PARIS—Tracking disease impact in patients with multiple sclerosis (MS) by predictable loss of economically important milestones trajectory, beyond what can be documented by EDSS, MRI, or apparent or reported relapse, can be accomplished by use of objective multidomain cognitive testing, according to a report presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Such a strategy can provide patient-centric information such as predicting likely loss of economically impactful abilities that are not completely dependent upon EDSS nor currently obtained in the course of traditional MS care or clinical trials. “This objective approach might provide a pathway towards actionable change by objectively monitoring disease progression in a way that EDSS and MRI are unable and that will likely impact therapy choice as well as timing of disease-modifying treatment change,” said Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, on behalf of his coauthors. “This approach can be incorporated into routine care and also can be utilized to easily and quantitatively track examiner independent multidomain cognitive impact longitudinally in a patient-centric manner in people with MS to perhaps improve care outcomes and reduce economic costs that accompany such increased disease burden.”

MS, which is usually characterized by relapses and progression, is traditionally measured by relapse rate reduction, changes in EDSS, and MRI findings. “EDSS change is primarily driven by physical findings or walking impairment, neither of which accounts for cognitive impact or reserve or accumulation of cognitive impairment,” Dr. Gudesblatt said. Cognitive impairment, he added, is not typically quantified or tracked in patients with MS in routine care or clinical trials. EDSS is also insensitive to the degree or types of cognitive impairment. Cognitive impairment, Dr. Gudesblatt and colleagues posit, impacts economically important abilities (eg, employment, ability to drive, and freedom from falls for both simple and complex daily activities) that are not addressed by traditional metrics.

Another layer of complexity is treatment choice. There are multiple available disease-modifying therapies of varied routes, dosing frequency, and efficacy. This makes individual treatment choice and timing of disease-modifying therapy change problematic. “A patient-centric objective analysis of disease trajectory and loss of economically important milestones relating to predictive loss of ability can supplement and perhaps improve alternative approaches to guide treatment choice, change, and timing,” Dr. Gudesblatt said.

An objective, quantitative, patient-centric, and granular EDSS-independent approach of likely disability trajectory might improve decision making regarding disease-modifying therapy choice and timing of change, offer a path to compare outcome measures across clinical trials, and possibly provide an opportunity to preempt the appearance of important disabilities that result in significantly increased cost of care and reduced quality of life. “Objective comprehensive analytics documenting unseen disease impact and change offer unique opportunities to improve care,” Dr. Gudesblatt said.

Toward this end, Dr. Gudesblatt and colleagues conducted a cross-sectional review of a prospective digital MS registry obtained in the course of routine care utilizing standardized computerized cognitive testing (NeuroTrax) to evaluate the relationship of cognitive impairment to disability. Cognitive impairment was defined as number of cognitive domains impaired (CDI) more than one standard deviation from age/education normal. Disability domains assessed were unemployment, loss of driving, and freedom from falls. Patients with an EDSS of less than 6 were included in the study cohort (ie, no one was included who was disabled to the point of requiring a cane to ambulate).

The researchers found that increasing accumulated number of CDI in patients with MS and an EDSS less than 6 is associated with likely progressive loss of:

• Employment (n = 543, CDI-0 = 61%, CDI-1 = 50%, CDI-2 = 43%, CDI-3 = 32%)
• Driving (n = 115, CDI-0 = 100%, CDI-1 = 66%, CDI-2 = 53%, CDI-3 = 21%)
• Freedom from falls (n = 159) for simple daily activities (CDI-0 = 77%, CDI-1 = 65%, CDI-2 = 37%, CDI-3 = 39%) and reduced freedom from falls for complex daily activities (CDI-0 = 72%, CDI-1 = 58%, CDI-2 = 36%, CDI-3 = 33%).

Increased risk of falls and reduced likelihood of employment and driving all represent significant impact on quality of life and result in increased economic burden and long-term costs of the disease, Dr. Gudesblatt and colleagues said.

PARIS—Tracking disease impact in patients with multiple sclerosis (MS) by predictable loss of economically important milestones trajectory, beyond what can be documented by EDSS, MRI, or apparent or reported relapse, can be accomplished by use of objective multidomain cognitive testing, according to a report presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Such a strategy can provide patient-centric information such as predicting likely loss of economically impactful abilities that are not completely dependent upon EDSS nor currently obtained in the course of traditional MS care or clinical trials. “This objective approach might provide a pathway towards actionable change by objectively monitoring disease progression in a way that EDSS and MRI are unable and that will likely impact therapy choice as well as timing of disease-modifying treatment change,” said Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, on behalf of his coauthors. “This approach can be incorporated into routine care and also can be utilized to easily and quantitatively track examiner independent multidomain cognitive impact longitudinally in a patient-centric manner in people with MS to perhaps improve care outcomes and reduce economic costs that accompany such increased disease burden.”

MS, which is usually characterized by relapses and progression, is traditionally measured by relapse rate reduction, changes in EDSS, and MRI findings. “EDSS change is primarily driven by physical findings or walking impairment, neither of which accounts for cognitive impact or reserve or accumulation of cognitive impairment,” Dr. Gudesblatt said. Cognitive impairment, he added, is not typically quantified or tracked in patients with MS in routine care or clinical trials. EDSS is also insensitive to the degree or types of cognitive impairment. Cognitive impairment, Dr. Gudesblatt and colleagues posit, impacts economically important abilities (eg, employment, ability to drive, and freedom from falls for both simple and complex daily activities) that are not addressed by traditional metrics.

Another layer of complexity is treatment choice. There are multiple available disease-modifying therapies of varied routes, dosing frequency, and efficacy. This makes individual treatment choice and timing of disease-modifying therapy change problematic. “A patient-centric objective analysis of disease trajectory and loss of economically important milestones relating to predictive loss of ability can supplement and perhaps improve alternative approaches to guide treatment choice, change, and timing,” Dr. Gudesblatt said.

An objective, quantitative, patient-centric, and granular EDSS-independent approach of likely disability trajectory might improve decision making regarding disease-modifying therapy choice and timing of change, offer a path to compare outcome measures across clinical trials, and possibly provide an opportunity to preempt the appearance of important disabilities that result in significantly increased cost of care and reduced quality of life. “Objective comprehensive analytics documenting unseen disease impact and change offer unique opportunities to improve care,” Dr. Gudesblatt said.

Toward this end, Dr. Gudesblatt and colleagues conducted a cross-sectional review of a prospective digital MS registry obtained in the course of routine care utilizing standardized computerized cognitive testing (NeuroTrax) to evaluate the relationship of cognitive impairment to disability. Cognitive impairment was defined as number of cognitive domains impaired (CDI) more than one standard deviation from age/education normal. Disability domains assessed were unemployment, loss of driving, and freedom from falls. Patients with an EDSS of less than 6 were included in the study cohort (ie, no one was included who was disabled to the point of requiring a cane to ambulate).

The researchers found that increasing accumulated number of CDI in patients with MS and an EDSS less than 6 is associated with likely progressive loss of:

• Employment (n = 543, CDI-0 = 61%, CDI-1 = 50%, CDI-2 = 43%, CDI-3 = 32%)
• Driving (n = 115, CDI-0 = 100%, CDI-1 = 66%, CDI-2 = 53%, CDI-3 = 21%)
• Freedom from falls (n = 159) for simple daily activities (CDI-0 = 77%, CDI-1 = 65%, CDI-2 = 37%, CDI-3 = 39%) and reduced freedom from falls for complex daily activities (CDI-0 = 72%, CDI-1 = 58%, CDI-2 = 36%, CDI-3 = 33%).

Increased risk of falls and reduced likelihood of employment and driving all represent significant impact on quality of life and result in increased economic burden and long-term costs of the disease, Dr. Gudesblatt and colleagues said.

PARIS—Tracking disease impact in patients with multiple sclerosis (MS) by predictable loss of economically important milestones trajectory, beyond what can be documented by EDSS, MRI, or apparent or reported relapse, can be accomplished by use of objective multidomain cognitive testing, according to a report presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Such a strategy can provide patient-centric information such as predicting likely loss of economically impactful abilities that are not completely dependent upon EDSS nor currently obtained in the course of traditional MS care or clinical trials. “This objective approach might provide a pathway towards actionable change by objectively monitoring disease progression in a way that EDSS and MRI are unable and that will likely impact therapy choice as well as timing of disease-modifying treatment change,” said Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, on behalf of his coauthors. “This approach can be incorporated into routine care and also can be utilized to easily and quantitatively track examiner independent multidomain cognitive impact longitudinally in a patient-centric manner in people with MS to perhaps improve care outcomes and reduce economic costs that accompany such increased disease burden.”

MS, which is usually characterized by relapses and progression, is traditionally measured by relapse rate reduction, changes in EDSS, and MRI findings. “EDSS change is primarily driven by physical findings or walking impairment, neither of which accounts for cognitive impact or reserve or accumulation of cognitive impairment,” Dr. Gudesblatt said. Cognitive impairment, he added, is not typically quantified or tracked in patients with MS in routine care or clinical trials. EDSS is also insensitive to the degree or types of cognitive impairment. Cognitive impairment, Dr. Gudesblatt and colleagues posit, impacts economically important abilities (eg, employment, ability to drive, and freedom from falls for both simple and complex daily activities) that are not addressed by traditional metrics.

Another layer of complexity is treatment choice. There are multiple available disease-modifying therapies of varied routes, dosing frequency, and efficacy. This makes individual treatment choice and timing of disease-modifying therapy change problematic. “A patient-centric objective analysis of disease trajectory and loss of economically important milestones relating to predictive loss of ability can supplement and perhaps improve alternative approaches to guide treatment choice, change, and timing,” Dr. Gudesblatt said.

An objective, quantitative, patient-centric, and granular EDSS-independent approach of likely disability trajectory might improve decision making regarding disease-modifying therapy choice and timing of change, offer a path to compare outcome measures across clinical trials, and possibly provide an opportunity to preempt the appearance of important disabilities that result in significantly increased cost of care and reduced quality of life. “Objective comprehensive analytics documenting unseen disease impact and change offer unique opportunities to improve care,” Dr. Gudesblatt said.

Toward this end, Dr. Gudesblatt and colleagues conducted a cross-sectional review of a prospective digital MS registry obtained in the course of routine care utilizing standardized computerized cognitive testing (NeuroTrax) to evaluate the relationship of cognitive impairment to disability. Cognitive impairment was defined as number of cognitive domains impaired (CDI) more than one standard deviation from age/education normal. Disability domains assessed were unemployment, loss of driving, and freedom from falls. Patients with an EDSS of less than 6 were included in the study cohort (ie, no one was included who was disabled to the point of requiring a cane to ambulate).

The researchers found that increasing accumulated number of CDI in patients with MS and an EDSS less than 6 is associated with likely progressive loss of:

• Employment (n = 543, CDI-0 = 61%, CDI-1 = 50%, CDI-2 = 43%, CDI-3 = 32%)
• Driving (n = 115, CDI-0 = 100%, CDI-1 = 66%, CDI-2 = 53%, CDI-3 = 21%)
• Freedom from falls (n = 159) for simple daily activities (CDI-0 = 77%, CDI-1 = 65%, CDI-2 = 37%, CDI-3 = 39%) and reduced freedom from falls for complex daily activities (CDI-0 = 72%, CDI-1 = 58%, CDI-2 = 36%, CDI-3 = 33%).

Increased risk of falls and reduced likelihood of employment and driving all represent significant impact on quality of life and result in increased economic burden and long-term costs of the disease, Dr. Gudesblatt and colleagues said.

What do patients need to know about arboviruses?

Dengue is the most common arbovirus worldwide, with more than 300 million individuals infected each year, most of them asymptomatic carriers. It is the most common febrile illness in travelers returning from Southeast Asia, South America, and the Caribbean. Dengue symptoms typically begin 3 to 12 days after exposure and may include fever; headache; conjunctivitis; and a biphasic rash that begins with blanching macular erythema, which patients may mistake for sunburn, followed by a morbilliform to petechial rash with islands of sparing (white islands in a sea of red). Severe dengue (formerly known as dengue hemorrhagic fever) may present with dramatic skin and mucosal hemorrhage including purpura, hemorrhagic bullae, and bleeding from orifices and injection sites, with associated thrombocytopenia and hypotension (dengue shock syndrome). Patients with onset of such symptoms need to go to the emergency department for inpatient management.

