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Race, ethnicity may influence outcomes after supratentorial intracerebral hemorrhage
researchers reported Jan. 22 in Neurology.
“There has been considerable research on stroke in older people, but there is still much to be learned about stroke in younger people and how it affects people of different races and ethnicities,” study author Daniel Woo, MD, professor of neurology at the University of Cincinnati, said in a news release. “Our study found that, even when you account for factors that affect outcomes, such as how big the stroke is, race and ethnicity were still independent predictors of how well people would recover.”
A subset of ERICH participants
To examine predictors of functional outcome in young patients with ICH, researchers analyzed data from a subset of patients in the Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study. ERICH enrolled patients with nontraumatic ICHs at 42 sites in the United States. It included 1,000 non-Hispanic black patients, 1,000 non-Hispanic white patients, and 1,000 Hispanic patients. Participants self-reported race and ethnicity.
Lead author Laura C. Miyares from Yale School of Medicine in New Haven, Conn., and colleagues analyzed data from 418 patients in ERICH who were aged 18-49 years and had supratentorial ICH. The cohort had an average age of 43 years, and 69% were male. In this subset, 41% were black, 12% were white, and 47% were Hispanic.
The primary outcome was modified Rankin Scale (mRS) score 3 months after the ICH, and the investigators defined a poor outcome as a score of 4 or greater. At 3 months, 35% had a poor functional outcome. Approximately 18% were unable to walk without assistance and attend to their bodily needs (mRS 4); 8% were bedridden, incontinent, and required nursing care (mRS 5); and 10% had died (mRS 6).
The percentage of patients with a poor functional outcome was 52% among white patients, 35% among black patients, and 31% among Hispanic patients. In a univariable analysis, black patients had a 51% reduction in odds of a poor outcome, compared with white patients, and Hispanic patients had a 59% reduction.
“The association between race/ethnicity and 3-month post-ICH functional outcome remained significant after adjusting for age, sex, premorbid disability, ICH location, ICH volume, [intraventricular hemorrhage] extension, systolic blood pressure, and [Glasgow Coma Scale] score on admission,” the researchers said. “In multivariable analysis, using white patients as the reference category, black patients had a 58% reduction in the odds of poor functional outcome at 3 months and Hispanic patients had a 66% reduction in the same odds.”
Their analysis identified the importance of other risk factors as well. “The volume of the hematoma, the most powerful predictor of outcome in older patients with ICH, was also found to be the most significant predictor of poor outcome in young patients,” they said.
Vascular risks and oral anticoagulants
About 80% of the young adults with ICH had a history of diagnosed hypertension. In nearly half, the condition was untreated. “After hypertension, the most common stroke risk factors in the young were diabetes, high cholesterol, smoking, and alcohol abuse,” the authors said. “In combination, these results indicate that vascular risk factors, especially untreated, could explain a large proportion of cases of ICH in the young.”
“Our results also point to treatment with oral anticoagulants before hospitalization as a potential mediator of the effect of race/ethnicity on short-term functional outcomes,” they said. About 8% of the white patients used oral anticoagulants, compared with 4% of the black patients and 1% of the Hispanic patients. Oral anticoagulant treatment “is a known risk factor for ICH and an established predictor of poor outcome in this condition. However, because only a small proportion of enrolled young patients with ICH were on [oral anticoagulants] prior to presentation, these results should be further validated by future studies.”
The study’s limitations include the broad categorization of racial and ethnic groups, the fact that younger patients with supratentorial ICH were more likely to be black or Hispanic and less likely to be white, and the exclusion of a significant proportion of cases of young white patients with smaller ICH volumes because of missing data, the researchers noted. Although the cohort was large, researchers may need to study more patients to capture differences among racial and ethnic groups, the investigators said.
The association between race/ethnicity and functional outcome could relate to “distinct pathophysiologies of the initial bleed or unique mechanisms of secondary injury,” the researchers suggested. “Future studies are necessary to probe the potential biological and social mediators of these findings to elucidate the role of race/ethnicity in ICH severity and functional recovery, and to develop improved prognostication for a racially varied population.”
ERICH is supported by the National Institute of Neurological Disorders and Stroke. Authors disclosed grants from the government, professional societies, and a university.
SOURCE: Miyares LC et al. Neurology. 2020 Jan 22. doi: 10.1212/WNL.0000000000008930.
researchers reported Jan. 22 in Neurology.
“There has been considerable research on stroke in older people, but there is still much to be learned about stroke in younger people and how it affects people of different races and ethnicities,” study author Daniel Woo, MD, professor of neurology at the University of Cincinnati, said in a news release. “Our study found that, even when you account for factors that affect outcomes, such as how big the stroke is, race and ethnicity were still independent predictors of how well people would recover.”
A subset of ERICH participants
To examine predictors of functional outcome in young patients with ICH, researchers analyzed data from a subset of patients in the Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study. ERICH enrolled patients with nontraumatic ICHs at 42 sites in the United States. It included 1,000 non-Hispanic black patients, 1,000 non-Hispanic white patients, and 1,000 Hispanic patients. Participants self-reported race and ethnicity.
Lead author Laura C. Miyares from Yale School of Medicine in New Haven, Conn., and colleagues analyzed data from 418 patients in ERICH who were aged 18-49 years and had supratentorial ICH. The cohort had an average age of 43 years, and 69% were male. In this subset, 41% were black, 12% were white, and 47% were Hispanic.
The primary outcome was modified Rankin Scale (mRS) score 3 months after the ICH, and the investigators defined a poor outcome as a score of 4 or greater. At 3 months, 35% had a poor functional outcome. Approximately 18% were unable to walk without assistance and attend to their bodily needs (mRS 4); 8% were bedridden, incontinent, and required nursing care (mRS 5); and 10% had died (mRS 6).
The percentage of patients with a poor functional outcome was 52% among white patients, 35% among black patients, and 31% among Hispanic patients. In a univariable analysis, black patients had a 51% reduction in odds of a poor outcome, compared with white patients, and Hispanic patients had a 59% reduction.
“The association between race/ethnicity and 3-month post-ICH functional outcome remained significant after adjusting for age, sex, premorbid disability, ICH location, ICH volume, [intraventricular hemorrhage] extension, systolic blood pressure, and [Glasgow Coma Scale] score on admission,” the researchers said. “In multivariable analysis, using white patients as the reference category, black patients had a 58% reduction in the odds of poor functional outcome at 3 months and Hispanic patients had a 66% reduction in the same odds.”
Their analysis identified the importance of other risk factors as well. “The volume of the hematoma, the most powerful predictor of outcome in older patients with ICH, was also found to be the most significant predictor of poor outcome in young patients,” they said.
Vascular risks and oral anticoagulants
About 80% of the young adults with ICH had a history of diagnosed hypertension. In nearly half, the condition was untreated. “After hypertension, the most common stroke risk factors in the young were diabetes, high cholesterol, smoking, and alcohol abuse,” the authors said. “In combination, these results indicate that vascular risk factors, especially untreated, could explain a large proportion of cases of ICH in the young.”
“Our results also point to treatment with oral anticoagulants before hospitalization as a potential mediator of the effect of race/ethnicity on short-term functional outcomes,” they said. About 8% of the white patients used oral anticoagulants, compared with 4% of the black patients and 1% of the Hispanic patients. Oral anticoagulant treatment “is a known risk factor for ICH and an established predictor of poor outcome in this condition. However, because only a small proportion of enrolled young patients with ICH were on [oral anticoagulants] prior to presentation, these results should be further validated by future studies.”
The study’s limitations include the broad categorization of racial and ethnic groups, the fact that younger patients with supratentorial ICH were more likely to be black or Hispanic and less likely to be white, and the exclusion of a significant proportion of cases of young white patients with smaller ICH volumes because of missing data, the researchers noted. Although the cohort was large, researchers may need to study more patients to capture differences among racial and ethnic groups, the investigators said.
The association between race/ethnicity and functional outcome could relate to “distinct pathophysiologies of the initial bleed or unique mechanisms of secondary injury,” the researchers suggested. “Future studies are necessary to probe the potential biological and social mediators of these findings to elucidate the role of race/ethnicity in ICH severity and functional recovery, and to develop improved prognostication for a racially varied population.”
ERICH is supported by the National Institute of Neurological Disorders and Stroke. Authors disclosed grants from the government, professional societies, and a university.
SOURCE: Miyares LC et al. Neurology. 2020 Jan 22. doi: 10.1212/WNL.0000000000008930.
researchers reported Jan. 22 in Neurology.
“There has been considerable research on stroke in older people, but there is still much to be learned about stroke in younger people and how it affects people of different races and ethnicities,” study author Daniel Woo, MD, professor of neurology at the University of Cincinnati, said in a news release. “Our study found that, even when you account for factors that affect outcomes, such as how big the stroke is, race and ethnicity were still independent predictors of how well people would recover.”
A subset of ERICH participants
To examine predictors of functional outcome in young patients with ICH, researchers analyzed data from a subset of patients in the Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study. ERICH enrolled patients with nontraumatic ICHs at 42 sites in the United States. It included 1,000 non-Hispanic black patients, 1,000 non-Hispanic white patients, and 1,000 Hispanic patients. Participants self-reported race and ethnicity.
Lead author Laura C. Miyares from Yale School of Medicine in New Haven, Conn., and colleagues analyzed data from 418 patients in ERICH who were aged 18-49 years and had supratentorial ICH. The cohort had an average age of 43 years, and 69% were male. In this subset, 41% were black, 12% were white, and 47% were Hispanic.
The primary outcome was modified Rankin Scale (mRS) score 3 months after the ICH, and the investigators defined a poor outcome as a score of 4 or greater. At 3 months, 35% had a poor functional outcome. Approximately 18% were unable to walk without assistance and attend to their bodily needs (mRS 4); 8% were bedridden, incontinent, and required nursing care (mRS 5); and 10% had died (mRS 6).
The percentage of patients with a poor functional outcome was 52% among white patients, 35% among black patients, and 31% among Hispanic patients. In a univariable analysis, black patients had a 51% reduction in odds of a poor outcome, compared with white patients, and Hispanic patients had a 59% reduction.
“The association between race/ethnicity and 3-month post-ICH functional outcome remained significant after adjusting for age, sex, premorbid disability, ICH location, ICH volume, [intraventricular hemorrhage] extension, systolic blood pressure, and [Glasgow Coma Scale] score on admission,” the researchers said. “In multivariable analysis, using white patients as the reference category, black patients had a 58% reduction in the odds of poor functional outcome at 3 months and Hispanic patients had a 66% reduction in the same odds.”
Their analysis identified the importance of other risk factors as well. “The volume of the hematoma, the most powerful predictor of outcome in older patients with ICH, was also found to be the most significant predictor of poor outcome in young patients,” they said.
Vascular risks and oral anticoagulants
About 80% of the young adults with ICH had a history of diagnosed hypertension. In nearly half, the condition was untreated. “After hypertension, the most common stroke risk factors in the young were diabetes, high cholesterol, smoking, and alcohol abuse,” the authors said. “In combination, these results indicate that vascular risk factors, especially untreated, could explain a large proportion of cases of ICH in the young.”
“Our results also point to treatment with oral anticoagulants before hospitalization as a potential mediator of the effect of race/ethnicity on short-term functional outcomes,” they said. About 8% of the white patients used oral anticoagulants, compared with 4% of the black patients and 1% of the Hispanic patients. Oral anticoagulant treatment “is a known risk factor for ICH and an established predictor of poor outcome in this condition. However, because only a small proportion of enrolled young patients with ICH were on [oral anticoagulants] prior to presentation, these results should be further validated by future studies.”
The study’s limitations include the broad categorization of racial and ethnic groups, the fact that younger patients with supratentorial ICH were more likely to be black or Hispanic and less likely to be white, and the exclusion of a significant proportion of cases of young white patients with smaller ICH volumes because of missing data, the researchers noted. Although the cohort was large, researchers may need to study more patients to capture differences among racial and ethnic groups, the investigators said.
The association between race/ethnicity and functional outcome could relate to “distinct pathophysiologies of the initial bleed or unique mechanisms of secondary injury,” the researchers suggested. “Future studies are necessary to probe the potential biological and social mediators of these findings to elucidate the role of race/ethnicity in ICH severity and functional recovery, and to develop improved prognostication for a racially varied population.”
