs. –0.5%; P = .02). Also, fewer teriflunomide-treated patients showed signs of annualized PBVC above a mean annualized brain volume loss rate threshold of 0.4% (25.9% vs. 58.6%; P = .01).
As for adverse effects, rashes affected none of the teriflunomide group but 28% of the dimethyl fumarate group. The teriflunomide group experienced skin reactions (12%) and diarrhea (16%), while these adverse events were not reported in the dimethyl fumarate group.
The study authors reported a variety of disclosures, and several are employees of Sanofi. Dr. Cohan reported a variety of disclosures, including multiple relationships with Sanofi.
SAN DIEGO – New industry-funded research finds that
“The fundamental conclusion is that there’s little to separate them. If you look at efficacy, safety, and MRI scanning, there were no differences between the two medications that matter. ... Both drugs can be used with equal confidence,” said Stanley Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore.
Dr. Cohan spoke in a video interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
The researchers analyzed retrospective data collected in the phase 4 Teri-RADAR study, which tracked two groups of 50 patients each at MS centers in the United States as they took 14 mg of teriflunomide (Aubagio) daily or 240 mg of delayed-release dimethyl fumarate (Tecfidera) twice daily.
In both groups, participants had an average age of about 49 years, about three-quarters were women, and about 93% were white. Twenty-two percent of those in the teriflunomide group had relapses in the 18 months before the index date, compared with 10% of the dimethyl fumarate group.
The study – funded by Sanofi, maker of teriflunomide – followed up with patients at a mean of 15-16 months.
Mean annualized percentage of brain volume change (PBVC) was lower in teriflunomide-treated patients, compared with those treated with dimethyl fumarate (–0.2% vs. –0.5%; P = .02). Also, fewer teriflunomide-treated patients showed signs of annualized PBVC above a mean annualized brain volume loss rate threshold of 0.4% (25.9% vs. 58.6%; P = .01).
As for adverse effects, rashes affected none of the teriflunomide group but 28% of the dimethyl fumarate group. The teriflunomide group experienced skin reactions (12%) and diarrhea (16%), while these adverse events were not reported in the dimethyl fumarate group.
The study authors reported a variety of disclosures, and several are employees of Sanofi. Dr. Cohan reported a variety of disclosures, including multiple relationships with Sanofi.
SAN DIEGO – New industry-funded research finds that
“The fundamental conclusion is that there’s little to separate them. If you look at efficacy, safety, and MRI scanning, there were no differences between the two medications that matter. ... Both drugs can be used with equal confidence,” said Stanley Cohan, MD, PhD, medical director of Providence MS Center in Portland, Ore.
Dr. Cohan spoke in a video interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
The researchers analyzed retrospective data collected in the phase 4 Teri-RADAR study, which tracked two groups of 50 patients each at MS centers in the United States as they took 14 mg of teriflunomide (Aubagio) daily or 240 mg of delayed-release dimethyl fumarate (Tecfidera) twice daily.
In both groups, participants had an average age of about 49 years, about three-quarters were women, and about 93% were white. Twenty-two percent of those in the teriflunomide group had relapses in the 18 months before the index date, compared with 10% of the dimethyl fumarate group.
The study – funded by Sanofi, maker of teriflunomide – followed up with patients at a mean of 15-16 months.
Mean annualized percentage of brain volume change (PBVC) was lower in teriflunomide-treated patients, compared with those treated with dimethyl fumarate (–0.2% vs. –0.5%; P = .02). Also, fewer teriflunomide-treated patients showed signs of annualized PBVC above a mean annualized brain volume loss rate threshold of 0.4% (25.9% vs. 58.6%; P = .01).
As for adverse effects, rashes affected none of the teriflunomide group but 28% of the dimethyl fumarate group. The teriflunomide group experienced skin reactions (12%) and diarrhea (16%), while these adverse events were not reported in the dimethyl fumarate group.
