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Protein may be therapeutic target for MM
Preclinical research suggests the protein BMI-1 may be a therapeutic target for multiple myeloma (MM).
Researchers found that BMI-1 inhibition, with a drug called PTC-209, induced apoptosis in MM cell lines and primary cells.
In addition, PTC-209’s anti-myeloma activity was enhanced by inhibitors targeting EZH2 and BET bromodomains.
The researchers reported these results in Oncotarget.
The team noted that previous studies have suggested epigenetic alterations are involved in the development of MM. They chose to focus the current study on BMI-1 because it’s part of a protein complex involved in epigenetic regulation and could therefore be a potential target for influencing MM development.
“We used the substance PTC-209, which we know inhibits BMI-1, and treated cultivated multiple myeloma cells,” said study author Mohammad Alzrigat, PhD, of Uppsala University in Uppsala, Sweden.
“We used both cell lines that are continuously kept as cultivated cells and cells that were purified from multiple myeloma patients, either newly diagnosed or at relapse. In all cases, we found that [PTC-209] decreased cell survival, which indicates that PTC-209 has an anti-myeloma effect.”
The researchers said PTC-209 demonstrated “potent anti-myeloma activity, reducing the viability of MM cell lines at concentrations ranging up to 1.6 μM over 48 hours of treatment.” INA-6 was the cell line that proved most responsive to PTC-209, and U266-1970 was the least responsive.
The team also found that a 10 μM concentration of PTC-209 reduced the viability of all primary MM cells. This anti-myeloma activity was independent of disease state (whether patients were newly diagnosed or had relapsed disease) and cytogenetic karyotype.
“Our study showed that PTC-209 most likely functions as an anti-myeloma agent by inhibiting the production of BMI-1,” said study author Helena Jernberg-Wiklund, PhD, also of Uppsala University.
“We also saw that when PTC-209 was combined with other substances that inhibit epigenetic alterations, the myeloma cells’ survival was reduced even further compared to when only PTC-209 was used.”
Specifically, the researchers observed synergistic and additive activity when PTC-209 was combined with the EZH2 inhibitor UNC1999 and the BET inhibitor JQ1.
“Our results have both increased our understanding of how epigenetic alterations affect cancer development and shown how inhibiting these mechanisms in combination could potentially be utilized for future treatment of multiple myeloma patients, especially at relapse,” Dr Jernberg-Wiklund said. 
Preclinical research suggests the protein BMI-1 may be a therapeutic target for multiple myeloma (MM).
Researchers found that BMI-1 inhibition, with a drug called PTC-209, induced apoptosis in MM cell lines and primary cells.
In addition, PTC-209’s anti-myeloma activity was enhanced by inhibitors targeting EZH2 and BET bromodomains.
The researchers reported these results in Oncotarget.
The team noted that previous studies have suggested epigenetic alterations are involved in the development of MM. They chose to focus the current study on BMI-1 because it’s part of a protein complex involved in epigenetic regulation and could therefore be a potential target for influencing MM development.
“We used the substance PTC-209, which we know inhibits BMI-1, and treated cultivated multiple myeloma cells,” said study author Mohammad Alzrigat, PhD, of Uppsala University in Uppsala, Sweden.
“We used both cell lines that are continuously kept as cultivated cells and cells that were purified from multiple myeloma patients, either newly diagnosed or at relapse. In all cases, we found that [PTC-209] decreased cell survival, which indicates that PTC-209 has an anti-myeloma effect.”
The researchers said PTC-209 demonstrated “potent anti-myeloma activity, reducing the viability of MM cell lines at concentrations ranging up to 1.6 μM over 48 hours of treatment.” INA-6 was the cell line that proved most responsive to PTC-209, and U266-1970 was the least responsive.
The team also found that a 10 μM concentration of PTC-209 reduced the viability of all primary MM cells. This anti-myeloma activity was independent of disease state (whether patients were newly diagnosed or had relapsed disease) and cytogenetic karyotype.
“Our study showed that PTC-209 most likely functions as an anti-myeloma agent by inhibiting the production of BMI-1,” said study author Helena Jernberg-Wiklund, PhD, also of Uppsala University.
“We also saw that when PTC-209 was combined with other substances that inhibit epigenetic alterations, the myeloma cells’ survival was reduced even further compared to when only PTC-209 was used.”
Specifically, the researchers observed synergistic and additive activity when PTC-209 was combined with the EZH2 inhibitor UNC1999 and the BET inhibitor JQ1.
“Our results have both increased our understanding of how epigenetic alterations affect cancer development and shown how inhibiting these mechanisms in combination could potentially be utilized for future treatment of multiple myeloma patients, especially at relapse,” Dr Jernberg-Wiklund said.
Preclinical research suggests the protein BMI-1 may be a therapeutic target for multiple myeloma (MM).
Researchers found that BMI-1 inhibition, with a drug called PTC-209, induced apoptosis in MM cell lines and primary cells.
In addition, PTC-209’s anti-myeloma activity was enhanced by inhibitors targeting EZH2 and BET bromodomains.
The researchers reported these results in Oncotarget.
The team noted that previous studies have suggested epigenetic alterations are involved in the development of MM. They chose to focus the current study on BMI-1 because it’s part of a protein complex involved in epigenetic regulation and could therefore be a potential target for influencing MM development.
“We used the substance PTC-209, which we know inhibits BMI-1, and treated cultivated multiple myeloma cells,” said study author Mohammad Alzrigat, PhD, of Uppsala University in Uppsala, Sweden.
“We used both cell lines that are continuously kept as cultivated cells and cells that were purified from multiple myeloma patients, either newly diagnosed or at relapse. In all cases, we found that [PTC-209] decreased cell survival, which indicates that PTC-209 has an anti-myeloma effect.”
The researchers said PTC-209 demonstrated “potent anti-myeloma activity, reducing the viability of MM cell lines at concentrations ranging up to 1.6 μM over 48 hours of treatment.” INA-6 was the cell line that proved most responsive to PTC-209, and U266-1970 was the least responsive.
The team also found that a 10 μM concentration of PTC-209 reduced the viability of all primary MM cells. This anti-myeloma activity was independent of disease state (whether patients were newly diagnosed or had relapsed disease) and cytogenetic karyotype.
“Our study showed that PTC-209 most likely functions as an anti-myeloma agent by inhibiting the production of BMI-1,” said study author Helena Jernberg-Wiklund, PhD, also of Uppsala University.
“We also saw that when PTC-209 was combined with other substances that inhibit epigenetic alterations, the myeloma cells’ survival was reduced even further compared to when only PTC-209 was used.”
Specifically, the researchers observed synergistic and additive activity when PTC-209 was combined with the EZH2 inhibitor UNC1999 and the BET inhibitor JQ1.
“Our results have both increased our understanding of how epigenetic alterations affect cancer development and shown how inhibiting these mechanisms in combination could potentially be utilized for future treatment of multiple myeloma patients, especially at relapse,” Dr Jernberg-Wiklund said.
Update on Diabetes Medications
Location matters when it comes to thyroidectomy rates
Thyroidectomy rates differ widely across the United States, according to a cross-sectional analysis of Medicare beneficiaries, but researchers aren’t sure what’s driving the variation.
There was a 6.2-fold difference in thyroidectomy rates across U.S. hospital referral regions in 2014, ranging from 22 to 139 per 100,000 Medicare beneficiaries. The national average was 60 procedures per 100,000 Medicare beneficiaries, David O. Francis, MD, of the University of Wisconsin, Madison, and his coauthors, reported (JAMA Otolaryngol Head Neck Surg. 2017 Oct 12. doi: 10.1001/jamaoto.2017.1746).
The researchers conducted a cross-sectional analysis of 15,888 Medicare beneficiaries aged 65 years and older who underwent a thyroidectomy in 2014. Of the thyroidectomies performed, 7,056 were partial and 8,382 were total thyroidectomies. They compared the frequency of partial and total thyroidectomies to total prostatectomy rates (high variation) and hospitalizations for hip fractures (low variation).
The stark variation in thyroidectomy outpaced those in hip fracture hospitalization (2.2-fold variation) and radical prostatectomy (5.6-fold variation) across U.S. hospital referral regions.
Higher rates of thyroidectomy were seen in Southern, Central, and certain urban regions of the United States.
But the variation in rates did not correlate with health care availability, socioeconomic status, or the availability of surgeons. This suggests that variation is caused by something other than disease burden. The researchers speculated that the “variability in thyroid surgery rates in areas with similar access to surgical services largely relates to local beliefs and practice patterns.”
The researchers also noted that the findings, which are based on Medicare data, may not be generalizable to young patients who account for more than half of all thyroidectomies performed in the United States.
The study was funded by the Department of Veterans Affairs and the Dartmouth Institute for Health Policy & Clinical Practice, with salary support from the National Institutes of Health. The researchers reported having no relevant conflicts of interest.
Thyroidectomy rates differ widely across the United States, according to a cross-sectional analysis of Medicare beneficiaries, but researchers aren’t sure what’s driving the variation.
There was a 6.2-fold difference in thyroidectomy rates across U.S. hospital referral regions in 2014, ranging from 22 to 139 per 100,000 Medicare beneficiaries. The national average was 60 procedures per 100,000 Medicare beneficiaries, David O. Francis, MD, of the University of Wisconsin, Madison, and his coauthors, reported (JAMA Otolaryngol Head Neck Surg. 2017 Oct 12. doi: 10.1001/jamaoto.2017.1746).