ERICH is supported by the National Institute of Neurological Disorders and Stroke. Authors disclosed grants from the government, professional societies, and a university.
SOURCE: Miyares LC et al. Neurology. 2020 Jan 22. doi: 10.1212/WNL.0000000000008930.
FROM NEUROLOGY
Key clinical point: Among young adults with supratentorial intracerebral hemorrhage (ICH), black race and Hispanic ethnicity are associated with better functional outcomes, compared with white race.
Major finding: In multivariable analysis, black patients had a 58% reduction in the odds of poor functional outcome at 3 months, compared with white patients, and Hispanic patients had a 66% reduction.
Study details: An analysis of data from a subset of 418 patients in the Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study.
Disclosures: ERICH is supported by the National Institute of Neurological Disorders and Stroke. Authors disclosed grants from the government, professional societies, and a university.
Source: Miyares LC et al. Neurology. 2020 Jan 22. doi: 10.1212/WNL.0000000000008930.
European marketing of Picato suspended while skin cancer risk reviewed
As a precaution, the European Medicines Agency (EMA) has recommended that patients stop using ingenol mebutate (Picato) while the agency continues to review the safety of the topical treatment, which is indicated for the treatment of actinic keratosis in Europe and the United States.
No such action has been taken in the United States.
The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is reviewing data on skin cancer in patients treated with ingenol mebutate. In a trial comparing Picato and imiquimod, skin cancer was more common in the areas treated with Picato than in areas treated with imiquimod, the statement said.
“While uncertainties remain, the EMA said in a Jan. 17 news release. “The PRAC has therefore recommended suspending the medicine’s marketing authorization as a precaution and noted that alternative treatments are available.”
FDA is looking at the situation
LEO Pharma, the company that markets Picato, announced on Jan. 9 that it was initiating voluntary withdrawal of marketing authorization and possible voluntary withdrawal of Picato in the European Union (EU) and European Economic Area (EEA). The statement says, however, that “LEO Pharma has carefully reviewed the information received from PRAC, and the company disagrees with the ongoing assessment of PRAC.” There are “no additional safety data and it is LEO Pharma’s position that there is no evidence of a causal relationship or plausible mechanism hypothesis between the use of Picato and the development of skin malignancies.” An update added to the press release on Jan. 17 restates that the company disagrees with the assessment of PRAC.
“This matter does not affect Picato in the U.S., and there are no new developments in the [United States]. Picato continues to be available to patients in the U.S. We remain in dialogue with the U.S. Food and Drug Administration about Picato in the EU/EEA,” Rhonda Sciarra, associate director of global external communications for LEO Pharma, said in an email. “We remain committed to ensuring patient safety, rigorous pharmacovigilance monitoring, and transparency,” she added.
The FDA “is gathering data and information to investigate the safety concern related to Picato,” a spokesperson for the FDA told Dermatology News. “We are committed to sharing relevant findings when we have sufficient understanding of the situation and of what actions should be taken,” he added.
Examining the data
The EMA announcement described data about the risk of skin cancer in studies of Picato. A 3-year study in 484 patients found a higher incidence of skin malignancy with ingenol mebutate than with the comparator, imiquimod. In all, 3.3% of patients developed cancer in the ingenol mebutate group, compared with 0.4% in the comparator group.
In an 8-week vehicle-controlled trial in 1,262 patients, there were more skin tumors in patients who received ingenol mebutate than in those in the vehicle arm (1.0% vs. 0.1%).
In addition, according to the EMA statement, in four trials of a related ester that included 1,234 patients, a higher incidence of skin tumors occurred with the related drug, ingenol disoxate, than with a vehicle control (7.7% vs. 2.9%). PRAC considered these data because ingenol disoxate and ingenol mebutate are closely related, the EMA said.
“Health care professionals should stop prescribing Picato and consider different treatment options while authorities review the data,” according to the European agency. “Health care professionals should advise patients to be vigilant for any skin lesions developing and to seek medical advice promptly should any occur,” the statement adds.
Picato has been authorized in the EU since 2012, and the FDA approved Picato the same year. Patients have received about 2.8 million treatment courses in that time, according to the LEO Pharma press release.
As a precaution, the European Medicines Agency (EMA) has recommended that patients stop using ingenol mebutate (Picato) while the agency continues to review the safety of the topical treatment, which is indicated for the treatment of actinic keratosis in Europe and the United States.
No such action has been taken in the United States.
The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is reviewing data on skin cancer in patients treated with ingenol mebutate. In a trial comparing Picato and imiquimod, skin cancer was more common in the areas treated with Picato than in areas treated with imiquimod, the statement said.
“While uncertainties remain, the EMA said in a Jan. 17 news release. “The PRAC has therefore recommended suspending the medicine’s marketing authorization as a precaution and noted that alternative treatments are available.”
FDA is looking at the situation
LEO Pharma, the company that markets Picato, announced on Jan. 9 that it was initiating voluntary withdrawal of marketing authorization and possible voluntary withdrawal of Picato in the European Union (EU) and European Economic Area (EEA). The statement says, however, that “LEO Pharma has carefully reviewed the information received from PRAC, and the company disagrees with the ongoing assessment of PRAC.” There are “no additional safety data and it is LEO Pharma’s position that there is no evidence of a causal relationship or plausible mechanism hypothesis between the use of Picato and the development of skin malignancies.” An update added to the press release on Jan. 17 restates that the company disagrees with the assessment of PRAC.
“This matter does not affect Picato in the U.S., and there are no new developments in the [United States]. Picato continues to be available to patients in the U.S. We remain in dialogue with the U.S. Food and Drug Administration about Picato in the EU/EEA,” Rhonda Sciarra, associate director of global external communications for LEO Pharma, said in an email. “We remain committed to ensuring patient safety, rigorous pharmacovigilance monitoring, and transparency,” she added.
The FDA “is gathering data and information to investigate the safety concern related to Picato,” a spokesperson for the FDA told Dermatology News. “We are committed to sharing relevant findings when we have sufficient understanding of the situation and of what actions should be taken,” he added.
Examining the data
The EMA announcement described data about the risk of skin cancer in studies of Picato. A 3-year study in 484 patients found a higher incidence of skin malignancy with ingenol mebutate than with the comparator, imiquimod. In all, 3.3% of patients developed cancer in the ingenol mebutate group, compared with 0.4% in the comparator group.
In an 8-week vehicle-controlled trial in 1,262 patients, there were more skin tumors in patients who received ingenol mebutate than in those in the vehicle arm (1.0% vs. 0.1%).
In addition, according to the EMA statement, in four trials of a related ester that included 1,234 patients, a higher incidence of skin tumors occurred with the related drug, ingenol disoxate, than with a vehicle control (7.7% vs. 2.9%). PRAC considered these data because ingenol disoxate and ingenol mebutate are closely related, the EMA said.
“Health care professionals should stop prescribing Picato and consider different treatment options while authorities review the data,” according to the European agency. “Health care professionals should advise patients to be vigilant for any skin lesions developing and to seek medical advice promptly should any occur,” the statement adds.
Picato has been authorized in the EU since 2012, and the FDA approved Picato the same year. Patients have received about 2.8 million treatment courses in that time, according to the LEO Pharma press release.
As a precaution, the European Medicines Agency (EMA) has recommended that patients stop using ingenol mebutate (Picato) while the agency continues to review the safety of the topical treatment, which is indicated for the treatment of actinic keratosis in Europe and the United States.
No such action has been taken in the United States.
The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is reviewing data on skin cancer in patients treated with ingenol mebutate. In a trial comparing Picato and imiquimod, skin cancer was more common in the areas treated with Picato than in areas treated with imiquimod, the statement said.
“While uncertainties remain, the EMA said in a Jan. 17 news release. “The PRAC has therefore recommended suspending the medicine’s marketing authorization as a precaution and noted that alternative treatments are available.”
FDA is looking at the situation
LEO Pharma, the company that markets Picato, announced on Jan. 9 that it was initiating voluntary withdrawal of marketing authorization and possible voluntary withdrawal of Picato in the European Union (EU) and European Economic Area (EEA). The statement says, however, that “LEO Pharma has carefully reviewed the information received from PRAC, and the company disagrees with the ongoing assessment of PRAC.” There are “no additional safety data and it is LEO Pharma’s position that there is no evidence of a causal relationship or plausible mechanism hypothesis between the use of Picato and the development of skin malignancies.” An update added to the press release on Jan. 17 restates that the company disagrees with the assessment of PRAC.
“This matter does not affect Picato in the U.S., and there are no new developments in the [United States]. Picato continues to be available to patients in the U.S. We remain in dialogue with the U.S. Food and Drug Administration about Picato in the EU/EEA,” Rhonda Sciarra, associate director of global external communications for LEO Pharma, said in an email. “We remain committed to ensuring patient safety, rigorous pharmacovigilance monitoring, and transparency,” she added.
The FDA “is gathering data and information to investigate the safety concern related to Picato,” a spokesperson for the FDA told Dermatology News. “We are committed to sharing relevant findings when we have sufficient understanding of the situation and of what actions should be taken,” he added.
Examining the data
The EMA announcement described data about the risk of skin cancer in studies of Picato. A 3-year study in 484 patients found a higher incidence of skin malignancy with ingenol mebutate than with the comparator, imiquimod. In all, 3.3% of patients developed cancer in the ingenol mebutate group, compared with 0.4% in the comparator group.
In an 8-week vehicle-controlled trial in 1,262 patients, there were more skin tumors in patients who received ingenol mebutate than in those in the vehicle arm (1.0% vs. 0.1%).
In addition, according to the EMA statement, in four trials of a related ester that included 1,234 patients, a higher incidence of skin tumors occurred with the related drug, ingenol disoxate, than with a vehicle control (7.7% vs. 2.9%). PRAC considered these data because ingenol disoxate and ingenol mebutate are closely related, the EMA said.
“Health care professionals should stop prescribing Picato and consider different treatment options while authorities review the data,” according to the European agency. “Health care professionals should advise patients to be vigilant for any skin lesions developing and to seek medical advice promptly should any occur,” the statement adds.
Picato has been authorized in the EU since 2012, and the FDA approved Picato the same year. Patients have received about 2.8 million treatment courses in that time, according to the LEO Pharma press release.
Value analysis of JAK inhibitors for RA hampered by limited data
Adequate evidence shows that adding a Janus kinase (JAK) inhibitor to conventional disease-modifying antirheumatic drug therapy provides a net health benefit for patients with rheumatoid arthritis, compared with conventional drugs alone, according to a report by an independent research institute. But the long-term economic value of JAK inhibitors for rheumatoid arthritis is less clear, the report by the Institute for Clinical and Economic Review (ICER) indicates.
ICER on Jan. 9 released a finalized report and policy recommendations on JAK inhibitors and biosimilars for rheumatoid arthritis. The report reviews current evidence for JAK inhibitors for adults with moderately active to severely active rheumatoid arthritis.
Since the nonprofit’s 2017 review of targeted immune modulators for rheumatoid arthritis, two JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq), were approved by the Food and Drug Administration. At a December 2019 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s independent evidence appraisal committees, panelists reviewed recent evidence.
A pricey comparator
In ICER’s analysis, the JAK inhibitor upadacitinib reached common thresholds for cost-effectiveness when compared with adalimumab (Humira). Nevertheless, the 14 members of the independent evidence appraisal committee voted that upadacitinib’s long-term economic value was “low” (8 votes) or “intermediate” (6 votes). Concerns about the generalizability of phase 3 clinical trial data to patients in the real world were among the reservations noted by panelists. Furthermore, “legitimate questions remain about whether or not adalimumab, launched 17 years ago, is fairly priced to begin with,” Pamela Bradt, MD, MPH, ICER’s chief scientific officer, said in a news release.
The panel did not vote on the economic value of tofacitinib (Xeljanz) or baricitinib, the two other JAK inhibitors that are approved for rheumatoid arthritis, because head-to-head evidence against adalimumab was insufficient, ICER said.
“Rheumatoid arthritis is a progressively disabling condition, and patients are fortunate to have multiple therapy options – including biosimilars – that effectively slow disease progression,” Dr. Bradt said. “Many economists might expect medicines to become more affordable in an increasingly crowded therapeutic class; however, because the current rebate structure has erected barriers between patients and several emerging RA therapies, traditional market dynamics have been unable to drive down prices.”