The study authors reported a variety of disclosures, and several are employees of Sanofi. Dr. Cohan reported a variety of disclosures, including multiple relationships with Sanofi.
REPORTING FROM ACTRIMS Forum 2018
VIDEO: Advanced practice providers take on many roles in MS care
SAN DIEGO – A new survey suggests that advanced practice providers who care for multiple sclerosis patients are highly satisfied with their jobs, which encompass a wide range of responsibilities.
Researchers received survey responses from 215 nurse practitioners and 395 physician assistants who answered Web questionnaires in 2016 and 2017. Of those who care for multiple sclerosis (MS) patients, 92.5% and 77.8% respectively said they provide at least 9 of 11 services, such as direct care, supportive services, and care coordination.
“Nurse practitioners in particular are providing lots of different services from diagnosis to education to symptom management,” said Michael T. Halpern, MD, PhD, MPH, of Temple University, Philadelphia. “Physician assistants are also providing a diverse range of MS services, but not as frequently as nurse practitioners.”
Dr. Halpern was the presenting author of the study reporting the survey results. He spoke in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study findings were presented.
Advanced practice providers also reported high levels of job satisfaction. About 80% in both groups reported being very or extremely satisfied with their careers and with their colleagues; 90% of nurse practitioners reported being very or extremely satisfied by their relationships with patients, as did 86% of physician assistants.
The providers “appear to really enjoy working with individuals with MS,” Dr. Halpern said. But he cautioned that there’s a need for additional training for these providers; some respondents said their lack of knowledge was a hindrance to care.
The study was funded by the National Multiple Sclerosis Society. Dr. Halpern reported no relevant disclosures.
SAN DIEGO – A new survey suggests that advanced practice providers who care for multiple sclerosis patients are highly satisfied with their jobs, which encompass a wide range of responsibilities.
Researchers received survey responses from 215 nurse practitioners and 395 physician assistants who answered Web questionnaires in 2016 and 2017. Of those who care for multiple sclerosis (MS) patients, 92.5% and 77.8% respectively said they provide at least 9 of 11 services, such as direct care, supportive services, and care coordination.
“Nurse practitioners in particular are providing lots of different services from diagnosis to education to symptom management,” said Michael T. Halpern, MD, PhD, MPH, of Temple University, Philadelphia. “Physician assistants are also providing a diverse range of MS services, but not as frequently as nurse practitioners.”
Dr. Halpern was the presenting author of the study reporting the survey results. He spoke in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study findings were presented.
Advanced practice providers also reported high levels of job satisfaction. About 80% in both groups reported being very or extremely satisfied with their careers and with their colleagues; 90% of nurse practitioners reported being very or extremely satisfied by their relationships with patients, as did 86% of physician assistants.
The providers “appear to really enjoy working with individuals with MS,” Dr. Halpern said. But he cautioned that there’s a need for additional training for these providers; some respondents said their lack of knowledge was a hindrance to care.
The study was funded by the National Multiple Sclerosis Society. Dr. Halpern reported no relevant disclosures.
SAN DIEGO – A new survey suggests that advanced practice providers who care for multiple sclerosis patients are highly satisfied with their jobs, which encompass a wide range of responsibilities.
Researchers received survey responses from 215 nurse practitioners and 395 physician assistants who answered Web questionnaires in 2016 and 2017. Of those who care for multiple sclerosis (MS) patients, 92.5% and 77.8% respectively said they provide at least 9 of 11 services, such as direct care, supportive services, and care coordination.
“Nurse practitioners in particular are providing lots of different services from diagnosis to education to symptom management,” said Michael T. Halpern, MD, PhD, MPH, of Temple University, Philadelphia. “Physician assistants are also providing a diverse range of MS services, but not as frequently as nurse practitioners.”
Dr. Halpern was the presenting author of the study reporting the survey results. He spoke in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study findings were presented.
