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Itchy rash on forearms
The FP strongly suspected that this was a case of nummular eczema, based on the round shape of the plaques, but the location of the lesions suggested psoriasis. The FP also considered tinea corporis with psoriasis in the differential.
The FP checked the patient's scalp, nails, and umbilicus for other signs of psoriasis and found none. He also performed a potassium hydroxide (KOH) preparation, which was negative for hyphae and fungal elements. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) To be sure that this wasn’t psoriasis, the FP also performed a punch biopsy. (The pathology subsequently came back positive for nummular eczema.) Ultimately, the yellow crusting, along with the round shape of the plaques, supported a diagnosis of nummular eczema. (“Nummus” is Latin for “coin.”)
Treatment for nummular eczema typically includes clobetasol, an ultra-high-potency corticosteroid. (The patient’s lack of response to the over-the-counter [1%] hydrocortisone was not unusual for nummular eczema because it is a low-potency steroid.) The FP in this case prescribed 0.05% clobetasol ointment to be applied twice daily to the lesions until the follow-up appointment 10 days later. At follow-up, the patient reported that the itching had almost completely resolved and the lesions were looking much better. The stitch from the biopsy was removed and the patient was told to continue using the clobetasol until the lesions completely resolved.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Wah Y, Usatine R. Eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
The FP strongly suspected that this was a case of nummular eczema, based on the round shape of the plaques, but the location of the lesions suggested psoriasis. The FP also considered tinea corporis with psoriasis in the differential.
The FP checked the patient's scalp, nails, and umbilicus for other signs of psoriasis and found none. He also performed a potassium hydroxide (KOH) preparation, which was negative for hyphae and fungal elements. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) To be sure that this wasn’t psoriasis, the FP also performed a punch biopsy. (The pathology subsequently came back positive for nummular eczema.) Ultimately, the yellow crusting, along with the round shape of the plaques, supported a diagnosis of nummular eczema. (“Nummus” is Latin for “coin.”)
Treatment for nummular eczema typically includes clobetasol, an ultra-high-potency corticosteroid. (The patient’s lack of response to the over-the-counter [1%] hydrocortisone was not unusual for nummular eczema because it is a low-potency steroid.) The FP in this case prescribed 0.05% clobetasol ointment to be applied twice daily to the lesions until the follow-up appointment 10 days later. At follow-up, the patient reported that the itching had almost completely resolved and the lesions were looking much better. The stitch from the biopsy was removed and the patient was told to continue using the clobetasol until the lesions completely resolved.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Wah Y, Usatine R. Eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
The FP strongly suspected that this was a case of nummular eczema, based on the round shape of the plaques, but the location of the lesions suggested psoriasis. The FP also considered tinea corporis with psoriasis in the differential.
The FP checked the patient's scalp, nails, and umbilicus for other signs of psoriasis and found none. He also performed a potassium hydroxide (KOH) preparation, which was negative for hyphae and fungal elements. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) To be sure that this wasn’t psoriasis, the FP also performed a punch biopsy. (The pathology subsequently came back positive for nummular eczema.) Ultimately, the yellow crusting, along with the round shape of the plaques, supported a diagnosis of nummular eczema. (“Nummus” is Latin for “coin.”)
Treatment for nummular eczema typically includes clobetasol, an ultra-high-potency corticosteroid. (The patient’s lack of response to the over-the-counter [1%] hydrocortisone was not unusual for nummular eczema because it is a low-potency steroid.) The FP in this case prescribed 0.05% clobetasol ointment to be applied twice daily to the lesions until the follow-up appointment 10 days later. At follow-up, the patient reported that the itching had almost completely resolved and the lesions were looking much better. The stitch from the biopsy was removed and the patient was told to continue using the clobetasol until the lesions completely resolved.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Wah Y, Usatine R. Eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
Alternating therapy in renal cell carcinoma fails to show an advantage
There was no efficacy or safety advantage for alternating everolimus with pazopanib over pazopanib alone in patients with metastatic or locally advanced clear cell renal cell carcinoma (ccRCC), according to a newly published randomized trial.