Weighing efficacy and cost
Panelists found that the net health benefit provided by upadacitinib is superior to that provided by adalimumab. At the same time, they said that there is insufficient head-to-head evidence to distinguish between the net health benefit of upadacitinib and tofacitinib or to demonstrate that tofacitinib is superior to adalimumab. Evidence comparing baricitinib to adalimumab does not exist.
CTAF members unanimously agreed that adequate evidence demonstrates that the biosimilar infliximab-dyyb (Inflectra) is clinically equivalent to its reference biologic, infliximab (Remicade).
Economic modeling demonstrated that upadacitinib plus a conventional drug achieves marginally higher quality of life than adalimumab plus a conventional drug does, at similar costs. “Based on this comparison with adalimumab, ICER’s value-based price benchmark range for upadacitinib is between $44,000 and $45,000,” according to the ICER news release. “This benchmark represents a 25% discount off of upadacitinib’s annual list price of $59,860, a suggested discount that is consistent with the rebates we assume the manufacturer is currently offering.”
After the voting session, various experts, including clinicians, patient advocates, and representatives from manufacturers and insurance companies, made the following policy recommendations:
- Regulatory intervention may be needed to ensure that drug prices do not continue to increase further from reasonable alignment with added benefits for patients.
- Insurers, pharmacy benefit managers, and employers should increase transparency around the role of discounts and rebates in formulary design.
- Policymakers should aim to create a system that rewards lower-priced biosimilar treatment options.
The findings of the clinical review by the Institute for Clinical and Economic Review (ICER) are generally in line with our clinical perceptions. We have an increasing number of treatment options for our RA patients, and the results of this review support the efficacy of tofacitinib and upadacitinib, compared with currently available biologic treatments. While ICER’s voting panel did find the data supported the superiority of upadacitinib over adalimumab, the cost analysis notes a WAC (wholesale acquisition cost) for upadacitinib of $59,860. While at expected discounted rates it is felt to be cost effective when compared with adalimumab, it is difficult to know what this means since ICER found adalimumab itself not to be cost effective, compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in its 2017 review.
ICER’s focus is drug pricing and cost effectiveness, so obviously our biologic drugs are in the institute’s crosshairs. This review provided context for a policy roundtable discussion that included patient, payer, and manufacturer input, as well as American College of Rheumatology (ACR) input. We are thankful that ACR had a seat at the table, and thankful ICER is attempting to bring light to the important issues and barriers that perpetuate high drug prices in our marketplace. The discussion was wide ranging but focused on step-edit policies, the role of pharmacy benefit managers (PBMs) in perpetuating high drug prices and the relatively slow uptake of biosimilars in our marketplace.
These issues are critical to every practicing rheumatologist because we each deal daily with the hassles of step-edit/fail-first policies, which hijack our otherwise thoughtful and evidence-based decision making regarding the best treatments for our patients. We know how much (unreimbursed) time it takes our staff to sort through these step edits and prior authorizations, and we have seen recent data regarding how these policies delay care and harm patients. We were thankful to see ICER validate these concerns and note that their suggested guidelines for rational step therapy somewhat mirror those in the Safe Step Act, which ACR supports on a federal legislative level. ACR continues to vigorously support the grandfathering of any patient on an effective treatment, regardless of changes in insurance or formulary; this was an issue of robust debate at their meeting, and this patient-centric position is not uniformly held among policymakers, unfortunately.
ACR agrees with ICER’s conclusion that transparency in the PBM system regarding rebates should be promoted and that opaque rebate negotiations between PBMs and manufacturers both incentivize higher prices and block access to the marketplace for cheaper biosimilar options.
Additionally, ICER and ACR agree about the critical role that biosimilar uptake will play in controlling drug costs. While we do not yet have any biosimilars that have been deemed interchangeable by the Food and Drug Administration, we agree with ICER that data regarding comparable efficacy and safety of biosimilars to their originator products is very reassuring. While the decision to switch to a biosimilar should be an individual decision between a provider and patient, and while we recognize with frustration that many FDA-approved biosimilars are not commercially available because of patent law, it is clear that the current costs of our biologic drugs are not sustainable and the uptake of biosimilars will be critical if we hope our health care economy can continue to support coverage of these life-changing drugs in years to come. We agree with ICER that it is incumbent upon prescribers to reassure our patients regarding the safety and efficacy of these drugs.
Christopher Phillips, MD , is a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the ACR, under the guidance of the Committee on Rheumatologic Care. He attended the initial ICER rheumatoid arthritis review meeting in 2017 on behalf of ACR. In 2019, Dr. Phillips served as a reviewer and clinical expert to the ICER panel and participated in the policy roundtable discussion.
The findings of the clinical review by the Institute for Clinical and Economic Review (ICER) are generally in line with our clinical perceptions. We have an increasing number of treatment options for our RA patients, and the results of this review support the efficacy of tofacitinib and upadacitinib, compared with currently available biologic treatments. While ICER’s voting panel did find the data supported the superiority of upadacitinib over adalimumab, the cost analysis notes a WAC (wholesale acquisition cost) for upadacitinib of $59,860. While at expected discounted rates it is felt to be cost effective when compared with adalimumab, it is difficult to know what this means since ICER found adalimumab itself not to be cost effective, compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in its 2017 review.
ICER’s focus is drug pricing and cost effectiveness, so obviously our biologic drugs are in the institute’s crosshairs. This review provided context for a policy roundtable discussion that included patient, payer, and manufacturer input, as well as American College of Rheumatology (ACR) input. We are thankful that ACR had a seat at the table, and thankful ICER is attempting to bring light to the important issues and barriers that perpetuate high drug prices in our marketplace. The discussion was wide ranging but focused on step-edit policies, the role of pharmacy benefit managers (PBMs) in perpetuating high drug prices and the relatively slow uptake of biosimilars in our marketplace.
These issues are critical to every practicing rheumatologist because we each deal daily with the hassles of step-edit/fail-first policies, which hijack our otherwise thoughtful and evidence-based decision making regarding the best treatments for our patients. We know how much (unreimbursed) time it takes our staff to sort through these step edits and prior authorizations, and we have seen recent data regarding how these policies delay care and harm patients. We were thankful to see ICER validate these concerns and note that their suggested guidelines for rational step therapy somewhat mirror those in the Safe Step Act, which ACR supports on a federal legislative level. ACR continues to vigorously support the grandfathering of any patient on an effective treatment, regardless of changes in insurance or formulary; this was an issue of robust debate at their meeting, and this patient-centric position is not uniformly held among policymakers, unfortunately.
ACR agrees with ICER’s conclusion that transparency in the PBM system regarding rebates should be promoted and that opaque rebate negotiations between PBMs and manufacturers both incentivize higher prices and block access to the marketplace for cheaper biosimilar options.
Additionally, ICER and ACR agree about the critical role that biosimilar uptake will play in controlling drug costs. While we do not yet have any biosimilars that have been deemed interchangeable by the Food and Drug Administration, we agree with ICER that data regarding comparable efficacy and safety of biosimilars to their originator products is very reassuring. While the decision to switch to a biosimilar should be an individual decision between a provider and patient, and while we recognize with frustration that many FDA-approved biosimilars are not commercially available because of patent law, it is clear that the current costs of our biologic drugs are not sustainable and the uptake of biosimilars will be critical if we hope our health care economy can continue to support coverage of these life-changing drugs in years to come. We agree with ICER that it is incumbent upon prescribers to reassure our patients regarding the safety and efficacy of these drugs.
Christopher Phillips, MD , is a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the ACR, under the guidance of the Committee on Rheumatologic Care. He attended the initial ICER rheumatoid arthritis review meeting in 2017 on behalf of ACR. In 2019, Dr. Phillips served as a reviewer and clinical expert to the ICER panel and participated in the policy roundtable discussion.
The findings of the clinical review by the Institute for Clinical and Economic Review (ICER) are generally in line with our clinical perceptions. We have an increasing number of treatment options for our RA patients, and the results of this review support the efficacy of tofacitinib and upadacitinib, compared with currently available biologic treatments. While ICER’s voting panel did find the data supported the superiority of upadacitinib over adalimumab, the cost analysis notes a WAC (wholesale acquisition cost) for upadacitinib of $59,860. While at expected discounted rates it is felt to be cost effective when compared with adalimumab, it is difficult to know what this means since ICER found adalimumab itself not to be cost effective, compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), in its 2017 review.
ICER’s focus is drug pricing and cost effectiveness, so obviously our biologic drugs are in the institute’s crosshairs. This review provided context for a policy roundtable discussion that included patient, payer, and manufacturer input, as well as American College of Rheumatology (ACR) input. We are thankful that ACR had a seat at the table, and thankful ICER is attempting to bring light to the important issues and barriers that perpetuate high drug prices in our marketplace. The discussion was wide ranging but focused on step-edit policies, the role of pharmacy benefit managers (PBMs) in perpetuating high drug prices and the relatively slow uptake of biosimilars in our marketplace.
These issues are critical to every practicing rheumatologist because we each deal daily with the hassles of step-edit/fail-first policies, which hijack our otherwise thoughtful and evidence-based decision making regarding the best treatments for our patients. We know how much (unreimbursed) time it takes our staff to sort through these step edits and prior authorizations, and we have seen recent data regarding how these policies delay care and harm patients. We were thankful to see ICER validate these concerns and note that their suggested guidelines for rational step therapy somewhat mirror those in the Safe Step Act, which ACR supports on a federal legislative level. ACR continues to vigorously support the grandfathering of any patient on an effective treatment, regardless of changes in insurance or formulary; this was an issue of robust debate at their meeting, and this patient-centric position is not uniformly held among policymakers, unfortunately.
ACR agrees with ICER’s conclusion that transparency in the PBM system regarding rebates should be promoted and that opaque rebate negotiations between PBMs and manufacturers both incentivize higher prices and block access to the marketplace for cheaper biosimilar options.
Additionally, ICER and ACR agree about the critical role that biosimilar uptake will play in controlling drug costs. While we do not yet have any biosimilars that have been deemed interchangeable by the Food and Drug Administration, we agree with ICER that data regarding comparable efficacy and safety of biosimilars to their originator products is very reassuring. While the decision to switch to a biosimilar should be an individual decision between a provider and patient, and while we recognize with frustration that many FDA-approved biosimilars are not commercially available because of patent law, it is clear that the current costs of our biologic drugs are not sustainable and the uptake of biosimilars will be critical if we hope our health care economy can continue to support coverage of these life-changing drugs in years to come. We agree with ICER that it is incumbent upon prescribers to reassure our patients regarding the safety and efficacy of these drugs.
Christopher Phillips, MD , is a community rheumatologist in Paducah, Ky., who serves as chair of the insurance subcommittee of the ACR, under the guidance of the Committee on Rheumatologic Care. He attended the initial ICER rheumatoid arthritis review meeting in 2017 on behalf of ACR. In 2019, Dr. Phillips served as a reviewer and clinical expert to the ICER panel and participated in the policy roundtable discussion.
Adequate evidence shows that adding a Janus kinase (JAK) inhibitor to conventional disease-modifying antirheumatic drug therapy provides a net health benefit for patients with rheumatoid arthritis, compared with conventional drugs alone, according to a report by an independent research institute. But the long-term economic value of JAK inhibitors for rheumatoid arthritis is less clear, the report by the Institute for Clinical and Economic Review (ICER) indicates.
ICER on Jan. 9 released a finalized report and policy recommendations on JAK inhibitors and biosimilars for rheumatoid arthritis. The report reviews current evidence for JAK inhibitors for adults with moderately active to severely active rheumatoid arthritis.
Since the nonprofit’s 2017 review of targeted immune modulators for rheumatoid arthritis, two JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq), were approved by the Food and Drug Administration. At a December 2019 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s independent evidence appraisal committees, panelists reviewed recent evidence.
A pricey comparator
In ICER’s analysis, the JAK inhibitor upadacitinib reached common thresholds for cost-effectiveness when compared with adalimumab (Humira). Nevertheless, the 14 members of the independent evidence appraisal committee voted that upadacitinib’s long-term economic value was “low” (8 votes) or “intermediate” (6 votes). Concerns about the generalizability of phase 3 clinical trial data to patients in the real world were among the reservations noted by panelists. Furthermore, “legitimate questions remain about whether or not adalimumab, launched 17 years ago, is fairly priced to begin with,” Pamela Bradt, MD, MPH, ICER’s chief scientific officer, said in a news release.