Advanced practice providers also reported high levels of job satisfaction. About 80% in both groups reported being very or extremely satisfied with their careers and with their colleagues; 90% of nurse practitioners reported being very or extremely satisfied by their relationships with patients, as did 86% of physician assistants.
The providers “appear to really enjoy working with individuals with MS,” Dr. Halpern said. But he cautioned that there’s a need for additional training for these providers; some respondents said their lack of knowledge was a hindrance to care.
The study was funded by the National Multiple Sclerosis Society. Dr. Halpern reported no relevant disclosures.
REPORTING FROM ACTRIMS FORUM 2018
Trial of clozapine, risperidone halted in MS
SAN DIEGO – New Zealand researchers halted a small trial that was testing the use of the antipsychotics clozapine and risperidone to treat progressive multiple sclerosis because significant side effects caused participants to withdraw.
The adverse events appeared even though the doses were much smaller than those routinely given to patients with psychiatric illnesses. “The neurologists realized it was in the participants’ best interest to stop,” said study lead author Anne Camille La Flamme, PhD, of Victoria University of Wellington (New Zealand). “Adverse events included dizziness, muscle weakness, and falls.”
The researchers launched the study – a blinded, randomized, placebo-controlled trial – to learn whether the two antipsychotic drugs, also known by the brand names Clozaril and Risperdal, have potential as treatments for progressive multiple sclerosis.
Previous in-vitro research had linked the drugs to anti-inflammatory effects in the central nervous system, Dr. La Flamme said, and researchers believed that the progressive form of MS might be especially vulnerable to their effects because of high immune system involvement.
The researchers planned to randomly assign three groups of 12 patients per arm to placebo, clozapine, and risperidone.
For clozapine, “the doses were very low, much lower than you’d expect for psychiatric use,” Dr. La Flamme said. A typical dose for psychiatric disorders is about 350 mg/day, she said, and the trial aimed to use 100-150 mg/day with an eye toward preventing dose-dependent side effects.
As for risperidone, a typical dose is about 4 mg/day, and the trial began at 2 mg/day and would increase to 3.5 mg/day, she said.
Three subjects in the clozapine group had to withdraw within 2 weeks when their doses had only reached an average of 35 mg/day. Two of three in the risperidone group withdrew within 4 months.
In light of the adverse effects, “it was deemed not wise to continue,” Dr. La Flamme said.
The placebo group, meanwhile, completed the trial at 178 days and had adverse effects that were more indicative of MS, she said.
What happened? One possibility is that disability from MS made the adverse events more evident, Dr. La Flamme said. Another possible explanation is that the underlying MS physiology changed the targets of the medications, she said.
“We have no conclusive evidence that would suggest one over the other,” she said. “But a lot of the evidence supports the idea that it’s a change in the physiology, that something about those pathways has been altered.”
It’s clear, she said, that the doses of the drugs in the trial were not appropriate. However, a big question remains: “We do not know whether these medicines are effective at reducing neuroinflammation.”
It’s possible, she said, that a “whisper of a dose” could still be effective. “It may get back to how these agents metabolize and become an active form.”
The study was funded by New Zealand’s Ministry of Business, Innovation and Employment. Dr. La Flamme disclosed that the study team has a patent for repurposing of clozapine and risperidone to treat MS.
SOURCE: La Flamme A et al. ACTRIMS Forum 2018, abstract P031.
SAN DIEGO – New Zealand researchers halted a small trial that was testing the use of the antipsychotics clozapine and risperidone to treat progressive multiple sclerosis because significant side effects caused participants to withdraw.
The adverse events appeared even though the doses were much smaller than those routinely given to patients with psychiatric illnesses. “The neurologists realized it was in the participants’ best interest to stop,” said study lead author Anne Camille La Flamme, PhD, of Victoria University of Wellington (New Zealand). “Adverse events included dizziness, muscle weakness, and falls.”
The researchers launched the study – a blinded, randomized, placebo-controlled trial – to learn whether the two antipsychotic drugs, also known by the brand names Clozaril and Risperdal, have potential as treatments for progressive multiple sclerosis.
