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FDA approves new injection product to reduce preterm birth risk
Makena, a progestin injection for the prevention of preterm birth that has been approved for use since 2011, has received U.S. Food and Drug Administration approval for a subcutaneous auto-injection product to supplant its intramuscular injection formulation, announced its manufacturer, AMAG Pharmaceuticals, on Feb. 14.
The intramuscular injection’s 7-year orphan drug exclusivity expired earlier in February. AMAG plans to offer both products priced at parity, according to the company’s press release. The newer product has a smaller, thinner needle. Both products are intended for use in a woman who has a singleton pregnancy of less than 37 weeks’ gestation and who has had a prior spontaneous preterm singleton delivery. The intramuscular injection is available in both single-dose and multidose vials.
Makena revenues in 2017 were nearly $400 million. The drug was the subject of a price controversy in 2011 under its maker at the time, KV Pharmaceutical, which subsequently cut the price by more than half.
The injection has several contraindications, including blood clots and hormone-sensitive cancers. Its efficacy is based on an improved number of women who used it and were delivered at more than 37 weeks’ gestation rather than on a directly demonstrated clinical benefit in neonatal morbidity or mortality.
Read more in AMAG’s press release.
Makena, a progestin injection for the prevention of preterm birth that has been approved for use since 2011, has received U.S. Food and Drug Administration approval for a subcutaneous auto-injection product to supplant its intramuscular injection formulation, announced its manufacturer, AMAG Pharmaceuticals, on Feb. 14.
The intramuscular injection’s 7-year orphan drug exclusivity expired earlier in February. AMAG plans to offer both products priced at parity, according to the company’s press release. The newer product has a smaller, thinner needle. Both products are intended for use in a woman who has a singleton pregnancy of less than 37 weeks’ gestation and who has had a prior spontaneous preterm singleton delivery. The intramuscular injection is available in both single-dose and multidose vials.
Makena revenues in 2017 were nearly $400 million. The drug was the subject of a price controversy in 2011 under its maker at the time, KV Pharmaceutical, which subsequently cut the price by more than half.
The injection has several contraindications, including blood clots and hormone-sensitive cancers. Its efficacy is based on an improved number of women who used it and were delivered at more than 37 weeks’ gestation rather than on a directly demonstrated clinical benefit in neonatal morbidity or mortality.
Read more in AMAG’s press release.
Makena, a progestin injection for the prevention of preterm birth that has been approved for use since 2011, has received U.S. Food and Drug Administration approval for a subcutaneous auto-injection product to supplant its intramuscular injection formulation, announced its manufacturer, AMAG Pharmaceuticals, on Feb. 14.
The intramuscular injection’s 7-year orphan drug exclusivity expired earlier in February. AMAG plans to offer both products priced at parity, according to the company’s press release. The newer product has a smaller, thinner needle. Both products are intended for use in a woman who has a singleton pregnancy of less than 37 weeks’ gestation and who has had a prior spontaneous preterm singleton delivery. The intramuscular injection is available in both single-dose and multidose vials.
Makena revenues in 2017 were nearly $400 million. The drug was the subject of a price controversy in 2011 under its maker at the time, KV Pharmaceutical, which subsequently cut the price by more than half.
The injection has several contraindications, including blood clots and hormone-sensitive cancers. Its efficacy is based on an improved number of women who used it and were delivered at more than 37 weeks’ gestation rather than on a directly demonstrated clinical benefit in neonatal morbidity or mortality.
Read more in AMAG’s press release.
Screening for adolescent idiopathic scoliosis
The United States Preventive Services Task Force (USPSTF) has issued recommendations on screening for idiopathic scoliosis in asymptomatic children and adolescents aged 10-18 years.1 This recommendation concluded that the current evidence on the benefits and harms of screening is insufficient (I statement) and updated its 2004 recommendation against routine screening, in which it had concluded that the harms of screening exceeded the potential benefits (D recommendation).
Importance
Screening methods
The USPSTF concluded that currently available screening tests can accurately detect adolescent idiopathic scoliosis. Screening methods include visual inspection using the forward bend test, use of scoliometer measurement of the angle of trunk rotation during forward bend test with a rotation of 5 degrees–7 degrees recommended to be referred for radiography, and Moiré topography that enumerates asymmetric contour lines on the back (values greater than 2 are referred to radiography).
The USPSTF reviewed seven fair-quality observational studies (n = 447,243) and concluded that screening with a combination of forward bend test, scoliometer measurement and that Moiré topography had the highest sensitivity (93.8%) and specificity (99.2%), a low false-negative rate (6.2%), the lowest false-positive rate (0.8%), and the highest positive predictive value (81%). Sensitivity was lower when screening programs used only one or two screening tests, and single screening tests were associated with highest false-positive rates.
In general, the potential harms associated with false-positive results include psychological harm, chest radiation exposure, and other unnecessary treatment, but the USPSTF did not find evidence on the direct harms of screening.
Effectiveness of intervention or treatment
Bracing: The USPSTF found five studies (n = 651) that evaluated the effectiveness of treatment with three different types of braces. The average ages of participants ranged from 12 to 13 years, and their curvature severity varied from Cobb angle of 20 degrees to 30 degrees. The largest study (n = 242) was a good-quality, international, controlled clinical trial known as the Bracing in Adolescent Idiopathic Scoliosis Trial; it demonstrated significant benefit and quality-of-life outcomes associated with bracing for 18 hours/day. In this study, the rate of treatment success in the as-treated analysis was 72% in the intervention group and 48% in the control group. The rate of treatment success in the intention-to-treat analysis was 75% in the intervention group and 42% in the control group. The number needed to treat was three to prevent one case of curvature progression past 50%.
Exercise: The USPSTF found just two trials (n = 184) that evaluated the effectiveness of tailored physiotherapeutic, scoliosis-specific exercise treatments. The participants were older than 10 years and had Cobb angles ranging from 10 degrees to 25 degrees. At the 12-month follow-up, the studies showed significant improvement, including those in quality-of-life measures. In one of the trials, the intervention group had a Cobb angle reduction of 4.9 degrees while the control group had an increase of 2.8 degrees.
Harms: Only one good-quality study (n = 242) reported harms of bracing, which include skin problems, body pain, physical limitations, anxiety, and depression. The USPSTF did not find any studies that assessed the harms of treatment with exercise or surgery.
Association between spinal curvature severity and adult health outcomes
The USPSTF did not find any studies that directly addressed whether changes in the severity of spinal curvature in adolescence resulted in changes in adult health outcomes. The USPSTF did review two fair-quality retrospective, observational, long-term, follow-up analyses (n = 339) of adults diagnosed with idiopathic scoliosis in adolescence and treated with either bracing or surgery. Quality of life measurements, pulmonary consequences, and pregnancy outcomes were not significantly different between the two treatment groups or between those treated and those simply observed. However, those treated with bracing did report more negative treatment experience and body distortion.
Recommendation of others
The Scoliosis Research Society, American Academy of Orthopedic Surgeons, Pediatric Orthopedic Society of North America, and American Academy of Pediatrics issued a joint position statement in September 2015 recommending that screening examinations for scoliosis should be performed for females at ages 10 and 12 years and for males at either 13 or 14 years.2
Their rationale, articulated in the statement and in an editorial in JAMA accompanying the publication of the USPSTF statement, is primarily based on findings in the Bracing in Adolescent Idiopathic Scoliosis Trial that showed a 56% decrease in the rate of progression of moderate curves to greater than 50 degrees. The evidence that intervention works – along with concerns about costs, family burden, loss of school time, risks of surgical complications, and the 22% need for long-term revision surgery – makes avoidance of progression of curves in scoliosis a high-value issue. In addition, they reasoned, the screening trials from which the false-positive values were derived were primarily school-based screening and not done in physician offices.
The Bottom Line
Although the joint statement made by pediatric orthopedic societies and the American Academy of Pediatrics had recommended screening examinations, the USPSTF concluded that the current evidence is insufficient and that the balance of benefits and harms of screening for adolescent (aged 10-18 years) idiopathic scoliosis (Cobb angle greater than 10 degrees) cannot be determined, giving an “I” recommendation.
Dr. Aarisha Shrestha is a first-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Jefferson Health.
References
1. US Preventive Services Task Force. JAMA. 2018;319(2):165–72.
2. HreskoMT et al. SRS/POSNA/AAOS/AAP position statement: Screening for the early detection for idiopathic scoliosis in adolescents. 2015. Accessed December 8, 2017.
The United States Preventive Services Task Force (USPSTF) has issued recommendations on screening for idiopathic scoliosis in asymptomatic children and adolescents aged 10-18 years.1 This recommendation concluded that the current evidence on the benefits and harms of screening is insufficient (I statement) and updated its 2004 recommendation against routine screening, in which it had concluded that the harms of screening exceeded the potential benefits (D recommendation).
Importance
Screening methods
The USPSTF concluded that currently available screening tests can accurately detect adolescent idiopathic scoliosis. Screening methods include visual inspection using the forward bend test, use of scoliometer measurement of the angle of trunk rotation during forward bend test with a rotation of 5 degrees–7 degrees recommended to be referred for radiography, and Moiré topography that enumerates asymmetric contour lines on the back (values greater than 2 are referred to radiography).
The USPSTF reviewed seven fair-quality observational studies (n = 447,243) and concluded that screening with a combination of forward bend test, scoliometer measurement and that Moiré topography had the highest sensitivity (93.8%) and specificity (99.2%), a low false-negative rate (6.2%), the lowest false-positive rate (0.8%), and the highest positive predictive value (81%). Sensitivity was lower when screening programs used only one or two screening tests, and single screening tests were associated with highest false-positive rates.
In general, the potential harms associated with false-positive results include psychological harm, chest radiation exposure, and other unnecessary treatment, but the USPSTF did not find evidence on the direct harms of screening.
Effectiveness of intervention or treatment
Bracing: The USPSTF found five studies (n = 651) that evaluated the effectiveness of treatment with three different types of braces. The average ages of participants ranged from 12 to 13 years, and their curvature severity varied from Cobb angle of 20 degrees to 30 degrees. The largest study (n = 242) was a good-quality, international, controlled clinical trial known as the Bracing in Adolescent Idiopathic Scoliosis Trial; it demonstrated significant benefit and quality-of-life outcomes associated with bracing for 18 hours/day. In this study, the rate of treatment success in the as-treated analysis was 72% in the intervention group and 48% in the control group. The rate of treatment success in the intention-to-treat analysis was 75% in the intervention group and 42% in the control group. The number needed to treat was three to prevent one case of curvature progression past 50%.
Exercise: The USPSTF found just two trials (n = 184) that evaluated the effectiveness of tailored physiotherapeutic, scoliosis-specific exercise treatments. The participants were older than 10 years and had Cobb angles ranging from 10 degrees to 25 degrees. At the 12-month follow-up, the studies showed significant improvement, including those in quality-of-life measures. In one of the trials, the intervention group had a Cobb angle reduction of 4.9 degrees while the control group had an increase of 2.8 degrees.
Harms: Only one good-quality study (n = 242) reported harms of bracing, which include skin problems, body pain, physical limitations, anxiety, and depression. The USPSTF did not find any studies that assessed the harms of treatment with exercise or surgery.
Association between spinal curvature severity and adult health outcomes
The USPSTF did not find any studies that directly addressed whether changes in the severity of spinal curvature in adolescence resulted in changes in adult health outcomes. The USPSTF did review two fair-quality retrospective, observational, long-term, follow-up analyses (n = 339) of adults diagnosed with idiopathic scoliosis in adolescence and treated with either bracing or surgery. Quality of life measurements, pulmonary consequences, and pregnancy outcomes were not significantly different between the two treatment groups or between those treated and those simply observed. However, those treated with bracing did report more negative treatment experience and body distortion.
Recommendation of others
The Scoliosis Research Society, American Academy of Orthopedic Surgeons, Pediatric Orthopedic Society of North America, and American Academy of Pediatrics issued a joint position statement in September 2015 recommending that screening examinations for scoliosis should be performed for females at ages 10 and 12 years and for males at either 13 or 14 years.2
Their rationale, articulated in the statement and in an editorial in JAMA accompanying the publication of the USPSTF statement, is primarily based on findings in the Bracing in Adolescent Idiopathic Scoliosis Trial that showed a 56% decrease in the rate of progression of moderate curves to greater than 50 degrees. The evidence that intervention works – along with concerns about costs, family burden, loss of school time, risks of surgical complications, and the 22% need for long-term revision surgery – makes avoidance of progression of curves in scoliosis a high-value issue. In addition, they reasoned, the screening trials from which the false-positive values were derived were primarily school-based screening and not done in physician offices.
The Bottom Line
Although the joint statement made by pediatric orthopedic societies and the American Academy of Pediatrics had recommended screening examinations, the USPSTF concluded that the current evidence is insufficient and that the balance of benefits and harms of screening for adolescent (aged 10-18 years) idiopathic scoliosis (Cobb angle greater than 10 degrees) cannot be determined, giving an “I” recommendation.