Individuals living in the United States should be particularly aware of West Nile virus, with infections reported in all US states in 2017, except Alaska and Hawaii thus far. Transmitted by the bite of the Culex mosquito, most infections are symptomatic; however, up to 20% of patients may present with nonspecific symptoms such as mild febrile or flulike symptoms, nonspecific morbilliform rash, and headaches, and up to 1% of patients may develop encephalitis or meningitis, with approximately 10% mortality rates.

What are your go-to treatments?

Arboviral infections generally are self-limited and there are no specific treatments available. Supportive care, including fluid resuscitation, and analgesia (if needed for joint, muscle, or bone pain) are the mainstays of management. Diagnoses generally are confirmed via viral polymerase chain reaction from serum (<7 days), IgM enzyme-linked immunosorbent assay (>4 days), or IgG serologies for later presentations.

Patients should avoid the use of nonsteroidal anti-inflammatory drugs if there is a possibility of dengue virus infection, as they may potentiate the risk for hemorrhagic complications in patients with severe dengue. Instead, acetaminophen is recommended for analgesia and antipyretic purposes, if needed.

How do you recommend patients prevent infection while traveling?

Primary prevention of infection and secondary prevention of transmission are important. Although mosquito bed netting is helpful in preventing some mosquito-borne viruses, many arboviruses (ie, dengue, Zika, chikun-gunya) are transmitted by primarily daytime-biting Aedes mosquitoes. In an endemic area, travelers should try to stay within air-conditioned buildings with intact window and door screens. When outdoors, wear long sleeves and pants and use Environmental Protection Agency-registered mosquito repellents. Conventional repellents include the following:

• DEET: concentrations 10% to 30% are safe for children 2 months and older and pregnant women; concentrations around 10% are effective for periods of approximately 2 hours; as the concentration of DEET increases, the duration of protection increases.
• Picaridin: concentrations of 5% to 20%; effective for 4 to 8 hours depending on the concentration; most effective concentration is 20%; is not effective against ticks.  

Biopesticide repellents include the following:

• IR3535 (ethyl butylacetylaminopropionate): concentration 10% to 30% has been used as an insect repellent in Europe for 20 years with no substantial adverse effects.
• 2-undecanone: a natural compound from leaves and stems of the wild tomato plant; is a biopesticide product less toxic than conventional pesticides.
• Oil of lemon eucalyptus (OLE) or PMD (the synthesized version of OLE): concentration 30%; "pure" oil of lemon eucalyptus (essential oil not formulated as a repellent) is not recommended.
• Natural oils (eg, soybean, lemongrass, citronella, cedar, peppermint, lavender, geranium) are exempted from Environmental Protection Agency registration; duration of effectiveness is estimated between 30 minutes and 2 hours.

Products that combine sunscreen and repellent are not recommended because sunscreen may need to be reapplied, increasing the toxicity of the repellent. Use separate products, applying sunscreen first and then applying the repellent.

Permethrin-treated clothing may provide an additional measure of protection, though in some endemic areas, resistance has been reported.

Because sexual transmission has been reported for Zika virus (between both male and female partners), any known or possibly infected persons should use condoms. Durations of abstinence or protected sex recommendations vary by situation and more detailed recommendations can be found from the Centers for Disease Control and Prevention. Pregnant women and women trying to get pregnant should take preventive measures with respect to Zika due to the possibility of the virus causing severe birth defects (congenital Zika syndrome) including microcephaly, joint deformities, ocular damage, and hypertonia.

What do patients need to know about arboviruses?

Dengue is the most common arbovirus worldwide, with more than 300 million individuals infected each year, most of them asymptomatic carriers. It is the most common febrile illness in travelers returning from Southeast Asia, South America, and the Caribbean. Dengue symptoms typically begin 3 to 12 days after exposure and may include fever; headache; conjunctivitis; and a biphasic rash that begins with blanching macular erythema, which patients may mistake for sunburn, followed by a morbilliform to petechial rash with islands of sparing (white islands in a sea of red). Severe dengue (formerly known as dengue hemorrhagic fever) may present with dramatic skin and mucosal hemorrhage including purpura, hemorrhagic bullae, and bleeding from orifices and injection sites, with associated thrombocytopenia and hypotension (dengue shock syndrome). Patients with onset of such symptoms need to go to the emergency department for inpatient management.

Individuals living in the United States should be particularly aware of West Nile virus, with infections reported in all US states in 2017, except Alaska and Hawaii thus far. Transmitted by the bite of the Culex mosquito, most infections are symptomatic; however, up to 20% of patients may present with nonspecific symptoms such as mild febrile or flulike symptoms, nonspecific morbilliform rash, and headaches, and up to 1% of patients may develop encephalitis or meningitis, with approximately 10% mortality rates.

What are your go-to treatments?

Arboviral infections generally are self-limited and there are no specific treatments available. Supportive care, including fluid resuscitation, and analgesia (if needed for joint, muscle, or bone pain) are the mainstays of management. Diagnoses generally are confirmed via viral polymerase chain reaction from serum (<7 days), IgM enzyme-linked immunosorbent assay (>4 days), or IgG serologies for later presentations.

Patients should avoid the use of nonsteroidal anti-inflammatory drugs if there is a possibility of dengue virus infection, as they may potentiate the risk for hemorrhagic complications in patients with severe dengue. Instead, acetaminophen is recommended for analgesia and antipyretic purposes, if needed.

How do you recommend patients prevent infection while traveling?

Primary prevention of infection and secondary prevention of transmission are important. Although mosquito bed netting is helpful in preventing some mosquito-borne viruses, many arboviruses (ie, dengue, Zika, chikun-gunya) are transmitted by primarily daytime-biting Aedes mosquitoes. In an endemic area, travelers should try to stay within air-conditioned buildings with intact window and door screens. When outdoors, wear long sleeves and pants and use Environmental Protection Agency-registered mosquito repellents. Conventional repellents include the following:

• DEET: concentrations 10% to 30% are safe for children 2 months and older and pregnant women; concentrations around 10% are effective for periods of approximately 2 hours; as the concentration of DEET increases, the duration of protection increases.
• Picaridin: concentrations of 5% to 20%; effective for 4 to 8 hours depending on the concentration; most effective concentration is 20%; is not effective against ticks.  

Biopesticide repellents include the following:

• IR3535 (ethyl butylacetylaminopropionate): concentration 10% to 30% has been used as an insect repellent in Europe for 20 years with no substantial adverse effects.
• 2-undecanone: a natural compound from leaves and stems of the wild tomato plant; is a biopesticide product less toxic than conventional pesticides.
• Oil of lemon eucalyptus (OLE) or PMD (the synthesized version of OLE): concentration 30%; "pure" oil of lemon eucalyptus (essential oil not formulated as a repellent) is not recommended.
• Natural oils (eg, soybean, lemongrass, citronella, cedar, peppermint, lavender, geranium) are exempted from Environmental Protection Agency registration; duration of effectiveness is estimated between 30 minutes and 2 hours.

Products that combine sunscreen and repellent are not recommended because sunscreen may need to be reapplied, increasing the toxicity of the repellent. Use separate products, applying sunscreen first and then applying the repellent.

Permethrin-treated clothing may provide an additional measure of protection, though in some endemic areas, resistance has been reported.

Because sexual transmission has been reported for Zika virus (between both male and female partners), any known or possibly infected persons should use condoms. Durations of abstinence or protected sex recommendations vary by situation and more detailed recommendations can be found from the Centers for Disease Control and Prevention. Pregnant women and women trying to get pregnant should take preventive measures with respect to Zika due to the possibility of the virus causing severe birth defects (congenital Zika syndrome) including microcephaly, joint deformities, ocular damage, and hypertonia.

What do patients need to know about arboviruses?

Dengue is the most common arbovirus worldwide, with more than 300 million individuals infected each year, most of them asymptomatic carriers. It is the most common febrile illness in travelers returning from Southeast Asia, South America, and the Caribbean. Dengue symptoms typically begin 3 to 12 days after exposure and may include fever; headache; conjunctivitis; and a biphasic rash that begins with blanching macular erythema, which patients may mistake for sunburn, followed by a morbilliform to petechial rash with islands of sparing (white islands in a sea of red). Severe dengue (formerly known as dengue hemorrhagic fever) may present with dramatic skin and mucosal hemorrhage including purpura, hemorrhagic bullae, and bleeding from orifices and injection sites, with associated thrombocytopenia and hypotension (dengue shock syndrome). Patients with onset of such symptoms need to go to the emergency department for inpatient management.

Individuals living in the United States should be particularly aware of West Nile virus, with infections reported in all US states in 2017, except Alaska and Hawaii thus far. Transmitted by the bite of the Culex mosquito, most infections are symptomatic; however, up to 20% of patients may present with nonspecific symptoms such as mild febrile or flulike symptoms, nonspecific morbilliform rash, and headaches, and up to 1% of patients may develop encephalitis or meningitis, with approximately 10% mortality rates.

What are your go-to treatments?

Arboviral infections generally are self-limited and there are no specific treatments available. Supportive care, including fluid resuscitation, and analgesia (if needed for joint, muscle, or bone pain) are the mainstays of management. Diagnoses generally are confirmed via viral polymerase chain reaction from serum (<7 days), IgM enzyme-linked immunosorbent assay (>4 days), or IgG serologies for later presentations.

Patients should avoid the use of nonsteroidal anti-inflammatory drugs if there is a possibility of dengue virus infection, as they may potentiate the risk for hemorrhagic complications in patients with severe dengue. Instead, acetaminophen is recommended for analgesia and antipyretic purposes, if needed.

How do you recommend patients prevent infection while traveling?

Primary prevention of infection and secondary prevention of transmission are important. Although mosquito bed netting is helpful in preventing some mosquito-borne viruses, many arboviruses (ie, dengue, Zika, chikun-gunya) are transmitted by primarily daytime-biting Aedes mosquitoes. In an endemic area, travelers should try to stay within air-conditioned buildings with intact window and door screens. When outdoors, wear long sleeves and pants and use Environmental Protection Agency-registered mosquito repellents. Conventional repellents include the following:

• DEET: concentrations 10% to 30% are safe for children 2 months and older and pregnant women; concentrations around 10% are effective for periods of approximately 2 hours; as the concentration of DEET increases, the duration of protection increases.
• Picaridin: concentrations of 5% to 20%; effective for 4 to 8 hours depending on the concentration; most effective concentration is 20%; is not effective against ticks.  

Biopesticide repellents include the following:

• IR3535 (ethyl butylacetylaminopropionate): concentration 10% to 30% has been used as an insect repellent in Europe for 20 years with no substantial adverse effects.
• 2-undecanone: a natural compound from leaves and stems of the wild tomato plant; is a biopesticide product less toxic than conventional pesticides.
• Oil of lemon eucalyptus (OLE) or PMD (the synthesized version of OLE): concentration 30%; "pure" oil of lemon eucalyptus (essential oil not formulated as a repellent) is not recommended.
• Natural oils (eg, soybean, lemongrass, citronella, cedar, peppermint, lavender, geranium) are exempted from Environmental Protection Agency registration; duration of effectiveness is estimated between 30 minutes and 2 hours.

Products that combine sunscreen and repellent are not recommended because sunscreen may need to be reapplied, increasing the toxicity of the repellent. Use separate products, applying sunscreen first and then applying the repellent.

Permethrin-treated clothing may provide an additional measure of protection, though in some endemic areas, resistance has been reported.

Because sexual transmission has been reported for Zika virus (between both male and female partners), any known or possibly infected persons should use condoms. Durations of abstinence or protected sex recommendations vary by situation and more detailed recommendations can be found from the Centers for Disease Control and Prevention. Pregnant women and women trying to get pregnant should take preventive measures with respect to Zika due to the possibility of the virus causing severe birth defects (congenital Zika syndrome) including microcephaly, joint deformities, ocular damage, and hypertonia.

PARIS—Clinical efficacy of alemtuzumab was maintained for seven years in patients who had inadequate response to prior therapy, despite 47% receiving no additional treatment since the initial two courses of alemtuzumab, according to study data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. In addition, 44% of patients showed improvement in disability, researchers reported. “These findings suggest that alemtuzumab may provide a unique treatment approach for patients with relapsing-remitting multiple sclerosis (RRMS), offering durable efficacy in the absence of continuous treatment,” said Barry Singer, MD, Director of the MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis.

Alemtuzumab Treatment: Then

In the CARE-MS II trial, alemtuzumab significantly improved clinical outcomes compared with subcutaneous interferon beta-1a over two years in patients with active RRMS and an inadequate response to prior therapy. Durable efficacy of alemtuzumab was demonstrated over six years in a completed extension study in the absence of continuous treatment. Patients in the CARE-MS II study received two courses of alemtuzumab 12 mg/day (five days of therapy at baseline and three days of therapy 12 months later). In the extension study, patients could receive as-needed alemtuzumab retreatment (12 mg/day on three consecutive days at least 12 months after a previous course for relapse or MRI activity) or other disease-modifying therapy per investigator discretion. Patients completing at least 48 months of the extension could enroll in the five-year TOPAZ study for further long-term evaluation.