Previous in-vitro research had linked the drugs to anti-inflammatory effects in the central nervous system, Dr. La Flamme said, and researchers believed that the progressive form of MS might be especially vulnerable to their effects because of high immune system involvement.
The researchers planned to randomly assign three groups of 12 patients per arm to placebo, clozapine, and risperidone.
For clozapine, “the doses were very low, much lower than you’d expect for psychiatric use,” Dr. La Flamme said. A typical dose for psychiatric disorders is about 350 mg/day, she said, and the trial aimed to use 100-150 mg/day with an eye toward preventing dose-dependent side effects.
As for risperidone, a typical dose is about 4 mg/day, and the trial began at 2 mg/day and would increase to 3.5 mg/day, she said.
Three subjects in the clozapine group had to withdraw within 2 weeks when their doses had only reached an average of 35 mg/day. Two of three in the risperidone group withdrew within 4 months.
In light of the adverse effects, “it was deemed not wise to continue,” Dr. La Flamme said.
The placebo group, meanwhile, completed the trial at 178 days and had adverse effects that were more indicative of MS, she said.
What happened? One possibility is that disability from MS made the adverse events more evident, Dr. La Flamme said. Another possible explanation is that the underlying MS physiology changed the targets of the medications, she said.
“We have no conclusive evidence that would suggest one over the other,” she said. “But a lot of the evidence supports the idea that it’s a change in the physiology, that something about those pathways has been altered.”
It’s clear, she said, that the doses of the drugs in the trial were not appropriate. However, a big question remains: “We do not know whether these medicines are effective at reducing neuroinflammation.”
It’s possible, she said, that a “whisper of a dose” could still be effective. “It may get back to how these agents metabolize and become an active form.”
The study was funded by New Zealand’s Ministry of Business, Innovation and Employment. Dr. La Flamme disclosed that the study team has a patent for repurposing of clozapine and risperidone to treat MS.
SOURCE: La Flamme A et al. ACTRIMS Forum 2018, abstract P031.
SAN DIEGO – New Zealand researchers halted a small trial that was testing the use of the antipsychotics clozapine and risperidone to treat progressive multiple sclerosis because significant side effects caused participants to withdraw.
The adverse events appeared even though the doses were much smaller than those routinely given to patients with psychiatric illnesses. “The neurologists realized it was in the participants’ best interest to stop,” said study lead author Anne Camille La Flamme, PhD, of Victoria University of Wellington (New Zealand). “Adverse events included dizziness, muscle weakness, and falls.”
The researchers launched the study – a blinded, randomized, placebo-controlled trial – to learn whether the two antipsychotic drugs, also known by the brand names Clozaril and Risperdal, have potential as treatments for progressive multiple sclerosis.
Previous in-vitro research had linked the drugs to anti-inflammatory effects in the central nervous system, Dr. La Flamme said, and researchers believed that the progressive form of MS might be especially vulnerable to their effects because of high immune system involvement.
The researchers planned to randomly assign three groups of 12 patients per arm to placebo, clozapine, and risperidone.
For clozapine, “the doses were very low, much lower than you’d expect for psychiatric use,” Dr. La Flamme said. A typical dose for psychiatric disorders is about 350 mg/day, she said, and the trial aimed to use 100-150 mg/day with an eye toward preventing dose-dependent side effects.
As for risperidone, a typical dose is about 4 mg/day, and the trial began at 2 mg/day and would increase to 3.5 mg/day, she said.
Three subjects in the clozapine group had to withdraw within 2 weeks when their doses had only reached an average of 35 mg/day. Two of three in the risperidone group withdrew within 4 months.
In light of the adverse effects, “it was deemed not wise to continue,” Dr. La Flamme said.
The placebo group, meanwhile, completed the trial at 178 days and had adverse effects that were more indicative of MS, she said.