The researchers conducted a cross-sectional analysis of 15,888 Medicare beneficiaries aged 65 years and older who underwent a thyroidectomy in 2014. Of the thyroidectomies performed, 7,056 were partial and 8,382 were total thyroidectomies. They compared the frequency of partial and total thyroidectomies to total prostatectomy rates (high variation) and hospitalizations for hip fractures (low variation).
The stark variation in thyroidectomy outpaced those in hip fracture hospitalization (2.2-fold variation) and radical prostatectomy (5.6-fold variation) across U.S. hospital referral regions.
Higher rates of thyroidectomy were seen in Southern, Central, and certain urban regions of the United States.
But the variation in rates did not correlate with health care availability, socioeconomic status, or the availability of surgeons. This suggests that variation is caused by something other than disease burden. The researchers speculated that the “variability in thyroid surgery rates in areas with similar access to surgical services largely relates to local beliefs and practice patterns.”
The researchers also noted that the findings, which are based on Medicare data, may not be generalizable to young patients who account for more than half of all thyroidectomies performed in the United States.
The study was funded by the Department of Veterans Affairs and the Dartmouth Institute for Health Policy & Clinical Practice, with salary support from the National Institutes of Health. The researchers reported having no relevant conflicts of interest.
Thyroidectomy rates differ widely across the United States, according to a cross-sectional analysis of Medicare beneficiaries, but researchers aren’t sure what’s driving the variation.
There was a 6.2-fold difference in thyroidectomy rates across U.S. hospital referral regions in 2014, ranging from 22 to 139 per 100,000 Medicare beneficiaries. The national average was 60 procedures per 100,000 Medicare beneficiaries, David O. Francis, MD, of the University of Wisconsin, Madison, and his coauthors, reported (JAMA Otolaryngol Head Neck Surg. 2017 Oct 12. doi: 10.1001/jamaoto.2017.1746).
The researchers conducted a cross-sectional analysis of 15,888 Medicare beneficiaries aged 65 years and older who underwent a thyroidectomy in 2014. Of the thyroidectomies performed, 7,056 were partial and 8,382 were total thyroidectomies. They compared the frequency of partial and total thyroidectomies to total prostatectomy rates (high variation) and hospitalizations for hip fractures (low variation).
The stark variation in thyroidectomy outpaced those in hip fracture hospitalization (2.2-fold variation) and radical prostatectomy (5.6-fold variation) across U.S. hospital referral regions.
Higher rates of thyroidectomy were seen in Southern, Central, and certain urban regions of the United States.
But the variation in rates did not correlate with health care availability, socioeconomic status, or the availability of surgeons. This suggests that variation is caused by something other than disease burden. The researchers speculated that the “variability in thyroid surgery rates in areas with similar access to surgical services largely relates to local beliefs and practice patterns.”
The researchers also noted that the findings, which are based on Medicare data, may not be generalizable to young patients who account for more than half of all thyroidectomies performed in the United States.
The study was funded by the Department of Veterans Affairs and the Dartmouth Institute for Health Policy & Clinical Practice, with salary support from the National Institutes of Health. The researchers reported having no relevant conflicts of interest.
FROM JAMA OTOLARYNGOLOGY–HEAD & NECK SURGERY
Key clinical point:
Major finding: Thyroidectomy rates vary 6.2-fold across U.S. hospital referral regions.
Data source: A cross-sectional analysis of Medicare data for 15,888 patients in 2014.
Disclosures: This study was funded by the Department of Veterans Affairs and the Dartmouth Institute for Health Policy & Clinical Practice, with salary support from the National Institutes of Health. The researchers reported having no relevant conflicts of interest.
Better trials, more cooperation needed to improve continuous glucose monitoring devices
When continuous glucose monitoring (CGM) devices were first introduced, many thought they would revolutionize intensive insulin therapy for patients with diabetes. More than 15 years later, uptake is increasing but still remains low.
An expert working group convened by the (Diabetes Care. 2017 Oct 25. doi: 10.2337/dci17-0043).
“The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and health outcomes for more people with diabetes,” John R. Petrie, MD, of the University of Glasgow, Scotland, and members of the working group wrote in the joint scientific statement.
Barriers to the uptake of CGM devices include cost and “human factors” issues such as the need for more audible alarms and easier-to-read displays, according to the joint statement. A lack of standardization in displaying results and uncertainty over the best way to use CGM data are also obstacles to widespread adoption.
The working group called for a systematic premarketing and postapproval evaluation of CGM system performance, as well as greater investment in clinical trials, including head-to-head comparisons and large independent registry studies. Other recommendations include the need for standardization of glucose data reporting, improved consistency and accessibility of postmarketing safety reports, and increased communication and cooperation between the various stakeholder groups.
The most important recommendation from the working group is the call for stakeholders to cooperate and communicate regularly, said A. Jay Cohen, MD, medical director of the Endocrine Clinic in Memphis, Tenn.
“That’s going to drive the momentum of change that’s going to help patients, and it’s also going to drive innovation,” he said.
After reviewing the joint scientific statement, Dr. Cohen said he would strongly encourage collaboration between stakeholders in government, insurance, clinical practice, industry, and patients to advance the use of CGM systems.
“The CGM systems have been not evolutionary, but revolutionary, in improvement in care for persons with diabetes and their families,” Dr. Cohen said. “They are a game changer, and besides … this unequivocally saves employers and insurers money, so it’s very cost effective in a very intuitive way.”
The joint scientific statement is based on review of more than 50 data sources, including recent clinical trials, research abstracts, regulatory authority databases, manufacturing company documents, and the clinical experience of the committee members.
“The guidelines set forth by this scientific statement will greatly inform providers and further advance the standardization, accuracy, and safety of CGM systems,” William T. Cefalu, MD, chief scientific, medical, and mission officer of the ADA, said in a statement.
Most members of the working group have relationships with industry, but industry “is considered to have had no impact on the manuscript or its content by reviewers from the ADA and EASD.”
When continuous glucose monitoring (CGM) devices were first introduced, many thought they would revolutionize intensive insulin therapy for patients with diabetes. More than 15 years later, uptake is increasing but still remains low.
An expert working group convened by the (Diabetes Care. 2017 Oct 25. doi: 10.2337/dci17-0043).
“The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and health outcomes for more people with diabetes,” John R. Petrie, MD, of the University of Glasgow, Scotland, and members of the working group wrote in the joint scientific statement.
Barriers to the uptake of CGM devices include cost and “human factors” issues such as the need for more audible alarms and easier-to-read displays, according to the joint statement. A lack of standardization in displaying results and uncertainty over the best way to use CGM data are also obstacles to widespread adoption.
The working group called for a systematic premarketing and postapproval evaluation of CGM system performance, as well as greater investment in clinical trials, including head-to-head comparisons and large independent registry studies. Other recommendations include the need for standardization of glucose data reporting, improved consistency and accessibility of postmarketing safety reports, and increased communication and cooperation between the various stakeholder groups.
The most important recommendation from the working group is the call for stakeholders to cooperate and communicate regularly, said A. Jay Cohen, MD, medical director of the Endocrine Clinic in Memphis, Tenn.
“That’s going to drive the momentum of change that’s going to help patients, and it’s also going to drive innovation,” he said.
After reviewing the joint scientific statement, Dr. Cohen said he would strongly encourage collaboration between stakeholders in government, insurance, clinical practice, industry, and patients to advance the use of CGM systems.
“The CGM systems have been not evolutionary, but revolutionary, in improvement in care for persons with diabetes and their families,” Dr. Cohen said. “They are a game changer, and besides … this unequivocally saves employers and insurers money, so it’s very cost effective in a very intuitive way.”
The joint scientific statement is based on review of more than 50 data sources, including recent clinical trials, research abstracts, regulatory authority databases, manufacturing company documents, and the clinical experience of the committee members.
“The guidelines set forth by this scientific statement will greatly inform providers and further advance the standardization, accuracy, and safety of CGM systems,” William T. Cefalu, MD, chief scientific, medical, and mission officer of the ADA, said in a statement.
Most members of the working group have relationships with industry, but industry “is considered to have had no impact on the manuscript or its content by reviewers from the ADA and EASD.”
When continuous glucose monitoring (CGM) devices were first introduced, many thought they would revolutionize intensive insulin therapy for patients with diabetes. More than 15 years later, uptake is increasing but still remains low.
An expert working group convened by the (Diabetes Care. 2017 Oct 25. doi: 10.2337/dci17-0043).
“The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and health outcomes for more people with diabetes,” John R. Petrie, MD, of the University of Glasgow, Scotland, and members of the working group wrote in the joint scientific statement.
Barriers to the uptake of CGM devices include cost and “human factors” issues such as the need for more audible alarms and easier-to-read displays, according to the joint statement. A lack of standardization in displaying results and uncertainty over the best way to use CGM data are also obstacles to widespread adoption.
The working group called for a systematic premarketing and postapproval evaluation of CGM system performance, as well as greater investment in clinical trials, including head-to-head comparisons and large independent registry studies. Other recommendations include the need for standardization of glucose data reporting, improved consistency and accessibility of postmarketing safety reports, and increased communication and cooperation between the various stakeholder groups.
The most important recommendation from the working group is the call for stakeholders to cooperate and communicate regularly, said A. Jay Cohen, MD, medical director of the Endocrine Clinic in Memphis, Tenn.
“That’s going to drive the momentum of change that’s going to help patients, and it’s also going to drive innovation,” he said.
After reviewing the joint scientific statement, Dr. Cohen said he would strongly encourage collaboration between stakeholders in government, insurance, clinical practice, industry, and patients to advance the use of CGM systems.