The study hypothesis was that alternating the two drugs would improve outcomes and reduce toxicity, but differences between arms for the major outcomes were not clinically significant, according to results of a multicenter trial led by Geert A. Cirkel, MD, of the department of medical oncology, University Medical Center, Utrecht, the Netherlands.
Investigators randomized 101 patients with histologically confirmed ccRCC to receive 8 weeks of pazopanib in a daily dose of 800 mg alternated with 8 weeks of everolimus in a daily dose of 10 mg or 800 mg per day of continuous pazopanib. Patients remained on either regimen until disease progression.
Median time until first progression or death was 7.4 months for the experimental alternating arm versus 9.4 months for the control arm of continuous single-agent pazopanib (P = .37), Dr. Cirkel and associates reported (JAMA Onc. 2017 Apr 1. doi: 10.1001/jamaoncol.2016.5202).
Progression-free survival after starting on a second-line therapy was 20.2 months for the alternating treatment vs. 14.5 months for the control, but the confidence intervals were wide, and the difference was not significant (P = .86).
There was no apparent toxicity or tolerability advantage from alternating therapy. Nearly 40% of patients in both arms required pazopanib dose reductions, while 14% in the alternating arm also required an everolimus dose reduction. The incidence of serious adverse events possibly related to treatment was comparable between arms.
Quality of life was measured with several tools, including the Functional Assessment of Cancer Therapy – Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS), but no significant differences between treatment arms were observed in any measure.
Current guidelines recommend pazopanib, which is a tyrosine kinase inhibitor of the vascular endothelial growth factor receptor, as a first-line therapy in ccRCC. Everolimus, an inhibitor of mammalian target of rapamycin, is recommended in the second-line setting. Noting that resistance to pazopanib has been shown to be reversible after a period of withdrawal in experimental studies, the authors had speculated an on-off strategy with everolimus might better preserve the efficacy of pazopanib, providing longer periods of disease control. They had also hypothesized that the cumulative adverse events might be less if the drugs were sequenced, allowing recovery from each set of drug-specific adverse events.
Several potential explanations were offered for the lack of improved efficacy from alternating everolimus with pazopanib. For one, the improved activity of pazopanib after withdrawal in experimental models was observed after drug-free periods. The authors questioned whether a period of tumor regrowth may be needed in order to overcome pazopanib resistance.
The study may still have supported the use of an alternating regimen if the alternating therapy had led to a significantly improved quality of life, but the authors found none, a outcome that they characterized as unexpected. They concluded that there are no apparent advantages for the alternating regimen of pazopanib and everolimus relative to pazopanib alone.
There was no efficacy or safety advantage for alternating everolimus with pazopanib over pazopanib alone in patients with metastatic or locally advanced clear cell renal cell carcinoma (ccRCC), according to a newly published randomized trial.
The study hypothesis was that alternating the two drugs would improve outcomes and reduce toxicity, but differences between arms for the major outcomes were not clinically significant, according to results of a multicenter trial led by Geert A. Cirkel, MD, of the department of medical oncology, University Medical Center, Utrecht, the Netherlands.
Investigators randomized 101 patients with histologically confirmed ccRCC to receive 8 weeks of pazopanib in a daily dose of 800 mg alternated with 8 weeks of everolimus in a daily dose of 10 mg or 800 mg per day of continuous pazopanib. Patients remained on either regimen until disease progression.
Median time until first progression or death was 7.4 months for the experimental alternating arm versus 9.4 months for the control arm of continuous single-agent pazopanib (P = .37), Dr. Cirkel and associates reported (JAMA Onc. 2017 Apr 1. doi: 10.1001/jamaoncol.2016.5202).
Progression-free survival after starting on a second-line therapy was 20.2 months for the alternating treatment vs. 14.5 months for the control, but the confidence intervals were wide, and the difference was not significant (P = .86).