What happened? One possibility is that disability from MS made the adverse events more evident, Dr. La Flamme said. Another possible explanation is that the underlying MS physiology changed the targets of the medications, she said.
“We have no conclusive evidence that would suggest one over the other,” she said. “But a lot of the evidence supports the idea that it’s a change in the physiology, that something about those pathways has been altered.”
It’s clear, she said, that the doses of the drugs in the trial were not appropriate. However, a big question remains: “We do not know whether these medicines are effective at reducing neuroinflammation.”
It’s possible, she said, that a “whisper of a dose” could still be effective. “It may get back to how these agents metabolize and become an active form.”
The study was funded by New Zealand’s Ministry of Business, Innovation and Employment. Dr. La Flamme disclosed that the study team has a patent for repurposing of clozapine and risperidone to treat MS.
SOURCE: La Flamme A et al. ACTRIMS Forum 2018, abstract P031.
REPORTING FROM ACTRIMS Forum 2018
VIDEO: Oral ozanimod shows promise for relapsing MS
SAN DIEGO – A pair of phase 3 studies offer promising results regarding the safety and efficacy of ozanimod, an experimental immunomodulator, in the treatment of relapsing multiple sclerosis (RMS).
The medication targets sphingosine 1-phosphate 1 and 5 receptors. Industry-funded researchers tested it in two studies against interferon beta-1a.
One study, called SUNBEAM, tested once-daily oral ozanimod (1 mg or 0.5 mg with 7-day dose escalation) against interferon beta-1a (via 30 mcg weekly intramuscular injection) for at least 12 months in 1,346 patients with RMS. The annualized relapse rate, the primary endpoint, was lower in the ozanimod groups versus interferon. For the 1-mg dose, it was 0.181 (P less than .0001), and for 0.5-mg dose, 0.241 (P = .0013).
The number of serious treatment-emergent adverse events in the three groups was low, ranging from 2.5% to 3.5%.
The other study, called RADIANCE, was a similar trial that lasted 24 months. In it, the rate of serious treatment-emergent adverse events in the three groups were similar, ranging from 6.4% to 7.1%.
Ozanimod offers “an excellent therapeutic benefit for patients and a very clean safety profile,” said Bruce Cree, MD, PhD, clinical research director at the University of California, San Francisco, Multiple Sclerosis Center. He is an author on both studies and spoke in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
He said the ozanimod should be especially useful as a first-line treatment for MS. The drug is currently being evaluated by the Food and Drug Administration for an RMS indication, and it is also being developed for Crohn’s disease and ulcerative colitis, he said.
The study was funded by Receptos, a wholly owned subsidiary of Celgene. Dr. Cree reported that he has been a consultant to AbbVie, Biogen, EMD Serono, Genzyme, Novartis, and Shire.
SOURCE: Cree B et al. ACTRIMS Forum 2018, abstract P030, and Comi G et al. ACTRIMS Forum 2018, abstract P023
SAN DIEGO – A pair of phase 3 studies offer promising results regarding the safety and efficacy of ozanimod, an experimental immunomodulator, in the treatment of relapsing multiple sclerosis (RMS).
The medication targets sphingosine 1-phosphate 1 and 5 receptors. Industry-funded researchers tested it in two studies against interferon beta-1a.
One study, called SUNBEAM, tested once-daily oral ozanimod (1 mg or 0.5 mg with 7-day dose escalation) against interferon beta-1a (via 30 mcg weekly intramuscular injection) for at least 12 months in 1,346 patients with RMS. The annualized relapse rate, the primary endpoint, was lower in the ozanimod groups versus interferon. For the 1-mg dose, it was 0.181 (P less than .0001), and for 0.5-mg dose, 0.241 (P = .0013).
The number of serious treatment-emergent adverse events in the three groups was low, ranging from 2.5% to 3.5%.
The other study, called RADIANCE, was a similar trial that lasted 24 months. In it, the rate of serious treatment-emergent adverse events in the three groups were similar, ranging from 6.4% to 7.1%.