Alemtuzumab Treatment: Now

The goal of the TOPAZ study was to evaluate the seven-year efficacy and safety of alemtuzumab in patients with RRMS who received alemtuzumab in the CARE-MS II trial. In TOPAZ, patients could receive alemtuzumab retreatment 12 months or more after a previous course or other disease-modifying therapy at any time point (both per investigator discretion; no criteria). MRI scans were done annually. Annualized relapse rate, six-month confirmed disability worsening, six-month confirmed disability improvement, no evidence of disease activity (NEDA), and adverse events were analyzed in TOPAZ.

In total, 338 of 393 (86%) CARE-MS II patients who entered the extension remained on study until the end of year six and then entered TOPAZ; 317 (94%) remained on study through year seven. Annualized release rate remained low (0.14 at year seven) and the proportion of patients with stable or improved Expanded Disability Status Scale score remained high (73% at year seven). Through year seven, 69% of patients were free from six-month confirmed disability worsening, 44% achieved six-month confirmed disability improvement, and the majority achieved NEDA each year. These effects were achieved with 47% of patients receiving no additional treatment (alemtuzumab or other disease-modifying treatment) after their initial two courses of alemtuzumab. Incidences of overall adverse events, infusion-associated reactions, and infections decreased over time and were reduced, compared with those in the two-year core study. Thyroid adverse events incidence peaked at year three and then declined.

PARIS—Clinical efficacy of alemtuzumab was maintained for seven years in patients who had inadequate response to prior therapy, despite 47% receiving no additional treatment since the initial two courses of alemtuzumab, according to study data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. In addition, 44% of patients showed improvement in disability, researchers reported. “These findings suggest that alemtuzumab may provide a unique treatment approach for patients with relapsing-remitting multiple sclerosis (RRMS), offering durable efficacy in the absence of continuous treatment,” said Barry Singer, MD, Director of the MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis.

Alemtuzumab Treatment: Then

In the CARE-MS II trial, alemtuzumab significantly improved clinical outcomes compared with subcutaneous interferon beta-1a over two years in patients with active RRMS and an inadequate response to prior therapy. Durable efficacy of alemtuzumab was demonstrated over six years in a completed extension study in the absence of continuous treatment. Patients in the CARE-MS II study received two courses of alemtuzumab 12 mg/day (five days of therapy at baseline and three days of therapy 12 months later). In the extension study, patients could receive as-needed alemtuzumab retreatment (12 mg/day on three consecutive days at least 12 months after a previous course for relapse or MRI activity) or other disease-modifying therapy per investigator discretion. Patients completing at least 48 months of the extension could enroll in the five-year TOPAZ study for further long-term evaluation.

Alemtuzumab Treatment: Now

The goal of the TOPAZ study was to evaluate the seven-year efficacy and safety of alemtuzumab in patients with RRMS who received alemtuzumab in the CARE-MS II trial. In TOPAZ, patients could receive alemtuzumab retreatment 12 months or more after a previous course or other disease-modifying therapy at any time point (both per investigator discretion; no criteria). MRI scans were done annually. Annualized relapse rate, six-month confirmed disability worsening, six-month confirmed disability improvement, no evidence of disease activity (NEDA), and adverse events were analyzed in TOPAZ.

In total, 338 of 393 (86%) CARE-MS II patients who entered the extension remained on study until the end of year six and then entered TOPAZ; 317 (94%) remained on study through year seven. Annualized release rate remained low (0.14 at year seven) and the proportion of patients with stable or improved Expanded Disability Status Scale score remained high (73% at year seven). Through year seven, 69% of patients were free from six-month confirmed disability worsening, 44% achieved six-month confirmed disability improvement, and the majority achieved NEDA each year. These effects were achieved with 47% of patients receiving no additional treatment (alemtuzumab or other disease-modifying treatment) after their initial two courses of alemtuzumab. Incidences of overall adverse events, infusion-associated reactions, and infections decreased over time and were reduced, compared with those in the two-year core study. Thyroid adverse events incidence peaked at year three and then declined.

PARIS—Clinical efficacy of alemtuzumab was maintained for seven years in patients who had inadequate response to prior therapy, despite 47% receiving no additional treatment since the initial two courses of alemtuzumab, according to study data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. In addition, 44% of patients showed improvement in disability, researchers reported. “These findings suggest that alemtuzumab may provide a unique treatment approach for patients with relapsing-remitting multiple sclerosis (RRMS), offering durable efficacy in the absence of continuous treatment,” said Barry Singer, MD, Director of the MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis.

Alemtuzumab Treatment: Then

In the CARE-MS II trial, alemtuzumab significantly improved clinical outcomes compared with subcutaneous interferon beta-1a over two years in patients with active RRMS and an inadequate response to prior therapy. Durable efficacy of alemtuzumab was demonstrated over six years in a completed extension study in the absence of continuous treatment. Patients in the CARE-MS II study received two courses of alemtuzumab 12 mg/day (five days of therapy at baseline and three days of therapy 12 months later). In the extension study, patients could receive as-needed alemtuzumab retreatment (12 mg/day on three consecutive days at least 12 months after a previous course for relapse or MRI activity) or other disease-modifying therapy per investigator discretion. Patients completing at least 48 months of the extension could enroll in the five-year TOPAZ study for further long-term evaluation.

Alemtuzumab Treatment: Now

The goal of the TOPAZ study was to evaluate the seven-year efficacy and safety of alemtuzumab in patients with RRMS who received alemtuzumab in the CARE-MS II trial. In TOPAZ, patients could receive alemtuzumab retreatment 12 months or more after a previous course or other disease-modifying therapy at any time point (both per investigator discretion; no criteria). MRI scans were done annually. Annualized relapse rate, six-month confirmed disability worsening, six-month confirmed disability improvement, no evidence of disease activity (NEDA), and adverse events were analyzed in TOPAZ.

In total, 338 of 393 (86%) CARE-MS II patients who entered the extension remained on study until the end of year six and then entered TOPAZ; 317 (94%) remained on study through year seven. Annualized release rate remained low (0.14 at year seven) and the proportion of patients with stable or improved Expanded Disability Status Scale score remained high (73% at year seven). Through year seven, 69% of patients were free from six-month confirmed disability worsening, 44% achieved six-month confirmed disability improvement, and the majority achieved NEDA each year. These effects were achieved with 47% of patients receiving no additional treatment (alemtuzumab or other disease-modifying treatment) after their initial two courses of alemtuzumab. Incidences of overall adverse events, infusion-associated reactions, and infections decreased over time and were reduced, compared with those in the two-year core study. Thyroid adverse events incidence peaked at year three and then declined.

BOSTON – Despite years of frustrating failures, Alzheimer’s researchers keep punching away at beta-amyloid brain plaques, now apparently with a highly focused one-two of “more drug, given sooner.”

Solanezumab and gantenerumab – both of which failed in earlier phase 3 studies – will be pushed forward now at much higher doses, the Alzheimer’s disease research community learned at the opening session of the Clinical Trials on Alzheimer’s Disease conference.

Trifonenko/Thinkstock

[email protected]

On Twitter @alz_gal

BOSTON – Despite years of frustrating failures, Alzheimer’s researchers keep punching away at beta-amyloid brain plaques, now apparently with a highly focused one-two of “more drug, given sooner.”

Solanezumab and gantenerumab – both of which failed in earlier phase 3 studies – will be pushed forward now at much higher doses, the Alzheimer’s disease research community learned at the opening session of the Clinical Trials on Alzheimer’s Disease conference.

Trifonenko/Thinkstock

[email protected]

On Twitter @alz_gal

BOSTON – Despite years of frustrating failures, Alzheimer’s researchers keep punching away at beta-amyloid brain plaques, now apparently with a highly focused one-two of “more drug, given sooner.”

Solanezumab and gantenerumab – both of which failed in earlier phase 3 studies – will be pushed forward now at much higher doses, the Alzheimer’s disease research community learned at the opening session of the Clinical Trials on Alzheimer’s Disease conference.

Trifonenko/Thinkstock

[email protected]

On Twitter @alz_gal

Case Report

A 65-year-old man presented with multiple anesthetic, annular, erythematous, scaly plaques with a raised border of 6 weeks’ duration that were unresponsive to topical steroid therapy. Four plaques were noted on the lower back ranging from 2 to 4 cm in diameter as well as a fifth plaque on the anterior portion of the right ankle that was approximately 6×6 cm. He denied fever, malaise, muscle weakness, changes in vision, or sensory deficits outside of the lesions themselves. The patient also denied any recent travel to endemic areas or exposure to armadillos.

Biopsies were taken from lesions on the lumbar back and anterior aspect of the right ankle (Figure 1A). Hematoxylin and eosin staining revealed a granulomatous infiltrate spreading along neurovascular structures (Figure 2). Granulomas also were identified in the dermal interstitium exhibiting partial necrosis (Figure 2 inset). Conspicuous distension of lymphovascular and perineural areas also was noted. Immunohistochemical studies with S-100 and neurofilament stains allowed insight into the pathomechanism of the clinically observed anesthesia, as nerve fibers were identified showing different stages of damage elicited by the granulomatous inflammatory infiltrate (Figure 3). Fite staining was positive for occasional bacilli within histiocytes (Figure 3A inset). Despite the clinical, histologic, and immunohistochemical evidence, the patient had no known exposure to leprosy; consequently, a polymerase chain reaction (PCR) assay was ordered for confirmation of the diagnosis. Surprisingly, the PCR was positive for Mycobacterium leprae DNA. These findings were consistent with borderline tuberculoid leprosy.

The case was reported to the National Hansen’s Disease Program (Baton Rouge, Louisiana). The patient was started on rifampicin 600 mg once monthly and dapsone 100 mg once daily for 6 months. The lesions exhibited marked improvement after completion of therapy (Figure 1B).

Comment

Disease Transmission
Hansen disease, also known as leprosy, is a chronic granulomatous infectious disease that is caused by M leprae, an obligate intracellular bacillus aerobe.¹ The mechanism of spread of M leprae is not clear. It is thought to be transmitted via respiratory droplets, though it may occur through injured skin.² Studies have suggested that in addition to humans, nine-banded armadillos are a source of infection.^2,3 Exposure to infected individuals, particularly multibacillary patients, increases the likelihood of contracting leprosy.²

According to the Centers for Disease Control and Prevention, 81 cases of Hansen disease were diagnosed in the United States in 2013,⁴ compared to 178 cases registered in 2015.⁵ Cases from Hawaii, Texas, California, Louisiana, New York, and Florida made up 72% (129/178) of the reported cases. There was an increase from 34 cases to 49 cases in Florida from 2014 to 2015.⁵ The spread of leprosy throughout Florida may be from the merge of 2 armadillo populations, an M leprae–infected population migrating east from Texas and one from south central Florida that historically had not been infected with M leprae until recently.^3,6 Our patient did not have any known exposures to armadillos.

Classification and Presentation
The clinical presentation of Hansen disease is widely variable, as it can present at any point along a spectrum ranging from tuberculoid leprosy to lepromatous leprosy with borderline conditions in between, according to the Ridley-Jopling critera.⁷ The World Health Organization also classifies leprosy based on the number of acid-fast bacilli seen in a skin smear as either paucibacillary or multibacillary.² The paucibacillary classification correlates with tuberculoid, borderline tuberculoid, and indeterminate leprosy, and multibacillary correlates with borderline lepromatous and lepromatous leprosy. Paucibacillary leprosy usually presents with a less dramatic clinical picture than multibacillary leprosy. The clinical presentation is dependent on the magnitude of immune response to M leprae.²

Paucibacillary infection occurs when the body generates a strong cell-mediated immune response against the bacteria,⁸ which causes the activation and proliferation of CD4 and CD8 T cells, limiting the spread of the mycobacterium. Subsequently, the patient typically presents with a mild clinical picture with few skin lesions and limited nerve involvement.⁸ The skin lesions are papules or plaques with raised borders that are usually hypopigmented on dark skin and erythematous on light skin. Nerve involvement in paucibacillary forms of leprosy include sensory impairment and anhidrosis within the lesions. Nerve enlargement usually affects superficial nerves, with the posterior tibial nerve being most commonly affected.