Dr. Aarisha Shrestha is a first-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Jefferson Health.
References
1. US Preventive Services Task Force. JAMA. 2018;319(2):165–72.
2. HreskoMT et al. SRS/POSNA/AAOS/AAP position statement: Screening for the early detection for idiopathic scoliosis in adolescents. 2015. Accessed December 8, 2017.
The United States Preventive Services Task Force (USPSTF) has issued recommendations on screening for idiopathic scoliosis in asymptomatic children and adolescents aged 10-18 years.1 This recommendation concluded that the current evidence on the benefits and harms of screening is insufficient (I statement) and updated its 2004 recommendation against routine screening, in which it had concluded that the harms of screening exceeded the potential benefits (D recommendation).
Importance
Screening methods
The USPSTF concluded that currently available screening tests can accurately detect adolescent idiopathic scoliosis. Screening methods include visual inspection using the forward bend test, use of scoliometer measurement of the angle of trunk rotation during forward bend test with a rotation of 5 degrees–7 degrees recommended to be referred for radiography, and Moiré topography that enumerates asymmetric contour lines on the back (values greater than 2 are referred to radiography).
The USPSTF reviewed seven fair-quality observational studies (n = 447,243) and concluded that screening with a combination of forward bend test, scoliometer measurement and that Moiré topography had the highest sensitivity (93.8%) and specificity (99.2%), a low false-negative rate (6.2%), the lowest false-positive rate (0.8%), and the highest positive predictive value (81%). Sensitivity was lower when screening programs used only one or two screening tests, and single screening tests were associated with highest false-positive rates.
In general, the potential harms associated with false-positive results include psychological harm, chest radiation exposure, and other unnecessary treatment, but the USPSTF did not find evidence on the direct harms of screening.
Effectiveness of intervention or treatment
Bracing: The USPSTF found five studies (n = 651) that evaluated the effectiveness of treatment with three different types of braces. The average ages of participants ranged from 12 to 13 years, and their curvature severity varied from Cobb angle of 20 degrees to 30 degrees. The largest study (n = 242) was a good-quality, international, controlled clinical trial known as the Bracing in Adolescent Idiopathic Scoliosis Trial; it demonstrated significant benefit and quality-of-life outcomes associated with bracing for 18 hours/day. In this study, the rate of treatment success in the as-treated analysis was 72% in the intervention group and 48% in the control group. The rate of treatment success in the intention-to-treat analysis was 75% in the intervention group and 42% in the control group. The number needed to treat was three to prevent one case of curvature progression past 50%.
Exercise: The USPSTF found just two trials (n = 184) that evaluated the effectiveness of tailored physiotherapeutic, scoliosis-specific exercise treatments. The participants were older than 10 years and had Cobb angles ranging from 10 degrees to 25 degrees. At the 12-month follow-up, the studies showed significant improvement, including those in quality-of-life measures. In one of the trials, the intervention group had a Cobb angle reduction of 4.9 degrees while the control group had an increase of 2.8 degrees.
Harms: Only one good-quality study (n = 242) reported harms of bracing, which include skin problems, body pain, physical limitations, anxiety, and depression. The USPSTF did not find any studies that assessed the harms of treatment with exercise or surgery.
Association between spinal curvature severity and adult health outcomes
The USPSTF did not find any studies that directly addressed whether changes in the severity of spinal curvature in adolescence resulted in changes in adult health outcomes. The USPSTF did review two fair-quality retrospective, observational, long-term, follow-up analyses (n = 339) of adults diagnosed with idiopathic scoliosis in adolescence and treated with either bracing or surgery. Quality of life measurements, pulmonary consequences, and pregnancy outcomes were not significantly different between the two treatment groups or between those treated and those simply observed. However, those treated with bracing did report more negative treatment experience and body distortion.
Recommendation of others
The Scoliosis Research Society, American Academy of Orthopedic Surgeons, Pediatric Orthopedic Society of North America, and American Academy of Pediatrics issued a joint position statement in September 2015 recommending that screening examinations for scoliosis should be performed for females at ages 10 and 12 years and for males at either 13 or 14 years.2
Their rationale, articulated in the statement and in an editorial in JAMA accompanying the publication of the USPSTF statement, is primarily based on findings in the Bracing in Adolescent Idiopathic Scoliosis Trial that showed a 56% decrease in the rate of progression of moderate curves to greater than 50 degrees. The evidence that intervention works – along with concerns about costs, family burden, loss of school time, risks of surgical complications, and the 22% need for long-term revision surgery – makes avoidance of progression of curves in scoliosis a high-value issue. In addition, they reasoned, the screening trials from which the false-positive values were derived were primarily school-based screening and not done in physician offices.
The Bottom Line
Although the joint statement made by pediatric orthopedic societies and the American Academy of Pediatrics had recommended screening examinations, the USPSTF concluded that the current evidence is insufficient and that the balance of benefits and harms of screening for adolescent (aged 10-18 years) idiopathic scoliosis (Cobb angle greater than 10 degrees) cannot be determined, giving an “I” recommendation.
Dr. Aarisha Shrestha is a first-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Jefferson Health.
References
1. US Preventive Services Task Force. JAMA. 2018;319(2):165–72.
2. HreskoMT et al. SRS/POSNA/AAOS/AAP position statement: Screening for the early detection for idiopathic scoliosis in adolescents. 2015. Accessed December 8, 2017.
Denosumab on par with zoledronic acid for multiple myeloma bone disease
Denosumab was noninferior to zoledronic acid at delaying skeletal-related events in patients with newly diagnosed multiple myeloma and one or more lytic bone lesions, according to findings from an international randomized trial.
In a phase 3 double-blind, double-dummy, controlled trial, patients were randomly assigned to receive either subcutaneous denosumab or intravenous zoledronic acid, plus the investigator’s choice of first-line antimyeloma therapy. The primary endpoint of noninferiority of denosumab at preventing time to first skeletal-related event, compared with zoledronic acid, was met, reported Noopur Raje, MD, of the Massachusetts General Hospital Cancer Center, Boston, and colleagues.
Median progression-free survival, an exploratory endpoint, was significantly longer with denosumab – 46.1 months vs. 35.4 months – translating into a hazard ratio of 0.82 (P = .036) for progression on denosumab. There was no difference in overall survival, however.
Denosumab is a monoclonal antibody that binds to and inactivates receptor activator of nuclear factor kappa-B ligand, a promoter of osteoclast formation, activation, and survival. Zoledronic acid is a bisphosphonate that may have antimyeloma effects, the investigators noted.
“The greater progression-free survival with denosumab than with zoledronic acid is compelling in view of the previous preclinical and clinical evidence supporting an anti-RANKL[receptor factor kappa-B ligand]–mediated, antimyeloma effect. These results, in combination with the improved renal adverse event profile, support denosumab as an additional option to the standard of care for patients with multiple myeloma,” the investigators wrote in The Lancet Oncology.
The trial included 1,718 patients age 18 and older treated at 259 centers in 29 countries. All patients had newly diagnosed multiple myeloma with at least one documented lytic bone lesion. The patients were randomly assigned to denosumab or zoledronic acid, and were stratified by intent to undergo autologous stem cell transplant, antimyeloma therapy regimen, stage according to the International Staging System, previous skeletal-related events, and region.
As noted, the trial met the primary endpoint of noninferiority of denosumab, with a hazard ratio for time to first skeletal-related event vs. zoledronic acid of 0.98 (P = .010).
The safety analysis, which included all patients who were randomized and received at least one dose of study medication (850 on denosumab and 852 on zoledronic acid) showed that the agents were associated with similar incidences of neutropenia, thrombocytopenia, anemia, febrile neutropenia, and pneumonia. The incidence of renal toxicity, however, was lower with denosumab than with zoledronic acid (10% vs. 17%, respectively), whereas hypocalcemia was higher with denosumab (17% vs. 12%). There were no significant differences in the incidence of osteonecrosis of the jaw, a common problem with osteoclast inhibitors.
There was one treatment-related death, a case of cardiac arrest in a patient treated with zoledronic acid.
The investigators noted that the study was limited by a lack of response data, and by the fact that patients with creatinine clearance less than 30 mL/minute were not enrolled because of study blinding and the product label of zoledronic acid.
The study was sponsored by Amgen. Dr. Raje and multiple coauthors disclosed personal fees from Amgen and other companies. Three of the coauthors are current or former Amgen employees.
SOURCE: Raje NS et al. Lancet Oncol. 2018 Feb 8. doi: 10.1016/S1470-2045(18)30072-X.
The study by Dr. Raje and colleagues is the largest placebo-controlled study ever done in patients with myeloma, but there are still many questions about how to move forward with this treatment. For instance, since only patients with myeloma-related bone disease at diagnosis were enrolled, the benefit of denosumab in patients without bone disease is uncertain. Additionally, the study did not show a survival benefit for denosumab over zoledronic acid.
Cost is also a factor, as denosumab is a higher priced treatment and requires continuous therapy. New treatment options, such as anti-CD38 monoclonal antibodies, are also available. It’s unclear how denosumab adds value in the context of these new therapies.
Meletios A. Dimopoulos, MD, and Efstathios Kastritis, MD, are with the department of clinical therapeutics at the National and Kapodistrian University of Athens, Greece. Dr. Dimopoulos had received honoraria from Celgene, Amgen, Takeda, Janssen, and Novartis. Dr. Kastritis has received honoraria from Janssen, Amgen, Prothena, Takeda, and Genesis Pharma. Their remarks are adapted from an accompanying editorial (Lancet Oncol. 2018 Feb 8. doi: 10.1016/S1470-2045(18)30075-5).
The study by Dr. Raje and colleagues is the largest placebo-controlled study ever done in patients with myeloma, but there are still many questions about how to move forward with this treatment. For instance, since only patients with myeloma-related bone disease at diagnosis were enrolled, the benefit of denosumab in patients without bone disease is uncertain. Additionally, the study did not show a survival benefit for denosumab over zoledronic acid.
Cost is also a factor, as denosumab is a higher priced treatment and requires continuous therapy. New treatment options, such as anti-CD38 monoclonal antibodies, are also available. It’s unclear how denosumab adds value in the context of these new therapies.
Meletios A. Dimopoulos, MD, and Efstathios Kastritis, MD, are with the department of clinical therapeutics at the National and Kapodistrian University of Athens, Greece. Dr. Dimopoulos had received honoraria from Celgene, Amgen, Takeda, Janssen, and Novartis. Dr. Kastritis has received honoraria from Janssen, Amgen, Prothena, Takeda, and Genesis Pharma. Their remarks are adapted from an accompanying editorial (Lancet Oncol. 2018 Feb 8. doi: 10.1016/S1470-2045(18)30075-5).
The study by Dr. Raje and colleagues is the largest placebo-controlled study ever done in patients with myeloma, but there are still many questions about how to move forward with this treatment. For instance, since only patients with myeloma-related bone disease at diagnosis were enrolled, the benefit of denosumab in patients without bone disease is uncertain. Additionally, the study did not show a survival benefit for denosumab over zoledronic acid.
Cost is also a factor, as denosumab is a higher priced treatment and requires continuous therapy. New treatment options, such as anti-CD38 monoclonal antibodies, are also available. It’s unclear how denosumab adds value in the context of these new therapies.
Meletios A. Dimopoulos, MD, and Efstathios Kastritis, MD, are with the department of clinical therapeutics at the National and Kapodistrian University of Athens, Greece. Dr. Dimopoulos had received honoraria from Celgene, Amgen, Takeda, Janssen, and Novartis. Dr. Kastritis has received honoraria from Janssen, Amgen, Prothena, Takeda, and Genesis Pharma. Their remarks are adapted from an accompanying editorial (Lancet Oncol. 2018 Feb 8. doi: 10.1016/S1470-2045(18)30075-5).
Denosumab was noninferior to zoledronic acid at delaying skeletal-related events in patients with newly diagnosed multiple myeloma and one or more lytic bone lesions, according to findings from an international randomized trial.
In a phase 3 double-blind, double-dummy, controlled trial, patients were randomly assigned to receive either subcutaneous denosumab or intravenous zoledronic acid, plus the investigator’s choice of first-line antimyeloma therapy. The primary endpoint of noninferiority of denosumab at preventing time to first skeletal-related event, compared with zoledronic acid, was met, reported Noopur Raje, MD, of the Massachusetts General Hospital Cancer Center, Boston, and colleagues.
Median progression-free survival, an exploratory endpoint, was significantly longer with denosumab – 46.1 months vs. 35.4 months – translating into a hazard ratio of 0.82 (P = .036) for progression on denosumab. There was no difference in overall survival, however.