Ozanimod offers “an excellent therapeutic benefit for patients and a very clean safety profile,” said Bruce Cree, MD, PhD, clinical research director at the University of California, San Francisco, Multiple Sclerosis Center. He is an author on both studies and spoke in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
He said the ozanimod should be especially useful as a first-line treatment for MS. The drug is currently being evaluated by the Food and Drug Administration for an RMS indication, and it is also being developed for Crohn’s disease and ulcerative colitis, he said.
The study was funded by Receptos, a wholly owned subsidiary of Celgene. Dr. Cree reported that he has been a consultant to AbbVie, Biogen, EMD Serono, Genzyme, Novartis, and Shire.
SOURCE: Cree B et al. ACTRIMS Forum 2018, abstract P030, and Comi G et al. ACTRIMS Forum 2018, abstract P023
SAN DIEGO – A pair of phase 3 studies offer promising results regarding the safety and efficacy of ozanimod, an experimental immunomodulator, in the treatment of relapsing multiple sclerosis (RMS).
The medication targets sphingosine 1-phosphate 1 and 5 receptors. Industry-funded researchers tested it in two studies against interferon beta-1a.
One study, called SUNBEAM, tested once-daily oral ozanimod (1 mg or 0.5 mg with 7-day dose escalation) against interferon beta-1a (via 30 mcg weekly intramuscular injection) for at least 12 months in 1,346 patients with RMS. The annualized relapse rate, the primary endpoint, was lower in the ozanimod groups versus interferon. For the 1-mg dose, it was 0.181 (P less than .0001), and for 0.5-mg dose, 0.241 (P = .0013).
The number of serious treatment-emergent adverse events in the three groups was low, ranging from 2.5% to 3.5%.
The other study, called RADIANCE, was a similar trial that lasted 24 months. In it, the rate of serious treatment-emergent adverse events in the three groups were similar, ranging from 6.4% to 7.1%.
Ozanimod offers “an excellent therapeutic benefit for patients and a very clean safety profile,” said Bruce Cree, MD, PhD, clinical research director at the University of California, San Francisco, Multiple Sclerosis Center. He is an author on both studies and spoke in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
He said the ozanimod should be especially useful as a first-line treatment for MS. The drug is currently being evaluated by the Food and Drug Administration for an RMS indication, and it is also being developed for Crohn’s disease and ulcerative colitis, he said.
The study was funded by Receptos, a wholly owned subsidiary of Celgene. Dr. Cree reported that he has been a consultant to AbbVie, Biogen, EMD Serono, Genzyme, Novartis, and Shire.
SOURCE: Cree B et al. ACTRIMS Forum 2018, abstract P030, and Comi G et al. ACTRIMS Forum 2018, abstract P023
REPORTING FROM ACTRIMS FORUM 2018
MS may be a transmissible protein misfolding disorder, study suggests
SAN DIEGO – MS may even be caused by prions, potentially putting it into the same category as Creutzfeldt-Jakob disease.
Researchers don’t think MS is contagious between humans. But their findings in mice do suggest that the disease is transmissible from “a seed of protein misfolding,” Shigeki Tsutsui, DVM, PhD, of the University of Calgary (Alta.), said in an interview in advance of his presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“The next question is: ‘What is actually causing primary damage?’ ” he said. “Our hypothesis is that it’s protein misfolding. If protein misfolding targets the central neuron cells, then those damaged cells release a kind of a trigger to start an immune response.”
This isn’t an unusual concept. Protein misfolding is believed to cause several chronic neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis, Dr. Tsutsui said.
The researchers focused on the potential transmissibility of human prion protein “since we thought that the prion protein might be the candidate causing the MS,” he said.
Prion diseases are extremely rare and often deadly. They appear when normal cellular prion proteins are induced to misfold when they come in contact with infectious agents known as prions.