“The CGM systems have been not evolutionary, but revolutionary, in improvement in care for persons with diabetes and their families,” Dr. Cohen said. “They are a game changer, and besides … this unequivocally saves employers and insurers money, so it’s very cost effective in a very intuitive way.”
The joint scientific statement is based on review of more than 50 data sources, including recent clinical trials, research abstracts, regulatory authority databases, manufacturing company documents, and the clinical experience of the committee members.
“The guidelines set forth by this scientific statement will greatly inform providers and further advance the standardization, accuracy, and safety of CGM systems,” William T. Cefalu, MD, chief scientific, medical, and mission officer of the ADA, said in a statement.
Most members of the working group have relationships with industry, but industry “is considered to have had no impact on the manuscript or its content by reviewers from the ADA and EASD.”
FROM DIABETES CARE
Generic, brand-name levothyroxine have similar cardiovascular outcomes
VICTORIA, B.C. – Hypothyroid patients have similar cardiovascular outcomes in the shorter term whether they take generic or brand-name levothyroxine, results of a retrospective propensity-matched cohort study reported at the annual meeting of the American Thyroid Association suggest.
Investigators led by Robert Smallridge, MD, an endocrinologist at the Mayo Clinic, in Jacksonville, Fla., used a large administrative database to study nearly 88,000 treatment-naive hypothyroid patients (most having benign thyroid disease) who started levothyroxine.
However, monthly total medication costs with the brand-name medication were more than twice those with the generic.
“I don’t think we are ready yet to say everybody ought to be on generic,” Dr. Smallridge said in an interview, citing the limited treatment duration captured in the study because patients switched medications or changed insurers. “But I think, at least in the short term, it’s giving us some data that we can build upon.”
He and his coinvestigators plan additional analyses looking at longer-term users, other types of thyroid hormone preparations, and the very small group of patients who had thyroid cancer.
“I primarily take care of cancer patients, and we purposely push these patients to slightly lower [thyroid-stimulating hormone levels] in general, which presumably is going to increase your risk of atrial fibrillation and could affect these events,” he said. “The numbers are somewhat smaller, clearly, but I’d like to see that explored also, to see if there is a difference between brand and generics in that subset who are probably getting a little bit more thyroid medication.”
Both hypothyroidism and its overtreatment with thyroid hormone therapy can increase cardiovascular risk, Dr. Smallridge noted.
For the study, the investigators analyzed data from a large administrative claims database (OptumLabs Data Warehouse) for the years 2006-2014. Patients having any prior use of any thyroid hormone preparation, amiodarone, or lithium were excluded. And patients were censored if they left the insurance plan, stopped treatment, or switched medication category.
The investigators identified 201,056 hypothyroid patients who started some type of thyroid hormone therapy. The majority (70.8%) started generic levothyroxine, and 22.1% started brand-name levothyroxine (Synthroid, Levoxyl, Tirosint, Unithroid). The small remaining group started another thyroid extract, triiodothyronine (T3), or a compounded preparation.
Primary care physicians were the main identifiable prescribers (60.3%), followed by endocrinologists (10.8%). “Endocrinologists tended to prescribe brand significantly more than the primary care physicians,” Dr. Smallridge said.
The investigators used propensity matching on a variety of factors (age, sex, race, census region, Charlson comorbidity index, year of index prescription, and a dozen baseline comorbidities) to compare patients starting brand-name versus generic levothyroxine. Outcomes were assessed during a median follow-up of 1 year (range, 0-9.3 years).
Event rates per 1,000 patient-years with branded versus generic levothyroxine were similar for atrial fibrillation (2.19 vs. 1.82; hazard ratio, 1.22, P = .19), myocardial infarction (1.83 vs. 2.12; HR, 0.86, P = .35), and congestive heart failure (2.00 vs. 2.27; HR, 0.88, P = .41). There was a borderline-significant difference on hospitalization for stroke, with marginally lower risk with brand-name levothyroxine (2.38 vs. 3.10; HR, 0.77; P = .05).
Findings were essentially the same in age-stratified analyses, splitting patients into subgroups younger and older than age 65.
When average 30-day costs were compared for users of branded versus generic levothyroxine, total cost for the branded drug was more than twice as high ($18.47 vs. $8.18).
“Thyroid preparations have been the most prescribed drug in the United States for several recent years. In the neighborhood of 25 million different patients a year take thyroid medications,” Dr. Smallridge said. “In terms of the dollars spent, it’s considerably less than some of the other drugs out there. But because of sheer numbers of patients, in terms of impact on health care dollars, it’s still a significant amount of money. And this is a lifelong treatment – once you go on thyroid hormones, you’re on them for life.”
The study had several strengths. “This is a very large, diverse, real-world population across the entire country with a wide range of ages,” Dr. Smallridge explained. “We got pharmacy claims documenting that they were continuing to get the refills, although we didn’t do pill counts, so we don’t know whether they were taking the medication. And a really important thing was the propensity score matching.”
At the same time, limitations included possible variations in coding and billing, and some residual confounding. “Key issues are that we need more data on longer-term follow-up, and we didn’t have lab values,” he added.
Dr. Smallridge reported that he had no relevant conflicts of interest.
VICTORIA, B.C. – Hypothyroid patients have similar cardiovascular outcomes in the shorter term whether they take generic or brand-name levothyroxine, results of a retrospective propensity-matched cohort study reported at the annual meeting of the American Thyroid Association suggest.
Investigators led by Robert Smallridge, MD, an endocrinologist at the Mayo Clinic, in Jacksonville, Fla., used a large administrative database to study nearly 88,000 treatment-naive hypothyroid patients (most having benign thyroid disease) who started levothyroxine.
However, monthly total medication costs with the brand-name medication were more than twice those with the generic.
“I don’t think we are ready yet to say everybody ought to be on generic,” Dr. Smallridge said in an interview, citing the limited treatment duration captured in the study because patients switched medications or changed insurers. “But I think, at least in the short term, it’s giving us some data that we can build upon.”
He and his coinvestigators plan additional analyses looking at longer-term users, other types of thyroid hormone preparations, and the very small group of patients who had thyroid cancer.
“I primarily take care of cancer patients, and we purposely push these patients to slightly lower [thyroid-stimulating hormone levels] in general, which presumably is going to increase your risk of atrial fibrillation and could affect these events,” he said. “The numbers are somewhat smaller, clearly, but I’d like to see that explored also, to see if there is a difference between brand and generics in that subset who are probably getting a little bit more thyroid medication.”
Both hypothyroidism and its overtreatment with thyroid hormone therapy can increase cardiovascular risk, Dr. Smallridge noted.
For the study, the investigators analyzed data from a large administrative claims database (OptumLabs Data Warehouse) for the years 2006-2014. Patients having any prior use of any thyroid hormone preparation, amiodarone, or lithium were excluded. And patients were censored if they left the insurance plan, stopped treatment, or switched medication category.
The investigators identified 201,056 hypothyroid patients who started some type of thyroid hormone therapy. The majority (70.8%) started generic levothyroxine, and 22.1% started brand-name levothyroxine (Synthroid, Levoxyl, Tirosint, Unithroid). The small remaining group started another thyroid extract, triiodothyronine (T3), or a compounded preparation.
Primary care physicians were the main identifiable prescribers (60.3%), followed by endocrinologists (10.8%). “Endocrinologists tended to prescribe brand significantly more than the primary care physicians,” Dr. Smallridge said.
The investigators used propensity matching on a variety of factors (age, sex, race, census region, Charlson comorbidity index, year of index prescription, and a dozen baseline comorbidities) to compare patients starting brand-name versus generic levothyroxine. Outcomes were assessed during a median follow-up of 1 year (range, 0-9.3 years).
Event rates per 1,000 patient-years with branded versus generic levothyroxine were similar for atrial fibrillation (2.19 vs. 1.82; hazard ratio, 1.22, P = .19), myocardial infarction (1.83 vs. 2.12; HR, 0.86, P = .35), and congestive heart failure (2.00 vs. 2.27; HR, 0.88, P = .41). There was a borderline-significant difference on hospitalization for stroke, with marginally lower risk with brand-name levothyroxine (2.38 vs. 3.10; HR, 0.77; P = .05).
Findings were essentially the same in age-stratified analyses, splitting patients into subgroups younger and older than age 65.
When average 30-day costs were compared for users of branded versus generic levothyroxine, total cost for the branded drug was more than twice as high ($18.47 vs. $8.18).
“Thyroid preparations have been the most prescribed drug in the United States for several recent years. In the neighborhood of 25 million different patients a year take thyroid medications,” Dr. Smallridge said. “In terms of the dollars spent, it’s considerably less than some of the other drugs out there. But because of sheer numbers of patients, in terms of impact on health care dollars, it’s still a significant amount of money. And this is a lifelong treatment – once you go on thyroid hormones, you’re on them for life.”
The study had several strengths. “This is a very large, diverse, real-world population across the entire country with a wide range of ages,” Dr. Smallridge explained. “We got pharmacy claims documenting that they were continuing to get the refills, although we didn’t do pill counts, so we don’t know whether they were taking the medication. And a really important thing was the propensity score matching.”
At the same time, limitations included possible variations in coding and billing, and some residual confounding. “Key issues are that we need more data on longer-term follow-up, and we didn’t have lab values,” he added.
Dr. Smallridge reported that he had no relevant conflicts of interest.
VICTORIA, B.C. – Hypothyroid patients have similar cardiovascular outcomes in the shorter term whether they take generic or brand-name levothyroxine, results of a retrospective propensity-matched cohort study reported at the annual meeting of the American Thyroid Association suggest.