Denosumab is a monoclonal antibody that binds to and inactivates receptor activator of nuclear factor kappa-B ligand, a promoter of osteoclast formation, activation, and survival. Zoledronic acid is a bisphosphonate that may have antimyeloma effects, the investigators noted.
“The greater progression-free survival with denosumab than with zoledronic acid is compelling in view of the previous preclinical and clinical evidence supporting an anti-RANKL[receptor factor kappa-B ligand]–mediated, antimyeloma effect. These results, in combination with the improved renal adverse event profile, support denosumab as an additional option to the standard of care for patients with multiple myeloma,” the investigators wrote in The Lancet Oncology.
The trial included 1,718 patients age 18 and older treated at 259 centers in 29 countries. All patients had newly diagnosed multiple myeloma with at least one documented lytic bone lesion. The patients were randomly assigned to denosumab or zoledronic acid, and were stratified by intent to undergo autologous stem cell transplant, antimyeloma therapy regimen, stage according to the International Staging System, previous skeletal-related events, and region.
As noted, the trial met the primary endpoint of noninferiority of denosumab, with a hazard ratio for time to first skeletal-related event vs. zoledronic acid of 0.98 (P = .010).
The safety analysis, which included all patients who were randomized and received at least one dose of study medication (850 on denosumab and 852 on zoledronic acid) showed that the agents were associated with similar incidences of neutropenia, thrombocytopenia, anemia, febrile neutropenia, and pneumonia. The incidence of renal toxicity, however, was lower with denosumab than with zoledronic acid (10% vs. 17%, respectively), whereas hypocalcemia was higher with denosumab (17% vs. 12%). There were no significant differences in the incidence of osteonecrosis of the jaw, a common problem with osteoclast inhibitors.
There was one treatment-related death, a case of cardiac arrest in a patient treated with zoledronic acid.
The investigators noted that the study was limited by a lack of response data, and by the fact that patients with creatinine clearance less than 30 mL/minute were not enrolled because of study blinding and the product label of zoledronic acid.
The study was sponsored by Amgen. Dr. Raje and multiple coauthors disclosed personal fees from Amgen and other companies. Three of the coauthors are current or former Amgen employees.
SOURCE: Raje NS et al. Lancet Oncol. 2018 Feb 8. doi: 10.1016/S1470-2045(18)30072-X.
Denosumab was noninferior to zoledronic acid at delaying skeletal-related events in patients with newly diagnosed multiple myeloma and one or more lytic bone lesions, according to findings from an international randomized trial.
In a phase 3 double-blind, double-dummy, controlled trial, patients were randomly assigned to receive either subcutaneous denosumab or intravenous zoledronic acid, plus the investigator’s choice of first-line antimyeloma therapy. The primary endpoint of noninferiority of denosumab at preventing time to first skeletal-related event, compared with zoledronic acid, was met, reported Noopur Raje, MD, of the Massachusetts General Hospital Cancer Center, Boston, and colleagues.
Median progression-free survival, an exploratory endpoint, was significantly longer with denosumab – 46.1 months vs. 35.4 months – translating into a hazard ratio of 0.82 (P = .036) for progression on denosumab. There was no difference in overall survival, however.
Denosumab is a monoclonal antibody that binds to and inactivates receptor activator of nuclear factor kappa-B ligand, a promoter of osteoclast formation, activation, and survival. Zoledronic acid is a bisphosphonate that may have antimyeloma effects, the investigators noted.
“The greater progression-free survival with denosumab than with zoledronic acid is compelling in view of the previous preclinical and clinical evidence supporting an anti-RANKL[receptor factor kappa-B ligand]–mediated, antimyeloma effect. These results, in combination with the improved renal adverse event profile, support denosumab as an additional option to the standard of care for patients with multiple myeloma,” the investigators wrote in The Lancet Oncology.
The trial included 1,718 patients age 18 and older treated at 259 centers in 29 countries. All patients had newly diagnosed multiple myeloma with at least one documented lytic bone lesion. The patients were randomly assigned to denosumab or zoledronic acid, and were stratified by intent to undergo autologous stem cell transplant, antimyeloma therapy regimen, stage according to the International Staging System, previous skeletal-related events, and region.
As noted, the trial met the primary endpoint of noninferiority of denosumab, with a hazard ratio for time to first skeletal-related event vs. zoledronic acid of 0.98 (P = .010).
The safety analysis, which included all patients who were randomized and received at least one dose of study medication (850 on denosumab and 852 on zoledronic acid) showed that the agents were associated with similar incidences of neutropenia, thrombocytopenia, anemia, febrile neutropenia, and pneumonia. The incidence of renal toxicity, however, was lower with denosumab than with zoledronic acid (10% vs. 17%, respectively), whereas hypocalcemia was higher with denosumab (17% vs. 12%). There were no significant differences in the incidence of osteonecrosis of the jaw, a common problem with osteoclast inhibitors.
There was one treatment-related death, a case of cardiac arrest in a patient treated with zoledronic acid.
The investigators noted that the study was limited by a lack of response data, and by the fact that patients with creatinine clearance less than 30 mL/minute were not enrolled because of study blinding and the product label of zoledronic acid.
The study was sponsored by Amgen. Dr. Raje and multiple coauthors disclosed personal fees from Amgen and other companies. Three of the coauthors are current or former Amgen employees.
SOURCE: Raje NS et al. Lancet Oncol. 2018 Feb 8. doi: 10.1016/S1470-2045(18)30072-X.
FROM LANCET ONCOLOGY
Key clinical point: Denosumab was noninferior to zoledronic acid for time to skeletal-related events in patients with multiple myeloma with bone involvement.
Major finding: The hazard ratio for noninferiority of denosumab was 0.98 (P = .010).
Data source: A phase 3 randomized double-blind, double-dummy, controlled trial in 1,718 patients with newly diagnosed multiple myeloma with one or more lytic bone lesions.
Disclosures: The study was sponsored by Amgen. Dr. Raje and multiple coauthors disclosed personal fees from Amgen and other companies. Three of the coauthors are current or former Amgen employees.
Source: Raje NS et al. Lancet Oncol. 2018 Feb 8. doi: 10.1016/S1470-2045(18)30072-X.
Set realistic expectations prior to perioral rejuvenation procedures
MIAMI – The success of perioral rejuvenation depends in large part on setting realistic expectations. But there are also tips and tricks to individualizing the technique for each patient that can lead to better outcomes and greater satisfaction – whether patients receive injections into the fine lines above the lip, full-field erbium laser resurfacing, neuromodulator treatment, or a combination approach, according to Joel L. Cohen, MD.
When a patient presents with major lines in the perioral area, an “orange peel” texture, and/or elastotic changes, laser resurfacing can be an appropriate option. “Full field erbium laser resurfacing can give patients a nice improvement of upper lip lines and even a nice contraction of oral commissure,” Dr. Cohen said at the Orlando Dermatology Aesthetic and Clinical Conference.
Although each treatment is individualized to the patient, “I tend to do full field erbium resurfacing around the mouth and eyes, and fractional ablative resurfacing around the rest of the face,” said Dr. Cohen, an aesthetic dermatologist and Mohs surgeon in private practice in metropolitan Denver.
More downtime is associated with laser resurfacing compared with fillers or neuromodulator injections, but long-term patient satisfaction, even with improvement in quality of life for some patients (who become less anxious about these lines and more self-confident), can make this approach worthwhile. During his presentation, Dr. Cohen showed photos of many of his treated patients, including one woman whose grandchildren he said had been commenting about the “orange peel texture of her upper lip,” until she completed the resurfacing treatment.
Keep expectations realistic
Dr. Cohen recommended counseling patients about the potential benefits – and the caveats – associated with full-field erbium heavier resurfacing. “Make sure people understand they will look terrible for several days after heavy resurfacing, usually taking about 10-12 days to re-epithelialize,” he said. “We need to tell patients that the perioral area typically manifests more lines than other areas, so we need treat this area differently than just ablative fractional resurfacing in many cases.”
He explained that with heavier resurfacing procedures, it helps to show patients what is expected over the days to weeks in the healing process. They need to understand and see photos that show that the full-field erbium areas will have a yellow fibrinous healing response for the first week or so, which looks very different from the fractional ablative-treated areas (which are more typically red, weepy, and swollen).
He encourages these patients to come back a few days after the procedure to check their healing and review wound-care instructions, especially for patients who have deeper full-field perioral erbium resurfacing (those who are treated with 450-700 microns). Another tip he provided is to have these postresurfacing patients enter/exit through a separate entrance and also sit in a separate cosmetic waiting room at off-hours.
Re-epithelialization generally takes about 10-12 days for most people, with a maximal improvement at approximately 3 months, Dr. Cohen said. “Some patients can see not only significant improvement of upper lip lines, but often a nice contraction of the oral commissure even before fillers are performed to buttress the marionette area and oral commissure,” he said.
With full-field ablative resurfacing in specific areas, rather than simply fractional ablative resurfacing, it is also important to educate patients that some postinflammatory erythema is expected, which, in some cases, may persist for a few months. “In my experience, topical vasoconstrictors don’t seem to help minimize prolonged redness in the full-field erbium areas, but potent topical steroids can be beneficial,” Dr. Cohen said.
More tips for success
Injected local anesthesia is warranted prior to heavier laser resurfacing to keep patients as comfortable as possible. An infraorbital block with an added submucosal/sulcus block with plain lidocaine can be a good approach, he noted. Different perioral and facial areas have different degrees of lines, requiring different laser settings. He prefers to use plain lidocaine perioral blocks, “so that I can theoretically best see the endpoint pinpoint bleeding,” he said, adding that “significant pinpoint bleeding is a good place to stop.”
Typically, he uses a neuromodulator a week or two before full-field perioral erbium resurfacing. “I choose not to give a neuromodulator on the same day as I am concerned about swelling or manipulation of the skin causing unwanted spread to adjacent musculature,” Dr. Cohen said.
Another tip is to take photos with more than one device. “Standardized photos may lose detail of etched lines; we take both iPad and standardized camera system photos,” he said, adding that it is important that clinic staff are proficient at taking proper before-and-after photos, making sure, for example, that the patient does not have confounding makeup or lipstick on for photos, and patient positioning is consistent.
He said it is imperative to emphasize the importance of diligent sun protection for several months after the laser procedure. “Every patient reassures us they use sunscreen, but we often don’t know what sunscreen they are using or how frequently they are using it,” Dr. Cohen said. “If they don’t follow our specific instructions to use a physical block sunscreen, they will significantly increase their risk of developing postinflammatory hyperpigmentation. This caveat applies all year round, and isn’t just for those that go to the beach or play golf, but is also especially important for those patients that ski or hike at higher altitudes.”
Depending on the degree of etched-in lines in the perioral area, one perioral full-field laser resurfacing treatment is generally sufficient for most patients to see significant improvement. For those with more severe etched lines and/or bigger goals for improvement, additional treatments can be performed – but he generally waits about 3 months to see the overall effect of the initial treatment session.
If patients have just a few discrete etched-lines on each side of the upper lip, fillers can be helpful. But, the number and caliber of fine lines on the cutaneous lip limit how much a dermatologist can realistically treat. “So for people with many, many etched-in lines on the cutaneous lip, I explain that fillers are not the right tool for the job – and that they need heavier laser resurfacing.” And those patients really concerned about downtime need to understand that the bruising that can occur with fillers for several days can lead to some degree of social downtime as well.
Options to treat perioral lines not ‘etched in’
Sometimes younger patients, those in their late 20s to early 40s, present with concerns about their perioral appearance. Although they do not have lines at rest yet, they can be unhappy with the muscle columns that appear above their lips with animation that begin to cause lines at rest imprinted in the skin. And many of these women complain that their lipstick bleeds into this area,” Dr. Cohen said. “These patients without etched lines can be treated with a neuromodulator alone to soften the mechanical action of the orbicularis oris muscle,” he pointed out.
Dr. Cohen disclosed having participated in clinical trials and/or having served as a consultant for Merz, Allergan, Galderma, Suneva, Sciton, and Lutronic.
MIAMI – The success of perioral rejuvenation depends in large part on setting realistic expectations. But there are also tips and tricks to individualizing the technique for each patient that can lead to better outcomes and greater satisfaction – whether patients receive injections into the fine lines above the lip, full-field erbium laser resurfacing, neuromodulator treatment, or a combination approach, according to Joel L. Cohen, MD.
When a patient presents with major lines in the perioral area, an “orange peel” texture, and/or elastotic changes, laser resurfacing can be an appropriate option. “Full field erbium laser resurfacing can give patients a nice improvement of upper lip lines and even a nice contraction of oral commissure,” Dr. Cohen said at the Orlando Dermatology Aesthetic and Clinical Conference.
Although each treatment is individualized to the patient, “I tend to do full field erbium resurfacing around the mouth and eyes, and fractional ablative resurfacing around the rest of the face,” said Dr. Cohen, an aesthetic dermatologist and Mohs surgeon in private practice in metropolitan Denver.