In humans, prion diseases include Creutzfeldt-Jakob disease, fatal familial insomnia, and kuru (a condition spread among cannibals who eat the brains of other humans). Most famously, a variant of Creutzfeldt-Jakob disease has been linked – but not conclusively – to the eating of meat from cows infected with mad cow disease.
Depending on the condition, prion diseases can appear spontaneously, via inheritance or through infection.
In the new study, researchers intracerebrally injected brain homogenate from 10 patients with primary or secondary-progressive MS into 36 transgenic mice. All the mice over-expressed human prion protein. A control group of 23 mice were injected with homogenate from six donor brains.
At 6-12 months, the control mice did not develop pathology. However, the mice injected with brain matter from MS patients developed various levels of significant pathology. The researchers also managed to transmit illness from affected mice into another group of transgenic mice that over-expressed human prion protein via injection of brain homogenate.
While the mice in the study represent “a very extreme case” since their levels of prion protein expression were very high, it’s clear that “MS is actually transmissible,” Dr. Tsutsui said.
The study authors speculate that pathogenic prion protein triggers an autoimmune response by degenerating myelin and causing the release of cellular debris.
Could MS also be contagious? It may not be, even if it’s a prion disease, Dr. Tsutsui said. Some prion disease variants are neither contagious nor infectious.
The researchers plan to study the animal model they’ve created and explore the potential for its use in research, Dr. Tsutsui said.
The authors have no disclosures with the exception of one who disclosed serving as deputy editor of the Multiple Sclerosis Journal. Funding sources include Canada Research Chairs, Alberta Innovates-Health Solutions, and the Alberta Prion Research Institute.
SOURCE: Tsutsui S et al. ACTRIMS Forum 2018 Abstract LB282.
SAN DIEGO – MS may even be caused by prions, potentially putting it into the same category as Creutzfeldt-Jakob disease.
Researchers don’t think MS is contagious between humans. But their findings in mice do suggest that the disease is transmissible from “a seed of protein misfolding,” Shigeki Tsutsui, DVM, PhD, of the University of Calgary (Alta.), said in an interview in advance of his presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“The next question is: ‘What is actually causing primary damage?’ ” he said. “Our hypothesis is that it’s protein misfolding. If protein misfolding targets the central neuron cells, then those damaged cells release a kind of a trigger to start an immune response.”
This isn’t an unusual concept. Protein misfolding is believed to cause several chronic neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis, Dr. Tsutsui said.
The researchers focused on the potential transmissibility of human prion protein “since we thought that the prion protein might be the candidate causing the MS,” he said.
Prion diseases are extremely rare and often deadly. They appear when normal cellular prion proteins are induced to misfold when they come in contact with infectious agents known as prions.
In humans, prion diseases include Creutzfeldt-Jakob disease, fatal familial insomnia, and kuru (a condition spread among cannibals who eat the brains of other humans). Most famously, a variant of Creutzfeldt-Jakob disease has been linked – but not conclusively – to the eating of meat from cows infected with mad cow disease.
Depending on the condition, prion diseases can appear spontaneously, via inheritance or through infection.
In the new study, researchers intracerebrally injected brain homogenate from 10 patients with primary or secondary-progressive MS into 36 transgenic mice. All the mice over-expressed human prion protein. A control group of 23 mice were injected with homogenate from six donor brains.
At 6-12 months, the control mice did not develop pathology. However, the mice injected with brain matter from MS patients developed various levels of significant pathology. The researchers also managed to transmit illness from affected mice into another group of transgenic mice that over-expressed human prion protein via injection of brain homogenate.
While the mice in the study represent “a very extreme case” since their levels of prion protein expression were very high, it’s clear that “MS is actually transmissible,” Dr. Tsutsui said.
The study authors speculate that pathogenic prion protein triggers an autoimmune response by degenerating myelin and causing the release of cellular debris.
Could MS also be contagious? It may not be, even if it’s a prion disease, Dr. Tsutsui said. Some prion disease variants are neither contagious nor infectious.