Investigators led by Robert Smallridge, MD, an endocrinologist at the Mayo Clinic, in Jacksonville, Fla., used a large administrative database to study nearly 88,000 treatment-naive hypothyroid patients (most having benign thyroid disease) who started levothyroxine.
However, monthly total medication costs with the brand-name medication were more than twice those with the generic.
“I don’t think we are ready yet to say everybody ought to be on generic,” Dr. Smallridge said in an interview, citing the limited treatment duration captured in the study because patients switched medications or changed insurers. “But I think, at least in the short term, it’s giving us some data that we can build upon.”
He and his coinvestigators plan additional analyses looking at longer-term users, other types of thyroid hormone preparations, and the very small group of patients who had thyroid cancer.
“I primarily take care of cancer patients, and we purposely push these patients to slightly lower [thyroid-stimulating hormone levels] in general, which presumably is going to increase your risk of atrial fibrillation and could affect these events,” he said. “The numbers are somewhat smaller, clearly, but I’d like to see that explored also, to see if there is a difference between brand and generics in that subset who are probably getting a little bit more thyroid medication.”
Both hypothyroidism and its overtreatment with thyroid hormone therapy can increase cardiovascular risk, Dr. Smallridge noted.
For the study, the investigators analyzed data from a large administrative claims database (OptumLabs Data Warehouse) for the years 2006-2014. Patients having any prior use of any thyroid hormone preparation, amiodarone, or lithium were excluded. And patients were censored if they left the insurance plan, stopped treatment, or switched medication category.
The investigators identified 201,056 hypothyroid patients who started some type of thyroid hormone therapy. The majority (70.8%) started generic levothyroxine, and 22.1% started brand-name levothyroxine (Synthroid, Levoxyl, Tirosint, Unithroid). The small remaining group started another thyroid extract, triiodothyronine (T3), or a compounded preparation.
Primary care physicians were the main identifiable prescribers (60.3%), followed by endocrinologists (10.8%). “Endocrinologists tended to prescribe brand significantly more than the primary care physicians,” Dr. Smallridge said.
The investigators used propensity matching on a variety of factors (age, sex, race, census region, Charlson comorbidity index, year of index prescription, and a dozen baseline comorbidities) to compare patients starting brand-name versus generic levothyroxine. Outcomes were assessed during a median follow-up of 1 year (range, 0-9.3 years).
Event rates per 1,000 patient-years with branded versus generic levothyroxine were similar for atrial fibrillation (2.19 vs. 1.82; hazard ratio, 1.22, P = .19), myocardial infarction (1.83 vs. 2.12; HR, 0.86, P = .35), and congestive heart failure (2.00 vs. 2.27; HR, 0.88, P = .41). There was a borderline-significant difference on hospitalization for stroke, with marginally lower risk with brand-name levothyroxine (2.38 vs. 3.10; HR, 0.77; P = .05).
Findings were essentially the same in age-stratified analyses, splitting patients into subgroups younger and older than age 65.
When average 30-day costs were compared for users of branded versus generic levothyroxine, total cost for the branded drug was more than twice as high ($18.47 vs. $8.18).
“Thyroid preparations have been the most prescribed drug in the United States for several recent years. In the neighborhood of 25 million different patients a year take thyroid medications,” Dr. Smallridge said. “In terms of the dollars spent, it’s considerably less than some of the other drugs out there. But because of sheer numbers of patients, in terms of impact on health care dollars, it’s still a significant amount of money. And this is a lifelong treatment – once you go on thyroid hormones, you’re on them for life.”
The study had several strengths. “This is a very large, diverse, real-world population across the entire country with a wide range of ages,” Dr. Smallridge explained. “We got pharmacy claims documenting that they were continuing to get the refills, although we didn’t do pill counts, so we don’t know whether they were taking the medication. And a really important thing was the propensity score matching.”
At the same time, limitations included possible variations in coding and billing, and some residual confounding. “Key issues are that we need more data on longer-term follow-up, and we didn’t have lab values,” he added.
Dr. Smallridge reported that he had no relevant conflicts of interest.
AT ATA 2017
Key clinical point:
Major finding: Patients taking brand-name versus generic levothyroxine had similar risks of hospitalization for atrial fibrillation (HR, 1.22; P = .19), myocardial infarction (0.86; P = .35), congestive heart failure (0.88; P = .41), and stroke (0.77; P = .05).
Data source: A retrospective cohort study of 87,902 propensity-matched hypothyroid patients starting generic or brand-name levothyroxine.
Disclosures: Dr. Smallridge reported that he had no relevant conflicts of interest.
Rethinking lithium: It keeps patients with unipolar depression out of the hospital
PARIS – What’s the most effective medication for preventing rehospitalization in patients previously admitted for severe unipolar depression?
The answer, based upon a study of all 123,712 patients hospitalized for severe unipolar depression in Finland during 1987-2012, might come as a surprise. The medication that most effectively kept patients from returning to the hospital wasn’t a selective serotonin reuptake inhibitor (SSRI), a serotonin-norepinephrine reuptake inhibitor (SNRI), or an atypical antipsychotic. It was lithium, Markku Lahteenvuo, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
Using comprehensive nationwide databases, he and his coinvestigators followed these 123,712 hospitalized patients for a mean of 7.9 years, during which 49,146 of them had a total of 153,784 rehospitalizations for mental disorders. The investigators analyzed what psychotropic drugs the patients were taking when rehospitalized, as well as the drugs they were taking when they were out of hospital. Individuals served as their own controls in order to eliminate selection bias.
In an analysis adjusted for time since diagnosis of unipolar depression, the temporal order of prescribed drugs, and other concomitant medications, the use of lithium was associated with a 53% reduction in the risk of readmission, compared with nonuse.
Patients using lithium as monotherapy for their depression were 69% less likely to be rehospitalized than if they were not, whereas patients on lithium with antidepressants had a more modest 50% reduction in rehospitalization risk, reported Dr. Lahteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland in Kuopio.
After lithium, clozapine was the drug associated with the next lowest risk of rehospitalization for a mental disorder. Patients on that drug were 35% less likely to be rehospitalized; however, clozapine wasn’t widely prescribed in patients with severe unipolar depression.
Antidepressants as a broad class were associated with a statistically significant 10% increase in risk of rehospitalization for a mental disorder. But within that category there were a couple of exceptions: Amitriptyline, which was widely prescribed, particularly in the early years of the study period, was associated with a 25% reduction in rehospitalization, compared with no use. And doxepin was associated with a 15% reduction.
Antipsychotics were associated with an overall 16% increased risk of rehospitalization, compared with no use. But there were some notable exceptions within this class of drugs. Both quetiapine and aripiprazole were associated with an 18% risk reduction.
The investigators also analyzed all-cause rehospitalizations, including acute myocardial infarction and all other somatic diseases, as well as mental disorders. During follow-up, 98,662 patients who had been hospitalized for severe unipolar depression had a collective total of 592,926 all-cause rehospitalizations.
Dr. Lahteenvuo said he had expected that lithium’s strong showing in preventing psychiatric rehospitalization might be offset by an increased risk of hospitalization for other conditions, because of the drug’s well-established association with thyroid, renal, and other toxicities. But that was not the case. Patients on lithium without antidepressants were 49% less likely to have an all-cause hospitalization than when they were not using the drug, and patients on lithium with antidepressants had a 42% reduction in risk.
”It seems that lithium also shielded the patients from going to the hospital for any somatic reason. So lithium seems to be safe and prevents various somatic hospitalizations as well. Whether that’s due to the drug’s enhancement of your ability to live your life, eat healthy, exercise, and give you energy to have good lifestyle habits, or it actually has an anti-inflammatory effect or other disease-modifying effect, we do not know,” Dr. Lahteenvuo said.
Lithium has traditionally been prescribed mainly as third-line therapy in treatment-refractory patients for severe unipolar depression. The Finnish data suggest it’s time to reconsider that strategy.
“We think lithium should be considered for a wider audience, keeping in mind of course that it can cause thyroid and kidney toxicity,” Dr. Lahteenvuo said.
Patients taking clozapine were 30% less likely to have an all-cause hospitalization than nonusers. Aripiprazole was associated with a 21% reduction in risk, quetiapine had a 12% risk reduction, amitriptyline had an 11% risk reduction, and doxepin had a 12% risk reduction.
In contrast, all-cause hospitalization was 12% more likely when patients were taking chronic benzodiazepines and 8% more likely while on hypnotics.
The full study results were published in the Lancet Psychiatry (2017 Jul;4[7]:547-53).
Dr. Lahteenvuo reported having no financial conflicts of interest related to the study, which was funded by the Finnish Ministry of Health.
PARIS – What’s the most effective medication for preventing rehospitalization in patients previously admitted for severe unipolar depression?
The answer, based upon a study of all 123,712 patients hospitalized for severe unipolar depression in Finland during 1987-2012, might come as a surprise. The medication that most effectively kept patients from returning to the hospital wasn’t a selective serotonin reuptake inhibitor (SSRI), a serotonin-norepinephrine reuptake inhibitor (SNRI), or an atypical antipsychotic. It was lithium, Markku Lahteenvuo, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
Using comprehensive nationwide databases, he and his coinvestigators followed these 123,712 hospitalized patients for a mean of 7.9 years, during which 49,146 of them had a total of 153,784 rehospitalizations for mental disorders. The investigators analyzed what psychotropic drugs the patients were taking when rehospitalized, as well as the drugs they were taking when they were out of hospital. Individuals served as their own controls in order to eliminate selection bias.
In an analysis adjusted for time since diagnosis of unipolar depression, the temporal order of prescribed drugs, and other concomitant medications, the use of lithium was associated with a 53% reduction in the risk of readmission, compared with nonuse.