More downtime is associated with laser resurfacing compared with fillers or neuromodulator injections, but long-term patient satisfaction, even with improvement in quality of life for some patients (who become less anxious about these lines and more self-confident), can make this approach worthwhile. During his presentation, Dr. Cohen showed photos of many of his treated patients, including one woman whose grandchildren he said had been commenting about the “orange peel texture of her upper lip,” until she completed the resurfacing treatment.
Keep expectations realistic
Dr. Cohen recommended counseling patients about the potential benefits – and the caveats – associated with full-field erbium heavier resurfacing. “Make sure people understand they will look terrible for several days after heavy resurfacing, usually taking about 10-12 days to re-epithelialize,” he said. “We need to tell patients that the perioral area typically manifests more lines than other areas, so we need treat this area differently than just ablative fractional resurfacing in many cases.”
He explained that with heavier resurfacing procedures, it helps to show patients what is expected over the days to weeks in the healing process. They need to understand and see photos that show that the full-field erbium areas will have a yellow fibrinous healing response for the first week or so, which looks very different from the fractional ablative-treated areas (which are more typically red, weepy, and swollen).
He encourages these patients to come back a few days after the procedure to check their healing and review wound-care instructions, especially for patients who have deeper full-field perioral erbium resurfacing (those who are treated with 450-700 microns). Another tip he provided is to have these postresurfacing patients enter/exit through a separate entrance and also sit in a separate cosmetic waiting room at off-hours.
Re-epithelialization generally takes about 10-12 days for most people, with a maximal improvement at approximately 3 months, Dr. Cohen said. “Some patients can see not only significant improvement of upper lip lines, but often a nice contraction of the oral commissure even before fillers are performed to buttress the marionette area and oral commissure,” he said.
With full-field ablative resurfacing in specific areas, rather than simply fractional ablative resurfacing, it is also important to educate patients that some postinflammatory erythema is expected, which, in some cases, may persist for a few months. “In my experience, topical vasoconstrictors don’t seem to help minimize prolonged redness in the full-field erbium areas, but potent topical steroids can be beneficial,” Dr. Cohen said.
More tips for success
Injected local anesthesia is warranted prior to heavier laser resurfacing to keep patients as comfortable as possible. An infraorbital block with an added submucosal/sulcus block with plain lidocaine can be a good approach, he noted. Different perioral and facial areas have different degrees of lines, requiring different laser settings. He prefers to use plain lidocaine perioral blocks, “so that I can theoretically best see the endpoint pinpoint bleeding,” he said, adding that “significant pinpoint bleeding is a good place to stop.”
Typically, he uses a neuromodulator a week or two before full-field perioral erbium resurfacing. “I choose not to give a neuromodulator on the same day as I am concerned about swelling or manipulation of the skin causing unwanted spread to adjacent musculature,” Dr. Cohen said.
Another tip is to take photos with more than one device. “Standardized photos may lose detail of etched lines; we take both iPad and standardized camera system photos,” he said, adding that it is important that clinic staff are proficient at taking proper before-and-after photos, making sure, for example, that the patient does not have confounding makeup or lipstick on for photos, and patient positioning is consistent.
He said it is imperative to emphasize the importance of diligent sun protection for several months after the laser procedure. “Every patient reassures us they use sunscreen, but we often don’t know what sunscreen they are using or how frequently they are using it,” Dr. Cohen said. “If they don’t follow our specific instructions to use a physical block sunscreen, they will significantly increase their risk of developing postinflammatory hyperpigmentation. This caveat applies all year round, and isn’t just for those that go to the beach or play golf, but is also especially important for those patients that ski or hike at higher altitudes.”
Depending on the degree of etched-in lines in the perioral area, one perioral full-field laser resurfacing treatment is generally sufficient for most patients to see significant improvement. For those with more severe etched lines and/or bigger goals for improvement, additional treatments can be performed – but he generally waits about 3 months to see the overall effect of the initial treatment session.
If patients have just a few discrete etched-lines on each side of the upper lip, fillers can be helpful. But, the number and caliber of fine lines on the cutaneous lip limit how much a dermatologist can realistically treat. “So for people with many, many etched-in lines on the cutaneous lip, I explain that fillers are not the right tool for the job – and that they need heavier laser resurfacing.” And those patients really concerned about downtime need to understand that the bruising that can occur with fillers for several days can lead to some degree of social downtime as well.
Options to treat perioral lines not ‘etched in’
Sometimes younger patients, those in their late 20s to early 40s, present with concerns about their perioral appearance. Although they do not have lines at rest yet, they can be unhappy with the muscle columns that appear above their lips with animation that begin to cause lines at rest imprinted in the skin. And many of these women complain that their lipstick bleeds into this area,” Dr. Cohen said. “These patients without etched lines can be treated with a neuromodulator alone to soften the mechanical action of the orbicularis oris muscle,” he pointed out.
Dr. Cohen disclosed having participated in clinical trials and/or having served as a consultant for Merz, Allergan, Galderma, Suneva, Sciton, and Lutronic.
MIAMI – The success of perioral rejuvenation depends in large part on setting realistic expectations. But there are also tips and tricks to individualizing the technique for each patient that can lead to better outcomes and greater satisfaction – whether patients receive injections into the fine lines above the lip, full-field erbium laser resurfacing, neuromodulator treatment, or a combination approach, according to Joel L. Cohen, MD.
When a patient presents with major lines in the perioral area, an “orange peel” texture, and/or elastotic changes, laser resurfacing can be an appropriate option. “Full field erbium laser resurfacing can give patients a nice improvement of upper lip lines and even a nice contraction of oral commissure,” Dr. Cohen said at the Orlando Dermatology Aesthetic and Clinical Conference.
Although each treatment is individualized to the patient, “I tend to do full field erbium resurfacing around the mouth and eyes, and fractional ablative resurfacing around the rest of the face,” said Dr. Cohen, an aesthetic dermatologist and Mohs surgeon in private practice in metropolitan Denver.
More downtime is associated with laser resurfacing compared with fillers or neuromodulator injections, but long-term patient satisfaction, even with improvement in quality of life for some patients (who become less anxious about these lines and more self-confident), can make this approach worthwhile. During his presentation, Dr. Cohen showed photos of many of his treated patients, including one woman whose grandchildren he said had been commenting about the “orange peel texture of her upper lip,” until she completed the resurfacing treatment.
Keep expectations realistic
Dr. Cohen recommended counseling patients about the potential benefits – and the caveats – associated with full-field erbium heavier resurfacing. “Make sure people understand they will look terrible for several days after heavy resurfacing, usually taking about 10-12 days to re-epithelialize,” he said. “We need to tell patients that the perioral area typically manifests more lines than other areas, so we need treat this area differently than just ablative fractional resurfacing in many cases.”
He explained that with heavier resurfacing procedures, it helps to show patients what is expected over the days to weeks in the healing process. They need to understand and see photos that show that the full-field erbium areas will have a yellow fibrinous healing response for the first week or so, which looks very different from the fractional ablative-treated areas (which are more typically red, weepy, and swollen).
He encourages these patients to come back a few days after the procedure to check their healing and review wound-care instructions, especially for patients who have deeper full-field perioral erbium resurfacing (those who are treated with 450-700 microns). Another tip he provided is to have these postresurfacing patients enter/exit through a separate entrance and also sit in a separate cosmetic waiting room at off-hours.
Re-epithelialization generally takes about 10-12 days for most people, with a maximal improvement at approximately 3 months, Dr. Cohen said. “Some patients can see not only significant improvement of upper lip lines, but often a nice contraction of the oral commissure even before fillers are performed to buttress the marionette area and oral commissure,” he said.
With full-field ablative resurfacing in specific areas, rather than simply fractional ablative resurfacing, it is also important to educate patients that some postinflammatory erythema is expected, which, in some cases, may persist for a few months. “In my experience, topical vasoconstrictors don’t seem to help minimize prolonged redness in the full-field erbium areas, but potent topical steroids can be beneficial,” Dr. Cohen said.
More tips for success
Injected local anesthesia is warranted prior to heavier laser resurfacing to keep patients as comfortable as possible. An infraorbital block with an added submucosal/sulcus block with plain lidocaine can be a good approach, he noted. Different perioral and facial areas have different degrees of lines, requiring different laser settings. He prefers to use plain lidocaine perioral blocks, “so that I can theoretically best see the endpoint pinpoint bleeding,” he said, adding that “significant pinpoint bleeding is a good place to stop.”
Typically, he uses a neuromodulator a week or two before full-field perioral erbium resurfacing. “I choose not to give a neuromodulator on the same day as I am concerned about swelling or manipulation of the skin causing unwanted spread to adjacent musculature,” Dr. Cohen said.
Another tip is to take photos with more than one device. “Standardized photos may lose detail of etched lines; we take both iPad and standardized camera system photos,” he said, adding that it is important that clinic staff are proficient at taking proper before-and-after photos, making sure, for example, that the patient does not have confounding makeup or lipstick on for photos, and patient positioning is consistent.
He said it is imperative to emphasize the importance of diligent sun protection for several months after the laser procedure. “Every patient reassures us they use sunscreen, but we often don’t know what sunscreen they are using or how frequently they are using it,” Dr. Cohen said. “If they don’t follow our specific instructions to use a physical block sunscreen, they will significantly increase their risk of developing postinflammatory hyperpigmentation. This caveat applies all year round, and isn’t just for those that go to the beach or play golf, but is also especially important for those patients that ski or hike at higher altitudes.”
Depending on the degree of etched-in lines in the perioral area, one perioral full-field laser resurfacing treatment is generally sufficient for most patients to see significant improvement. For those with more severe etched lines and/or bigger goals for improvement, additional treatments can be performed – but he generally waits about 3 months to see the overall effect of the initial treatment session.
If patients have just a few discrete etched-lines on each side of the upper lip, fillers can be helpful. But, the number and caliber of fine lines on the cutaneous lip limit how much a dermatologist can realistically treat. “So for people with many, many etched-in lines on the cutaneous lip, I explain that fillers are not the right tool for the job – and that they need heavier laser resurfacing.” And those patients really concerned about downtime need to understand that the bruising that can occur with fillers for several days can lead to some degree of social downtime as well.
Options to treat perioral lines not ‘etched in’
Sometimes younger patients, those in their late 20s to early 40s, present with concerns about their perioral appearance. Although they do not have lines at rest yet, they can be unhappy with the muscle columns that appear above their lips with animation that begin to cause lines at rest imprinted in the skin. And many of these women complain that their lipstick bleeds into this area,” Dr. Cohen said. “These patients without etched lines can be treated with a neuromodulator alone to soften the mechanical action of the orbicularis oris muscle,” he pointed out.
Dr. Cohen disclosed having participated in clinical trials and/or having served as a consultant for Merz, Allergan, Galderma, Suneva, Sciton, and Lutronic.
EXPERT ANALYSIS FROM ODAC 2018
Anticoagulation use in new-onset secondary atrial fibrillation
Background: Data on the efficacy of anticoagulation to reduce stroke risk in patients with new-onset atrial fibrillation due to acute coronary syndrome (ACS), acute pulmonary disease (APD), and sepsis are limited.
Study design: Retrospective cohort study.
Setting: All hospitals in Quebec.
Synopsis: Authors included 2,304 patients aged 65 and older with new atrial fibrillation secondary to ACS, APD, and sepsis. Anticoagulation was started for 38.4%, 34.1%, and 27.7% of these patients and the incidence of stroke was 5.4%, 3.9%, and 5.8% in the ACS, APD, and sepsis populations, respectively. After 3 years, anticoagulation use was not associated with a lower risk of ischemic stroke in any cohort. In a multivariate analysis adjusted for the HAS-BLED score, anticoagulation was associated with a higher risk of bleeding in patients with APD (odds ratio, 1.72; 95% confidence interval, 1.23-2.39) but not in ACS or sepsis.
The major limitation of this study was the reliance on administrative data alone, making it difficult to confirm and capture all patients with transient atrial fibrillation.
Bottom line: Anticoagulation use in patients with secondary atrial fibrillation may not be associated with a reduction in ischemic strokes, but may be associated with an increased bleeding risk in patients with atrial fibrillation secondary to acute pulmonary disease.
Citation: Quon MJ et al. Anticoagulant use and risk of ischemic stroke and bleeding in patients with secondary atrial fibrillation associated with acute coronary syndromes, acute pulmonary disease, or sepsis. JACC: Clinical Electrophysiology. Article in Press.
Dr. Gala is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, Boston.
Background: Data on the efficacy of anticoagulation to reduce stroke risk in patients with new-onset atrial fibrillation due to acute coronary syndrome (ACS), acute pulmonary disease (APD), and sepsis are limited.
Study design: Retrospective cohort study.
Setting: All hospitals in Quebec.