The researchers plan to study the animal model they’ve created and explore the potential for its use in research, Dr. Tsutsui said.
The authors have no disclosures with the exception of one who disclosed serving as deputy editor of the Multiple Sclerosis Journal. Funding sources include Canada Research Chairs, Alberta Innovates-Health Solutions, and the Alberta Prion Research Institute.
SOURCE: Tsutsui S et al. ACTRIMS Forum 2018 Abstract LB282.
SAN DIEGO – MS may even be caused by prions, potentially putting it into the same category as Creutzfeldt-Jakob disease.
Researchers don’t think MS is contagious between humans. But their findings in mice do suggest that the disease is transmissible from “a seed of protein misfolding,” Shigeki Tsutsui, DVM, PhD, of the University of Calgary (Alta.), said in an interview in advance of his presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“The next question is: ‘What is actually causing primary damage?’ ” he said. “Our hypothesis is that it’s protein misfolding. If protein misfolding targets the central neuron cells, then those damaged cells release a kind of a trigger to start an immune response.”
This isn’t an unusual concept. Protein misfolding is believed to cause several chronic neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis, Dr. Tsutsui said.
The researchers focused on the potential transmissibility of human prion protein “since we thought that the prion protein might be the candidate causing the MS,” he said.
Prion diseases are extremely rare and often deadly. They appear when normal cellular prion proteins are induced to misfold when they come in contact with infectious agents known as prions.
In humans, prion diseases include Creutzfeldt-Jakob disease, fatal familial insomnia, and kuru (a condition spread among cannibals who eat the brains of other humans). Most famously, a variant of Creutzfeldt-Jakob disease has been linked – but not conclusively – to the eating of meat from cows infected with mad cow disease.
Depending on the condition, prion diseases can appear spontaneously, via inheritance or through infection.
In the new study, researchers intracerebrally injected brain homogenate from 10 patients with primary or secondary-progressive MS into 36 transgenic mice. All the mice over-expressed human prion protein. A control group of 23 mice were injected with homogenate from six donor brains.
At 6-12 months, the control mice did not develop pathology. However, the mice injected with brain matter from MS patients developed various levels of significant pathology. The researchers also managed to transmit illness from affected mice into another group of transgenic mice that over-expressed human prion protein via injection of brain homogenate.
While the mice in the study represent “a very extreme case” since their levels of prion protein expression were very high, it’s clear that “MS is actually transmissible,” Dr. Tsutsui said.
The study authors speculate that pathogenic prion protein triggers an autoimmune response by degenerating myelin and causing the release of cellular debris.
Could MS also be contagious? It may not be, even if it’s a prion disease, Dr. Tsutsui said. Some prion disease variants are neither contagious nor infectious.
The researchers plan to study the animal model they’ve created and explore the potential for its use in research, Dr. Tsutsui said.
The authors have no disclosures with the exception of one who disclosed serving as deputy editor of the Multiple Sclerosis Journal. Funding sources include Canada Research Chairs, Alberta Innovates-Health Solutions, and the Alberta Prion Research Institute.
SOURCE: Tsutsui S et al. ACTRIMS Forum 2018 Abstract LB282.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point: Translational research suggests the primary damage in MS may be caused by transmissible protein misfolding.
Major finding: Transgenic mice over-expressing human prion protein that were injected with brain matter from MS patients developed various levels of significant pathology, and brain homogenate from these mice could transmit illness to naive transgenic mice.
Study details: Transgenic mice over-expressing human prion protein received intracerebral injection of brain homogenate from patients with primary or secondary-progressive MS
Disclosures: The authors have no disclosures with the exception of one who disclosed serving as deputy editor of the Multiple Sclerosis Journal. Funding sources include Canada Research Chairs, Alberta Innovates-Health Solutions, and the Alberta Prion Research Institute.
Source: Tsutsui S et al. ACTRIMS Forum 2018 Abstract LB282.