The panel did not vote on the economic value of tofacitinib (Xeljanz) or baricitinib, the two other JAK inhibitors that are approved for rheumatoid arthritis, because head-to-head evidence against adalimumab was insufficient, ICER said.
“Rheumatoid arthritis is a progressively disabling condition, and patients are fortunate to have multiple therapy options – including biosimilars – that effectively slow disease progression,” Dr. Bradt said. “Many economists might expect medicines to become more affordable in an increasingly crowded therapeutic class; however, because the current rebate structure has erected barriers between patients and several emerging RA therapies, traditional market dynamics have been unable to drive down prices.”
Weighing efficacy and cost
Panelists found that the net health benefit provided by upadacitinib is superior to that provided by adalimumab. At the same time, they said that there is insufficient head-to-head evidence to distinguish between the net health benefit of upadacitinib and tofacitinib or to demonstrate that tofacitinib is superior to adalimumab. Evidence comparing baricitinib to adalimumab does not exist.
CTAF members unanimously agreed that adequate evidence demonstrates that the biosimilar infliximab-dyyb (Inflectra) is clinically equivalent to its reference biologic, infliximab (Remicade).
Economic modeling demonstrated that upadacitinib plus a conventional drug achieves marginally higher quality of life than adalimumab plus a conventional drug does, at similar costs. “Based on this comparison with adalimumab, ICER’s value-based price benchmark range for upadacitinib is between $44,000 and $45,000,” according to the ICER news release. “This benchmark represents a 25% discount off of upadacitinib’s annual list price of $59,860, a suggested discount that is consistent with the rebates we assume the manufacturer is currently offering.”
After the voting session, various experts, including clinicians, patient advocates, and representatives from manufacturers and insurance companies, made the following policy recommendations:
- Regulatory intervention may be needed to ensure that drug prices do not continue to increase further from reasonable alignment with added benefits for patients.
- Insurers, pharmacy benefit managers, and employers should increase transparency around the role of discounts and rebates in formulary design.
- Policymakers should aim to create a system that rewards lower-priced biosimilar treatment options.
Adequate evidence shows that adding a Janus kinase (JAK) inhibitor to conventional disease-modifying antirheumatic drug therapy provides a net health benefit for patients with rheumatoid arthritis, compared with conventional drugs alone, according to a report by an independent research institute. But the long-term economic value of JAK inhibitors for rheumatoid arthritis is less clear, the report by the Institute for Clinical and Economic Review (ICER) indicates.
ICER on Jan. 9 released a finalized report and policy recommendations on JAK inhibitors and biosimilars for rheumatoid arthritis. The report reviews current evidence for JAK inhibitors for adults with moderately active to severely active rheumatoid arthritis.
Since the nonprofit’s 2017 review of targeted immune modulators for rheumatoid arthritis, two JAK inhibitors, baricitinib (Olumiant) and upadacitinib (Rinvoq), were approved by the Food and Drug Administration. At a December 2019 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s independent evidence appraisal committees, panelists reviewed recent evidence.
A pricey comparator
In ICER’s analysis, the JAK inhibitor upadacitinib reached common thresholds for cost-effectiveness when compared with adalimumab (Humira). Nevertheless, the 14 members of the independent evidence appraisal committee voted that upadacitinib’s long-term economic value was “low” (8 votes) or “intermediate” (6 votes). Concerns about the generalizability of phase 3 clinical trial data to patients in the real world were among the reservations noted by panelists. Furthermore, “legitimate questions remain about whether or not adalimumab, launched 17 years ago, is fairly priced to begin with,” Pamela Bradt, MD, MPH, ICER’s chief scientific officer, said in a news release.
The panel did not vote on the economic value of tofacitinib (Xeljanz) or baricitinib, the two other JAK inhibitors that are approved for rheumatoid arthritis, because head-to-head evidence against adalimumab was insufficient, ICER said.
“Rheumatoid arthritis is a progressively disabling condition, and patients are fortunate to have multiple therapy options – including biosimilars – that effectively slow disease progression,” Dr. Bradt said. “Many economists might expect medicines to become more affordable in an increasingly crowded therapeutic class; however, because the current rebate structure has erected barriers between patients and several emerging RA therapies, traditional market dynamics have been unable to drive down prices.”
Weighing efficacy and cost
Panelists found that the net health benefit provided by upadacitinib is superior to that provided by adalimumab. At the same time, they said that there is insufficient head-to-head evidence to distinguish between the net health benefit of upadacitinib and tofacitinib or to demonstrate that tofacitinib is superior to adalimumab. Evidence comparing baricitinib to adalimumab does not exist.
CTAF members unanimously agreed that adequate evidence demonstrates that the biosimilar infliximab-dyyb (Inflectra) is clinically equivalent to its reference biologic, infliximab (Remicade).
Economic modeling demonstrated that upadacitinib plus a conventional drug achieves marginally higher quality of life than adalimumab plus a conventional drug does, at similar costs. “Based on this comparison with adalimumab, ICER’s value-based price benchmark range for upadacitinib is between $44,000 and $45,000,” according to the ICER news release. “This benchmark represents a 25% discount off of upadacitinib’s annual list price of $59,860, a suggested discount that is consistent with the rebates we assume the manufacturer is currently offering.”
After the voting session, various experts, including clinicians, patient advocates, and representatives from manufacturers and insurance companies, made the following policy recommendations:
- Regulatory intervention may be needed to ensure that drug prices do not continue to increase further from reasonable alignment with added benefits for patients.
- Insurers, pharmacy benefit managers, and employers should increase transparency around the role of discounts and rebates in formulary design.
- Policymakers should aim to create a system that rewards lower-priced biosimilar treatment options.
Children with resistant UTIs unexpectedly may respond to discordant antibiotics
Children with urinary tract infections (UTIs) may improve clinically, and pyuria may resolve, during empiric treatment with an antibiotic that turns out to be discordant, according a retrospective study in Pediatrics.
“The low rate of care escalation and high rate of clinical improvement while on discordant antibiotics suggests that, for most patients, it would be reasonable to continue current empiric antibiotic practices until urine culture sensitivities return,” said first author Marie E. Wang, MD, a pediatric hospitalist at Stanford (Calif.) University, and colleagues.
The researchers examined the initial clinical response and escalation of care for 316 children with UTIs who received therapy to which the infecting isolate was not susceptible. The study included patients who had infections that were resistant to third-generation cephalosporins – that is, urinalysis found that the infections were not susceptible to ceftriaxone or cefotaxime in vitro. Before the resistant organisms were identified, however, the patients were started on discordant antibiotics.
Escalation of care was uncommon
The patients had a median age of 2.4 years, and 78% were girls. Approximately 90% were started on a cephalosporin, and about 65% received a first-generation cephalosporin. Patients presented during 2012-2017 to one of five children’s hospitals or to a large managed care organization with 10 hospitals in the United States. The investigators defined care escalation as a visit to the emergency department, hospitalization, or transfer to the ICU.
In all, seven patients (2%) had escalation of care on discordant antibiotics. Four children visited an emergency department without hospitalization, and three children were hospitalized because of persistent symptoms.
Among 230 cases for which the researchers had data about clinical response at a median follow-up of 3 days, 84% “had overall clinical improvement while on discordant antibiotics,” the authors said.
For 22 children who had repeat urine testing while on discordant antibiotics, 53% had resolution of pyuria, and 32% had improvement of pyuria, whereas 16% did not have improvement. Of the three patients without improvement, one had no change, and two had worsening.
Of 17 patients who had a repeat urine culture on discordant therapy, 65% had a negative repeat culture, and 18% grew the same pathogen with a decreased colony count. Two patients had a colony count that remained unchanged, and one patient had an increased colony count.
Small studies outside the United States have reported similar results, the researchers noted. Spontaneous resolution of UTIs or antibiotics reaching a sufficient concentration in the urine and renal parenchyma to achieve a clinical response are possible explanations for the findings, they wrote.
“Few children required escalation of care and most experienced initial clinical improvement,” noted Dr. Wang and colleagues. “Furthermore, in the small group of children that underwent repeat urine testing while on discordant therapy, most had resolution or improvement in pyuria and sterilization of their urine cultures. Our findings suggest that Additionally, given that these patients initially received what would generally be considered inadequate treatment, our findings may provide some insight into the natural history of UTIs and/or trigger further investigation into the relationship between in vitro urine culture susceptibilities and in vivo clinical response to treatment.”
‘Caution is needed’
The study “highlights an intriguing observation about children with UTIs unexpectedly responding to discordant antibiotic therapy,” Tej K. Mattoo, MD, and Basim I. Asmar, MD, wrote in an accompanying commentary.(doi: 10.1542/peds.2019-3512). Dr. Mattoo and Dr. Asmar, a pediatric nephrologist and a specialist in pediatric infectious diseases, respectively, at Wayne State University and affiliated with Children’s Hospital of Michigan, both in Detroit.
In an inpatient setting, it may be easy for physicians to reassess patients “once urine culture results reveal resistance to the treating antibiotic,” they noted. In an ambulatory setting, however, “it is likely that some patients will receive a full course of an antibiotic that does not have in vitro activity against the urinary pathogen.”
Physicians have a responsibility to use antibiotics judiciously, they said. Widely accepted principles include avoiding repeated courses of antibiotics, diagnosing UTIs appropriately, and not treating asymptomatic bacteriuria.
The study had no external funding. The authors had no relevant financial disclosures.
SOURCE: Wang ME et al. Pediatrics. 2020 Jan 17. doi: 10.1542/peds.2019-1608.
This article was updated 2/4/2020.
Children with urinary tract infections (UTIs) may improve clinically, and pyuria may resolve, during empiric treatment with an antibiotic that turns out to be discordant, according a retrospective study in Pediatrics.
“The low rate of care escalation and high rate of clinical improvement while on discordant antibiotics suggests that, for most patients, it would be reasonable to continue current empiric antibiotic practices until urine culture sensitivities return,” said first author Marie E. Wang, MD, a pediatric hospitalist at Stanford (Calif.) University, and colleagues.
The researchers examined the initial clinical response and escalation of care for 316 children with UTIs who received therapy to which the infecting isolate was not susceptible. The study included patients who had infections that were resistant to third-generation cephalosporins – that is, urinalysis found that the infections were not susceptible to ceftriaxone or cefotaxime in vitro. Before the resistant organisms were identified, however, the patients were started on discordant antibiotics.
Escalation of care was uncommon
The patients had a median age of 2.4 years, and 78% were girls. Approximately 90% were started on a cephalosporin, and about 65% received a first-generation cephalosporin. Patients presented during 2012-2017 to one of five children’s hospitals or to a large managed care organization with 10 hospitals in the United States. The investigators defined care escalation as a visit to the emergency department, hospitalization, or transfer to the ICU.
In all, seven patients (2%) had escalation of care on discordant antibiotics. Four children visited an emergency department without hospitalization, and three children were hospitalized because of persistent symptoms.
Among 230 cases for which the researchers had data about clinical response at a median follow-up of 3 days, 84% “had overall clinical improvement while on discordant antibiotics,” the authors said.
For 22 children who had repeat urine testing while on discordant antibiotics, 53% had resolution of pyuria, and 32% had improvement of pyuria, whereas 16% did not have improvement. Of the three patients without improvement, one had no change, and two had worsening.
Of 17 patients who had a repeat urine culture on discordant therapy, 65% had a negative repeat culture, and 18% grew the same pathogen with a decreased colony count. Two patients had a colony count that remained unchanged, and one patient had an increased colony count.
Small studies outside the United States have reported similar results, the researchers noted. Spontaneous resolution of UTIs or antibiotics reaching a sufficient concentration in the urine and renal parenchyma to achieve a clinical response are possible explanations for the findings, they wrote.
“Few children required escalation of care and most experienced initial clinical improvement,” noted Dr. Wang and colleagues. “Furthermore, in the small group of children that underwent repeat urine testing while on discordant therapy, most had resolution or improvement in pyuria and sterilization of their urine cultures. Our findings suggest that Additionally, given that these patients initially received what would generally be considered inadequate treatment, our findings may provide some insight into the natural history of UTIs and/or trigger further investigation into the relationship between in vitro urine culture susceptibilities and in vivo clinical response to treatment.”