Multibacillary leprosy presents with systemic involvement due to a weak cell-mediated immune response. Patients generally present with diffuse, poorly defined nodules; greater nerve impairment; and other systemic symptoms such as blindness, swelling of the fingers and toes, and testicular atrophy (in men). Additionally, enlargement of the earlobes and widening of the nasal bridge may contribute to the appearance of leonine facies. Nerve impairment in multibacillary forms of leprosy may be more severe, including more diffuse sensory involvement (eg, stocking glove–pattern neuropathy, nerve-trunk palsies), which ultimately may lead to foot drop, claw toe, and lagophthalmos.⁸

In addition to the clinical presentation, the histology of the paucibacillary and multibacillary types differ. Multibacillary leprosy shows diffuse histiocytes without granulomas and multiple bacilli seen on Fite staining.⁸ In the paucibacillary form, there are well-formed granulomas with Langerhans giant cells and a perineural lymphocytic infiltrate seen on hematoxylin and eosin staining with rare acid-fast bacilli seen on Fite staining.

To diagnose leprosy, at least one of the following 3 clinical signs must be present: (1) a hypopigmented or erythematous lesion with loss of sensation, (2) thickened peripheral nerve, or (3) acid-fast bacilli on slit-skin smear.²

Management
The World Health Organization guidelines involve multidrug therapy over an extended period of time.² For adults, the paucibacillary regimen includes rifampicin 600 mg once monthly and dapsone 100 mg once daily for 6 months. The adult regimen for multibacillary leprosy includes clofazimine 300 mg once monthly and 50 mg once daily, in addition to rifampicin 600 mg once monthly and dapsone 100 mg once daily for 12 months. If classification cannot be determined, it is recommended the patient be treated for multibacillary disease.²

Reversal Reactions
During the course of the disease, patients may upgrade (to a less severe form) or downgrade (to a more severe form) between the tuberculoid, borderline, and lepromatous forms.⁸ The patient’s clinical picture also may change with complications of leprosy, which include type 1 and type 2 reactions. Type 1 reaction is a reversal reaction seen in 15% to 30% of patients at risk, usually those with borderline forms of leprosy.⁹ Reversal reactions usually manifest as erythema and edema of current skin lesions, formation of new tumid lesions, and tenderness of peripheral nerves with loss of nerve function.⁸ Treatment of reversal reactions involves systemic corticosteroids.¹⁰ Type 2 reaction is classified as erythema nodosum leprosum. It presents within the first 2 years of treatment in approximately 20% of lepromatous patients and approximately 10% of borderline lepromatous patients but is rare in paucibacillary infections.¹¹ It presents with fever and crops of pink nodules and may include iritis, neuritis, lymphadenitis, orchitis, dactylitis, arthritis, and proteinuria.⁸ Treatment options for erythema nodosum leprosum include corticosteroids, clofazimine, and thalidomide.^12,13

Conclusion

Hansen disease is a rare condition in the United States. This case is unique because, to our knowledge, it is the first known PCR-confirmed case of Hansen disease in Okeechobee County, Florida. Additionally, the patient had no known exposure to M leprae. Exposure is increasing due to the increased geographical range of infected armadillos. Infection rates also may rise due to travel to endemic countries. Initially lesions may appear as innocuous erythematous plaques. When they do not respond to standard therapy, infectious agents such as M leprae should be part of the differential diagnosis. Because hematoxylin and eosin staining does not always yield results, if clinical suspicion is present, PCR should be performed. If a patient meets the clinical and histological diagnosis, the case should be reported to the National Hansen’s Disease Program.

After completion of treatment, our patient has shown excellent results. He has not yet demonstrated a reversal reaction; however, he may still be at risk, as it most commonly presents 2 months after starting treatment but can present years after treatment has been initiated.⁸ Cutaneous leprosy must be considered in the differential diagnosis for steroid-nonresponsive skin lesions, particularly in states such as Florida with a documented increase in incidence.

Acknowledgment
We thank Sharon Barrineau, ARNP (Okeechobee, Florida), for her acumen, contributions, and support on this case.

Case Report

A 65-year-old man presented with multiple anesthetic, annular, erythematous, scaly plaques with a raised border of 6 weeks’ duration that were unresponsive to topical steroid therapy. Four plaques were noted on the lower back ranging from 2 to 4 cm in diameter as well as a fifth plaque on the anterior portion of the right ankle that was approximately 6×6 cm. He denied fever, malaise, muscle weakness, changes in vision, or sensory deficits outside of the lesions themselves. The patient also denied any recent travel to endemic areas or exposure to armadillos.

Biopsies were taken from lesions on the lumbar back and anterior aspect of the right ankle (Figure 1A). Hematoxylin and eosin staining revealed a granulomatous infiltrate spreading along neurovascular structures (Figure 2). Granulomas also were identified in the dermal interstitium exhibiting partial necrosis (Figure 2 inset). Conspicuous distension of lymphovascular and perineural areas also was noted. Immunohistochemical studies with S-100 and neurofilament stains allowed insight into the pathomechanism of the clinically observed anesthesia, as nerve fibers were identified showing different stages of damage elicited by the granulomatous inflammatory infiltrate (Figure 3). Fite staining was positive for occasional bacilli within histiocytes (Figure 3A inset). Despite the clinical, histologic, and immunohistochemical evidence, the patient had no known exposure to leprosy; consequently, a polymerase chain reaction (PCR) assay was ordered for confirmation of the diagnosis. Surprisingly, the PCR was positive for Mycobacterium leprae DNA. These findings were consistent with borderline tuberculoid leprosy.

The case was reported to the National Hansen’s Disease Program (Baton Rouge, Louisiana). The patient was started on rifampicin 600 mg once monthly and dapsone 100 mg once daily for 6 months. The lesions exhibited marked improvement after completion of therapy (Figure 1B).

Comment

Disease Transmission
Hansen disease, also known as leprosy, is a chronic granulomatous infectious disease that is caused by M leprae, an obligate intracellular bacillus aerobe.¹ The mechanism of spread of M leprae is not clear. It is thought to be transmitted via respiratory droplets, though it may occur through injured skin.² Studies have suggested that in addition to humans, nine-banded armadillos are a source of infection.^2,3 Exposure to infected individuals, particularly multibacillary patients, increases the likelihood of contracting leprosy.²

According to the Centers for Disease Control and Prevention, 81 cases of Hansen disease were diagnosed in the United States in 2013,⁴ compared to 178 cases registered in 2015.⁵ Cases from Hawaii, Texas, California, Louisiana, New York, and Florida made up 72% (129/178) of the reported cases. There was an increase from 34 cases to 49 cases in Florida from 2014 to 2015.⁵ The spread of leprosy throughout Florida may be from the merge of 2 armadillo populations, an M leprae–infected population migrating east from Texas and one from south central Florida that historically had not been infected with M leprae until recently.^3,6 Our patient did not have any known exposures to armadillos.

Classification and Presentation
The clinical presentation of Hansen disease is widely variable, as it can present at any point along a spectrum ranging from tuberculoid leprosy to lepromatous leprosy with borderline conditions in between, according to the Ridley-Jopling critera.⁷ The World Health Organization also classifies leprosy based on the number of acid-fast bacilli seen in a skin smear as either paucibacillary or multibacillary.² The paucibacillary classification correlates with tuberculoid, borderline tuberculoid, and indeterminate leprosy, and multibacillary correlates with borderline lepromatous and lepromatous leprosy. Paucibacillary leprosy usually presents with a less dramatic clinical picture than multibacillary leprosy. The clinical presentation is dependent on the magnitude of immune response to M leprae.²

Paucibacillary infection occurs when the body generates a strong cell-mediated immune response against the bacteria,⁸ which causes the activation and proliferation of CD4 and CD8 T cells, limiting the spread of the mycobacterium. Subsequently, the patient typically presents with a mild clinical picture with few skin lesions and limited nerve involvement.⁸ The skin lesions are papules or plaques with raised borders that are usually hypopigmented on dark skin and erythematous on light skin. Nerve involvement in paucibacillary forms of leprosy include sensory impairment and anhidrosis within the lesions. Nerve enlargement usually affects superficial nerves, with the posterior tibial nerve being most commonly affected.

Multibacillary leprosy presents with systemic involvement due to a weak cell-mediated immune response. Patients generally present with diffuse, poorly defined nodules; greater nerve impairment; and other systemic symptoms such as blindness, swelling of the fingers and toes, and testicular atrophy (in men). Additionally, enlargement of the earlobes and widening of the nasal bridge may contribute to the appearance of leonine facies. Nerve impairment in multibacillary forms of leprosy may be more severe, including more diffuse sensory involvement (eg, stocking glove–pattern neuropathy, nerve-trunk palsies), which ultimately may lead to foot drop, claw toe, and lagophthalmos.⁸

In addition to the clinical presentation, the histology of the paucibacillary and multibacillary types differ. Multibacillary leprosy shows diffuse histiocytes without granulomas and multiple bacilli seen on Fite staining.⁸ In the paucibacillary form, there are well-formed granulomas with Langerhans giant cells and a perineural lymphocytic infiltrate seen on hematoxylin and eosin staining with rare acid-fast bacilli seen on Fite staining.

To diagnose leprosy, at least one of the following 3 clinical signs must be present: (1) a hypopigmented or erythematous lesion with loss of sensation, (2) thickened peripheral nerve, or (3) acid-fast bacilli on slit-skin smear.²

Management
The World Health Organization guidelines involve multidrug therapy over an extended period of time.² For adults, the paucibacillary regimen includes rifampicin 600 mg once monthly and dapsone 100 mg once daily for 6 months. The adult regimen for multibacillary leprosy includes clofazimine 300 mg once monthly and 50 mg once daily, in addition to rifampicin 600 mg once monthly and dapsone 100 mg once daily for 12 months. If classification cannot be determined, it is recommended the patient be treated for multibacillary disease.²

Reversal Reactions
During the course of the disease, patients may upgrade (to a less severe form) or downgrade (to a more severe form) between the tuberculoid, borderline, and lepromatous forms.⁸ The patient’s clinical picture also may change with complications of leprosy, which include type 1 and type 2 reactions. Type 1 reaction is a reversal reaction seen in 15% to 30% of patients at risk, usually those with borderline forms of leprosy.⁹ Reversal reactions usually manifest as erythema and edema of current skin lesions, formation of new tumid lesions, and tenderness of peripheral nerves with loss of nerve function.⁸ Treatment of reversal reactions involves systemic corticosteroids.¹⁰ Type 2 reaction is classified as erythema nodosum leprosum. It presents within the first 2 years of treatment in approximately 20% of lepromatous patients and approximately 10% of borderline lepromatous patients but is rare in paucibacillary infections.¹¹ It presents with fever and crops of pink nodules and may include iritis, neuritis, lymphadenitis, orchitis, dactylitis, arthritis, and proteinuria.⁸ Treatment options for erythema nodosum leprosum include corticosteroids, clofazimine, and thalidomide.^12,13

Conclusion

Hansen disease is a rare condition in the United States. This case is unique because, to our knowledge, it is the first known PCR-confirmed case of Hansen disease in Okeechobee County, Florida. Additionally, the patient had no known exposure to M leprae. Exposure is increasing due to the increased geographical range of infected armadillos. Infection rates also may rise due to travel to endemic countries. Initially lesions may appear as innocuous erythematous plaques. When they do not respond to standard therapy, infectious agents such as M leprae should be part of the differential diagnosis. Because hematoxylin and eosin staining does not always yield results, if clinical suspicion is present, PCR should be performed. If a patient meets the clinical and histological diagnosis, the case should be reported to the National Hansen’s Disease Program.

After completion of treatment, our patient has shown excellent results. He has not yet demonstrated a reversal reaction; however, he may still be at risk, as it most commonly presents 2 months after starting treatment but can present years after treatment has been initiated.⁸ Cutaneous leprosy must be considered in the differential diagnosis for steroid-nonresponsive skin lesions, particularly in states such as Florida with a documented increase in incidence.

Acknowledgment
We thank Sharon Barrineau, ARNP (Okeechobee, Florida), for her acumen, contributions, and support on this case.

Case Report

A 65-year-old man presented with multiple anesthetic, annular, erythematous, scaly plaques with a raised border of 6 weeks’ duration that were unresponsive to topical steroid therapy. Four plaques were noted on the lower back ranging from 2 to 4 cm in diameter as well as a fifth plaque on the anterior portion of the right ankle that was approximately 6×6 cm. He denied fever, malaise, muscle weakness, changes in vision, or sensory deficits outside of the lesions themselves. The patient also denied any recent travel to endemic areas or exposure to armadillos.