Synopsis: Authors included 2,304 patients aged 65 and older with new atrial fibrillation secondary to ACS, APD, and sepsis. Anticoagulation was started for 38.4%, 34.1%, and 27.7% of these patients and the incidence of stroke was 5.4%, 3.9%, and 5.8% in the ACS, APD, and sepsis populations, respectively. After 3 years, anticoagulation use was not associated with a lower risk of ischemic stroke in any cohort. In a multivariate analysis adjusted for the HAS-BLED score, anticoagulation was associated with a higher risk of bleeding in patients with APD (odds ratio, 1.72; 95% confidence interval, 1.23-2.39) but not in ACS or sepsis.
The major limitation of this study was the reliance on administrative data alone, making it difficult to confirm and capture all patients with transient atrial fibrillation.
Bottom line: Anticoagulation use in patients with secondary atrial fibrillation may not be associated with a reduction in ischemic strokes, but may be associated with an increased bleeding risk in patients with atrial fibrillation secondary to acute pulmonary disease.
Citation: Quon MJ et al. Anticoagulant use and risk of ischemic stroke and bleeding in patients with secondary atrial fibrillation associated with acute coronary syndromes, acute pulmonary disease, or sepsis. JACC: Clinical Electrophysiology. Article in Press.
Dr. Gala is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, Boston.
Background: Data on the efficacy of anticoagulation to reduce stroke risk in patients with new-onset atrial fibrillation due to acute coronary syndrome (ACS), acute pulmonary disease (APD), and sepsis are limited.
Study design: Retrospective cohort study.
Setting: All hospitals in Quebec.
Synopsis: Authors included 2,304 patients aged 65 and older with new atrial fibrillation secondary to ACS, APD, and sepsis. Anticoagulation was started for 38.4%, 34.1%, and 27.7% of these patients and the incidence of stroke was 5.4%, 3.9%, and 5.8% in the ACS, APD, and sepsis populations, respectively. After 3 years, anticoagulation use was not associated with a lower risk of ischemic stroke in any cohort. In a multivariate analysis adjusted for the HAS-BLED score, anticoagulation was associated with a higher risk of bleeding in patients with APD (odds ratio, 1.72; 95% confidence interval, 1.23-2.39) but not in ACS or sepsis.
The major limitation of this study was the reliance on administrative data alone, making it difficult to confirm and capture all patients with transient atrial fibrillation.
Bottom line: Anticoagulation use in patients with secondary atrial fibrillation may not be associated with a reduction in ischemic strokes, but may be associated with an increased bleeding risk in patients with atrial fibrillation secondary to acute pulmonary disease.
Citation: Quon MJ et al. Anticoagulant use and risk of ischemic stroke and bleeding in patients with secondary atrial fibrillation associated with acute coronary syndromes, acute pulmonary disease, or sepsis. JACC: Clinical Electrophysiology. Article in Press.
Dr. Gala is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, Boston.
Exercise during chemotherapy may yield long-term physical benefits
ORLANDO – Physical exercise during adjuvant chemotherapy may lead to improved physical activity and decreased fatigue years after the treatment is completed, results of a recent analysis suggest.
Four years after participating in an exercise program that took place during cancer treatment, patients reported more moderate-to-vigorous activity and less fatigue, compared with patients who did not participate in the program, according to long-term follow-up results presented at the Cancer Survivorship Symposium.
“We think that offering exercise during cancer treatment, including chemotherapy, is recommended and has beneficial short- and long-term effects on health,” said Anne M. May, PhD, of University Medical Center, Utrecht, the Netherlands.
Speaking in a press conference at the symposium, Dr. May described results of the analysis, which included 128 patients who had previously participated in PACT, a 237-patient randomized controlled trial evaluating a supervised exercise program versus usual care in patients undergoing adjuvant treatment for breast or colon cancer.
The 18-week exercise program included moderate- to high-intensity aerobic and strength training under physical therapist supervision for 60 minutes twice weekly, plus home-based physical activity for 30 minutes three times weekly.
At 4 years’ follow-up, patients in the exercise group reported on average 90 minutes of moderate-to-vigorous exercise per week, compared to an average of 70 minutes per week in the usual care group (P less than .05), Dr. May reported at the symposium, which was sponsored by the American Academy of Family Physicians, the American College of Physicians, and the American Society of Clinical Oncology.
There was also a trend toward decreased fatigue reported in the exercise vs. usual care group, though the finding did not reach statistical significance, she said.
It is “encouraging” to see that this exercise program had a long-term impact on patients’ physical activity levels, said ASCO expert Timothy Gilligan, MD, MSc.
“I think the public sometimes gets jaded because the nutritional recommendations seem to change every year, but if you look at the research on exercise in health … it’s interesting how consistent the data is that exercise really is good for us – if we can only get people to do it,” said Dr. Gilligan, who moderated the press conference.
Dr. May said she had no disclosures to report for the study, which was supported by grants from the Dutch Cancer Society, the Dutch Pink Ribbon Foundation, and the Netherlands Organization for Health Research.
SOURCE: May AM et al. Cancer Survivorship Symposium, Abstract 99.
ORLANDO – Physical exercise during adjuvant chemotherapy may lead to improved physical activity and decreased fatigue years after the treatment is completed, results of a recent analysis suggest.
Four years after participating in an exercise program that took place during cancer treatment, patients reported more moderate-to-vigorous activity and less fatigue, compared with patients who did not participate in the program, according to long-term follow-up results presented at the Cancer Survivorship Symposium.
“We think that offering exercise during cancer treatment, including chemotherapy, is recommended and has beneficial short- and long-term effects on health,” said Anne M. May, PhD, of University Medical Center, Utrecht, the Netherlands.
Speaking in a press conference at the symposium, Dr. May described results of the analysis, which included 128 patients who had previously participated in PACT, a 237-patient randomized controlled trial evaluating a supervised exercise program versus usual care in patients undergoing adjuvant treatment for breast or colon cancer.
The 18-week exercise program included moderate- to high-intensity aerobic and strength training under physical therapist supervision for 60 minutes twice weekly, plus home-based physical activity for 30 minutes three times weekly.
At 4 years’ follow-up, patients in the exercise group reported on average 90 minutes of moderate-to-vigorous exercise per week, compared to an average of 70 minutes per week in the usual care group (P less than .05), Dr. May reported at the symposium, which was sponsored by the American Academy of Family Physicians, the American College of Physicians, and the American Society of Clinical Oncology.
There was also a trend toward decreased fatigue reported in the exercise vs. usual care group, though the finding did not reach statistical significance, she said.
It is “encouraging” to see that this exercise program had a long-term impact on patients’ physical activity levels, said ASCO expert Timothy Gilligan, MD, MSc.
“I think the public sometimes gets jaded because the nutritional recommendations seem to change every year, but if you look at the research on exercise in health … it’s interesting how consistent the data is that exercise really is good for us – if we can only get people to do it,” said Dr. Gilligan, who moderated the press conference.
Dr. May said she had no disclosures to report for the study, which was supported by grants from the Dutch Cancer Society, the Dutch Pink Ribbon Foundation, and the Netherlands Organization for Health Research.
SOURCE: May AM et al. Cancer Survivorship Symposium, Abstract 99.
ORLANDO – Physical exercise during adjuvant chemotherapy may lead to improved physical activity and decreased fatigue years after the treatment is completed, results of a recent analysis suggest.
Four years after participating in an exercise program that took place during cancer treatment, patients reported more moderate-to-vigorous activity and less fatigue, compared with patients who did not participate in the program, according to long-term follow-up results presented at the Cancer Survivorship Symposium.
“We think that offering exercise during cancer treatment, including chemotherapy, is recommended and has beneficial short- and long-term effects on health,” said Anne M. May, PhD, of University Medical Center, Utrecht, the Netherlands.
Speaking in a press conference at the symposium, Dr. May described results of the analysis, which included 128 patients who had previously participated in PACT, a 237-patient randomized controlled trial evaluating a supervised exercise program versus usual care in patients undergoing adjuvant treatment for breast or colon cancer.
The 18-week exercise program included moderate- to high-intensity aerobic and strength training under physical therapist supervision for 60 minutes twice weekly, plus home-based physical activity for 30 minutes three times weekly.
At 4 years’ follow-up, patients in the exercise group reported on average 90 minutes of moderate-to-vigorous exercise per week, compared to an average of 70 minutes per week in the usual care group (P less than .05), Dr. May reported at the symposium, which was sponsored by the American Academy of Family Physicians, the American College of Physicians, and the American Society of Clinical Oncology.
There was also a trend toward decreased fatigue reported in the exercise vs. usual care group, though the finding did not reach statistical significance, she said.
It is “encouraging” to see that this exercise program had a long-term impact on patients’ physical activity levels, said ASCO expert Timothy Gilligan, MD, MSc.
“I think the public sometimes gets jaded because the nutritional recommendations seem to change every year, but if you look at the research on exercise in health … it’s interesting how consistent the data is that exercise really is good for us – if we can only get people to do it,” said Dr. Gilligan, who moderated the press conference.
Dr. May said she had no disclosures to report for the study, which was supported by grants from the Dutch Cancer Society, the Dutch Pink Ribbon Foundation, and the Netherlands Organization for Health Research.
SOURCE: May AM et al. Cancer Survivorship Symposium, Abstract 99.
REPORTING FROM CSC 2018
Key clinical point: Exercise during adjuvant chemotherapy may lead to lower levels of fatigue and higher levels of physical activity years after treatment is completed.
Major finding: Four years after participating in an 18-week exercise program during cancer treatment, patients reported an average of 90 minutes of moderate-to-vigorous physical activity per day, compared with 70 minutes for patients who did not participate (P less than .05).
Study details: Long-term follow-up of 128 patients who had participated in the PACT study, a randomized controlled trial of a supervised exercise program versus usual care in breast and colon cancer patients undergoing adjuvant treatment including chemotherapy.
Disclosures: The authors reported no disclosures relevant to the study, which was supported by grants from the Dutch Cancer Society, the Dutch Pink Ribbon Foundation, and the Netherlands Organization for Health Research.
Source: May AM et al. Cancer Survivorship Symposium, Abstract 99.
Oral treatment for menorrhagia shows promise for melasma
SAN DIEGO – The use of , according to Amit Pandya, MD.
Tranexamic acid is also used to treat intraoperative hemorrhage, is available over the counter in some countries, and is used widely for treating melasma in East Asia, Dr. Pandya said at a meeting of the Skin of Color Society, held the day before the annual meeting of the American Academy of Dermatology.
Dr. Pandya, professor of dermatology at the University of Texas Southwestern, Dallas, described a woman with a 20-year history of melasma who had been treated with triple combination creams, chemical peels, and Fraxel lasers “to no avail,” similar to patients he sees in his practice every week. But after 3 months of treatment with 325 mg of tranexamic acid twice daily, triple combination cream, and visible light sunscreen, she was clearer than she had been for some time, he said.
Tranexamic acid “ blocks keratinocytes from causing plasminogen to go into plasmin,” and plasmin stimulates fibroblast growth factor production, which is “one of the most potent stimulants of melanin,” he explained.
In a retrospective study published in 2016, conducted by investigators at the National Skin Center in Singapore, 561 patients with melasma were treated with oral tranexamic acid for a median of 4 months, almost 90% of the patients improved. There was one serious adverse event, a deep vein thrombosis (J Am Acad Dermatol. 2016 Aug;75[2]:385-92). The other adverse effects were mild. When Dr. Pandya spoke with the investigators about this patient, he was told that the patient had not disclosed her true medical history, which included protein S deficiency and a strong family history of thrombotic events, which would have excluded her from treatment.
Of 2,000 published cases of melasma treated with tranexamic acid to date, “this is the only severe event ever seen with tranexamic acid,” he noted.
Dr. Pandya and his associates recently published the results of a study evaluating tranexamic acid in 44 Latino women with moderate to severe melasma, which he said was the first study of tranexamic acid in the Western hemisphere. For 3 months, the women were treated with 250 mg of tranexamic acid or placebo in combination with sunscreen in both groups, then sunscreen only for 3 months in both groups. The primary outcome was the change in the modified Melasma Area and Severity Index (mMASI) score.
“Results were spectacular,” he said. At 3 months, the mMASI score had improved by 49% among those in the tranexamic acid group, compared with 18% among those on placebo and sunscreen. After 3 months on sunscreen only, there was a 26% reduction in the mMASI score from baseline among those treated with tranexamic acid, compared with 19% in the placebo group. None of the patients in either group had severe adverse events (J Am Acad Dermatol. 2018 Feb;78[2]:363-9). Side effects include GI upset, reduced menstrual flow, myalgias, and headache.
Rebound after cessation of therapy is an issue, however, and was worse in the treated group “because more melanocytes are actually created when you reduce melanin. So once you stop the tranexamic acid, it rebounds,” Dr. Pandya said. Patients should use triple combination cream when they stop taking tranexamic acid, he advised.