Patients using lithium as monotherapy for their depression were 69% less likely to be rehospitalized than if they were not, whereas patients on lithium with antidepressants had a more modest 50% reduction in rehospitalization risk, reported Dr. Lahteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland in Kuopio.
After lithium, clozapine was the drug associated with the next lowest risk of rehospitalization for a mental disorder. Patients on that drug were 35% less likely to be rehospitalized; however, clozapine wasn’t widely prescribed in patients with severe unipolar depression.
Antidepressants as a broad class were associated with a statistically significant 10% increase in risk of rehospitalization for a mental disorder. But within that category there were a couple of exceptions: Amitriptyline, which was widely prescribed, particularly in the early years of the study period, was associated with a 25% reduction in rehospitalization, compared with no use. And doxepin was associated with a 15% reduction.
Antipsychotics were associated with an overall 16% increased risk of rehospitalization, compared with no use. But there were some notable exceptions within this class of drugs. Both quetiapine and aripiprazole were associated with an 18% risk reduction.
The investigators also analyzed all-cause rehospitalizations, including acute myocardial infarction and all other somatic diseases, as well as mental disorders. During follow-up, 98,662 patients who had been hospitalized for severe unipolar depression had a collective total of 592,926 all-cause rehospitalizations.
Dr. Lahteenvuo said he had expected that lithium’s strong showing in preventing psychiatric rehospitalization might be offset by an increased risk of hospitalization for other conditions, because of the drug’s well-established association with thyroid, renal, and other toxicities. But that was not the case. Patients on lithium without antidepressants were 49% less likely to have an all-cause hospitalization than when they were not using the drug, and patients on lithium with antidepressants had a 42% reduction in risk.
”It seems that lithium also shielded the patients from going to the hospital for any somatic reason. So lithium seems to be safe and prevents various somatic hospitalizations as well. Whether that’s due to the drug’s enhancement of your ability to live your life, eat healthy, exercise, and give you energy to have good lifestyle habits, or it actually has an anti-inflammatory effect or other disease-modifying effect, we do not know,” Dr. Lahteenvuo said.
Lithium has traditionally been prescribed mainly as third-line therapy in treatment-refractory patients for severe unipolar depression. The Finnish data suggest it’s time to reconsider that strategy.
“We think lithium should be considered for a wider audience, keeping in mind of course that it can cause thyroid and kidney toxicity,” Dr. Lahteenvuo said.
Patients taking clozapine were 30% less likely to have an all-cause hospitalization than nonusers. Aripiprazole was associated with a 21% reduction in risk, quetiapine had a 12% risk reduction, amitriptyline had an 11% risk reduction, and doxepin had a 12% risk reduction.
In contrast, all-cause hospitalization was 12% more likely when patients were taking chronic benzodiazepines and 8% more likely while on hypnotics.
The full study results were published in the Lancet Psychiatry (2017 Jul;4[7]:547-53).
Dr. Lahteenvuo reported having no financial conflicts of interest related to the study, which was funded by the Finnish Ministry of Health.
PARIS – What’s the most effective medication for preventing rehospitalization in patients previously admitted for severe unipolar depression?
The answer, based upon a study of all 123,712 patients hospitalized for severe unipolar depression in Finland during 1987-2012, might come as a surprise. The medication that most effectively kept patients from returning to the hospital wasn’t a selective serotonin reuptake inhibitor (SSRI), a serotonin-norepinephrine reuptake inhibitor (SNRI), or an atypical antipsychotic. It was lithium, Markku Lahteenvuo, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
Using comprehensive nationwide databases, he and his coinvestigators followed these 123,712 hospitalized patients for a mean of 7.9 years, during which 49,146 of them had a total of 153,784 rehospitalizations for mental disorders. The investigators analyzed what psychotropic drugs the patients were taking when rehospitalized, as well as the drugs they were taking when they were out of hospital. Individuals served as their own controls in order to eliminate selection bias.
In an analysis adjusted for time since diagnosis of unipolar depression, the temporal order of prescribed drugs, and other concomitant medications, the use of lithium was associated with a 53% reduction in the risk of readmission, compared with nonuse.
Patients using lithium as monotherapy for their depression were 69% less likely to be rehospitalized than if they were not, whereas patients on lithium with antidepressants had a more modest 50% reduction in rehospitalization risk, reported Dr. Lahteenvuo, a forensic psychiatrist at Niuvanniemi Hospital and the University of Eastern Finland in Kuopio.
After lithium, clozapine was the drug associated with the next lowest risk of rehospitalization for a mental disorder. Patients on that drug were 35% less likely to be rehospitalized; however, clozapine wasn’t widely prescribed in patients with severe unipolar depression.
Antidepressants as a broad class were associated with a statistically significant 10% increase in risk of rehospitalization for a mental disorder. But within that category there were a couple of exceptions: Amitriptyline, which was widely prescribed, particularly in the early years of the study period, was associated with a 25% reduction in rehospitalization, compared with no use. And doxepin was associated with a 15% reduction.
Antipsychotics were associated with an overall 16% increased risk of rehospitalization, compared with no use. But there were some notable exceptions within this class of drugs. Both quetiapine and aripiprazole were associated with an 18% risk reduction.
The investigators also analyzed all-cause rehospitalizations, including acute myocardial infarction and all other somatic diseases, as well as mental disorders. During follow-up, 98,662 patients who had been hospitalized for severe unipolar depression had a collective total of 592,926 all-cause rehospitalizations.
Dr. Lahteenvuo said he had expected that lithium’s strong showing in preventing psychiatric rehospitalization might be offset by an increased risk of hospitalization for other conditions, because of the drug’s well-established association with thyroid, renal, and other toxicities. But that was not the case. Patients on lithium without antidepressants were 49% less likely to have an all-cause hospitalization than when they were not using the drug, and patients on lithium with antidepressants had a 42% reduction in risk.
”It seems that lithium also shielded the patients from going to the hospital for any somatic reason. So lithium seems to be safe and prevents various somatic hospitalizations as well. Whether that’s due to the drug’s enhancement of your ability to live your life, eat healthy, exercise, and give you energy to have good lifestyle habits, or it actually has an anti-inflammatory effect or other disease-modifying effect, we do not know,” Dr. Lahteenvuo said.
Lithium has traditionally been prescribed mainly as third-line therapy in treatment-refractory patients for severe unipolar depression. The Finnish data suggest it’s time to reconsider that strategy.
“We think lithium should be considered for a wider audience, keeping in mind of course that it can cause thyroid and kidney toxicity,” Dr. Lahteenvuo said.
Patients taking clozapine were 30% less likely to have an all-cause hospitalization than nonusers. Aripiprazole was associated with a 21% reduction in risk, quetiapine had a 12% risk reduction, amitriptyline had an 11% risk reduction, and doxepin had a 12% risk reduction.
In contrast, all-cause hospitalization was 12% more likely when patients were taking chronic benzodiazepines and 8% more likely while on hypnotics.
The full study results were published in the Lancet Psychiatry (2017 Jul;4[7]:547-53).
Dr. Lahteenvuo reported having no financial conflicts of interest related to the study, which was funded by the Finnish Ministry of Health.
AT THE ECNP CONGRESS
Key clinical point:
Major finding: Patients on lithium alone were 69% less likely to be rehospitalized for a mental disorder than nonusers.
Data source: This cohort study included all 123,712 Finnish patients who were hospitalized for severe unipolar depression during 1987-2012, along with rehospitalizations during a mean 7.9 years of follow-up.
Disclosures: The study was funded by the Finnish Ministry of Health. The presenter reported having no financial conflicts.
Early referral recommended for high-risk port-wine stain cases
In high-risk port-wine stain phenotypes – forehead, hemifacial, and median – early referral to a pediatric neurologist is the best way to enable early symptom recognition of Sturge-Weber syndrome (SWS), according to results of a literature review.
If imaging is desired, electroencephalography (EEG) is cheaper and more minimally invasive than MRI (Pediatr Dermatol. 2017 Oct 16. doi: 10.1111/pde.13304).
Of the 34 studies analyzed, none examined the correlation between early detection of presymptomatic SWS and earlier seizure detection. There were also no data to verify improved outcomes with early detection, Michaela Zallmann, MD, of the department of dermatology at Eastern Health, Monash University, Box Hill, Australia, and her coauthors reported. While this indicates a need for further studies, it also shows a need for improved education and clinical monitoring as standard practice.
Additionally, negative imaging results do not obviate the possibility of SWS diagnosis, the investigators reported. In the studies that recorded false negatives, MRI was negative in 3%-6% of infants who later became symptomatic. Of the seven infants with false-negative results, four were less than 6 months old when the initial imaging was conducted. The investigators noted that it is not known at what age a negative MRI can reliably exclude SWS.
When imaging was used for early detection, EEG was shown to be safer and less expensive than MRI, according to the review. Of children who were not anesthetized for MRI, 30%-50% showed considerable distress, while EEG was shown to be minimally invasive. Findings from a retrospective chart review show that 14 MRIs were performed to detect one asymptomatic case of SWS, costing $11,768. In comparison, EEG costs $87 for a routine outpatient study.
“Demonstrating brain involvement on MRI in infants with high-risk PWS may facilitate more stringent counseling and monitoring, but … a negative MRI does not obviate the need for neurologic counseling and monitoring,” the investigators wrote. “Allaying anxiety about diagnostic uncertainty is not achieved using a scan but through detailed education, appropriate clinical monitoring, and nuanced reassurance.”
The investigators did not report any financial disclosures.