‘Caution is needed’
The study “highlights an intriguing observation about children with UTIs unexpectedly responding to discordant antibiotic therapy,” Tej K. Mattoo, MD, and Basim I. Asmar, MD, wrote in an accompanying commentary.(doi: 10.1542/peds.2019-3512). Dr. Mattoo and Dr. Asmar, a pediatric nephrologist and a specialist in pediatric infectious diseases, respectively, at Wayne State University and affiliated with Children’s Hospital of Michigan, both in Detroit.
In an inpatient setting, it may be easy for physicians to reassess patients “once urine culture results reveal resistance to the treating antibiotic,” they noted. In an ambulatory setting, however, “it is likely that some patients will receive a full course of an antibiotic that does not have in vitro activity against the urinary pathogen.”
Physicians have a responsibility to use antibiotics judiciously, they said. Widely accepted principles include avoiding repeated courses of antibiotics, diagnosing UTIs appropriately, and not treating asymptomatic bacteriuria.
The study had no external funding. The authors had no relevant financial disclosures.
SOURCE: Wang ME et al. Pediatrics. 2020 Jan 17. doi: 10.1542/peds.2019-1608.
This article was updated 2/4/2020.
Children with urinary tract infections (UTIs) may improve clinically, and pyuria may resolve, during empiric treatment with an antibiotic that turns out to be discordant, according a retrospective study in Pediatrics.
“The low rate of care escalation and high rate of clinical improvement while on discordant antibiotics suggests that, for most patients, it would be reasonable to continue current empiric antibiotic practices until urine culture sensitivities return,” said first author Marie E. Wang, MD, a pediatric hospitalist at Stanford (Calif.) University, and colleagues.
The researchers examined the initial clinical response and escalation of care for 316 children with UTIs who received therapy to which the infecting isolate was not susceptible. The study included patients who had infections that were resistant to third-generation cephalosporins – that is, urinalysis found that the infections were not susceptible to ceftriaxone or cefotaxime in vitro. Before the resistant organisms were identified, however, the patients were started on discordant antibiotics.
Escalation of care was uncommon
The patients had a median age of 2.4 years, and 78% were girls. Approximately 90% were started on a cephalosporin, and about 65% received a first-generation cephalosporin. Patients presented during 2012-2017 to one of five children’s hospitals or to a large managed care organization with 10 hospitals in the United States. The investigators defined care escalation as a visit to the emergency department, hospitalization, or transfer to the ICU.
In all, seven patients (2%) had escalation of care on discordant antibiotics. Four children visited an emergency department without hospitalization, and three children were hospitalized because of persistent symptoms.
Among 230 cases for which the researchers had data about clinical response at a median follow-up of 3 days, 84% “had overall clinical improvement while on discordant antibiotics,” the authors said.
For 22 children who had repeat urine testing while on discordant antibiotics, 53% had resolution of pyuria, and 32% had improvement of pyuria, whereas 16% did not have improvement. Of the three patients without improvement, one had no change, and two had worsening.
Of 17 patients who had a repeat urine culture on discordant therapy, 65% had a negative repeat culture, and 18% grew the same pathogen with a decreased colony count. Two patients had a colony count that remained unchanged, and one patient had an increased colony count.
Small studies outside the United States have reported similar results, the researchers noted. Spontaneous resolution of UTIs or antibiotics reaching a sufficient concentration in the urine and renal parenchyma to achieve a clinical response are possible explanations for the findings, they wrote.
“Few children required escalation of care and most experienced initial clinical improvement,” noted Dr. Wang and colleagues. “Furthermore, in the small group of children that underwent repeat urine testing while on discordant therapy, most had resolution or improvement in pyuria and sterilization of their urine cultures. Our findings suggest that Additionally, given that these patients initially received what would generally be considered inadequate treatment, our findings may provide some insight into the natural history of UTIs and/or trigger further investigation into the relationship between in vitro urine culture susceptibilities and in vivo clinical response to treatment.”
‘Caution is needed’
The study “highlights an intriguing observation about children with UTIs unexpectedly responding to discordant antibiotic therapy,” Tej K. Mattoo, MD, and Basim I. Asmar, MD, wrote in an accompanying commentary.(doi: 10.1542/peds.2019-3512). Dr. Mattoo and Dr. Asmar, a pediatric nephrologist and a specialist in pediatric infectious diseases, respectively, at Wayne State University and affiliated with Children’s Hospital of Michigan, both in Detroit.
In an inpatient setting, it may be easy for physicians to reassess patients “once urine culture results reveal resistance to the treating antibiotic,” they noted. In an ambulatory setting, however, “it is likely that some patients will receive a full course of an antibiotic that does not have in vitro activity against the urinary pathogen.”
Physicians have a responsibility to use antibiotics judiciously, they said. Widely accepted principles include avoiding repeated courses of antibiotics, diagnosing UTIs appropriately, and not treating asymptomatic bacteriuria.
The study had no external funding. The authors had no relevant financial disclosures.
SOURCE: Wang ME et al. Pediatrics. 2020 Jan 17. doi: 10.1542/peds.2019-1608.
This article was updated 2/4/2020.
FROM PEDIATRICS
FDA approves diazepam nasal spray for seizure clusters
The drug may be administered by a care partner outside of a medical setting for the treatment of intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient’s usual seizure pattern. The formulation is the first nasal spray approved by the FDA as a rescue treatment for people with epilepsy aged 6 years and older, according to Neurelis, the developer of the drug. Midazolam nasal spray, approved in May 2019, is indicated for patients with epilepsy aged 12 years and older.
Investigators evaluated the safety of diazepam nasal spray in a long-term, open-label, repeat-dose, clinical trial. The study enrolled 130 patients aged 6 years and older; more than 2,000 seizures were treated. The drug generally was safe and well tolerated, and the most common adverse reactions were somnolence, headache, and nasal discomfort.
The FDA has granted Valtoco 7 years of orphan drug exclusivity. In the United States, about 170,000 patients with epilepsy are at risk of cluster or acute repetitive seizures, the company said. Until recently, approved rescue medications had been rectally administered.
Patients may receive a second dose of diazepam nasal spray at least 4 hours after an initial dose if needed, but caregivers should not use more than two doses to treat a single episode, according to the prescribing information. In addition, the prescribing information recommends that diazepam nasal spray be used for no more than one episode every 5 days and no more than five episodes per month.
The drug may be administered by a care partner outside of a medical setting for the treatment of intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient’s usual seizure pattern. The formulation is the first nasal spray approved by the FDA as a rescue treatment for people with epilepsy aged 6 years and older, according to Neurelis, the developer of the drug. Midazolam nasal spray, approved in May 2019, is indicated for patients with epilepsy aged 12 years and older.
Investigators evaluated the safety of diazepam nasal spray in a long-term, open-label, repeat-dose, clinical trial. The study enrolled 130 patients aged 6 years and older; more than 2,000 seizures were treated. The drug generally was safe and well tolerated, and the most common adverse reactions were somnolence, headache, and nasal discomfort.
The FDA has granted Valtoco 7 years of orphan drug exclusivity. In the United States, about 170,000 patients with epilepsy are at risk of cluster or acute repetitive seizures, the company said. Until recently, approved rescue medications had been rectally administered.
Patients may receive a second dose of diazepam nasal spray at least 4 hours after an initial dose if needed, but caregivers should not use more than two doses to treat a single episode, according to the prescribing information. In addition, the prescribing information recommends that diazepam nasal spray be used for no more than one episode every 5 days and no more than five episodes per month.
The drug may be administered by a care partner outside of a medical setting for the treatment of intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient’s usual seizure pattern. The formulation is the first nasal spray approved by the FDA as a rescue treatment for people with epilepsy aged 6 years and older, according to Neurelis, the developer of the drug. Midazolam nasal spray, approved in May 2019, is indicated for patients with epilepsy aged 12 years and older.
Investigators evaluated the safety of diazepam nasal spray in a long-term, open-label, repeat-dose, clinical trial. The study enrolled 130 patients aged 6 years and older; more than 2,000 seizures were treated. The drug generally was safe and well tolerated, and the most common adverse reactions were somnolence, headache, and nasal discomfort.
The FDA has granted Valtoco 7 years of orphan drug exclusivity. In the United States, about 170,000 patients with epilepsy are at risk of cluster or acute repetitive seizures, the company said. Until recently, approved rescue medications had been rectally administered.
Patients may receive a second dose of diazepam nasal spray at least 4 hours after an initial dose if needed, but caregivers should not use more than two doses to treat a single episode, according to the prescribing information. In addition, the prescribing information recommends that diazepam nasal spray be used for no more than one episode every 5 days and no more than five episodes per month.
Optimal management of Barrett’s esophagus without high-grade dysplasia
, according to the study, which was published in Clinical Gastroenterology and Hepatology.
Clinical guidelines recommend surveillance or treatment of patients with Barrett’s esophagus, a precursor lesion for esophageal adenocarcinoma, depending on the presence and grade of dysplasia. For high-grade dysplasia, guidelines recommend endoscopic eradication therapy. For low-grade dysplasia, the optimal strategy is unclear, said first study author Amir-Houshang Omidvari, MD, MPH, a researcher at Erasmus MC University Medical Center Rotterdam (the Netherlands) and colleagues. In addition, the ideal surveillance interval for patients with nondysplastic Barrett’s esophagus is unknown.
Simulated cohorts
To identify optimal management strategies, the investigators simulated cohorts of 60-year-old patients with Barrett’s esophagus in the United States using three independent population-based models. They followed each cohort until death or age 100 years. The study compared disease progression without surveillance or treatment with 78 management strategies. The cost-effectiveness analyses used a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For low-grade dysplasia, the researchers assessed various surveillance intervals, endoscopic eradication therapy with confirmation of low-grade dysplasia by a repeat endoscopy after 2 months of high-dose acid suppression, and endoscopic eradication therapy without confirmatory testing. For nondysplastic Barrett’s esophagus, the researchers evaluated no surveillance and surveillance intervals of 1, 2, 3, 4, 5, or 10 years. The researchers made assumptions based on published data about rates of misdiagnosis, treatment efficacy, recurrence, complications, and other outcomes. They used Centers for Medicare & Medicaid Services reimbursement rates to evaluate costs. For all management strategies, the researchers assumed surveillance would stop at age 80 years.
In a simulated cohort of men with Barrett’s esophagus who did not receive surveillance or endoscopic eradication therapy, the models predicted an average esophageal adenocarcinoma cumulative incidence of 111 cases per 1,000 patients and mortality of 77 deaths per 1,000 patients, with a total cost of $5.7 million for their care. Management strategies “prevented 23%-75% of [esophageal adenocarcinoma] cases and decreased mortality by 31%-88% while increasing costs to $6.2-$17.3 million depending on the management strategy,” the authors said. The optimal cost-effective strategy – endoscopic eradication therapy for patients with low-grade dysplasia after endoscopic confirmation, and surveillance every 3 years for patients with nondysplastic Barrett’s esophagus – decreased esophageal adenocarcinoma incidence to 38 cases (–66%) and mortality to 15 deaths (–81%) per 1,000 patients, compared with natural history. This approach increased costs to $9.8 million and gained 358 QALYs.
The models predicted fewer esophageal adenocarcinoma cases in women without surveillance or treatment (75 cases per 1,000 patients). “Because of the higher incremental costs per QALY gained in women, the optimal strategy was surveillance every 5 years for [nondysplastic Barrett’s esophagus],” the researchers reported.
Avoiding misdiagnosis
“Despite the potential harms and cost of endoscopic therapy, [endoscopic eradication therapy of low-grade dysplasia] reduces the number of endoscopies required for surveillance ... because of prolonged surveillance intervals after successful treatment, and [it] generally prevents more [esophageal adenocarcinoma] cases than strategies using only surveillance,” wrote Dr. Omidvari and colleagues. Confirmation of low-grade dysplasia with repeat testing before treatment was more cost-effective than treatment without confirmatory testing. Although this approach requires one more endoscopy per patient, a decrease in inappropriate treatment of patients with false-positive low-grade dysplasia diagnoses compensates for the additional testing costs, they said.
The researchers noted that available data on long-term outcomes are limited. Nevertheless, the analysis may have important implications for patients with Barrett’s esophagus without dysplasia or with low-grade dysplasia, the authors said.
The National Institutes of Health/National Cancer Institute supported the study and provided funding for the authors.