However, he said that patients have called him within 1 month of stopping tranexamic acid, asking to restart treatment. He has had patients on tranexamic acid for 1 year or longer, without any side effects.
Women who are pregnant or nursing, have had two or more spontaneous abortions, are on oral contraceptives or other hormone-based birth control, have a history of thrombosis, are on blood thinners, are smokers, or have significant cardiovascular or respiratory disease, subarachnoid hemorrhage, any DVT, or a strong family history of thromboembolic events should not be treated with tranexamic acid.
Dr. Pandya pointed out that the 250-mg dose used in the study is not available in the United States, where only the 650-mg dose is available. So he writes a prescription for 650 mg a day, and tells patients to cut the pill in half and take a 325-mg dose twice a day (half in the morning and half at night).
At the Skin of Color Society meeting, Nahla Shihab, MD, of Universitas Indonesia, Jakarta, presented the results of a randomized, placebo-controlled study evaluating oral tranexamic acid plus hydroquinone cream in patients with moderate to severe melasma, in collaboration with UT Southwestern and Dr. Pandya. Patients were randomized to treatment with topical hydroquinone 4% cream, sunscreen, and tranexamic acid (250 mg twice a day), or hydroquinone 4% cream, sunscreen, and placebo for 3 months, followed by 3 months of sunscreen only.
At 12 weeks, those in the tranexamic acid group had a 55% decrease in the mMASI score, compared with 10.9% in the control group. After stopping treatment, some patients experienced relapses, similar to what has been observed in other studies, but “the severity was still lower than baseline,” Dr. Shihab reported.
In addition, the improvement in the mMASI score was higher than that seen in other studies, which could be due to a synergistic effect of the fibrin inhibitor with hydroquinone, she added. Another important finding was that improvements were noticeable after 2 weeks of treatment, “which suggests that the combination of oral tranexamic acid and hydroquinone has a rapid onset of action,” she said.
In both groups, 6% of the patients experienced erythema and pruritus, which resolved with continued use of hydroquinone, and one woman on tranexamic acid had menstrual cycle changes. Further studies should evaluate a longer duration of treatment and follow-up, with tranexamic acid and hydroquinone, and in combination with other treatments, Dr. Shihab said.
Dr. Pandya reported that he is a consultant to Aclaris Therapeutics and Pfizer, and has received grants/research funding from Incyte Corp. Dr. Shihab had no disclosures.
SAN DIEGO – The use of , according to Amit Pandya, MD.
Tranexamic acid is also used to treat intraoperative hemorrhage, is available over the counter in some countries, and is used widely for treating melasma in East Asia, Dr. Pandya said at a meeting of the Skin of Color Society, held the day before the annual meeting of the American Academy of Dermatology.
Dr. Pandya, professor of dermatology at the University of Texas Southwestern, Dallas, described a woman with a 20-year history of melasma who had been treated with triple combination creams, chemical peels, and Fraxel lasers “to no avail,” similar to patients he sees in his practice every week. But after 3 months of treatment with 325 mg of tranexamic acid twice daily, triple combination cream, and visible light sunscreen, she was clearer than she had been for some time, he said.
Tranexamic acid “ blocks keratinocytes from causing plasminogen to go into plasmin,” and plasmin stimulates fibroblast growth factor production, which is “one of the most potent stimulants of melanin,” he explained.
In a retrospective study published in 2016, conducted by investigators at the National Skin Center in Singapore, 561 patients with melasma were treated with oral tranexamic acid for a median of 4 months, almost 90% of the patients improved. There was one serious adverse event, a deep vein thrombosis (J Am Acad Dermatol. 2016 Aug;75[2]:385-92). The other adverse effects were mild. When Dr. Pandya spoke with the investigators about this patient, he was told that the patient had not disclosed her true medical history, which included protein S deficiency and a strong family history of thrombotic events, which would have excluded her from treatment.
Of 2,000 published cases of melasma treated with tranexamic acid to date, “this is the only severe event ever seen with tranexamic acid,” he noted.
Dr. Pandya and his associates recently published the results of a study evaluating tranexamic acid in 44 Latino women with moderate to severe melasma, which he said was the first study of tranexamic acid in the Western hemisphere. For 3 months, the women were treated with 250 mg of tranexamic acid or placebo in combination with sunscreen in both groups, then sunscreen only for 3 months in both groups. The primary outcome was the change in the modified Melasma Area and Severity Index (mMASI) score.
“Results were spectacular,” he said. At 3 months, the mMASI score had improved by 49% among those in the tranexamic acid group, compared with 18% among those on placebo and sunscreen. After 3 months on sunscreen only, there was a 26% reduction in the mMASI score from baseline among those treated with tranexamic acid, compared with 19% in the placebo group. None of the patients in either group had severe adverse events (J Am Acad Dermatol. 2018 Feb;78[2]:363-9). Side effects include GI upset, reduced menstrual flow, myalgias, and headache.
Rebound after cessation of therapy is an issue, however, and was worse in the treated group “because more melanocytes are actually created when you reduce melanin. So once you stop the tranexamic acid, it rebounds,” Dr. Pandya said. Patients should use triple combination cream when they stop taking tranexamic acid, he advised.
However, he said that patients have called him within 1 month of stopping tranexamic acid, asking to restart treatment. He has had patients on tranexamic acid for 1 year or longer, without any side effects.
Women who are pregnant or nursing, have had two or more spontaneous abortions, are on oral contraceptives or other hormone-based birth control, have a history of thrombosis, are on blood thinners, are smokers, or have significant cardiovascular or respiratory disease, subarachnoid hemorrhage, any DVT, or a strong family history of thromboembolic events should not be treated with tranexamic acid.
Dr. Pandya pointed out that the 250-mg dose used in the study is not available in the United States, where only the 650-mg dose is available. So he writes a prescription for 650 mg a day, and tells patients to cut the pill in half and take a 325-mg dose twice a day (half in the morning and half at night).
At the Skin of Color Society meeting, Nahla Shihab, MD, of Universitas Indonesia, Jakarta, presented the results of a randomized, placebo-controlled study evaluating oral tranexamic acid plus hydroquinone cream in patients with moderate to severe melasma, in collaboration with UT Southwestern and Dr. Pandya. Patients were randomized to treatment with topical hydroquinone 4% cream, sunscreen, and tranexamic acid (250 mg twice a day), or hydroquinone 4% cream, sunscreen, and placebo for 3 months, followed by 3 months of sunscreen only.
At 12 weeks, those in the tranexamic acid group had a 55% decrease in the mMASI score, compared with 10.9% in the control group. After stopping treatment, some patients experienced relapses, similar to what has been observed in other studies, but “the severity was still lower than baseline,” Dr. Shihab reported.
In addition, the improvement in the mMASI score was higher than that seen in other studies, which could be due to a synergistic effect of the fibrin inhibitor with hydroquinone, she added. Another important finding was that improvements were noticeable after 2 weeks of treatment, “which suggests that the combination of oral tranexamic acid and hydroquinone has a rapid onset of action,” she said.
In both groups, 6% of the patients experienced erythema and pruritus, which resolved with continued use of hydroquinone, and one woman on tranexamic acid had menstrual cycle changes. Further studies should evaluate a longer duration of treatment and follow-up, with tranexamic acid and hydroquinone, and in combination with other treatments, Dr. Shihab said.
Dr. Pandya reported that he is a consultant to Aclaris Therapeutics and Pfizer, and has received grants/research funding from Incyte Corp. Dr. Shihab had no disclosures.
SAN DIEGO – The use of , according to Amit Pandya, MD.
Tranexamic acid is also used to treat intraoperative hemorrhage, is available over the counter in some countries, and is used widely for treating melasma in East Asia, Dr. Pandya said at a meeting of the Skin of Color Society, held the day before the annual meeting of the American Academy of Dermatology.
Dr. Pandya, professor of dermatology at the University of Texas Southwestern, Dallas, described a woman with a 20-year history of melasma who had been treated with triple combination creams, chemical peels, and Fraxel lasers “to no avail,” similar to patients he sees in his practice every week. But after 3 months of treatment with 325 mg of tranexamic acid twice daily, triple combination cream, and visible light sunscreen, she was clearer than she had been for some time, he said.
Tranexamic acid “ blocks keratinocytes from causing plasminogen to go into plasmin,” and plasmin stimulates fibroblast growth factor production, which is “one of the most potent stimulants of melanin,” he explained.
In a retrospective study published in 2016, conducted by investigators at the National Skin Center in Singapore, 561 patients with melasma were treated with oral tranexamic acid for a median of 4 months, almost 90% of the patients improved. There was one serious adverse event, a deep vein thrombosis (J Am Acad Dermatol. 2016 Aug;75[2]:385-92). The other adverse effects were mild. When Dr. Pandya spoke with the investigators about this patient, he was told that the patient had not disclosed her true medical history, which included protein S deficiency and a strong family history of thrombotic events, which would have excluded her from treatment.
Of 2,000 published cases of melasma treated with tranexamic acid to date, “this is the only severe event ever seen with tranexamic acid,” he noted.
Dr. Pandya and his associates recently published the results of a study evaluating tranexamic acid in 44 Latino women with moderate to severe melasma, which he said was the first study of tranexamic acid in the Western hemisphere. For 3 months, the women were treated with 250 mg of tranexamic acid or placebo in combination with sunscreen in both groups, then sunscreen only for 3 months in both groups. The primary outcome was the change in the modified Melasma Area and Severity Index (mMASI) score.
“Results were spectacular,” he said. At 3 months, the mMASI score had improved by 49% among those in the tranexamic acid group, compared with 18% among those on placebo and sunscreen. After 3 months on sunscreen only, there was a 26% reduction in the mMASI score from baseline among those treated with tranexamic acid, compared with 19% in the placebo group. None of the patients in either group had severe adverse events (J Am Acad Dermatol. 2018 Feb;78[2]:363-9). Side effects include GI upset, reduced menstrual flow, myalgias, and headache.
Rebound after cessation of therapy is an issue, however, and was worse in the treated group “because more melanocytes are actually created when you reduce melanin. So once you stop the tranexamic acid, it rebounds,” Dr. Pandya said. Patients should use triple combination cream when they stop taking tranexamic acid, he advised.
However, he said that patients have called him within 1 month of stopping tranexamic acid, asking to restart treatment. He has had patients on tranexamic acid for 1 year or longer, without any side effects.
Women who are pregnant or nursing, have had two or more spontaneous abortions, are on oral contraceptives or other hormone-based birth control, have a history of thrombosis, are on blood thinners, are smokers, or have significant cardiovascular or respiratory disease, subarachnoid hemorrhage, any DVT, or a strong family history of thromboembolic events should not be treated with tranexamic acid.
Dr. Pandya pointed out that the 250-mg dose used in the study is not available in the United States, where only the 650-mg dose is available. So he writes a prescription for 650 mg a day, and tells patients to cut the pill in half and take a 325-mg dose twice a day (half in the morning and half at night).
At the Skin of Color Society meeting, Nahla Shihab, MD, of Universitas Indonesia, Jakarta, presented the results of a randomized, placebo-controlled study evaluating oral tranexamic acid plus hydroquinone cream in patients with moderate to severe melasma, in collaboration with UT Southwestern and Dr. Pandya. Patients were randomized to treatment with topical hydroquinone 4% cream, sunscreen, and tranexamic acid (250 mg twice a day), or hydroquinone 4% cream, sunscreen, and placebo for 3 months, followed by 3 months of sunscreen only.
At 12 weeks, those in the tranexamic acid group had a 55% decrease in the mMASI score, compared with 10.9% in the control group. After stopping treatment, some patients experienced relapses, similar to what has been observed in other studies, but “the severity was still lower than baseline,” Dr. Shihab reported.
In addition, the improvement in the mMASI score was higher than that seen in other studies, which could be due to a synergistic effect of the fibrin inhibitor with hydroquinone, she added. Another important finding was that improvements were noticeable after 2 weeks of treatment, “which suggests that the combination of oral tranexamic acid and hydroquinone has a rapid onset of action,” she said.
In both groups, 6% of the patients experienced erythema and pruritus, which resolved with continued use of hydroquinone, and one woman on tranexamic acid had menstrual cycle changes. Further studies should evaluate a longer duration of treatment and follow-up, with tranexamic acid and hydroquinone, and in combination with other treatments, Dr. Shihab said.
Dr. Pandya reported that he is a consultant to Aclaris Therapeutics and Pfizer, and has received grants/research funding from Incyte Corp. Dr. Shihab had no disclosures.
REPORTING FROM THE SKIN OF COLOR SOCIETY SCIENTIFIC SYMPOSIUM
VIDEO: Parabens named ‘nonallergen’ of the year
SAN DIEGO – With propylene glycol already declared 2018 Allergen of the Year in a published journal article, the news at the Allergen of the Year session of the American Contact Dermatitis Society was announcement of the 2019 pick, parabens.