Biopsies were taken from lesions on the lumbar back and anterior aspect of the right ankle (Figure 1A). Hematoxylin and eosin staining revealed a granulomatous infiltrate spreading along neurovascular structures (Figure 2). Granulomas also were identified in the dermal interstitium exhibiting partial necrosis (Figure 2 inset). Conspicuous distension of lymphovascular and perineural areas also was noted. Immunohistochemical studies with S-100 and neurofilament stains allowed insight into the pathomechanism of the clinically observed anesthesia, as nerve fibers were identified showing different stages of damage elicited by the granulomatous inflammatory infiltrate (Figure 3). Fite staining was positive for occasional bacilli within histiocytes (Figure 3A inset). Despite the clinical, histologic, and immunohistochemical evidence, the patient had no known exposure to leprosy; consequently, a polymerase chain reaction (PCR) assay was ordered for confirmation of the diagnosis. Surprisingly, the PCR was positive for Mycobacterium leprae DNA. These findings were consistent with borderline tuberculoid leprosy.

The case was reported to the National Hansen’s Disease Program (Baton Rouge, Louisiana). The patient was started on rifampicin 600 mg once monthly and dapsone 100 mg once daily for 6 months. The lesions exhibited marked improvement after completion of therapy (Figure 1B).

Comment

Disease Transmission
Hansen disease, also known as leprosy, is a chronic granulomatous infectious disease that is caused by M leprae, an obligate intracellular bacillus aerobe.¹ The mechanism of spread of M leprae is not clear. It is thought to be transmitted via respiratory droplets, though it may occur through injured skin.² Studies have suggested that in addition to humans, nine-banded armadillos are a source of infection.^2,3 Exposure to infected individuals, particularly multibacillary patients, increases the likelihood of contracting leprosy.²

According to the Centers for Disease Control and Prevention, 81 cases of Hansen disease were diagnosed in the United States in 2013,⁴ compared to 178 cases registered in 2015.⁵ Cases from Hawaii, Texas, California, Louisiana, New York, and Florida made up 72% (129/178) of the reported cases. There was an increase from 34 cases to 49 cases in Florida from 2014 to 2015.⁵ The spread of leprosy throughout Florida may be from the merge of 2 armadillo populations, an M leprae–infected population migrating east from Texas and one from south central Florida that historically had not been infected with M leprae until recently.^3,6 Our patient did not have any known exposures to armadillos.

Classification and Presentation
The clinical presentation of Hansen disease is widely variable, as it can present at any point along a spectrum ranging from tuberculoid leprosy to lepromatous leprosy with borderline conditions in between, according to the Ridley-Jopling critera.⁷ The World Health Organization also classifies leprosy based on the number of acid-fast bacilli seen in a skin smear as either paucibacillary or multibacillary.² The paucibacillary classification correlates with tuberculoid, borderline tuberculoid, and indeterminate leprosy, and multibacillary correlates with borderline lepromatous and lepromatous leprosy. Paucibacillary leprosy usually presents with a less dramatic clinical picture than multibacillary leprosy. The clinical presentation is dependent on the magnitude of immune response to M leprae.²

Paucibacillary infection occurs when the body generates a strong cell-mediated immune response against the bacteria,⁸ which causes the activation and proliferation of CD4 and CD8 T cells, limiting the spread of the mycobacterium. Subsequently, the patient typically presents with a mild clinical picture with few skin lesions and limited nerve involvement.⁸ The skin lesions are papules or plaques with raised borders that are usually hypopigmented on dark skin and erythematous on light skin. Nerve involvement in paucibacillary forms of leprosy include sensory impairment and anhidrosis within the lesions. Nerve enlargement usually affects superficial nerves, with the posterior tibial nerve being most commonly affected.

Multibacillary leprosy presents with systemic involvement due to a weak cell-mediated immune response. Patients generally present with diffuse, poorly defined nodules; greater nerve impairment; and other systemic symptoms such as blindness, swelling of the fingers and toes, and testicular atrophy (in men). Additionally, enlargement of the earlobes and widening of the nasal bridge may contribute to the appearance of leonine facies. Nerve impairment in multibacillary forms of leprosy may be more severe, including more diffuse sensory involvement (eg, stocking glove–pattern neuropathy, nerve-trunk palsies), which ultimately may lead to foot drop, claw toe, and lagophthalmos.⁸

In addition to the clinical presentation, the histology of the paucibacillary and multibacillary types differ. Multibacillary leprosy shows diffuse histiocytes without granulomas and multiple bacilli seen on Fite staining.⁸ In the paucibacillary form, there are well-formed granulomas with Langerhans giant cells and a perineural lymphocytic infiltrate seen on hematoxylin and eosin staining with rare acid-fast bacilli seen on Fite staining.

To diagnose leprosy, at least one of the following 3 clinical signs must be present: (1) a hypopigmented or erythematous lesion with loss of sensation, (2) thickened peripheral nerve, or (3) acid-fast bacilli on slit-skin smear.²

Management
The World Health Organization guidelines involve multidrug therapy over an extended period of time.² For adults, the paucibacillary regimen includes rifampicin 600 mg once monthly and dapsone 100 mg once daily for 6 months. The adult regimen for multibacillary leprosy includes clofazimine 300 mg once monthly and 50 mg once daily, in addition to rifampicin 600 mg once monthly and dapsone 100 mg once daily for 12 months. If classification cannot be determined, it is recommended the patient be treated for multibacillary disease.²

Reversal Reactions
During the course of the disease, patients may upgrade (to a less severe form) or downgrade (to a more severe form) between the tuberculoid, borderline, and lepromatous forms.⁸ The patient’s clinical picture also may change with complications of leprosy, which include type 1 and type 2 reactions. Type 1 reaction is a reversal reaction seen in 15% to 30% of patients at risk, usually those with borderline forms of leprosy.⁹ Reversal reactions usually manifest as erythema and edema of current skin lesions, formation of new tumid lesions, and tenderness of peripheral nerves with loss of nerve function.⁸ Treatment of reversal reactions involves systemic corticosteroids.¹⁰ Type 2 reaction is classified as erythema nodosum leprosum. It presents within the first 2 years of treatment in approximately 20% of lepromatous patients and approximately 10% of borderline lepromatous patients but is rare in paucibacillary infections.¹¹ It presents with fever and crops of pink nodules and may include iritis, neuritis, lymphadenitis, orchitis, dactylitis, arthritis, and proteinuria.⁸ Treatment options for erythema nodosum leprosum include corticosteroids, clofazimine, and thalidomide.^12,13

Conclusion

Hansen disease is a rare condition in the United States. This case is unique because, to our knowledge, it is the first known PCR-confirmed case of Hansen disease in Okeechobee County, Florida. Additionally, the patient had no known exposure to M leprae. Exposure is increasing due to the increased geographical range of infected armadillos. Infection rates also may rise due to travel to endemic countries. Initially lesions may appear as innocuous erythematous plaques. When they do not respond to standard therapy, infectious agents such as M leprae should be part of the differential diagnosis. Because hematoxylin and eosin staining does not always yield results, if clinical suspicion is present, PCR should be performed. If a patient meets the clinical and histological diagnosis, the case should be reported to the National Hansen’s Disease Program.

After completion of treatment, our patient has shown excellent results. He has not yet demonstrated a reversal reaction; however, he may still be at risk, as it most commonly presents 2 months after starting treatment but can present years after treatment has been initiated.⁸ Cutaneous leprosy must be considered in the differential diagnosis for steroid-nonresponsive skin lesions, particularly in states such as Florida with a documented increase in incidence.

Acknowledgment
We thank Sharon Barrineau, ARNP (Okeechobee, Florida), for her acumen, contributions, and support on this case.

Event-free survival at 24 months (EFS24) is predictive of survival in patients with peripheral T-cell lymphomas (PTCLs), according to new findings published in the Journal of Clinical Oncology.

Patients who were event free 2 years after diagnosis had a more favorable outcome, compared with those who relapsed within that time period. Some patients who remained event free for 24 months were potentially cured; conversely, events within 2 years were associated with an early death in almost all of those patients.

“Thus, EFS24 is a dichotomous end point that allows individualized risk prediction in patients with PTCL and can help inform patient counseling, biomarker discovery, clinical trial design, and precision medicine approaches,” wrote Matthew J. Maurer, MS, of the Mayo Clinic, Rochester, MN, and his coauthors (J Clin Oncol. 2017 Oct 26. doi: 10.1200/JCO.2017.73.8195).

PTCL is an uncommon and heterogeneous group of non-Hodgkin lymphomas that carry a very poor prognosis; most systemic cases are treated with anthracycline-based combination chemotherapy. Previous studies have reported that achieving EFS24 is predictive of excellent long-term outcomes, independent of baseline prognostic factors.

In this study Mr. Maurer and his coauthors assessed the association between EFS24 and overall survival in 775 patients with newly systemic PTCL who were diagnosed during 2000-2012 and received treatment with curative intent.

Among the entire cohort, 36% of patients achieved EFS24 while 64% did not, and the median overall survival following progression within that 2-year time period was 4.9 months (95% confidence interval, 3.8-5.9 months). The 5-year overall survival in the group that relapsed was 11%, with a standardized mortality ratio of 46.4 (95% CI, 41.8-51.3).

Conversely, among patients with EFS24, the median overall survival was not reached, and the 5-year overall survival was 78% (95% CI, 73%-84%). In this group, the 5-year risk of subsequent lymphoma relapse was 23%, and survival following a late relapse was generally poor (median of 10.3 months; 95% CI, 5.7-19.1 months). The best outcomes after achieving EFS24 were observed among patients aged 60 years or younger: These patients had a 5-year overall survival of 91%.

“The use of a dichotomous end point that allows individualized risk prediction is particularly important in rare diseases such as PTCL, where limited numbers of patients may make formal surrogate end point analysis difficult,” wrote the authors.

The study was supported by grants from the National Cancer Institute, the Terry Fox Research Institute, and the BC Cancer Foundation. Dr. Maurer reported research funding from Kite Pharma and Celgene, and several of the coauthors reported relationships with industry.

Event-free survival at 24 months (EFS24) is predictive of survival in patients with peripheral T-cell lymphomas (PTCLs), according to new findings published in the Journal of Clinical Oncology.

Patients who were event free 2 years after diagnosis had a more favorable outcome, compared with those who relapsed within that time period. Some patients who remained event free for 24 months were potentially cured; conversely, events within 2 years were associated with an early death in almost all of those patients.

“Thus, EFS24 is a dichotomous end point that allows individualized risk prediction in patients with PTCL and can help inform patient counseling, biomarker discovery, clinical trial design, and precision medicine approaches,” wrote Matthew J. Maurer, MS, of the Mayo Clinic, Rochester, MN, and his coauthors (J Clin Oncol. 2017 Oct 26. doi: 10.1200/JCO.2017.73.8195).

PTCL is an uncommon and heterogeneous group of non-Hodgkin lymphomas that carry a very poor prognosis; most systemic cases are treated with anthracycline-based combination chemotherapy. Previous studies have reported that achieving EFS24 is predictive of excellent long-term outcomes, independent of baseline prognostic factors.

In this study Mr. Maurer and his coauthors assessed the association between EFS24 and overall survival in 775 patients with newly systemic PTCL who were diagnosed during 2000-2012 and received treatment with curative intent.

Among the entire cohort, 36% of patients achieved EFS24 while 64% did not, and the median overall survival following progression within that 2-year time period was 4.9 months (95% confidence interval, 3.8-5.9 months). The 5-year overall survival in the group that relapsed was 11%, with a standardized mortality ratio of 46.4 (95% CI, 41.8-51.3).

Conversely, among patients with EFS24, the median overall survival was not reached, and the 5-year overall survival was 78% (95% CI, 73%-84%). In this group, the 5-year risk of subsequent lymphoma relapse was 23%, and survival following a late relapse was generally poor (median of 10.3 months; 95% CI, 5.7-19.1 months). The best outcomes after achieving EFS24 were observed among patients aged 60 years or younger: These patients had a 5-year overall survival of 91%.

“The use of a dichotomous end point that allows individualized risk prediction is particularly important in rare diseases such as PTCL, where limited numbers of patients may make formal surrogate end point analysis difficult,” wrote the authors.

The study was supported by grants from the National Cancer Institute, the Terry Fox Research Institute, and the BC Cancer Foundation. Dr. Maurer reported research funding from Kite Pharma and Celgene, and several of the coauthors reported relationships with industry.

Event-free survival at 24 months (EFS24) is predictive of survival in patients with peripheral T-cell lymphomas (PTCLs), according to new findings published in the Journal of Clinical Oncology.