SOURCE: Omidvari A-H et al. Clin Gastroenterol Hepatol. 2019 Dec 6. doi: 10.1016/j.cgh.2019.11.058.
, according to the study, which was published in Clinical Gastroenterology and Hepatology.
Clinical guidelines recommend surveillance or treatment of patients with Barrett’s esophagus, a precursor lesion for esophageal adenocarcinoma, depending on the presence and grade of dysplasia. For high-grade dysplasia, guidelines recommend endoscopic eradication therapy. For low-grade dysplasia, the optimal strategy is unclear, said first study author Amir-Houshang Omidvari, MD, MPH, a researcher at Erasmus MC University Medical Center Rotterdam (the Netherlands) and colleagues. In addition, the ideal surveillance interval for patients with nondysplastic Barrett’s esophagus is unknown.
Simulated cohorts
To identify optimal management strategies, the investigators simulated cohorts of 60-year-old patients with Barrett’s esophagus in the United States using three independent population-based models. They followed each cohort until death or age 100 years. The study compared disease progression without surveillance or treatment with 78 management strategies. The cost-effectiveness analyses used a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For low-grade dysplasia, the researchers assessed various surveillance intervals, endoscopic eradication therapy with confirmation of low-grade dysplasia by a repeat endoscopy after 2 months of high-dose acid suppression, and endoscopic eradication therapy without confirmatory testing. For nondysplastic Barrett’s esophagus, the researchers evaluated no surveillance and surveillance intervals of 1, 2, 3, 4, 5, or 10 years. The researchers made assumptions based on published data about rates of misdiagnosis, treatment efficacy, recurrence, complications, and other outcomes. They used Centers for Medicare & Medicaid Services reimbursement rates to evaluate costs. For all management strategies, the researchers assumed surveillance would stop at age 80 years.
In a simulated cohort of men with Barrett’s esophagus who did not receive surveillance or endoscopic eradication therapy, the models predicted an average esophageal adenocarcinoma cumulative incidence of 111 cases per 1,000 patients and mortality of 77 deaths per 1,000 patients, with a total cost of $5.7 million for their care. Management strategies “prevented 23%-75% of [esophageal adenocarcinoma] cases and decreased mortality by 31%-88% while increasing costs to $6.2-$17.3 million depending on the management strategy,” the authors said. The optimal cost-effective strategy – endoscopic eradication therapy for patients with low-grade dysplasia after endoscopic confirmation, and surveillance every 3 years for patients with nondysplastic Barrett’s esophagus – decreased esophageal adenocarcinoma incidence to 38 cases (–66%) and mortality to 15 deaths (–81%) per 1,000 patients, compared with natural history. This approach increased costs to $9.8 million and gained 358 QALYs.
The models predicted fewer esophageal adenocarcinoma cases in women without surveillance or treatment (75 cases per 1,000 patients). “Because of the higher incremental costs per QALY gained in women, the optimal strategy was surveillance every 5 years for [nondysplastic Barrett’s esophagus],” the researchers reported.
Avoiding misdiagnosis
“Despite the potential harms and cost of endoscopic therapy, [endoscopic eradication therapy of low-grade dysplasia] reduces the number of endoscopies required for surveillance ... because of prolonged surveillance intervals after successful treatment, and [it] generally prevents more [esophageal adenocarcinoma] cases than strategies using only surveillance,” wrote Dr. Omidvari and colleagues. Confirmation of low-grade dysplasia with repeat testing before treatment was more cost-effective than treatment without confirmatory testing. Although this approach requires one more endoscopy per patient, a decrease in inappropriate treatment of patients with false-positive low-grade dysplasia diagnoses compensates for the additional testing costs, they said.
The researchers noted that available data on long-term outcomes are limited. Nevertheless, the analysis may have important implications for patients with Barrett’s esophagus without dysplasia or with low-grade dysplasia, the authors said.
The National Institutes of Health/National Cancer Institute supported the study and provided funding for the authors.
SOURCE: Omidvari A-H et al. Clin Gastroenterol Hepatol. 2019 Dec 6. doi: 10.1016/j.cgh.2019.11.058.
, according to the study, which was published in Clinical Gastroenterology and Hepatology.
Clinical guidelines recommend surveillance or treatment of patients with Barrett’s esophagus, a precursor lesion for esophageal adenocarcinoma, depending on the presence and grade of dysplasia. For high-grade dysplasia, guidelines recommend endoscopic eradication therapy. For low-grade dysplasia, the optimal strategy is unclear, said first study author Amir-Houshang Omidvari, MD, MPH, a researcher at Erasmus MC University Medical Center Rotterdam (the Netherlands) and colleagues. In addition, the ideal surveillance interval for patients with nondysplastic Barrett’s esophagus is unknown.
Simulated cohorts
To identify optimal management strategies, the investigators simulated cohorts of 60-year-old patients with Barrett’s esophagus in the United States using three independent population-based models. They followed each cohort until death or age 100 years. The study compared disease progression without surveillance or treatment with 78 management strategies. The cost-effectiveness analyses used a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For low-grade dysplasia, the researchers assessed various surveillance intervals, endoscopic eradication therapy with confirmation of low-grade dysplasia by a repeat endoscopy after 2 months of high-dose acid suppression, and endoscopic eradication therapy without confirmatory testing. For nondysplastic Barrett’s esophagus, the researchers evaluated no surveillance and surveillance intervals of 1, 2, 3, 4, 5, or 10 years. The researchers made assumptions based on published data about rates of misdiagnosis, treatment efficacy, recurrence, complications, and other outcomes. They used Centers for Medicare & Medicaid Services reimbursement rates to evaluate costs. For all management strategies, the researchers assumed surveillance would stop at age 80 years.
In a simulated cohort of men with Barrett’s esophagus who did not receive surveillance or endoscopic eradication therapy, the models predicted an average esophageal adenocarcinoma cumulative incidence of 111 cases per 1,000 patients and mortality of 77 deaths per 1,000 patients, with a total cost of $5.7 million for their care. Management strategies “prevented 23%-75% of [esophageal adenocarcinoma] cases and decreased mortality by 31%-88% while increasing costs to $6.2-$17.3 million depending on the management strategy,” the authors said. The optimal cost-effective strategy – endoscopic eradication therapy for patients with low-grade dysplasia after endoscopic confirmation, and surveillance every 3 years for patients with nondysplastic Barrett’s esophagus – decreased esophageal adenocarcinoma incidence to 38 cases (–66%) and mortality to 15 deaths (–81%) per 1,000 patients, compared with natural history. This approach increased costs to $9.8 million and gained 358 QALYs.
The models predicted fewer esophageal adenocarcinoma cases in women without surveillance or treatment (75 cases per 1,000 patients). “Because of the higher incremental costs per QALY gained in women, the optimal strategy was surveillance every 5 years for [nondysplastic Barrett’s esophagus],” the researchers reported.
Avoiding misdiagnosis
“Despite the potential harms and cost of endoscopic therapy, [endoscopic eradication therapy of low-grade dysplasia] reduces the number of endoscopies required for surveillance ... because of prolonged surveillance intervals after successful treatment, and [it] generally prevents more [esophageal adenocarcinoma] cases than strategies using only surveillance,” wrote Dr. Omidvari and colleagues. Confirmation of low-grade dysplasia with repeat testing before treatment was more cost-effective than treatment without confirmatory testing. Although this approach requires one more endoscopy per patient, a decrease in inappropriate treatment of patients with false-positive low-grade dysplasia diagnoses compensates for the additional testing costs, they said.
The researchers noted that available data on long-term outcomes are limited. Nevertheless, the analysis may have important implications for patients with Barrett’s esophagus without dysplasia or with low-grade dysplasia, the authors said.
The National Institutes of Health/National Cancer Institute supported the study and provided funding for the authors.
SOURCE: Omidvari A-H et al. Clin Gastroenterol Hepatol. 2019 Dec 6. doi: 10.1016/j.cgh.2019.11.058.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Delayed clinical care after concussion may prolong recovery
, according to a study published Jan. 6 in JAMA Neurology.
In addition, more severe visual motion sensitivity symptoms are associated with longer recovery times, said lead author Anthony P. Kontos, PhD, and colleagues. Dr. Kontos is associate professor of orthopedic surgery at the University of Pittsburgh and the research director of the University of Pittsburgh Medical Center Sports Medicine Concussion Program.
“Without clinical guidance and behavioral management recommendations post injury, athletes may have been engaging in counterproductive recovery strategies, such as a strict rest or excessive physical activity,” the authors said. “This explanation is supported by the fact that athletes recovered in a similar amount of time after that first evaluation.”
Various factors may influence recovery after a concussion, including age, sex, and comorbidities. To examine the relationship between time since injury at the start of clinical care and recovery time, the investigators conducted a retrospective, cross-sectional study. They analyzed data from patients seen in a sports medicine clinic between August 2016 and March 2018. Eligible patients were aged 12-22 years and had a diagnosed, symptomatic, sport-related concussion. The researchers excluded patients with incomplete recovery data.
The investigators included 162 patients in their analyses; 98 of these patients were seen within 7 days of the injury, and 64 were seen 8-20 days after a concussion. Both groups had a mean age of 15 years and similar proportions of female patients (52% in the early-care group vs. 62.5% in the late-care group). At the first clinical visit, symptom severity and cognitive, ocular, and vestibular test results were similar in both groups.
The researchers defined recovery time as the number of days from injury until the date of clearance for a full return to play. Physicians cleared patients to return to play when they returned to preinjury levels of symptoms and preinjury performance on cognitive, ocular, and vestibular tests with no increase in symptoms after exertion.
Patients’ recovery times ranged from 9 to 299 days; the average recovery time was 57 days. Fifty-two percent of patients in the early-care group recovered in 30 days or fewer, compared with 19% of patients in late-care group. Patients in the early-care group had a mean recovery of 51.1 days, whereas patients in the late-care group had a mean recovery of 66 days.
In a logistic regression model, late care “was associated with a 5.8-times increased likelihood of a recovery longer than 30 days,” the researchers reported. Visual motion sensitivity symptoms also were associated with increased odds of protracted recovery (adjusted odds ratio, 4.5).
“Once care was established, time to recovery did not differ for athletes evaluated within the first week of injury compared with those evaluated 2-3 weeks post injury,” Dr. Kontos and colleagues concluded. “Education on injury and behavioral recommendations to optimize concussion recovery and earlier initiation of active rehabilitation strategies, including exertion and vestibular therapy, are plausible explanations for the association of a shorter recovery time with earlier care. However, future research should focus on the specific mechanisms by which earlier health care postconcussion promotes faster recovery and determine if these findings apply to other subpopulations, including military personnel.”
The researchers noted that they excluded from their analysis 254 patients who had incomplete recovery data but otherwise met inclusion criteria, which may have led to selection bias.
Dr. Kontos disclosed grants from the National Football League and personal fees from APA Books and University of Pittsburgh projects outside the scope of this study.
SOURCE: Kontos AP et al. JAMA Neurol. 2020 Jan 6. doi: 10.1001/jamaneurol.2019.4552.
, according to a study published Jan. 6 in JAMA Neurology.
In addition, more severe visual motion sensitivity symptoms are associated with longer recovery times, said lead author Anthony P. Kontos, PhD, and colleagues. Dr. Kontos is associate professor of orthopedic surgery at the University of Pittsburgh and the research director of the University of Pittsburgh Medical Center Sports Medicine Concussion Program.
“Without clinical guidance and behavioral management recommendations post injury, athletes may have been engaging in counterproductive recovery strategies, such as a strict rest or excessive physical activity,” the authors said. “This explanation is supported by the fact that athletes recovered in a similar amount of time after that first evaluation.”
Various factors may influence recovery after a concussion, including age, sex, and comorbidities. To examine the relationship between time since injury at the start of clinical care and recovery time, the investigators conducted a retrospective, cross-sectional study. They analyzed data from patients seen in a sports medicine clinic between August 2016 and March 2018. Eligible patients were aged 12-22 years and had a diagnosed, symptomatic, sport-related concussion. The researchers excluded patients with incomplete recovery data.
The investigators included 162 patients in their analyses; 98 of these patients were seen within 7 days of the injury, and 64 were seen 8-20 days after a concussion. Both groups had a mean age of 15 years and similar proportions of female patients (52% in the early-care group vs. 62.5% in the late-care group). At the first clinical visit, symptom severity and cognitive, ocular, and vestibular test results were similar in both groups.