In high-risk port-wine stain phenotypes – forehead, hemifacial, and median – early referral to a pediatric neurologist is the best way to enable early symptom recognition of Sturge-Weber syndrome (SWS), according to results of a literature review.
If imaging is desired, electroencephalography (EEG) is cheaper and more minimally invasive than MRI (Pediatr Dermatol. 2017 Oct 16. doi: 10.1111/pde.13304).
Of the 34 studies analyzed, none examined the correlation between early detection of presymptomatic SWS and earlier seizure detection. There were also no data to verify improved outcomes with early detection, Michaela Zallmann, MD, of the department of dermatology at Eastern Health, Monash University, Box Hill, Australia, and her coauthors reported. While this indicates a need for further studies, it also shows a need for improved education and clinical monitoring as standard practice.
Additionally, negative imaging results do not obviate the possibility of SWS diagnosis, the investigators reported. In the studies that recorded false negatives, MRI was negative in 3%-6% of infants who later became symptomatic. Of the seven infants with false-negative results, four were less than 6 months old when the initial imaging was conducted. The investigators noted that it is not known at what age a negative MRI can reliably exclude SWS.
When imaging was used for early detection, EEG was shown to be safer and less expensive than MRI, according to the review. Of children who were not anesthetized for MRI, 30%-50% showed considerable distress, while EEG was shown to be minimally invasive. Findings from a retrospective chart review show that 14 MRIs were performed to detect one asymptomatic case of SWS, costing $11,768. In comparison, EEG costs $87 for a routine outpatient study.
“Demonstrating brain involvement on MRI in infants with high-risk PWS may facilitate more stringent counseling and monitoring, but … a negative MRI does not obviate the need for neurologic counseling and monitoring,” the investigators wrote. “Allaying anxiety about diagnostic uncertainty is not achieved using a scan but through detailed education, appropriate clinical monitoring, and nuanced reassurance.”
The investigators did not report any financial disclosures.
In high-risk port-wine stain phenotypes – forehead, hemifacial, and median – early referral to a pediatric neurologist is the best way to enable early symptom recognition of Sturge-Weber syndrome (SWS), according to results of a literature review.
If imaging is desired, electroencephalography (EEG) is cheaper and more minimally invasive than MRI (Pediatr Dermatol. 2017 Oct 16. doi: 10.1111/pde.13304).
Of the 34 studies analyzed, none examined the correlation between early detection of presymptomatic SWS and earlier seizure detection. There were also no data to verify improved outcomes with early detection, Michaela Zallmann, MD, of the department of dermatology at Eastern Health, Monash University, Box Hill, Australia, and her coauthors reported. While this indicates a need for further studies, it also shows a need for improved education and clinical monitoring as standard practice.
Additionally, negative imaging results do not obviate the possibility of SWS diagnosis, the investigators reported. In the studies that recorded false negatives, MRI was negative in 3%-6% of infants who later became symptomatic. Of the seven infants with false-negative results, four were less than 6 months old when the initial imaging was conducted. The investigators noted that it is not known at what age a negative MRI can reliably exclude SWS.
When imaging was used for early detection, EEG was shown to be safer and less expensive than MRI, according to the review. Of children who were not anesthetized for MRI, 30%-50% showed considerable distress, while EEG was shown to be minimally invasive. Findings from a retrospective chart review show that 14 MRIs were performed to detect one asymptomatic case of SWS, costing $11,768. In comparison, EEG costs $87 for a routine outpatient study.
“Demonstrating brain involvement on MRI in infants with high-risk PWS may facilitate more stringent counseling and monitoring, but … a negative MRI does not obviate the need for neurologic counseling and monitoring,” the investigators wrote. “Allaying anxiety about diagnostic uncertainty is not achieved using a scan but through detailed education, appropriate clinical monitoring, and nuanced reassurance.”
The investigators did not report any financial disclosures.
Key clinical point:
Major finding: To identify one case of Sturge-Weber syndrome, MRI cost $11,768, compared with $87 for a routine outpatient EEG.
Data source: A literature review of 34 articles.
Disclosures: The investigators did not report any financial disclosures.
Lumateperone shows broad phase 3 potential for psychiatric disorders
PARIS – including Alzheimer’s disease, on the strength of strong performances in phase 2 studies, Cedric O’Gorman, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems, providing a unique mechanism of action well-suited for treatment of a range of neuropsychiatric disorders, observed Dr. O’Gorman, who was vice president of medical affairs at the drug’s developer, Intra-Cellular Therapies during the ECNP congress and is now senior vice president for clinical development and medical affairs at Axsome Therapeutics in New York.
At lower doses, lumateperone is a potent serotonin 5-HT2A receptor antagonist that shows promise as a treatment for primary insomnia as well as agitation and aggression in elderly patients with dementia. As the dose increases, lumateperone also serves as a mesolimbic and mesocortical dopamine receptor phosphoprotein modulator with dual properties, acting at the level of the dopamine D2 receptor both as a presynaptic partial agonist and a postsynaptic antagonist.
The drug also enhances NMDA- and AMPA-induced currents in medial prefrontal cortex pyramidal neurons via activation of the D1 receptor. These attributes provide antipsychotic and antidepressant efficacy.
Positron emission tomography studies in patients with schizophrenia have shown that lumateperone at 60 mg once daily effectively reduced psychosis symptoms at roughly 40% striatal D2 receptor occupancy, which is much lower than the occupancy level required by approved antipsychotic drugs. This attribute, coupled with the drug’s potent effects on serotonin 5-HT2A receptors, serotonin transporters, and D1 receptors, probably accounts for lumateperone’s antipsychotic efficacy and accompanying improved psychosocial function and minimal motor disturbances as demonstrated in the clinical trials, according to Dr. O’Gorman.
The two randomized, double-blind, multicenter, placebo-controlled phase 3 trials in schizophrenia totaled 1,146 patients. The trials included an arm in which patients were randomized to risperidone (Risperdal) at 4 mg/day. The lumateperone and risperidone groups showed similar improvement as measured by the Positive and Negative Syndrome Scale score.
However, lumateperone had a better safety profile, with significantly less weight gain than in the risperidone group. Moreover, lumateperone-treated patients didn’t experience the adverse changes in blood glucose, triglycerides, total cholesterol, and prolactin observed in the risperidone group.
The safety profile of lumateperone as documented in the various clinical trials to date is similar to placebo, Dr. O’Gorman reported.
PARIS – including Alzheimer’s disease, on the strength of strong performances in phase 2 studies, Cedric O’Gorman, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems, providing a unique mechanism of action well-suited for treatment of a range of neuropsychiatric disorders, observed Dr. O’Gorman, who was vice president of medical affairs at the drug’s developer, Intra-Cellular Therapies during the ECNP congress and is now senior vice president for clinical development and medical affairs at Axsome Therapeutics in New York.
At lower doses, lumateperone is a potent serotonin 5-HT2A receptor antagonist that shows promise as a treatment for primary insomnia as well as agitation and aggression in elderly patients with dementia. As the dose increases, lumateperone also serves as a mesolimbic and mesocortical dopamine receptor phosphoprotein modulator with dual properties, acting at the level of the dopamine D2 receptor both as a presynaptic partial agonist and a postsynaptic antagonist.
The drug also enhances NMDA- and AMPA-induced currents in medial prefrontal cortex pyramidal neurons via activation of the D1 receptor. These attributes provide antipsychotic and antidepressant efficacy.
Positron emission tomography studies in patients with schizophrenia have shown that lumateperone at 60 mg once daily effectively reduced psychosis symptoms at roughly 40% striatal D2 receptor occupancy, which is much lower than the occupancy level required by approved antipsychotic drugs. This attribute, coupled with the drug’s potent effects on serotonin 5-HT2A receptors, serotonin transporters, and D1 receptors, probably accounts for lumateperone’s antipsychotic efficacy and accompanying improved psychosocial function and minimal motor disturbances as demonstrated in the clinical trials, according to Dr. O’Gorman.
The two randomized, double-blind, multicenter, placebo-controlled phase 3 trials in schizophrenia totaled 1,146 patients. The trials included an arm in which patients were randomized to risperidone (Risperdal) at 4 mg/day. The lumateperone and risperidone groups showed similar improvement as measured by the Positive and Negative Syndrome Scale score.
However, lumateperone had a better safety profile, with significantly less weight gain than in the risperidone group. Moreover, lumateperone-treated patients didn’t experience the adverse changes in blood glucose, triglycerides, total cholesterol, and prolactin observed in the risperidone group.
The safety profile of lumateperone as documented in the various clinical trials to date is similar to placebo, Dr. O’Gorman reported.
PARIS – including Alzheimer’s disease, on the strength of strong performances in phase 2 studies, Cedric O’Gorman, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems, providing a unique mechanism of action well-suited for treatment of a range of neuropsychiatric disorders, observed Dr. O’Gorman, who was vice president of medical affairs at the drug’s developer, Intra-Cellular Therapies during the ECNP congress and is now senior vice president for clinical development and medical affairs at Axsome Therapeutics in New York.
At lower doses, lumateperone is a potent serotonin 5-HT2A receptor antagonist that shows promise as a treatment for primary insomnia as well as agitation and aggression in elderly patients with dementia. As the dose increases, lumateperone also serves as a mesolimbic and mesocortical dopamine receptor phosphoprotein modulator with dual properties, acting at the level of the dopamine D2 receptor both as a presynaptic partial agonist and a postsynaptic antagonist.
The drug also enhances NMDA- and AMPA-induced currents in medial prefrontal cortex pyramidal neurons via activation of the D1 receptor. These attributes provide antipsychotic and antidepressant efficacy.