Patients who were event free 2 years after diagnosis had a more favorable outcome, compared with those who relapsed within that time period. Some patients who remained event free for 24 months were potentially cured; conversely, events within 2 years were associated with an early death in almost all of those patients.

“Thus, EFS24 is a dichotomous end point that allows individualized risk prediction in patients with PTCL and can help inform patient counseling, biomarker discovery, clinical trial design, and precision medicine approaches,” wrote Matthew J. Maurer, MS, of the Mayo Clinic, Rochester, MN, and his coauthors (J Clin Oncol. 2017 Oct 26. doi: 10.1200/JCO.2017.73.8195).

PTCL is an uncommon and heterogeneous group of non-Hodgkin lymphomas that carry a very poor prognosis; most systemic cases are treated with anthracycline-based combination chemotherapy. Previous studies have reported that achieving EFS24 is predictive of excellent long-term outcomes, independent of baseline prognostic factors.

In this study Mr. Maurer and his coauthors assessed the association between EFS24 and overall survival in 775 patients with newly systemic PTCL who were diagnosed during 2000-2012 and received treatment with curative intent.

Among the entire cohort, 36% of patients achieved EFS24 while 64% did not, and the median overall survival following progression within that 2-year time period was 4.9 months (95% confidence interval, 3.8-5.9 months). The 5-year overall survival in the group that relapsed was 11%, with a standardized mortality ratio of 46.4 (95% CI, 41.8-51.3).

Conversely, among patients with EFS24, the median overall survival was not reached, and the 5-year overall survival was 78% (95% CI, 73%-84%). In this group, the 5-year risk of subsequent lymphoma relapse was 23%, and survival following a late relapse was generally poor (median of 10.3 months; 95% CI, 5.7-19.1 months). The best outcomes after achieving EFS24 were observed among patients aged 60 years or younger: These patients had a 5-year overall survival of 91%.

“The use of a dichotomous end point that allows individualized risk prediction is particularly important in rare diseases such as PTCL, where limited numbers of patients may make formal surrogate end point analysis difficult,” wrote the authors.

The study was supported by grants from the National Cancer Institute, the Terry Fox Research Institute, and the BC Cancer Foundation. Dr. Maurer reported research funding from Kite Pharma and Celgene, and several of the coauthors reported relationships with industry.

DENVER – A formal cost-effectiveness analysis indicates that transcatheter aortic valve replacement (TAVR) is substantially more cost effective than surgical valve replacement in patients at intermediate surgical risk similar to those enrolled in the landmark PARTNER 2 trial.

The analysis demonstrated that over a 1- and 2-year follow-up period, as well as with projected lifetime follow-up, TAVR entails both lower long-term costs and greater quality-adjusted life expectancy, David J. Cohen, MD, reported at the Transcatheter Cardiovascular Therapeutics annual educational meeting.

[email protected]

DENVER – A formal cost-effectiveness analysis indicates that transcatheter aortic valve replacement (TAVR) is substantially more cost effective than surgical valve replacement in patients at intermediate surgical risk similar to those enrolled in the landmark PARTNER 2 trial.

The analysis demonstrated that over a 1- and 2-year follow-up period, as well as with projected lifetime follow-up, TAVR entails both lower long-term costs and greater quality-adjusted life expectancy, David J. Cohen, MD, reported at the Transcatheter Cardiovascular Therapeutics annual educational meeting.

[email protected]

DENVER – A formal cost-effectiveness analysis indicates that transcatheter aortic valve replacement (TAVR) is substantially more cost effective than surgical valve replacement in patients at intermediate surgical risk similar to those enrolled in the landmark PARTNER 2 trial.

The analysis demonstrated that over a 1- and 2-year follow-up period, as well as with projected lifetime follow-up, TAVR entails both lower long-term costs and greater quality-adjusted life expectancy, David J. Cohen, MD, reported at the Transcatheter Cardiovascular Therapeutics annual educational meeting.

[email protected]

TORONTO – U.S.-based pulmonary and infectious disease specialists prefer interferon-gamma release assays (IGRA) over tuberculin skin tests (TST) for the diagnosis of latent TB infection, but may not fully understand how to use and interpret the test results, according to survey results presented at the CHEST annual meeting.

Adam G. Green, MD, conducted the research while he was a fellow in pulmonology/critical care at Montefiore Medical Center in New York. Dr. Green told attendees that about one-third of the world’s population are infected with TB and about 15 million of those live in the United States. Two-thirds of U.S. cases are seen in foreign-born individuals and are clustered in four states—New, York, California, Florida, and Texas.

Debra Beck/Frontline Medical News

TORONTO – U.S.-based pulmonary and infectious disease specialists prefer interferon-gamma release assays (IGRA) over tuberculin skin tests (TST) for the diagnosis of latent TB infection, but may not fully understand how to use and interpret the test results, according to survey results presented at the CHEST annual meeting.

Adam G. Green, MD, conducted the research while he was a fellow in pulmonology/critical care at Montefiore Medical Center in New York. Dr. Green told attendees that about one-third of the world’s population are infected with TB and about 15 million of those live in the United States. Two-thirds of U.S. cases are seen in foreign-born individuals and are clustered in four states—New, York, California, Florida, and Texas.

Debra Beck/Frontline Medical News

TORONTO – U.S.-based pulmonary and infectious disease specialists prefer interferon-gamma release assays (IGRA) over tuberculin skin tests (TST) for the diagnosis of latent TB infection, but may not fully understand how to use and interpret the test results, according to survey results presented at the CHEST annual meeting.

Adam G. Green, MD, conducted the research while he was a fellow in pulmonology/critical care at Montefiore Medical Center in New York. Dr. Green told attendees that about one-third of the world’s population are infected with TB and about 15 million of those live in the United States. Two-thirds of U.S. cases are seen in foreign-born individuals and are clustered in four states—New, York, California, Florida, and Texas.

Debra Beck/Frontline Medical News

SAN DIEGO – Implementation of strict operating room (OR) attire policies did not reduce the rates of superficial surgical site infections (SSIs), according to an analysis of more than 6,500 patients.

“SSIs are the most common cause of health care–associated infections in the U.S.,” study author Sandra Farach, MD, said at the annual clinical congress of the American College of Surgeons. “It’s estimated that SSIs occur in 2%-5% of patients undergoing inpatient surgery. They’re associated with significant patient morbidity and mortality and are a significant burden to the health care system, accounting for an estimated $3.5 to $10 billion in health care expenditures.”

In February 2015, the Association for periOperative Registered Nurses published recommendations on operating room attire, providing a guideline for modifying facility policies and regulatory requirements. It included stringent policies designed to minimize the exposed areas of skin and hair of operating room staff. “New attire policies were met with some criticism as there is a paucity of evidence-based data to support these recommendations,” said Dr. Farach, who helped conduct the study during her tenure as chief resident of general surgery at the University of Rochester (N.Y.) Medical Center.

Doug Brunk/Frontline Medical News

[email protected]

SAN DIEGO – Implementation of strict operating room (OR) attire policies did not reduce the rates of superficial surgical site infections (SSIs), according to an analysis of more than 6,500 patients.

“SSIs are the most common cause of health care–associated infections in the U.S.,” study author Sandra Farach, MD, said at the annual clinical congress of the American College of Surgeons. “It’s estimated that SSIs occur in 2%-5% of patients undergoing inpatient surgery. They’re associated with significant patient morbidity and mortality and are a significant burden to the health care system, accounting for an estimated $3.5 to $10 billion in health care expenditures.”

In February 2015, the Association for periOperative Registered Nurses published recommendations on operating room attire, providing a guideline for modifying facility policies and regulatory requirements. It included stringent policies designed to minimize the exposed areas of skin and hair of operating room staff. “New attire policies were met with some criticism as there is a paucity of evidence-based data to support these recommendations,” said Dr. Farach, who helped conduct the study during her tenure as chief resident of general surgery at the University of Rochester (N.Y.) Medical Center.

Doug Brunk/Frontline Medical News

[email protected]

SAN DIEGO – Implementation of strict operating room (OR) attire policies did not reduce the rates of superficial surgical site infections (SSIs), according to an analysis of more than 6,500 patients.

“SSIs are the most common cause of health care–associated infections in the U.S.,” study author Sandra Farach, MD, said at the annual clinical congress of the American College of Surgeons. “It’s estimated that SSIs occur in 2%-5% of patients undergoing inpatient surgery. They’re associated with significant patient morbidity and mortality and are a significant burden to the health care system, accounting for an estimated $3.5 to $10 billion in health care expenditures.”

In February 2015, the Association for periOperative Registered Nurses published recommendations on operating room attire, providing a guideline for modifying facility policies and regulatory requirements. It included stringent policies designed to minimize the exposed areas of skin and hair of operating room staff. “New attire policies were met with some criticism as there is a paucity of evidence-based data to support these recommendations,” said Dr. Farach, who helped conduct the study during her tenure as chief resident of general surgery at the University of Rochester (N.Y.) Medical Center.

Doug Brunk/Frontline Medical News

[email protected]

Can a Fatty Diet Increase Relapse Risk in Children With MS?

In children with multiple sclerosis (MS), high energy intake from fat, especially saturated fat, may increase the hazard of relapse, while vegetable intake may be independently protective, according to a study published online ahead of print October 9 in the Journal of Neurology, Neurosurgery & Psychiatry. A total of 219 patients with pediatric relapsing-remitting MS or clinically isolated syndrome with disease onset before age 18 and duration of less than four years were enrolled in a multicenter study that was completed at 11 pediatric MS centers. Investigators used the Block Kids Food Screener to examine dietary intake during the week before enrollment. Each 10% increase in energy intake from fat increased the hazard of relapse by 56%, and each 10% increase in saturated fat tripled this hazard.

Azary S, Schreiner T, Graves J, et al. Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017 Oct 9 [Epub ahead of print].

Cooling Reduces Risk of Epilepsy After Perinatal Asphyxia

Administering therapeutic hypothermia to babies with perinatal asphyxia can reduce their risk of epilepsy in childhood, according to a study published online ahead of print September 29 in Epilepsia. From 2006 to 2013, 151 infants with perinatal asphyxia underwent 72 hours of cooling. Clinical and amplitude-integrated EEG with single-channel EEG-verified neonatal seizures were treated with antiepileptic drugs (AEDs). MRI was assessed using a severity score that ranged from 0 to 11. One hundred thirty-four children were assessed at 18–24 months. Babies born after 2007 who received therapeutic hypothermia had a lower rate of epilepsy than those born before this method was introduced. At two years, 6% of the children had epilepsy, and 2% were receiving AEDs. Before therapeutic hypothermia was introduced, the rate of death or moderate or severe disability was about 66%.

Liu X, Jary S, Cowan F, Thoresen M. Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy. Epilepsia. 2017 Sep 29 [Epub ahead of print].

Risk Factors Are Increasing in People With Stroke

The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse in acute ischemic stroke increased between 2004 and 2014, according to a study published online ahead of print October 11 in Neurology. Researchers used the National Inpatient Sample to identify 922,451 adult hospitalizations for ischemic stroke. In all, 92.5% of patients with stroke had one or more risk factors. Age- and sex-adjusted prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse were 79%, 34%, 47%, 15%, and 2%, respectively. The prevalence of carotid stenosis, chronic renal failure, and coronary artery disease were 13%, 12%, and 27%, respectively. Risk factor prevalence varied by age, race, and sex. The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse increased annually by 1.4%, 2%, 7%, 5%, and 7%, respectively.

Otite FO, Liaw N, Khandelwal P, et al. Increasing prevalence of vascular risk factors in patients with stroke: a call to action. Neurology. 2017 Oct 11 [Epub ahead of print].

Transcranial Direct-Current Stimulation for MS-Related Fatigue

People with multiple sclerosis (MS) who undergo a noninvasive form of electrical brain stimulation have significantly reduced fatigue, according to a study published online ahead of print September 1 in the Multiple Sclerosis Journal. Twenty-seven people with MS were randomized to receive transcranial direct-current stimulation or a placebo while playing a cognitive training game that targets processing speed and working memory. After 20 sessions, participants reported their level of fatigue using the Patient-Reported Outcomes Measurement Information System. Higher numbers correlated with greater fatigue. The researchers reported a statistically significant reduction in the group that underwent transcranial direct-current stimulation, compared with the placebo group. Intervention participants had a 5.6-point drop in fatigue on average, while control participants had a 0.9-point increase in fatigue.