The researchers defined recovery time as the number of days from injury until the date of clearance for a full return to play. Physicians cleared patients to return to play when they returned to preinjury levels of symptoms and preinjury performance on cognitive, ocular, and vestibular tests with no increase in symptoms after exertion.
Patients’ recovery times ranged from 9 to 299 days; the average recovery time was 57 days. Fifty-two percent of patients in the early-care group recovered in 30 days or fewer, compared with 19% of patients in late-care group. Patients in the early-care group had a mean recovery of 51.1 days, whereas patients in the late-care group had a mean recovery of 66 days.
In a logistic regression model, late care “was associated with a 5.8-times increased likelihood of a recovery longer than 30 days,” the researchers reported. Visual motion sensitivity symptoms also were associated with increased odds of protracted recovery (adjusted odds ratio, 4.5).
“Once care was established, time to recovery did not differ for athletes evaluated within the first week of injury compared with those evaluated 2-3 weeks post injury,” Dr. Kontos and colleagues concluded. “Education on injury and behavioral recommendations to optimize concussion recovery and earlier initiation of active rehabilitation strategies, including exertion and vestibular therapy, are plausible explanations for the association of a shorter recovery time with earlier care. However, future research should focus on the specific mechanisms by which earlier health care postconcussion promotes faster recovery and determine if these findings apply to other subpopulations, including military personnel.”
The researchers noted that they excluded from their analysis 254 patients who had incomplete recovery data but otherwise met inclusion criteria, which may have led to selection bias.
Dr. Kontos disclosed grants from the National Football League and personal fees from APA Books and University of Pittsburgh projects outside the scope of this study.
SOURCE: Kontos AP et al. JAMA Neurol. 2020 Jan 6. doi: 10.1001/jamaneurol.2019.4552.
, according to a study published Jan. 6 in JAMA Neurology.
In addition, more severe visual motion sensitivity symptoms are associated with longer recovery times, said lead author Anthony P. Kontos, PhD, and colleagues. Dr. Kontos is associate professor of orthopedic surgery at the University of Pittsburgh and the research director of the University of Pittsburgh Medical Center Sports Medicine Concussion Program.
“Without clinical guidance and behavioral management recommendations post injury, athletes may have been engaging in counterproductive recovery strategies, such as a strict rest or excessive physical activity,” the authors said. “This explanation is supported by the fact that athletes recovered in a similar amount of time after that first evaluation.”
Various factors may influence recovery after a concussion, including age, sex, and comorbidities. To examine the relationship between time since injury at the start of clinical care and recovery time, the investigators conducted a retrospective, cross-sectional study. They analyzed data from patients seen in a sports medicine clinic between August 2016 and March 2018. Eligible patients were aged 12-22 years and had a diagnosed, symptomatic, sport-related concussion. The researchers excluded patients with incomplete recovery data.
The investigators included 162 patients in their analyses; 98 of these patients were seen within 7 days of the injury, and 64 were seen 8-20 days after a concussion. Both groups had a mean age of 15 years and similar proportions of female patients (52% in the early-care group vs. 62.5% in the late-care group). At the first clinical visit, symptom severity and cognitive, ocular, and vestibular test results were similar in both groups.
The researchers defined recovery time as the number of days from injury until the date of clearance for a full return to play. Physicians cleared patients to return to play when they returned to preinjury levels of symptoms and preinjury performance on cognitive, ocular, and vestibular tests with no increase in symptoms after exertion.
Patients’ recovery times ranged from 9 to 299 days; the average recovery time was 57 days. Fifty-two percent of patients in the early-care group recovered in 30 days or fewer, compared with 19% of patients in late-care group. Patients in the early-care group had a mean recovery of 51.1 days, whereas patients in the late-care group had a mean recovery of 66 days.
In a logistic regression model, late care “was associated with a 5.8-times increased likelihood of a recovery longer than 30 days,” the researchers reported. Visual motion sensitivity symptoms also were associated with increased odds of protracted recovery (adjusted odds ratio, 4.5).
“Once care was established, time to recovery did not differ for athletes evaluated within the first week of injury compared with those evaluated 2-3 weeks post injury,” Dr. Kontos and colleagues concluded. “Education on injury and behavioral recommendations to optimize concussion recovery and earlier initiation of active rehabilitation strategies, including exertion and vestibular therapy, are plausible explanations for the association of a shorter recovery time with earlier care. However, future research should focus on the specific mechanisms by which earlier health care postconcussion promotes faster recovery and determine if these findings apply to other subpopulations, including military personnel.”
The researchers noted that they excluded from their analysis 254 patients who had incomplete recovery data but otherwise met inclusion criteria, which may have led to selection bias.
Dr. Kontos disclosed grants from the National Football League and personal fees from APA Books and University of Pittsburgh projects outside the scope of this study.
SOURCE: Kontos AP et al. JAMA Neurol. 2020 Jan 6. doi: 10.1001/jamaneurol.2019.4552.
FROM JAMA NEUROLOGY
FDA approves Dayvigo for insomnia
Lemborexant will be available in 5-mg and 10-mg tablets after the Drug Enforcement Administration schedules the drug, which is expected to occur within 90 days, according to a statement from Eisai.
Lemborexant is an orexin receptor antagonist. Its approval is based on two phase 3 studies, SUNRISE 1 and SUNRISE 2, that included approximately 2,000 adults with insomnia. Investigators assessed lemborexant versus active comparators for as long as 1 month and versus placebo for 6 months.
In these studies, lemborexant significantly improved objective and subjective measures of sleep onset and sleep maintenance, compared with placebo. The medication was not associated with rebound insomnia or withdrawal effects after treatment discontinuation.
In the phase 3 trials, somnolence was the most common adverse reaction that occurred in at least 5% of patients who received lemborexant and at twice the rate in patients who received placebo (lemborexant 10 mg, 10%; lemborexant 5 mg, 7%; placebo, 1%).
In a middle-of-the-night safety study, lemborexant was associated with dose-dependent worsening on measures of attention and memory, compared with placebo. Treatment did not meaningfully affect ability to awaken to sound, however.
Previously reported data showed that lemborexant was effective in male and female patients and was well tolerated by both sexes and that the medication did not impair postural stability and driving performance.
Lemborexant will be available in 5-mg and 10-mg tablets after the Drug Enforcement Administration schedules the drug, which is expected to occur within 90 days, according to a statement from Eisai.
Lemborexant is an orexin receptor antagonist. Its approval is based on two phase 3 studies, SUNRISE 1 and SUNRISE 2, that included approximately 2,000 adults with insomnia. Investigators assessed lemborexant versus active comparators for as long as 1 month and versus placebo for 6 months.
In these studies, lemborexant significantly improved objective and subjective measures of sleep onset and sleep maintenance, compared with placebo. The medication was not associated with rebound insomnia or withdrawal effects after treatment discontinuation.
In the phase 3 trials, somnolence was the most common adverse reaction that occurred in at least 5% of patients who received lemborexant and at twice the rate in patients who received placebo (lemborexant 10 mg, 10%; lemborexant 5 mg, 7%; placebo, 1%).
In a middle-of-the-night safety study, lemborexant was associated with dose-dependent worsening on measures of attention and memory, compared with placebo. Treatment did not meaningfully affect ability to awaken to sound, however.
Previously reported data showed that lemborexant was effective in male and female patients and was well tolerated by both sexes and that the medication did not impair postural stability and driving performance.
Lemborexant will be available in 5-mg and 10-mg tablets after the Drug Enforcement Administration schedules the drug, which is expected to occur within 90 days, according to a statement from Eisai.
Lemborexant is an orexin receptor antagonist. Its approval is based on two phase 3 studies, SUNRISE 1 and SUNRISE 2, that included approximately 2,000 adults with insomnia. Investigators assessed lemborexant versus active comparators for as long as 1 month and versus placebo for 6 months.
In these studies, lemborexant significantly improved objective and subjective measures of sleep onset and sleep maintenance, compared with placebo. The medication was not associated with rebound insomnia or withdrawal effects after treatment discontinuation.
In the phase 3 trials, somnolence was the most common adverse reaction that occurred in at least 5% of patients who received lemborexant and at twice the rate in patients who received placebo (lemborexant 10 mg, 10%; lemborexant 5 mg, 7%; placebo, 1%).
In a middle-of-the-night safety study, lemborexant was associated with dose-dependent worsening on measures of attention and memory, compared with placebo. Treatment did not meaningfully affect ability to awaken to sound, however.
Previously reported data showed that lemborexant was effective in male and female patients and was well tolerated by both sexes and that the medication did not impair postural stability and driving performance.
FDA warns gabapentin, pregabalin may cause serious breathing problems
Elderly patients who take these drugs also are at increased risk of breathing problems, the announcement said.
Gabapentin (marketed as Neurontin, Gralise, and Horizant) and pregabalin (Lyrica and Lyrica CR) are used to treat seizures, nerve pain, and restless legs syndrome. Physicians increasingly are prescribing these medications, and people are misusing and abusing these drugs more frequently, the agency said. Gabapentin and pregabalin often are combined with central nervous system depressants such as opioids, antianxiety medicines, antidepressants, and antihistamines, which increases the risk of respiratory depression.
Conditions that reduce lung function, including chronic obstructive pulmonary disease (COPD), also increase the likelihood of breathing problems when taking gabapentin and pregabalin.
“There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone. We will continue to monitor these medicines as part of our routine monitoring of all FDA-approved drugs,” the announcement said.
The FDA is requiring new warnings about the risk of respiratory depression in the prescribing information of gabapentinoids. In addition, drug manufacturers must further assess the abuse potential of these drugs, particularly in combination with opioids.
Patients and caregivers should seek immediate medical attention for respiratory problems, which can be life threatening. Symptoms include confusion or disorientation; unusual dizziness or lightheadedness; extreme sleepiness or lethargy; slowed, shallow, or difficult breathing; unresponsiveness; and bluish-colored or tinted skin, especially on the lips, fingers, and toes.
Physicians should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when coprescribing these drugs with an opioid or other central nervous system depressant such as a benzodiazepine, according to the FDA.
The agency reviewed 49 case reports that were submitted between 2012 and 2017. Among these cases, 12 people died from respiratory depression with gabapentinoids. All of the patients who died had at least one risk factor.
Gabapentin first was approved in 1993, and pregabalin was approved in 2004. Drug adverse events and side effects can be reported online, the agency noted.
Elderly patients who take these drugs also are at increased risk of breathing problems, the announcement said.
Gabapentin (marketed as Neurontin, Gralise, and Horizant) and pregabalin (Lyrica and Lyrica CR) are used to treat seizures, nerve pain, and restless legs syndrome. Physicians increasingly are prescribing these medications, and people are misusing and abusing these drugs more frequently, the agency said. Gabapentin and pregabalin often are combined with central nervous system depressants such as opioids, antianxiety medicines, antidepressants, and antihistamines, which increases the risk of respiratory depression.
Conditions that reduce lung function, including chronic obstructive pulmonary disease (COPD), also increase the likelihood of breathing problems when taking gabapentin and pregabalin.
“There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone. We will continue to monitor these medicines as part of our routine monitoring of all FDA-approved drugs,” the announcement said.
The FDA is requiring new warnings about the risk of respiratory depression in the prescribing information of gabapentinoids. In addition, drug manufacturers must further assess the abuse potential of these drugs, particularly in combination with opioids.
Patients and caregivers should seek immediate medical attention for respiratory problems, which can be life threatening. Symptoms include confusion or disorientation; unusual dizziness or lightheadedness; extreme sleepiness or lethargy; slowed, shallow, or difficult breathing; unresponsiveness; and bluish-colored or tinted skin, especially on the lips, fingers, and toes.
Physicians should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when coprescribing these drugs with an opioid or other central nervous system depressant such as a benzodiazepine, according to the FDA.
The agency reviewed 49 case reports that were submitted between 2012 and 2017. Among these cases, 12 people died from respiratory depression with gabapentinoids. All of the patients who died had at least one risk factor.
Gabapentin first was approved in 1993, and pregabalin was approved in 2004. Drug adverse events and side effects can be reported online, the agency noted.
Elderly patients who take these drugs also are at increased risk of breathing problems, the announcement said.