Positron emission tomography studies in patients with schizophrenia have shown that lumateperone at 60 mg once daily effectively reduced psychosis symptoms at roughly 40% striatal D2 receptor occupancy, which is much lower than the occupancy level required by approved antipsychotic drugs. This attribute, coupled with the drug’s potent effects on serotonin 5-HT2A receptors, serotonin transporters, and D1 receptors, probably accounts for lumateperone’s antipsychotic efficacy and accompanying improved psychosocial function and minimal motor disturbances as demonstrated in the clinical trials, according to Dr. O’Gorman.
The two randomized, double-blind, multicenter, placebo-controlled phase 3 trials in schizophrenia totaled 1,146 patients. The trials included an arm in which patients were randomized to risperidone (Risperdal) at 4 mg/day. The lumateperone and risperidone groups showed similar improvement as measured by the Positive and Negative Syndrome Scale score.
However, lumateperone had a better safety profile, with significantly less weight gain than in the risperidone group. Moreover, lumateperone-treated patients didn’t experience the adverse changes in blood glucose, triglycerides, total cholesterol, and prolactin observed in the risperidone group.
The safety profile of lumateperone as documented in the various clinical trials to date is similar to placebo, Dr. O’Gorman reported.
EXPERT ANALYSIS FROM THE ECNP CONGRESS
Beyond the Kegel: the who, why, and how of pelvic floor PT
PHILADELPHIA – When a woman is referred for pelvic floor physical therapy, what’s involved? Is there evidence behind the treatments, and what exactly does pelvic floor therapy look like?
Denise Hartzell Leggin, a physical therapist who specializes in pelvic floor dysfunction, reviewed how the female pelvic floor can change with age, and provided the rationale for pelvic floor physical therapy (PT) at the annual meeting of the North American Menopause Society.
“Physical therapists treat musculoskeletal and neuromuscular dysfunctions,” said Ms. Hartzell Leggin. So, when a physician suspects a musculoskeletal cause for pelvic floor dysfunction, a PT referral may be appropriate, she said.
Why refer for PT?
As part of the aging process, pelvic floor dysfunction can coexist with the genitourinary syndrome of menopause (GSM), said Ms. Hartzell. Though the pathophysiology is not always clear, aging does have some effect on the pelvic floor musculature and, together with GSM, can contribute to women’s urogenital symptoms in later life.
These symptoms, she said, can be the harbingers of “a host of clinical conditions,” including urinary incontinence and fecal incontinence, constipation, and bladder-emptying problems. Also, changes in the pelvic musculature from childbirth, surgeries, and hypotonicity or hypertonicity can contribute to sexual dysfunction in later life, said Ms. Hartzell Leggin, who is affiliated with Good Shepherd Penn Partners and in private practice in the Philadelphia area.
The musculature of the pelvic floor functions as more than a bowl for carrying the pelvic organs, Ms. Hartzell Leggin said. The collective muscles and fascia form a sling that fills in the pelvic ring and functions as an integrated system with constant resting tone. But the musculature is also active and interactive.
“The diaphragm and the pelvic floor move in symmetry during respiration,” and pelvic floor tone tightens in anticipation of increased intra-abdominal pressure from a cough, a sneeze, or even a laugh. “These are active structures – the brain can talk to the pelvic floor and make it do something,” she said.
Who’s a good candidate?
Looking at risk factors for pelvic organ prolapse alone, Ms. Hartzell Leggin said these can include age, body mass index, a history of occupational or recreational heavy lifting, chronic cough, and even genetics.
However, one of the most significant risk factors for prolapse of pelvic organs is simply having had a vaginal delivery. Up to 50% of women who have delivered a child vaginally may eventually have some degree of pelvic organ prolapse, though not all women will be symptomatic, Ms. Hartzell Leggin said.
Since postsurgical pelvic organ prolapse rates may top 30% within 2 years, an initial referral for pelvic floor PT is a rational conservative approach, she said. And even if a patient progresses to surgery, PT may be a useful adjunct.
Pelvic floor dysfunction may also be considered if a diastasis recti is discovered on physical exam, or if the patient reports a linear abdominal bulge. Patients with diastasis recti are more likely to have pelvic floor dysfunction than the general population, she said, so it’s worth asking about any related symptoms.
For voiding issues, “conservative treatment is first-line,” said Ms. Hartzell Leggin, so a PT referral for pelvic floor therapy and, in some cases, some behavioral retraining can help with issues of urinary frequency and urgency. These are options that may be considered before prescribing anticholinergic medication, she said.
How does pelvic floor PT work?
When a physician refers a patient for pelvic floor PT, what’s the process? The physical therapy evaluation will begin with history taking, including the chief complaint, past medical and surgical history, and an obstetric/gynecologic/sexual history, said Ms. Hartzell Leggin. Medications are also reviewed.
The physical therapist’s examination should encompass a thorough orthopedic examination, with attention to the lumbar spine and hips, and posture and gait. An external and internal examination of the pelvic floor will look for muscle tone at rest and with strain, and for any defects or prolapse.
Pelvic floor strength is assessed according to ability to contract, with some assessment of strength available through palpation. More quantitative means may include manometry, dynamometry, or the use of progressive weighted vaginal cones.
There’s no single standardized measurement tool to assess pelvic floor strength. Palpation is a valuable tool for an experienced clinician, and it also can provide real-time feedback to the patient as she becomes more aware of her pelvic floor. The discipline is moving toward more standardized terminology, with several reporting scales now available to report pelvic floor strength, said Ms. Hartzell Leggin.
The Pelvic Floor Distress Inventory is a validated tool that captures information about the impact of pelvic floor dysfunction on a patient’s daily functioning. “I think I capture a lot when my patient comes in and completes that form,” said Ms. Hartzell Leggin. The Genitourinary Pain Index is another validated tool that measures urinary symptoms, pain, and associated quality of life impacts. Patients may be asked to keep a home therapy and symptom or voiding diary for additional information.
The pelvic floor PT treatment algorithm will vary, depending on whether there’s underlying hypertonicity or hypotonicity, but will involve pelvic floor exercises, soft tissue mobilization, and consideration of a variety of modalities including electrical stimulation and ultrasound. For hypertonicity, vaginal dilators may be used, while weighted vaginal cones may be used for hypotonicity.
Physical therapists should know when to refer a patient back to a physician and should always work as part of an interdisciplinary team, she said.
Ms. Hartzell Leggin reported that she is the president of Elite Rehabilitation Services in Audubon, Pa.
[email protected]
On Twitter @karioakes
PHILADELPHIA – When a woman is referred for pelvic floor physical therapy, what’s involved? Is there evidence behind the treatments, and what exactly does pelvic floor therapy look like?
Denise Hartzell Leggin, a physical therapist who specializes in pelvic floor dysfunction, reviewed how the female pelvic floor can change with age, and provided the rationale for pelvic floor physical therapy (PT) at the annual meeting of the North American Menopause Society.
“Physical therapists treat musculoskeletal and neuromuscular dysfunctions,” said Ms. Hartzell Leggin. So, when a physician suspects a musculoskeletal cause for pelvic floor dysfunction, a PT referral may be appropriate, she said.
Why refer for PT?
As part of the aging process, pelvic floor dysfunction can coexist with the genitourinary syndrome of menopause (GSM), said Ms. Hartzell. Though the pathophysiology is not always clear, aging does have some effect on the pelvic floor musculature and, together with GSM, can contribute to women’s urogenital symptoms in later life.
These symptoms, she said, can be the harbingers of “a host of clinical conditions,” including urinary incontinence and fecal incontinence, constipation, and bladder-emptying problems. Also, changes in the pelvic musculature from childbirth, surgeries, and hypotonicity or hypertonicity can contribute to sexual dysfunction in later life, said Ms. Hartzell Leggin, who is affiliated with Good Shepherd Penn Partners and in private practice in the Philadelphia area.
The musculature of the pelvic floor functions as more than a bowl for carrying the pelvic organs, Ms. Hartzell Leggin said. The collective muscles and fascia form a sling that fills in the pelvic ring and functions as an integrated system with constant resting tone. But the musculature is also active and interactive.
“The diaphragm and the pelvic floor move in symmetry during respiration,” and pelvic floor tone tightens in anticipation of increased intra-abdominal pressure from a cough, a sneeze, or even a laugh. “These are active structures – the brain can talk to the pelvic floor and make it do something,” she said.
Who’s a good candidate?
Looking at risk factors for pelvic organ prolapse alone, Ms. Hartzell Leggin said these can include age, body mass index, a history of occupational or recreational heavy lifting, chronic cough, and even genetics.
However, one of the most significant risk factors for prolapse of pelvic organs is simply having had a vaginal delivery. Up to 50% of women who have delivered a child vaginally may eventually have some degree of pelvic organ prolapse, though not all women will be symptomatic, Ms. Hartzell Leggin said.
Since postsurgical pelvic organ prolapse rates may top 30% within 2 years, an initial referral for pelvic floor PT is a rational conservative approach, she said. And even if a patient progresses to surgery, PT may be a useful adjunct.
Pelvic floor dysfunction may also be considered if a diastasis recti is discovered on physical exam, or if the patient reports a linear abdominal bulge. Patients with diastasis recti are more likely to have pelvic floor dysfunction than the general population, she said, so it’s worth asking about any related symptoms.
For voiding issues, “conservative treatment is first-line,” said Ms. Hartzell Leggin, so a PT referral for pelvic floor therapy and, in some cases, some behavioral retraining can help with issues of urinary frequency and urgency. These are options that may be considered before prescribing anticholinergic medication, she said.