Charvet LE, Dobbs B, Shaw MT, et al. Remotely supervised transcranial direct current stimulation for the treatment of fatigue in multiple sclerosis: results from a randomized, sham-controlled trial. Mult Scler. 2017 Sep 1 [Epub ahead of print].

New Genetic Risk Variants for RLS Identified

Thirteen previously unknown genetic risk variants for restless legs syndrome (RLS) have been identified, according to a study published in the November issue of Lancet Neurology. Researchers combined three genome-wide association studies’ datasets with diagnosis data collected from 2003 to 2017. The latter data came from interviews and questionnaires and included 15,126 cases and 95,725 controls. Significant genome-wide signals were tested for replication in an independent genome-wide association study of 30,770 cases and 286,913 controls. Investigators identified and replicated 13 new risk loci for RLS and confirmed six previously identified risk loci. MEIS1 was confirmed as the strongest genetic risk factor for RLS. Gene prioritization, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance, synapse formation, and neuronal specification.

Schormair B, Zhao C, Bell S, et al. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis. Lancet Neurol. 2017;16(11):898-907.

High Blood Pressure Associated With Increased Dementia Risk in Women

Hypertension is more common in men, but is only associated with dementia risk in women, according to a study published online ahead of print October 4 in Neurology. Researchers evaluated 5,646 members of a diverse integrated health care delivery system who had clinical examinations and health survey data from 1964 to 1973 (mean age, 32.7) and 1978 to 1985 (mean age, 44.3) and were members as of January 1, 1996 (mean age, 59.8). A total of 532 people were diagnosed with dementia. Mid-adulthood (circa age 44) hypertension was associated with 65% increased dementia risk among women, but not among men. Onset of hypertension in mid-adulthood predicted 73% higher dementia risk in women, compared with stable normotension. There was no evidence that hypertension or changes in hypertension increased dementia risk among men.

Gilsanz P, Mayeda ER, Glymour MM, et al. Female sex, early-onset hypertension, and risk of dementia. Neurology. 2017 Oct 4 [Epub ahead of print].

A Risk Factor for Major Bleeding During Treatment With NOACs

Among patients taking non-vitamin K oral anticoagulants (NOACs) for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin, compared with the use of NOACs alone, is associated with increased risk of major bleeding, according to a study published October 3 in JAMA. Researchers retrospectively examined data for 91,330 patients with nonvalvular atrial fibrillation who received at least one NOAC prescription of dabigatran, rivaroxaban, or apixaban from 2012 through 2016. They analyzed the bleeding risk associated with the concurrent use of 12 commonly prescribed medications. A total of 4,770 major bleeding events occurred. The incidence rate of major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin. Physicians prescribing NOACs should consider the potential risks associated with concomitant use of other drugs, the researchers said.

Chang SH, Chou IJ, Yeh YH, et al. Association between use of non-vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation. JAMA. 2017;318(13):1250-1259.

Discontinuing Aspirin Therapy May Increase Cardiovascular Risk

In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding is associated with a greater-than-30% increased risk of cardiovascular events, according to a study published September 26 in Circulation. Researchers performed a cohort study of 601,527 participants taking low-dose aspirin for heart attack and stroke prevention between 2005 and 2009. Participants were older than 40, cancer-free, and had an adherence rate of 80% or greater during the first year of treatment. During a median of 3.0 years of follow-up, 62,690 cardiovascular events were reported. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37), corresponding to an additional cardiovascular event observed per year in one of every 74 patients who discontinued aspirin.

Sundström J, Hedberg J, Thuresson M, et al. Low-dose aspirin discontinuation and risk of cardiovascular events: a Swedish nationwide, population-based cohort study. Circulation. 2017;136(13):1183-1192.

FDA Approves 80-mg Ingrezza Capsule for Tardive Dyskinesia

The FDA has approved an 80-mg capsule of Ingrezza (valbenazine) for the treatment of adults with tardive dyskinesia. In clinical studies, Ingrezza 80 mg provided significant, rapid, and meaningful improvement in tardive dyskinesia severity, compared with placebo, at six weeks. Results were seen as early as two weeks, and continued reductions were observed through 48 weeks of treatment. The drug was FDA-approved in April and has been available as 40-mg capsules. Neurocrine Biosciences markets Ingrezza.

FDA Approves Generic Version of Copaxone

The FDA has approved Mylan’s glatiramer acetate injection 40 mg/mL for thrice-weekly injection. The drug is a substitutable generic version of Teva’s Copaxone 40 mg/mL. The agency also approved Mylan’s glatiramer acetate injection 20 mg/mL for once-daily injection, a substitutable generic version of Teva’s Copaxone 20 mg/mL. Both products are indicated for the treatment of patients with relapsing forms of multiple sclerosis. As part of its applications, Mylan submitted side-by-side analyses demonstrating that its glatiramer acetate injections have the same active ingredient, dosage form, route of administration, and strength as their branded counterpart.

FDA Approves Gocovri for Dyskinesia in Parkinson’s Disease

The FDA has approved Gocovri (amantadine) extended-release capsules for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy with or without concomitant dopaminergic medications. Gocovri, previously granted orphan drug status by the FDA, is the first medicine approved by the FDA for this indication. Gocovri is a high-dose (274 mg) formulation of amantadine (equivalent to 340 mg of amantadine HCl) taken once-daily at bedtime that delivers consistently high levels of amantadine from the morning and throughout the day. Adamas Pharmaceuticals markets the drug.

FDA Has Approved Lyrica CR for Two Indications

The FDA has approved Lyrica CR (pregabalin) extended-release tablets CV as once-daily therapy for the management of neuropathic pain associated with diabetic peripheral neuropathy and the management of postherpetic neuralgia. The efficacy and safety of Lyrica CR in postherpetic neuralgia was established in a randomized placebo-controlled clinical trial conducted in 801 patients with postherpetic neuralgia who entered single-blind treatment with Lyrica CR. In the study, 73.6% of patients in the Lyrica CR group achieved at least 50% improvement in pain intensity, compared with 54.6% in the placebo group. The postherpetic neuralgia data also supported the diabetic peripheral neuropathy indication. Pfizer markets Lyrica CR.

—Kimberly Williams

Can a Fatty Diet Increase Relapse Risk in Children With MS?

In children with multiple sclerosis (MS), high energy intake from fat, especially saturated fat, may increase the hazard of relapse, while vegetable intake may be independently protective, according to a study published online ahead of print October 9 in the Journal of Neurology, Neurosurgery & Psychiatry. A total of 219 patients with pediatric relapsing-remitting MS or clinically isolated syndrome with disease onset before age 18 and duration of less than four years were enrolled in a multicenter study that was completed at 11 pediatric MS centers. Investigators used the Block Kids Food Screener to examine dietary intake during the week before enrollment. Each 10% increase in energy intake from fat increased the hazard of relapse by 56%, and each 10% increase in saturated fat tripled this hazard.

Azary S, Schreiner T, Graves J, et al. Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017 Oct 9 [Epub ahead of print].

Cooling Reduces Risk of Epilepsy After Perinatal Asphyxia

Administering therapeutic hypothermia to babies with perinatal asphyxia can reduce their risk of epilepsy in childhood, according to a study published online ahead of print September 29 in Epilepsia. From 2006 to 2013, 151 infants with perinatal asphyxia underwent 72 hours of cooling. Clinical and amplitude-integrated EEG with single-channel EEG-verified neonatal seizures were treated with antiepileptic drugs (AEDs). MRI was assessed using a severity score that ranged from 0 to 11. One hundred thirty-four children were assessed at 18–24 months. Babies born after 2007 who received therapeutic hypothermia had a lower rate of epilepsy than those born before this method was introduced. At two years, 6% of the children had epilepsy, and 2% were receiving AEDs. Before therapeutic hypothermia was introduced, the rate of death or moderate or severe disability was about 66%.

Liu X, Jary S, Cowan F, Thoresen M. Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy. Epilepsia. 2017 Sep 29 [Epub ahead of print].

Risk Factors Are Increasing in People With Stroke

The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse in acute ischemic stroke increased between 2004 and 2014, according to a study published online ahead of print October 11 in Neurology. Researchers used the National Inpatient Sample to identify 922,451 adult hospitalizations for ischemic stroke. In all, 92.5% of patients with stroke had one or more risk factors. Age- and sex-adjusted prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse were 79%, 34%, 47%, 15%, and 2%, respectively. The prevalence of carotid stenosis, chronic renal failure, and coronary artery disease were 13%, 12%, and 27%, respectively. Risk factor prevalence varied by age, race, and sex. The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse increased annually by 1.4%, 2%, 7%, 5%, and 7%, respectively.

Otite FO, Liaw N, Khandelwal P, et al. Increasing prevalence of vascular risk factors in patients with stroke: a call to action. Neurology. 2017 Oct 11 [Epub ahead of print].

Transcranial Direct-Current Stimulation for MS-Related Fatigue

People with multiple sclerosis (MS) who undergo a noninvasive form of electrical brain stimulation have significantly reduced fatigue, according to a study published online ahead of print September 1 in the Multiple Sclerosis Journal. Twenty-seven people with MS were randomized to receive transcranial direct-current stimulation or a placebo while playing a cognitive training game that targets processing speed and working memory. After 20 sessions, participants reported their level of fatigue using the Patient-Reported Outcomes Measurement Information System. Higher numbers correlated with greater fatigue. The researchers reported a statistically significant reduction in the group that underwent transcranial direct-current stimulation, compared with the placebo group. Intervention participants had a 5.6-point drop in fatigue on average, while control participants had a 0.9-point increase in fatigue.

Charvet LE, Dobbs B, Shaw MT, et al. Remotely supervised transcranial direct current stimulation for the treatment of fatigue in multiple sclerosis: results from a randomized, sham-controlled trial. Mult Scler. 2017 Sep 1 [Epub ahead of print].

New Genetic Risk Variants for RLS Identified

Thirteen previously unknown genetic risk variants for restless legs syndrome (RLS) have been identified, according to a study published in the November issue of Lancet Neurology. Researchers combined three genome-wide association studies’ datasets with diagnosis data collected from 2003 to 2017. The latter data came from interviews and questionnaires and included 15,126 cases and 95,725 controls. Significant genome-wide signals were tested for replication in an independent genome-wide association study of 30,770 cases and 286,913 controls. Investigators identified and replicated 13 new risk loci for RLS and confirmed six previously identified risk loci. MEIS1 was confirmed as the strongest genetic risk factor for RLS. Gene prioritization, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance, synapse formation, and neuronal specification.

Schormair B, Zhao C, Bell S, et al. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis. Lancet Neurol. 2017;16(11):898-907.

High Blood Pressure Associated With Increased Dementia Risk in Women

Hypertension is more common in men, but is only associated with dementia risk in women, according to a study published online ahead of print October 4 in Neurology. Researchers evaluated 5,646 members of a diverse integrated health care delivery system who had clinical examinations and health survey data from 1964 to 1973 (mean age, 32.7) and 1978 to 1985 (mean age, 44.3) and were members as of January 1, 1996 (mean age, 59.8). A total of 532 people were diagnosed with dementia. Mid-adulthood (circa age 44) hypertension was associated with 65% increased dementia risk among women, but not among men. Onset of hypertension in mid-adulthood predicted 73% higher dementia risk in women, compared with stable normotension. There was no evidence that hypertension or changes in hypertension increased dementia risk among men.

Gilsanz P, Mayeda ER, Glymour MM, et al. Female sex, early-onset hypertension, and risk of dementia. Neurology. 2017 Oct 4 [Epub ahead of print].

A Risk Factor for Major Bleeding During Treatment With NOACs

Among patients taking non-vitamin K oral anticoagulants (NOACs) for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin, compared with the use of NOACs alone, is associated with increased risk of major bleeding, according to a study published October 3 in JAMA. Researchers retrospectively examined data for 91,330 patients with nonvalvular atrial fibrillation who received at least one NOAC prescription of dabigatran, rivaroxaban, or apixaban from 2012 through 2016. They analyzed the bleeding risk associated with the concurrent use of 12 commonly prescribed medications. A total of 4,770 major bleeding events occurred. The incidence rate of major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin. Physicians prescribing NOACs should consider the potential risks associated with concomitant use of other drugs, the researchers said.

Chang SH, Chou IJ, Yeh YH, et al. Association between use of non-vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation. JAMA. 2017;318(13):1250-1259.