Gabapentin (marketed as Neurontin, Gralise, and Horizant) and pregabalin (Lyrica and Lyrica CR) are used to treat seizures, nerve pain, and restless legs syndrome. Physicians increasingly are prescribing these medications, and people are misusing and abusing these drugs more frequently, the agency said. Gabapentin and pregabalin often are combined with central nervous system depressants such as opioids, antianxiety medicines, antidepressants, and antihistamines, which increases the risk of respiratory depression.
Conditions that reduce lung function, including chronic obstructive pulmonary disease (COPD), also increase the likelihood of breathing problems when taking gabapentin and pregabalin.
“There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone. We will continue to monitor these medicines as part of our routine monitoring of all FDA-approved drugs,” the announcement said.
The FDA is requiring new warnings about the risk of respiratory depression in the prescribing information of gabapentinoids. In addition, drug manufacturers must further assess the abuse potential of these drugs, particularly in combination with opioids.
Patients and caregivers should seek immediate medical attention for respiratory problems, which can be life threatening. Symptoms include confusion or disorientation; unusual dizziness or lightheadedness; extreme sleepiness or lethargy; slowed, shallow, or difficult breathing; unresponsiveness; and bluish-colored or tinted skin, especially on the lips, fingers, and toes.
Physicians should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when coprescribing these drugs with an opioid or other central nervous system depressant such as a benzodiazepine, according to the FDA.
The agency reviewed 49 case reports that were submitted between 2012 and 2017. Among these cases, 12 people died from respiratory depression with gabapentinoids. All of the patients who died had at least one risk factor.
Gabapentin first was approved in 1993, and pregabalin was approved in 2004. Drug adverse events and side effects can be reported online, the agency noted.
FDA approves Vyondys 53 for Duchenne muscular dystrophy subtype
The Food and Drug Administration has granted accelerated approval to Vyondys 53 (golodirsen) to treat patients with Duchenne muscular dystrophy (DMD) who have a mutation of the dystrophin gene that is amenable to exon 53 skipping. About 8% of patients with DMD have this type of mutation. Further research is required to establish whether the antisense oligonucleotide provides clinical benefit, the agency said.
Separately, the agency approved the first newborn screening test for DMD.
DMD is a “rare and devastating disease,” said Billy Dunn, MD, acting director of the office of neuroscience in the FDA’s Center for Drug Evaluation and Research.
“Patients ... who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping will now have available the first treatment targeted specifically for this disease subtype,” Dr. Dunn said in a news release. “Use of the accelerated approval pathway will make Vyondys 53 available to patients based on initial data, and we look forward to learning more about the drug’s clinical benefit from the ongoing confirmatory clinical trial.”
A surrogate endpoint
The FDA approved Vyondys 53 based on the surrogate endpoint of increased dystrophin production in the skeletal muscle in some patients treated with the drug. Sarepta Therapeutics, the developer of Vyondys 53, evaluated the treatment in a two-part clinical study. In the first part, eight patients with DMD received Vyondys 53, and four received placebo. In the second part, 25 patients, including the 12 patients from the first part, received open-label treatment. Dystrophin levels increased from 0.10% of normal at baseline to 1.02% of normal after at least 48 weeks of treatment.
A placebo-controlled, confirmatory trial is expected to conclude by 2024, the company said. If the trial does not confirm clinical benefit, the FDA could withdraw approval of the drug.
The most common side effects in patients who received Vyondys 53 include headache, fever, fall, cough, vomiting, abdominal pain, cold symptoms, and nausea. Some patients had hypersensitivity reactions. Renal toxicity occurred in animal studies of golodirsen, but not in the clinical studies. Renal toxicity, however, has occurred after treatment with other antisense oligonucleotides, the FDA noted.
Sarepta said Vyondys 53, an injection, would be available immediately. The drug is the company’s second RNA exon-skipping treatment for DMD. The FDA approved the first treatment, Exondys 51 (eteplirsen), in 2016. Together, the two drugs can treat about 20% of patients with DMD, the company said.
Newborn screening
On the same day, Dec. 12, 2019, the FDA authorized marketing of the first test to aid in newborn screening for DMD. Although authorization for the GSP Neonatal Creatine Kinase–MM kit enables laboratories to add this test to their newborn screening panel, it “does not signal a recommendation for DMD to be added ... as a condition for which newborn screening is recommended,” the agency said. In addition, the FDA noted that the kit is not meant to diagnose DMD or to screen for other muscular dystrophies.
The GSP Neonatal Creatine Kinase–MM kit measures the concentration of CK-MM, a type of protein that increases when there is muscle damage. The test measures CK-MM in dried blood samples collected from a newborn’s heel 24-48 hours after birth. Elevated levels may indicate DMD, but physicians must confirm the diagnosis using other methods, such as muscle biopsies, genetic testing, and other laboratory tests.
DMD primarily affects boys, and patients often do not have a family history of the condition. About 1 in 3,600 male live-born infants worldwide have DMD. Symptom onset usually occurs between the ages of 3 and 5 years.
The FDA reviewed the kit through the de novo premarket review pathway for low to moderate risk devices. In a clinical study of 3,041 newborns, the kit identified the four screened newborns who had DMD-causing genetic mutations. In addition, the test correctly identified 30 samples from newborns with clinically confirmed cases of DMD.
PerkinElmer developed the GSP Neonatal Creatine Kinase–MM kit.
The Food and Drug Administration has granted accelerated approval to Vyondys 53 (golodirsen) to treat patients with Duchenne muscular dystrophy (DMD) who have a mutation of the dystrophin gene that is amenable to exon 53 skipping. About 8% of patients with DMD have this type of mutation. Further research is required to establish whether the antisense oligonucleotide provides clinical benefit, the agency said.
Separately, the agency approved the first newborn screening test for DMD.
DMD is a “rare and devastating disease,” said Billy Dunn, MD, acting director of the office of neuroscience in the FDA’s Center for Drug Evaluation and Research.
“Patients ... who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping will now have available the first treatment targeted specifically for this disease subtype,” Dr. Dunn said in a news release. “Use of the accelerated approval pathway will make Vyondys 53 available to patients based on initial data, and we look forward to learning more about the drug’s clinical benefit from the ongoing confirmatory clinical trial.”
A surrogate endpoint
The FDA approved Vyondys 53 based on the surrogate endpoint of increased dystrophin production in the skeletal muscle in some patients treated with the drug. Sarepta Therapeutics, the developer of Vyondys 53, evaluated the treatment in a two-part clinical study. In the first part, eight patients with DMD received Vyondys 53, and four received placebo. In the second part, 25 patients, including the 12 patients from the first part, received open-label treatment. Dystrophin levels increased from 0.10% of normal at baseline to 1.02% of normal after at least 48 weeks of treatment.
A placebo-controlled, confirmatory trial is expected to conclude by 2024, the company said. If the trial does not confirm clinical benefit, the FDA could withdraw approval of the drug.
The most common side effects in patients who received Vyondys 53 include headache, fever, fall, cough, vomiting, abdominal pain, cold symptoms, and nausea. Some patients had hypersensitivity reactions. Renal toxicity occurred in animal studies of golodirsen, but not in the clinical studies. Renal toxicity, however, has occurred after treatment with other antisense oligonucleotides, the FDA noted.
Sarepta said Vyondys 53, an injection, would be available immediately. The drug is the company’s second RNA exon-skipping treatment for DMD. The FDA approved the first treatment, Exondys 51 (eteplirsen), in 2016. Together, the two drugs can treat about 20% of patients with DMD, the company said.
Newborn screening
On the same day, Dec. 12, 2019, the FDA authorized marketing of the first test to aid in newborn screening for DMD. Although authorization for the GSP Neonatal Creatine Kinase–MM kit enables laboratories to add this test to their newborn screening panel, it “does not signal a recommendation for DMD to be added ... as a condition for which newborn screening is recommended,” the agency said. In addition, the FDA noted that the kit is not meant to diagnose DMD or to screen for other muscular dystrophies.
The GSP Neonatal Creatine Kinase–MM kit measures the concentration of CK-MM, a type of protein that increases when there is muscle damage. The test measures CK-MM in dried blood samples collected from a newborn’s heel 24-48 hours after birth. Elevated levels may indicate DMD, but physicians must confirm the diagnosis using other methods, such as muscle biopsies, genetic testing, and other laboratory tests.
DMD primarily affects boys, and patients often do not have a family history of the condition. About 1 in 3,600 male live-born infants worldwide have DMD. Symptom onset usually occurs between the ages of 3 and 5 years.
The FDA reviewed the kit through the de novo premarket review pathway for low to moderate risk devices. In a clinical study of 3,041 newborns, the kit identified the four screened newborns who had DMD-causing genetic mutations. In addition, the test correctly identified 30 samples from newborns with clinically confirmed cases of DMD.
PerkinElmer developed the GSP Neonatal Creatine Kinase–MM kit.
The Food and Drug Administration has granted accelerated approval to Vyondys 53 (golodirsen) to treat patients with Duchenne muscular dystrophy (DMD) who have a mutation of the dystrophin gene that is amenable to exon 53 skipping. About 8% of patients with DMD have this type of mutation. Further research is required to establish whether the antisense oligonucleotide provides clinical benefit, the agency said.
Separately, the agency approved the first newborn screening test for DMD.
DMD is a “rare and devastating disease,” said Billy Dunn, MD, acting director of the office of neuroscience in the FDA’s Center for Drug Evaluation and Research.
“Patients ... who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping will now have available the first treatment targeted specifically for this disease subtype,” Dr. Dunn said in a news release. “Use of the accelerated approval pathway will make Vyondys 53 available to patients based on initial data, and we look forward to learning more about the drug’s clinical benefit from the ongoing confirmatory clinical trial.”
A surrogate endpoint
The FDA approved Vyondys 53 based on the surrogate endpoint of increased dystrophin production in the skeletal muscle in some patients treated with the drug. Sarepta Therapeutics, the developer of Vyondys 53, evaluated the treatment in a two-part clinical study. In the first part, eight patients with DMD received Vyondys 53, and four received placebo. In the second part, 25 patients, including the 12 patients from the first part, received open-label treatment. Dystrophin levels increased from 0.10% of normal at baseline to 1.02% of normal after at least 48 weeks of treatment.
A placebo-controlled, confirmatory trial is expected to conclude by 2024, the company said. If the trial does not confirm clinical benefit, the FDA could withdraw approval of the drug.
The most common side effects in patients who received Vyondys 53 include headache, fever, fall, cough, vomiting, abdominal pain, cold symptoms, and nausea. Some patients had hypersensitivity reactions. Renal toxicity occurred in animal studies of golodirsen, but not in the clinical studies. Renal toxicity, however, has occurred after treatment with other antisense oligonucleotides, the FDA noted.
Sarepta said Vyondys 53, an injection, would be available immediately. The drug is the company’s second RNA exon-skipping treatment for DMD. The FDA approved the first treatment, Exondys 51 (eteplirsen), in 2016. Together, the two drugs can treat about 20% of patients with DMD, the company said.
Newborn screening
On the same day, Dec. 12, 2019, the FDA authorized marketing of the first test to aid in newborn screening for DMD. Although authorization for the GSP Neonatal Creatine Kinase–MM kit enables laboratories to add this test to their newborn screening panel, it “does not signal a recommendation for DMD to be added ... as a condition for which newborn screening is recommended,” the agency said. In addition, the FDA noted that the kit is not meant to diagnose DMD or to screen for other muscular dystrophies.
The GSP Neonatal Creatine Kinase–MM kit measures the concentration of CK-MM, a type of protein that increases when there is muscle damage. The test measures CK-MM in dried blood samples collected from a newborn’s heel 24-48 hours after birth. Elevated levels may indicate DMD, but physicians must confirm the diagnosis using other methods, such as muscle biopsies, genetic testing, and other laboratory tests.
DMD primarily affects boys, and patients often do not have a family history of the condition. About 1 in 3,600 male live-born infants worldwide have DMD. Symptom onset usually occurs between the ages of 3 and 5 years.
The FDA reviewed the kit through the de novo premarket review pathway for low to moderate risk devices. In a clinical study of 3,041 newborns, the kit identified the four screened newborns who had DMD-causing genetic mutations. In addition, the test correctly identified 30 samples from newborns with clinically confirmed cases of DMD.
PerkinElmer developed the GSP Neonatal Creatine Kinase–MM kit.