How does pelvic floor PT work?
When a physician refers a patient for pelvic floor PT, what’s the process? The physical therapy evaluation will begin with history taking, including the chief complaint, past medical and surgical history, and an obstetric/gynecologic/sexual history, said Ms. Hartzell Leggin. Medications are also reviewed.
The physical therapist’s examination should encompass a thorough orthopedic examination, with attention to the lumbar spine and hips, and posture and gait. An external and internal examination of the pelvic floor will look for muscle tone at rest and with strain, and for any defects or prolapse.
Pelvic floor strength is assessed according to ability to contract, with some assessment of strength available through palpation. More quantitative means may include manometry, dynamometry, or the use of progressive weighted vaginal cones.
There’s no single standardized measurement tool to assess pelvic floor strength. Palpation is a valuable tool for an experienced clinician, and it also can provide real-time feedback to the patient as she becomes more aware of her pelvic floor. The discipline is moving toward more standardized terminology, with several reporting scales now available to report pelvic floor strength, said Ms. Hartzell Leggin.
The Pelvic Floor Distress Inventory is a validated tool that captures information about the impact of pelvic floor dysfunction on a patient’s daily functioning. “I think I capture a lot when my patient comes in and completes that form,” said Ms. Hartzell Leggin. The Genitourinary Pain Index is another validated tool that measures urinary symptoms, pain, and associated quality of life impacts. Patients may be asked to keep a home therapy and symptom or voiding diary for additional information.
The pelvic floor PT treatment algorithm will vary, depending on whether there’s underlying hypertonicity or hypotonicity, but will involve pelvic floor exercises, soft tissue mobilization, and consideration of a variety of modalities including electrical stimulation and ultrasound. For hypertonicity, vaginal dilators may be used, while weighted vaginal cones may be used for hypotonicity.
Physical therapists should know when to refer a patient back to a physician and should always work as part of an interdisciplinary team, she said.
Ms. Hartzell Leggin reported that she is the president of Elite Rehabilitation Services in Audubon, Pa.
[email protected]
On Twitter @karioakes
PHILADELPHIA – When a woman is referred for pelvic floor physical therapy, what’s involved? Is there evidence behind the treatments, and what exactly does pelvic floor therapy look like?
Denise Hartzell Leggin, a physical therapist who specializes in pelvic floor dysfunction, reviewed how the female pelvic floor can change with age, and provided the rationale for pelvic floor physical therapy (PT) at the annual meeting of the North American Menopause Society.
“Physical therapists treat musculoskeletal and neuromuscular dysfunctions,” said Ms. Hartzell Leggin. So, when a physician suspects a musculoskeletal cause for pelvic floor dysfunction, a PT referral may be appropriate, she said.
Why refer for PT?
As part of the aging process, pelvic floor dysfunction can coexist with the genitourinary syndrome of menopause (GSM), said Ms. Hartzell. Though the pathophysiology is not always clear, aging does have some effect on the pelvic floor musculature and, together with GSM, can contribute to women’s urogenital symptoms in later life.
These symptoms, she said, can be the harbingers of “a host of clinical conditions,” including urinary incontinence and fecal incontinence, constipation, and bladder-emptying problems. Also, changes in the pelvic musculature from childbirth, surgeries, and hypotonicity or hypertonicity can contribute to sexual dysfunction in later life, said Ms. Hartzell Leggin, who is affiliated with Good Shepherd Penn Partners and in private practice in the Philadelphia area.
The musculature of the pelvic floor functions as more than a bowl for carrying the pelvic organs, Ms. Hartzell Leggin said. The collective muscles and fascia form a sling that fills in the pelvic ring and functions as an integrated system with constant resting tone. But the musculature is also active and interactive.
“The diaphragm and the pelvic floor move in symmetry during respiration,” and pelvic floor tone tightens in anticipation of increased intra-abdominal pressure from a cough, a sneeze, or even a laugh. “These are active structures – the brain can talk to the pelvic floor and make it do something,” she said.
Who’s a good candidate?
Looking at risk factors for pelvic organ prolapse alone, Ms. Hartzell Leggin said these can include age, body mass index, a history of occupational or recreational heavy lifting, chronic cough, and even genetics.
However, one of the most significant risk factors for prolapse of pelvic organs is simply having had a vaginal delivery. Up to 50% of women who have delivered a child vaginally may eventually have some degree of pelvic organ prolapse, though not all women will be symptomatic, Ms. Hartzell Leggin said.
Since postsurgical pelvic organ prolapse rates may top 30% within 2 years, an initial referral for pelvic floor PT is a rational conservative approach, she said. And even if a patient progresses to surgery, PT may be a useful adjunct.
Pelvic floor dysfunction may also be considered if a diastasis recti is discovered on physical exam, or if the patient reports a linear abdominal bulge. Patients with diastasis recti are more likely to have pelvic floor dysfunction than the general population, she said, so it’s worth asking about any related symptoms.
For voiding issues, “conservative treatment is first-line,” said Ms. Hartzell Leggin, so a PT referral for pelvic floor therapy and, in some cases, some behavioral retraining can help with issues of urinary frequency and urgency. These are options that may be considered before prescribing anticholinergic medication, she said.
How does pelvic floor PT work?
When a physician refers a patient for pelvic floor PT, what’s the process? The physical therapy evaluation will begin with history taking, including the chief complaint, past medical and surgical history, and an obstetric/gynecologic/sexual history, said Ms. Hartzell Leggin. Medications are also reviewed.
The physical therapist’s examination should encompass a thorough orthopedic examination, with attention to the lumbar spine and hips, and posture and gait. An external and internal examination of the pelvic floor will look for muscle tone at rest and with strain, and for any defects or prolapse.
Pelvic floor strength is assessed according to ability to contract, with some assessment of strength available through palpation. More quantitative means may include manometry, dynamometry, or the use of progressive weighted vaginal cones.
There’s no single standardized measurement tool to assess pelvic floor strength. Palpation is a valuable tool for an experienced clinician, and it also can provide real-time feedback to the patient as she becomes more aware of her pelvic floor. The discipline is moving toward more standardized terminology, with several reporting scales now available to report pelvic floor strength, said Ms. Hartzell Leggin.
The Pelvic Floor Distress Inventory is a validated tool that captures information about the impact of pelvic floor dysfunction on a patient’s daily functioning. “I think I capture a lot when my patient comes in and completes that form,” said Ms. Hartzell Leggin. The Genitourinary Pain Index is another validated tool that measures urinary symptoms, pain, and associated quality of life impacts. Patients may be asked to keep a home therapy and symptom or voiding diary for additional information.
The pelvic floor PT treatment algorithm will vary, depending on whether there’s underlying hypertonicity or hypotonicity, but will involve pelvic floor exercises, soft tissue mobilization, and consideration of a variety of modalities including electrical stimulation and ultrasound. For hypertonicity, vaginal dilators may be used, while weighted vaginal cones may be used for hypotonicity.
Physical therapists should know when to refer a patient back to a physician and should always work as part of an interdisciplinary team, she said.
Ms. Hartzell Leggin reported that she is the president of Elite Rehabilitation Services in Audubon, Pa.
[email protected]
On Twitter @karioakes
EXPERT ANALYSIS FROM NAMS 2017
Therapy receives rare pediatric disease designation
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to ATA230 for the treatment of congenital cytomegalovirus (CMV) infection.
ATA230 is an allogeneic T-cell immunotherapy targeting antigens expressed by CMV.
Rare pediatric disease designation is granted to drugs that show promise to treat orphan diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 and younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, a drug developer with rare pediatric disease designation that receives an approval of a new drug application is eligible for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
The company developing ATA230 is Atara Biotherapeutics, Inc. The company also received orphan designation for ATA230.
ATA230 trials
ATA230 has been investigated in phase 1 and 2 studies of immunocompromised patients with CMV viremia or disease who are refractory or resistant to antiviral drug treatment in the post-transplant setting.
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to ATA230 for the treatment of congenital cytomegalovirus (CMV) infection.
ATA230 is an allogeneic T-cell immunotherapy targeting antigens expressed by CMV.
Rare pediatric disease designation is granted to drugs that show promise to treat orphan diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 and younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, a drug developer with rare pediatric disease designation that receives an approval of a new drug application is eligible for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
The company developing ATA230 is Atara Biotherapeutics, Inc. The company also received orphan designation for ATA230.
ATA230 trials
ATA230 has been investigated in phase 1 and 2 studies of immunocompromised patients with CMV viremia or disease who are refractory or resistant to antiviral drug treatment in the post-transplant setting.
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.
The US Food and Drug Administration (FDA) has granted rare pediatric disease designation to ATA230 for the treatment of congenital cytomegalovirus (CMV) infection.
ATA230 is an allogeneic T-cell immunotherapy targeting antigens expressed by CMV.
Rare pediatric disease designation is granted to drugs that show promise to treat orphan diseases affecting fewer than 200,000 patients in the US, primarily patients age 18 and younger.
The designation provides incentives to advance the development of drugs for rare disease, including access to the FDA’s expedited review and approval programs.
Under the FDA’s Rare Pediatric Disease Priority Review Voucher Program, a drug developer with rare pediatric disease designation that receives an approval of a new drug application is eligible for a voucher that can be redeemed to obtain priority review for any subsequent marketing application.
The company developing ATA230 is Atara Biotherapeutics, Inc. The company also received orphan designation for ATA230.
ATA230 trials
ATA230 has been investigated in phase 1 and 2 studies of immunocompromised patients with CMV viremia or disease who are refractory or resistant to antiviral drug treatment in the post-transplant setting.
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.