Discontinuing Aspirin Therapy May Increase Cardiovascular Risk

In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding is associated with a greater-than-30% increased risk of cardiovascular events, according to a study published September 26 in Circulation. Researchers performed a cohort study of 601,527 participants taking low-dose aspirin for heart attack and stroke prevention between 2005 and 2009. Participants were older than 40, cancer-free, and had an adherence rate of 80% or greater during the first year of treatment. During a median of 3.0 years of follow-up, 62,690 cardiovascular events were reported. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37), corresponding to an additional cardiovascular event observed per year in one of every 74 patients who discontinued aspirin.

Sundström J, Hedberg J, Thuresson M, et al. Low-dose aspirin discontinuation and risk of cardiovascular events: a Swedish nationwide, population-based cohort study. Circulation. 2017;136(13):1183-1192.

FDA Approves 80-mg Ingrezza Capsule for Tardive Dyskinesia

The FDA has approved an 80-mg capsule of Ingrezza (valbenazine) for the treatment of adults with tardive dyskinesia. In clinical studies, Ingrezza 80 mg provided significant, rapid, and meaningful improvement in tardive dyskinesia severity, compared with placebo, at six weeks. Results were seen as early as two weeks, and continued reductions were observed through 48 weeks of treatment. The drug was FDA-approved in April and has been available as 40-mg capsules. Neurocrine Biosciences markets Ingrezza.

FDA Approves Generic Version of Copaxone

The FDA has approved Mylan’s glatiramer acetate injection 40 mg/mL for thrice-weekly injection. The drug is a substitutable generic version of Teva’s Copaxone 40 mg/mL. The agency also approved Mylan’s glatiramer acetate injection 20 mg/mL for once-daily injection, a substitutable generic version of Teva’s Copaxone 20 mg/mL. Both products are indicated for the treatment of patients with relapsing forms of multiple sclerosis. As part of its applications, Mylan submitted side-by-side analyses demonstrating that its glatiramer acetate injections have the same active ingredient, dosage form, route of administration, and strength as their branded counterpart.

FDA Approves Gocovri for Dyskinesia in Parkinson’s Disease

The FDA has approved Gocovri (amantadine) extended-release capsules for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy with or without concomitant dopaminergic medications. Gocovri, previously granted orphan drug status by the FDA, is the first medicine approved by the FDA for this indication. Gocovri is a high-dose (274 mg) formulation of amantadine (equivalent to 340 mg of amantadine HCl) taken once-daily at bedtime that delivers consistently high levels of amantadine from the morning and throughout the day. Adamas Pharmaceuticals markets the drug.

FDA Has Approved Lyrica CR for Two Indications

The FDA has approved Lyrica CR (pregabalin) extended-release tablets CV as once-daily therapy for the management of neuropathic pain associated with diabetic peripheral neuropathy and the management of postherpetic neuralgia. The efficacy and safety of Lyrica CR in postherpetic neuralgia was established in a randomized placebo-controlled clinical trial conducted in 801 patients with postherpetic neuralgia who entered single-blind treatment with Lyrica CR. In the study, 73.6% of patients in the Lyrica CR group achieved at least 50% improvement in pain intensity, compared with 54.6% in the placebo group. The postherpetic neuralgia data also supported the diabetic peripheral neuropathy indication. Pfizer markets Lyrica CR.

—Kimberly Williams

Can a Fatty Diet Increase Relapse Risk in Children With MS?

In children with multiple sclerosis (MS), high energy intake from fat, especially saturated fat, may increase the hazard of relapse, while vegetable intake may be independently protective, according to a study published online ahead of print October 9 in the Journal of Neurology, Neurosurgery & Psychiatry. A total of 219 patients with pediatric relapsing-remitting MS or clinically isolated syndrome with disease onset before age 18 and duration of less than four years were enrolled in a multicenter study that was completed at 11 pediatric MS centers. Investigators used the Block Kids Food Screener to examine dietary intake during the week before enrollment. Each 10% increase in energy intake from fat increased the hazard of relapse by 56%, and each 10% increase in saturated fat tripled this hazard.

Azary S, Schreiner T, Graves J, et al. Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017 Oct 9 [Epub ahead of print].

Cooling Reduces Risk of Epilepsy After Perinatal Asphyxia

Administering therapeutic hypothermia to babies with perinatal asphyxia can reduce their risk of epilepsy in childhood, according to a study published online ahead of print September 29 in Epilepsia. From 2006 to 2013, 151 infants with perinatal asphyxia underwent 72 hours of cooling. Clinical and amplitude-integrated EEG with single-channel EEG-verified neonatal seizures were treated with antiepileptic drugs (AEDs). MRI was assessed using a severity score that ranged from 0 to 11. One hundred thirty-four children were assessed at 18–24 months. Babies born after 2007 who received therapeutic hypothermia had a lower rate of epilepsy than those born before this method was introduced. At two years, 6% of the children had epilepsy, and 2% were receiving AEDs. Before therapeutic hypothermia was introduced, the rate of death or moderate or severe disability was about 66%.

Liu X, Jary S, Cowan F, Thoresen M. Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy. Epilepsia. 2017 Sep 29 [Epub ahead of print].

Risk Factors Are Increasing in People With Stroke

The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse in acute ischemic stroke increased between 2004 and 2014, according to a study published online ahead of print October 11 in Neurology. Researchers used the National Inpatient Sample to identify 922,451 adult hospitalizations for ischemic stroke. In all, 92.5% of patients with stroke had one or more risk factors. Age- and sex-adjusted prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse were 79%, 34%, 47%, 15%, and 2%, respectively. The prevalence of carotid stenosis, chronic renal failure, and coronary artery disease were 13%, 12%, and 27%, respectively. Risk factor prevalence varied by age, race, and sex. The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse increased annually by 1.4%, 2%, 7%, 5%, and 7%, respectively.

Otite FO, Liaw N, Khandelwal P, et al. Increasing prevalence of vascular risk factors in patients with stroke: a call to action. Neurology. 2017 Oct 11 [Epub ahead of print].

Transcranial Direct-Current Stimulation for MS-Related Fatigue

People with multiple sclerosis (MS) who undergo a noninvasive form of electrical brain stimulation have significantly reduced fatigue, according to a study published online ahead of print September 1 in the Multiple Sclerosis Journal. Twenty-seven people with MS were randomized to receive transcranial direct-current stimulation or a placebo while playing a cognitive training game that targets processing speed and working memory. After 20 sessions, participants reported their level of fatigue using the Patient-Reported Outcomes Measurement Information System. Higher numbers correlated with greater fatigue. The researchers reported a statistically significant reduction in the group that underwent transcranial direct-current stimulation, compared with the placebo group. Intervention participants had a 5.6-point drop in fatigue on average, while control participants had a 0.9-point increase in fatigue.

Charvet LE, Dobbs B, Shaw MT, et al. Remotely supervised transcranial direct current stimulation for the treatment of fatigue in multiple sclerosis: results from a randomized, sham-controlled trial. Mult Scler. 2017 Sep 1 [Epub ahead of print].

New Genetic Risk Variants for RLS Identified

Thirteen previously unknown genetic risk variants for restless legs syndrome (RLS) have been identified, according to a study published in the November issue of Lancet Neurology. Researchers combined three genome-wide association studies’ datasets with diagnosis data collected from 2003 to 2017. The latter data came from interviews and questionnaires and included 15,126 cases and 95,725 controls. Significant genome-wide signals were tested for replication in an independent genome-wide association study of 30,770 cases and 286,913 controls. Investigators identified and replicated 13 new risk loci for RLS and confirmed six previously identified risk loci. MEIS1 was confirmed as the strongest genetic risk factor for RLS. Gene prioritization, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance, synapse formation, and neuronal specification.

Schormair B, Zhao C, Bell S, et al. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis. Lancet Neurol. 2017;16(11):898-907.

High Blood Pressure Associated With Increased Dementia Risk in Women

Hypertension is more common in men, but is only associated with dementia risk in women, according to a study published online ahead of print October 4 in Neurology. Researchers evaluated 5,646 members of a diverse integrated health care delivery system who had clinical examinations and health survey data from 1964 to 1973 (mean age, 32.7) and 1978 to 1985 (mean age, 44.3) and were members as of January 1, 1996 (mean age, 59.8). A total of 532 people were diagnosed with dementia. Mid-adulthood (circa age 44) hypertension was associated with 65% increased dementia risk among women, but not among men. Onset of hypertension in mid-adulthood predicted 73% higher dementia risk in women, compared with stable normotension. There was no evidence that hypertension or changes in hypertension increased dementia risk among men.

Gilsanz P, Mayeda ER, Glymour MM, et al. Female sex, early-onset hypertension, and risk of dementia. Neurology. 2017 Oct 4 [Epub ahead of print].

A Risk Factor for Major Bleeding During Treatment With NOACs

Among patients taking non-vitamin K oral anticoagulants (NOACs) for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin, compared with the use of NOACs alone, is associated with increased risk of major bleeding, according to a study published October 3 in JAMA. Researchers retrospectively examined data for 91,330 patients with nonvalvular atrial fibrillation who received at least one NOAC prescription of dabigatran, rivaroxaban, or apixaban from 2012 through 2016. They analyzed the bleeding risk associated with the concurrent use of 12 commonly prescribed medications. A total of 4,770 major bleeding events occurred. The incidence rate of major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin. Physicians prescribing NOACs should consider the potential risks associated with concomitant use of other drugs, the researchers said.

Chang SH, Chou IJ, Yeh YH, et al. Association between use of non-vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation. JAMA. 2017;318(13):1250-1259.

Discontinuing Aspirin Therapy May Increase Cardiovascular Risk

In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding is associated with a greater-than-30% increased risk of cardiovascular events, according to a study published September 26 in Circulation. Researchers performed a cohort study of 601,527 participants taking low-dose aspirin for heart attack and stroke prevention between 2005 and 2009. Participants were older than 40, cancer-free, and had an adherence rate of 80% or greater during the first year of treatment. During a median of 3.0 years of follow-up, 62,690 cardiovascular events were reported. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37), corresponding to an additional cardiovascular event observed per year in one of every 74 patients who discontinued aspirin.

Sundström J, Hedberg J, Thuresson M, et al. Low-dose aspirin discontinuation and risk of cardiovascular events: a Swedish nationwide, population-based cohort study. Circulation. 2017;136(13):1183-1192.

FDA Approves 80-mg Ingrezza Capsule for Tardive Dyskinesia

The FDA has approved an 80-mg capsule of Ingrezza (valbenazine) for the treatment of adults with tardive dyskinesia. In clinical studies, Ingrezza 80 mg provided significant, rapid, and meaningful improvement in tardive dyskinesia severity, compared with placebo, at six weeks. Results were seen as early as two weeks, and continued reductions were observed through 48 weeks of treatment. The drug was FDA-approved in April and has been available as 40-mg capsules. Neurocrine Biosciences markets Ingrezza.

FDA Approves Generic Version of Copaxone

The FDA has approved Mylan’s glatiramer acetate injection 40 mg/mL for thrice-weekly injection. The drug is a substitutable generic version of Teva’s Copaxone 40 mg/mL. The agency also approved Mylan’s glatiramer acetate injection 20 mg/mL for once-daily injection, a substitutable generic version of Teva’s Copaxone 20 mg/mL. Both products are indicated for the treatment of patients with relapsing forms of multiple sclerosis. As part of its applications, Mylan submitted side-by-side analyses demonstrating that its glatiramer acetate injections have the same active ingredient, dosage form, route of administration, and strength as their branded counterpart.

FDA Approves Gocovri for Dyskinesia in Parkinson’s Disease

The FDA has approved Gocovri (amantadine) extended-release capsules for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy with or without concomitant dopaminergic medications. Gocovri, previously granted orphan drug status by the FDA, is the first medicine approved by the FDA for this indication. Gocovri is a high-dose (274 mg) formulation of amantadine (equivalent to 340 mg of amantadine HCl) taken once-daily at bedtime that delivers consistently high levels of amantadine from the morning and throughout the day. Adamas Pharmaceuticals markets the drug.

FDA Has Approved Lyrica CR for Two Indications

The FDA has approved Lyrica CR (pregabalin) extended-release tablets CV as once-daily therapy for the management of neuropathic pain associated with diabetic peripheral neuropathy and the management of postherpetic neuralgia. The efficacy and safety of Lyrica CR in postherpetic neuralgia was established in a randomized placebo-controlled clinical trial conducted in 801 patients with postherpetic neuralgia who entered single-blind treatment with Lyrica CR. In the study, 73.6% of patients in the Lyrica CR group achieved at least 50% improvement in pain intensity, compared with 54.6% in the placebo group. The postherpetic neuralgia data also supported the diabetic peripheral neuropathy indication. Pfizer markets Lyrica CR.

—Kimberly Williams