From a skin perspective, parabens are “perhaps the safest” preservative, but despite that they have a bad public reputation Donald V. Belsito, MD, said in his Allergen of the Year talk during the Society’s annual meeting held the day before the annual meeting of the American Academy of Dermatology.
There is an unfounded public perception that parabens cause endocrine disruption. Naming parabens the “nonallergen” of the year for 2019 is an effort to dispel this myth, Dr. Belsito said in a video interview.
The public prejudice against parabens, exacerbated by many products that tout being paraben free, has helped cause a crisis because preservative systems in general have been under attack and facing restrictions. Dr. Belsito cited European limitations on the preservative methylisothiazolinone (Allergen of the Year in 2013) and withdrawal of formaldehyde (2015 Allergen of the Year) from many products.
Dr. Belsito also highlighted why propylene glycol received the nod as 2018’s Allergen of the Year (Dermatitis. 2018 Jan/Feb;29[1]:3-5). Propylene glycol is a very ubiquitous emulsifier found in cosmetics, foods, and both topical and oral medications. Caution is needed when running a patch test on the agent to distinguish an irritation reaction from an allergic reaction. Interpreting the test result correctly is very important, said Dr. Belsito, professor of dermatology at Columbia University in New York.
Parabens is the 20th Allergen of the Year named by the Society, an annual event since 2000.
Dr. Belsito has participated in the program since its start.
SAN DIEGO – With propylene glycol already declared 2018 Allergen of the Year in a published journal article, the news at the Allergen of the Year session of the American Contact Dermatitis Society was announcement of the 2019 pick, parabens.
From a skin perspective, parabens are “perhaps the safest” preservative, but despite that they have a bad public reputation Donald V. Belsito, MD, said in his Allergen of the Year talk during the Society’s annual meeting held the day before the annual meeting of the American Academy of Dermatology.
There is an unfounded public perception that parabens cause endocrine disruption. Naming parabens the “nonallergen” of the year for 2019 is an effort to dispel this myth, Dr. Belsito said in a video interview.
The public prejudice against parabens, exacerbated by many products that tout being paraben free, has helped cause a crisis because preservative systems in general have been under attack and facing restrictions. Dr. Belsito cited European limitations on the preservative methylisothiazolinone (Allergen of the Year in 2013) and withdrawal of formaldehyde (2015 Allergen of the Year) from many products.
Dr. Belsito also highlighted why propylene glycol received the nod as 2018’s Allergen of the Year (Dermatitis. 2018 Jan/Feb;29[1]:3-5). Propylene glycol is a very ubiquitous emulsifier found in cosmetics, foods, and both topical and oral medications. Caution is needed when running a patch test on the agent to distinguish an irritation reaction from an allergic reaction. Interpreting the test result correctly is very important, said Dr. Belsito, professor of dermatology at Columbia University in New York.
Parabens is the 20th Allergen of the Year named by the Society, an annual event since 2000.
Dr. Belsito has participated in the program since its start.
SAN DIEGO – With propylene glycol already declared 2018 Allergen of the Year in a published journal article, the news at the Allergen of the Year session of the American Contact Dermatitis Society was announcement of the 2019 pick, parabens.
From a skin perspective, parabens are “perhaps the safest” preservative, but despite that they have a bad public reputation Donald V. Belsito, MD, said in his Allergen of the Year talk during the Society’s annual meeting held the day before the annual meeting of the American Academy of Dermatology.
There is an unfounded public perception that parabens cause endocrine disruption. Naming parabens the “nonallergen” of the year for 2019 is an effort to dispel this myth, Dr. Belsito said in a video interview.
The public prejudice against parabens, exacerbated by many products that tout being paraben free, has helped cause a crisis because preservative systems in general have been under attack and facing restrictions. Dr. Belsito cited European limitations on the preservative methylisothiazolinone (Allergen of the Year in 2013) and withdrawal of formaldehyde (2015 Allergen of the Year) from many products.
Dr. Belsito also highlighted why propylene glycol received the nod as 2018’s Allergen of the Year (Dermatitis. 2018 Jan/Feb;29[1]:3-5). Propylene glycol is a very ubiquitous emulsifier found in cosmetics, foods, and both topical and oral medications. Caution is needed when running a patch test on the agent to distinguish an irritation reaction from an allergic reaction. Interpreting the test result correctly is very important, said Dr. Belsito, professor of dermatology at Columbia University in New York.
Parabens is the 20th Allergen of the Year named by the Society, an annual event since 2000.
Dr. Belsito has participated in the program since its start.
FROM ACDS 18
Action to address gun violence is long overdue
On Feb. 14 in Parkland, Florida, 17 students and teachers were murdered in yet another school shooting. Yet another mass killing. More than a dozen others were injured and some are fighting for their lives under the care of physicians and nurses.
The pervasiveness of gun violence and the weapons used in these crimes have changed the way we live. In movie theaters, places of worship, offices, restaurants, night clubs and schools, people today make clear note of escape routes. Schools, including the one attacked yesterday, regularly practice for active shooter situations.
And in emergency departments and trauma centers, we struggle with much more complicated, dangerous injuries inflicted by lethal ammunition fired by military-grade weapons.
At the 2016 AMA Annual Meeting, which began the day after the deadly shooting at the Pulse Nightclub in Orlando, physicians from across the country and at every stage in their career spoke about treating gunshot victims and the scale of violence we are experiencing today. Their stories resonate as much today as they did nearly two years ago.
The shooting at Marjory Stoneman Douglas High School was the 30th mass shooting – a shooting in which four or more people are killed or injured – of 2018. It was also the 17th time a gun has been fired on the grounds of an American school this year. The problem is getting worse – the regularity of, and death from, mass shootings is increasing. With the shooting in Parkland, three of the 10 deadliest mass shootings in modern U.S. history have come in the past five months.
Time to act
Gun violence in America today is a public health crisis, one that requires a comprehensive and far-reaching solution. And that is not just my own sentiment; that is the determination of the AMA House of Delegates. With more than 30,000 American men, women and children dying from gun violence and firearm-related accidents each year, the time to act is now.
Today, more than ever before, America’s physicians must lend their voice and their considerable political muscle to force lawmakers to examine this urgent health crisis – through federally funded research – and take appropriate steps to address it. Let me be very clear about this. We are not talking about Second Amendment rights or restricting your ability to own a firearm.
We are talking about a public health crisis that our Congress has failed to address. This must end.
In the wake of the Sandy Hook shooting in 2012 – a massacre that left 20 first-graders and six adults dead – the AMA wrote to President Obama and to the leaders in the House and Senate. We expressed our sense of grief and sadness and offered our expertise and experience in finding workable, commonsense solutions to reduce the epidemic of gun violence – indeed the overall culture of violence – in America.
We noted that the relatively easy access to the increased firepower of assault weapons, semiautomatic firearms, high-capacity magazines, and high-velocity ammunition heightens the risk of multiple gunshot wounds and severe penetrating trauma, resulting in more critical injuries and deaths. Even for those who manage to survive gun violence involving these weapons, the severity and lasting impact of their wounds, disabilities and treatment leads to devastating consequences for the families affected and for society as a whole, contributing to high medical costs for treatment and recovery.
We called for renewing and strengthening the assault weapons ban, including banning high-capacity magazines, as a step in the right direction. We also called for more resources for safety education programs that promote more responsible use and storage of firearms, and noted that part of ensuring firearms safety means that physicians need to be able to have frank discussions with their patients and parents of patients about firearm safety issues and risks to help them safeguard their families from accidents.
We also urged the nation to strengthen its commitment and resources to comprehensive access to mental health services, including screening, prevention and treatment. While the overwhelming majority of patients with mental illness are not violent, physicians and other health professionals must be trained to respond to those who have a mental illness that might make them more prone to commit violence.
On an average day, more than 100 Americans die from gun violence and firearm-related accidents. In communities like yours – regardless of where you live or how safe it feels – people are losing their lives to this scourge.
For many Americans, gun violence used to be a distant idea relegated mostly to the nightly news, movies and faraway places. But today, in communities such as Parkland, it is horrifyingly real. The victims are our friends, neighbors and, unfathomably, our children.
As physicians, we have dedicated our lives to public health. And at the AMA, our mission is improving the health of the nation. That mission today must include determining the root causes of this epidemic and turning the tide on gun violence.
We must do more than pray for families who lost loved ones. It is time to act to prevent future deaths and injuries.
Dr. Barbe is president of the American Medical Association. His commentary originally was published on AMA Wire.
On Feb. 14 in Parkland, Florida, 17 students and teachers were murdered in yet another school shooting. Yet another mass killing. More than a dozen others were injured and some are fighting for their lives under the care of physicians and nurses.
The pervasiveness of gun violence and the weapons used in these crimes have changed the way we live. In movie theaters, places of worship, offices, restaurants, night clubs and schools, people today make clear note of escape routes. Schools, including the one attacked yesterday, regularly practice for active shooter situations.
And in emergency departments and trauma centers, we struggle with much more complicated, dangerous injuries inflicted by lethal ammunition fired by military-grade weapons.
At the 2016 AMA Annual Meeting, which began the day after the deadly shooting at the Pulse Nightclub in Orlando, physicians from across the country and at every stage in their career spoke about treating gunshot victims and the scale of violence we are experiencing today. Their stories resonate as much today as they did nearly two years ago.
The shooting at Marjory Stoneman Douglas High School was the 30th mass shooting – a shooting in which four or more people are killed or injured – of 2018. It was also the 17th time a gun has been fired on the grounds of an American school this year. The problem is getting worse – the regularity of, and death from, mass shootings is increasing. With the shooting in Parkland, three of the 10 deadliest mass shootings in modern U.S. history have come in the past five months.
Time to act
Gun violence in America today is a public health crisis, one that requires a comprehensive and far-reaching solution. And that is not just my own sentiment; that is the determination of the AMA House of Delegates. With more than 30,000 American men, women and children dying from gun violence and firearm-related accidents each year, the time to act is now.
Today, more than ever before, America’s physicians must lend their voice and their considerable political muscle to force lawmakers to examine this urgent health crisis – through federally funded research – and take appropriate steps to address it. Let me be very clear about this. We are not talking about Second Amendment rights or restricting your ability to own a firearm.
We are talking about a public health crisis that our Congress has failed to address. This must end.
In the wake of the Sandy Hook shooting in 2012 – a massacre that left 20 first-graders and six adults dead – the AMA wrote to President Obama and to the leaders in the House and Senate. We expressed our sense of grief and sadness and offered our expertise and experience in finding workable, commonsense solutions to reduce the epidemic of gun violence – indeed the overall culture of violence – in America.
We noted that the relatively easy access to the increased firepower of assault weapons, semiautomatic firearms, high-capacity magazines, and high-velocity ammunition heightens the risk of multiple gunshot wounds and severe penetrating trauma, resulting in more critical injuries and deaths. Even for those who manage to survive gun violence involving these weapons, the severity and lasting impact of their wounds, disabilities and treatment leads to devastating consequences for the families affected and for society as a whole, contributing to high medical costs for treatment and recovery.
We called for renewing and strengthening the assault weapons ban, including banning high-capacity magazines, as a step in the right direction. We also called for more resources for safety education programs that promote more responsible use and storage of firearms, and noted that part of ensuring firearms safety means that physicians need to be able to have frank discussions with their patients and parents of patients about firearm safety issues and risks to help them safeguard their families from accidents.
We also urged the nation to strengthen its commitment and resources to comprehensive access to mental health services, including screening, prevention and treatment. While the overwhelming majority of patients with mental illness are not violent, physicians and other health professionals must be trained to respond to those who have a mental illness that might make them more prone to commit violence.
On an average day, more than 100 Americans die from gun violence and firearm-related accidents. In communities like yours – regardless of where you live or how safe it feels – people are losing their lives to this scourge.
For many Americans, gun violence used to be a distant idea relegated mostly to the nightly news, movies and faraway places. But today, in communities such as Parkland, it is horrifyingly real. The victims are our friends, neighbors and, unfathomably, our children.
As physicians, we have dedicated our lives to public health. And at the AMA, our mission is improving the health of the nation. That mission today must include determining the root causes of this epidemic and turning the tide on gun violence.
We must do more than pray for families who lost loved ones. It is time to act to prevent future deaths and injuries.
Dr. Barbe is president of the American Medical Association. His commentary originally was published on AMA Wire.
On Feb. 14 in Parkland, Florida, 17 students and teachers were murdered in yet another school shooting. Yet another mass killing. More than a dozen others were injured and some are fighting for their lives under the care of physicians and nurses.
The pervasiveness of gun violence and the weapons used in these crimes have changed the way we live. In movie theaters, places of worship, offices, restaurants, night clubs and schools, people today make clear note of escape routes. Schools, including the one attacked yesterday, regularly practice for active shooter situations.
And in emergency departments and trauma centers, we struggle with much more complicated, dangerous injuries inflicted by lethal ammunition fired by military-grade weapons.
At the 2016 AMA Annual Meeting, which began the day after the deadly shooting at the Pulse Nightclub in Orlando, physicians from across the country and at every stage in their career spoke about treating gunshot victims and the scale of violence we are experiencing today. Their stories resonate as much today as they did nearly two years ago.
The shooting at Marjory Stoneman Douglas High School was the 30th mass shooting – a shooting in which four or more people are killed or injured – of 2018. It was also the 17th time a gun has been fired on the grounds of an American school this year. The problem is getting worse – the regularity of, and death from, mass shootings is increasing. With the shooting in Parkland, three of the 10 deadliest mass shootings in modern U.S. history have come in the past five months.
Time to act
Gun violence in America today is a public health crisis, one that requires a comprehensive and far-reaching solution. And that is not just my own sentiment; that is the determination of the AMA House of Delegates. With more than 30,000 American men, women and children dying from gun violence and firearm-related accidents each year, the time to act is now.
Today, more than ever before, America’s physicians must lend their voice and their considerable political muscle to force lawmakers to examine this urgent health crisis – through federally funded research – and take appropriate steps to address it. Let me be very clear about this. We are not talking about Second Amendment rights or restricting your ability to own a firearm.
We are talking about a public health crisis that our Congress has failed to address. This must end.
In the wake of the Sandy Hook shooting in 2012 – a massacre that left 20 first-graders and six adults dead – the AMA wrote to President Obama and to the leaders in the House and Senate. We expressed our sense of grief and sadness and offered our expertise and experience in finding workable, commonsense solutions to reduce the epidemic of gun violence – indeed the overall culture of violence – in America.
We noted that the relatively easy access to the increased firepower of assault weapons, semiautomatic firearms, high-capacity magazines, and high-velocity ammunition heightens the risk of multiple gunshot wounds and severe penetrating trauma, resulting in more critical injuries and deaths. Even for those who manage to survive gun violence involving these weapons, the severity and lasting impact of their wounds, disabilities and treatment leads to devastating consequences for the families affected and for society as a whole, contributing to high medical costs for treatment and recovery.
We called for renewing and strengthening the assault weapons ban, including banning high-capacity magazines, as a step in the right direction. We also called for more resources for safety education programs that promote more responsible use and storage of firearms, and noted that part of ensuring firearms safety means that physicians need to be able to have frank discussions with their patients and parents of patients about firearm safety issues and risks to help them safeguard their families from accidents.
We also urged the nation to strengthen its commitment and resources to comprehensive access to mental health services, including screening, prevention and treatment. While the overwhelming majority of patients with mental illness are not violent, physicians and other health professionals must be trained to respond to those who have a mental illness that might make them more prone to commit violence.
On an average day, more than 100 Americans die from gun violence and firearm-related accidents. In communities like yours – regardless of where you live or how safe it feels – people are losing their lives to this scourge.
For many Americans, gun violence used to be a distant idea relegated mostly to the nightly news, movies and faraway places. But today, in communities such as Parkland, it is horrifyingly real. The victims are our friends, neighbors and, unfathomably, our children.
As physicians, we have dedicated our lives to public health. And at the AMA, our mission is improving the health of the nation. That mission today must include determining the root causes of this epidemic and turning the tide on gun violence.
We must do more than pray for families who lost loved ones. It is time to act to prevent future deaths and injuries.
Dr. Barbe is president of the American Medical Association. His commentary originally was published on AMA Wire.
ANA assay results differ widely in established lupus patients
A new study that shows wide variation in the results of commercially-available assays used to detect antinuclear antibodies in people with established systemic lupus erythematosus has thrown into question the assays’ role in determining eligibility for trials as well as their role in clinical practice.
The study’s findings of negative results ranging from 5% to 22% of samples with three different commercially available immunofluorescence assays (IFAs), one ELISA assay, and one bead-based multiplex assay reveal that “ANA negativity can occur in established lupus not infrequently [and] the use of certain ANA assays could affect the frequency of screen failures in the trial setting as well as the eventual utilization of an agent if approved for serologically active patients,” David S. Pisetsky, MD, PhD, of Duke University, Durham, N.C., and his associates wrote in their report published in Annals of the Rheumatic Diseases.
People with systemic lupus erythematosus (SLE) have been thought to be “almost invariably” ANA positive, leaving the usual performance of testing to initial evaluation but not later unless a patient seeks care from another provider or undergoes screening to determine eligibility for entry into clinical trials of new therapeutic agents even though existing assays are not validated for this purpose. This practice first began with the development of the monoclonal antibody belimumab (Benlysta). Phase 2 trials showed that patients who were serologically positive (ANA and/or anti-DNA) were more likely to respond to the agent. Phase 3 trials that followed enrolled only serological positive patients and met their endpoints, the investigators explained.
“In view of the increasing use of ANA for determining trial eligibility, an explanation of these observations is important since it can impact both trial enrollment and eventual utilization of a product approved for autoantibody positive patients,” they wrote.
The research team assessed sera from 103 SLE patients using three different IFAs, an ELISA assay, and a bead-based multiplex assay. Results showed that the frequency of ANA positivity varied markedly depending on the assay platform and kit used. Among the IFA kits, negative results varied from 5 to 23 of 103 samples (4.9%-22.3%), although some samples had indeterminate results. Negative results occurred in 12 (11.7%) of the ELISA samples and in 14 (13.6%) of the multiplex assay samples.
Patients who consistently tested ANA positive in all assays differed from those who had discordant results among assays based on their likelihood of historical anti-double stranded DNA positivity and low levels of C3 complement.
This difference may have implications for the use of assays to determine eligibility for entry into a trial, the investigators noted. They advised that clinical trial protocols should specify which kits can be used to determine eligibility and how they characteristically perform, particularly for patients with established disease.
“Since the ANA assay used for screening is often not specified in protocols, the selection of a kit could lead to as much as a 17% change in the number of screen failures,” they speculated. “Correspondingly, for products approved for serologically active SLE, the use of certain assays could determine whether a patient meets criteria for its use.”
Future studies are needed to identify the assays that are most informative as theranostic biomarkers. Questions also remain over whether ANA positivity should be a criterion for trial entry in people with SLE of long duration, and if people with seronegative disease should be studied separately, they added.
The Lupus Industry Council supported the study. No authors had conflicts of interest to declare.
SOURCE: Pisetsky D et al. Ann Rheum Dis. 2018 Feb 9. doi: 10.1136/annrheumdis-2017-212599
A new study that shows wide variation in the results of commercially-available assays used to detect antinuclear antibodies in people with established systemic lupus erythematosus has thrown into question the assays’ role in determining eligibility for trials as well as their role in clinical practice.
The study’s findings of negative results ranging from 5% to 22% of samples with three different commercially available immunofluorescence assays (IFAs), one ELISA assay, and one bead-based multiplex assay reveal that “ANA negativity can occur in established lupus not infrequently [and] the use of certain ANA assays could affect the frequency of screen failures in the trial setting as well as the eventual utilization of an agent if approved for serologically active patients,” David S. Pisetsky, MD, PhD, of Duke University, Durham, N.C., and his associates wrote in their report published in Annals of the Rheumatic Diseases.
People with systemic lupus erythematosus (SLE) have been thought to be “almost invariably” ANA positive, leaving the usual performance of testing to initial evaluation but not later unless a patient seeks care from another provider or undergoes screening to determine eligibility for entry into clinical trials of new therapeutic agents even though existing assays are not validated for this purpose. This practice first began with the development of the monoclonal antibody belimumab (Benlysta). Phase 2 trials showed that patients who were serologically positive (ANA and/or anti-DNA) were more likely to respond to the agent. Phase 3 trials that followed enrolled only serological positive patients and met their endpoints, the investigators explained.
“In view of the increasing use of ANA for determining trial eligibility, an explanation of these observations is important since it can impact both trial enrollment and eventual utilization of a product approved for autoantibody positive patients,” they wrote.
The research team assessed sera from 103 SLE patients using three different IFAs, an ELISA assay, and a bead-based multiplex assay. Results showed that the frequency of ANA positivity varied markedly depending on the assay platform and kit used. Among the IFA kits, negative results varied from 5 to 23 of 103 samples (4.9%-22.3%), although some samples had indeterminate results. Negative results occurred in 12 (11.7%) of the ELISA samples and in 14 (13.6%) of the multiplex assay samples.
Patients who consistently tested ANA positive in all assays differed from those who had discordant results among assays based on their likelihood of historical anti-double stranded DNA positivity and low levels of C3 complement.
This difference may have implications for the use of assays to determine eligibility for entry into a trial, the investigators noted. They advised that clinical trial protocols should specify which kits can be used to determine eligibility and how they characteristically perform, particularly for patients with established disease.
“Since the ANA assay used for screening is often not specified in protocols, the selection of a kit could lead to as much as a 17% change in the number of screen failures,” they speculated. “Correspondingly, for products approved for serologically active SLE, the use of certain assays could determine whether a patient meets criteria for its use.”
Future studies are needed to identify the assays that are most informative as theranostic biomarkers. Questions also remain over whether ANA positivity should be a criterion for trial entry in people with SLE of long duration, and if people with seronegative disease should be studied separately, they added.
The Lupus Industry Council supported the study. No authors had conflicts of interest to declare.
SOURCE: Pisetsky D et al. Ann Rheum Dis. 2018 Feb 9. doi: 10.1136/annrheumdis-2017-212599
A new study that shows wide variation in the results of commercially-available assays used to detect antinuclear antibodies in people with established systemic lupus erythematosus has thrown into question the assays’ role in determining eligibility for trials as well as their role in clinical practice.
The study’s findings of negative results ranging from 5% to 22% of samples with three different commercially available immunofluorescence assays (IFAs), one ELISA assay, and one bead-based multiplex assay reveal that “ANA negativity can occur in established lupus not infrequently [and] the use of certain ANA assays could affect the frequency of screen failures in the trial setting as well as the eventual utilization of an agent if approved for serologically active patients,” David S. Pisetsky, MD, PhD, of Duke University, Durham, N.C., and his associates wrote in their report published in Annals of the Rheumatic Diseases.
People with systemic lupus erythematosus (SLE) have been thought to be “almost invariably” ANA positive, leaving the usual performance of testing to initial evaluation but not later unless a patient seeks care from another provider or undergoes screening to determine eligibility for entry into clinical trials of new therapeutic agents even though existing assays are not validated for this purpose. This practice first began with the development of the monoclonal antibody belimumab (Benlysta). Phase 2 trials showed that patients who were serologically positive (ANA and/or anti-DNA) were more likely to respond to the agent. Phase 3 trials that followed enrolled only serological positive patients and met their endpoints, the investigators explained.
“In view of the increasing use of ANA for determining trial eligibility, an explanation of these observations is important since it can impact both trial enrollment and eventual utilization of a product approved for autoantibody positive patients,” they wrote.
The research team assessed sera from 103 SLE patients using three different IFAs, an ELISA assay, and a bead-based multiplex assay. Results showed that the frequency of ANA positivity varied markedly depending on the assay platform and kit used. Among the IFA kits, negative results varied from 5 to 23 of 103 samples (4.9%-22.3%), although some samples had indeterminate results. Negative results occurred in 12 (11.7%) of the ELISA samples and in 14 (13.6%) of the multiplex assay samples.
Patients who consistently tested ANA positive in all assays differed from those who had discordant results among assays based on their likelihood of historical anti-double stranded DNA positivity and low levels of C3 complement.
This difference may have implications for the use of assays to determine eligibility for entry into a trial, the investigators noted. They advised that clinical trial protocols should specify which kits can be used to determine eligibility and how they characteristically perform, particularly for patients with established disease.
“Since the ANA assay used for screening is often not specified in protocols, the selection of a kit could lead to as much as a 17% change in the number of screen failures,” they speculated. “Correspondingly, for products approved for serologically active SLE, the use of certain assays could determine whether a patient meets criteria for its use.”
Future studies are needed to identify the assays that are most informative as theranostic biomarkers. Questions also remain over whether ANA positivity should be a criterion for trial entry in people with SLE of long duration, and if people with seronegative disease should be studied separately, they added.
The Lupus Industry Council supported the study. No authors had conflicts of interest to declare.
SOURCE: Pisetsky D et al. Ann Rheum Dis. 2018 Feb 9. doi: 10.1136/annrheumdis-2017-212599
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Main finding: ANA negativity varied from 5% to 22% of sera samples from 103 SLE patients with established disease.
Data source: Sera from 103 SLE patients were assessed using three different commercially available immunofluorescence assays, one ELISA assay, and one bead-based multiplex assay.
Disclosures: The Lupus Industry Council supported the study. No authors had conflicts of interest to declare.
Source: Pisetsky D et al. Ann Rheum Dis. 2018 Feb 9. doi: 10.1136/annrheumdis-2017-212599.