There was no apparent toxicity or tolerability advantage from alternating therapy. Nearly 40% of patients in both arms required pazopanib dose reductions, while 14% in the alternating arm also required an everolimus dose reduction. The incidence of serious adverse events possibly related to treatment was comparable between arms.
Quality of life was measured with several tools, including the Functional Assessment of Cancer Therapy – Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS), but no significant differences between treatment arms were observed in any measure.
Current guidelines recommend pazopanib, which is a tyrosine kinase inhibitor of the vascular endothelial growth factor receptor, as a first-line therapy in ccRCC. Everolimus, an inhibitor of mammalian target of rapamycin, is recommended in the second-line setting. Noting that resistance to pazopanib has been shown to be reversible after a period of withdrawal in experimental studies, the authors had speculated an on-off strategy with everolimus might better preserve the efficacy of pazopanib, providing longer periods of disease control. They had also hypothesized that the cumulative adverse events might be less if the drugs were sequenced, allowing recovery from each set of drug-specific adverse events.
Several potential explanations were offered for the lack of improved efficacy from alternating everolimus with pazopanib. For one, the improved activity of pazopanib after withdrawal in experimental models was observed after drug-free periods. The authors questioned whether a period of tumor regrowth may be needed in order to overcome pazopanib resistance.
The study may still have supported the use of an alternating regimen if the alternating therapy had led to a significantly improved quality of life, but the authors found none, a outcome that they characterized as unexpected. They concluded that there are no apparent advantages for the alternating regimen of pazopanib and everolimus relative to pazopanib alone.
There was no efficacy or safety advantage for alternating everolimus with pazopanib over pazopanib alone in patients with metastatic or locally advanced clear cell renal cell carcinoma (ccRCC), according to a newly published randomized trial.
The study hypothesis was that alternating the two drugs would improve outcomes and reduce toxicity, but differences between arms for the major outcomes were not clinically significant, according to results of a multicenter trial led by Geert A. Cirkel, MD, of the department of medical oncology, University Medical Center, Utrecht, the Netherlands.
Investigators randomized 101 patients with histologically confirmed ccRCC to receive 8 weeks of pazopanib in a daily dose of 800 mg alternated with 8 weeks of everolimus in a daily dose of 10 mg or 800 mg per day of continuous pazopanib. Patients remained on either regimen until disease progression.
Median time until first progression or death was 7.4 months for the experimental alternating arm versus 9.4 months for the control arm of continuous single-agent pazopanib (P = .37), Dr. Cirkel and associates reported (JAMA Onc. 2017 Apr 1. doi: 10.1001/jamaoncol.2016.5202).
Progression-free survival after starting on a second-line therapy was 20.2 months for the alternating treatment vs. 14.5 months for the control, but the confidence intervals were wide, and the difference was not significant (P = .86).
There was no apparent toxicity or tolerability advantage from alternating therapy. Nearly 40% of patients in both arms required pazopanib dose reductions, while 14% in the alternating arm also required an everolimus dose reduction. The incidence of serious adverse events possibly related to treatment was comparable between arms.
Quality of life was measured with several tools, including the Functional Assessment of Cancer Therapy – Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS), but no significant differences between treatment arms were observed in any measure.
Current guidelines recommend pazopanib, which is a tyrosine kinase inhibitor of the vascular endothelial growth factor receptor, as a first-line therapy in ccRCC. Everolimus, an inhibitor of mammalian target of rapamycin, is recommended in the second-line setting. Noting that resistance to pazopanib has been shown to be reversible after a period of withdrawal in experimental studies, the authors had speculated an on-off strategy with everolimus might better preserve the efficacy of pazopanib, providing longer periods of disease control. They had also hypothesized that the cumulative adverse events might be less if the drugs were sequenced, allowing recovery from each set of drug-specific adverse events.
Several potential explanations were offered for the lack of improved efficacy from alternating everolimus with pazopanib. For one, the improved activity of pazopanib after withdrawal in experimental models was observed after drug-free periods. The authors questioned whether a period of tumor regrowth may be needed in order to overcome pazopanib resistance.
The study may still have supported the use of an alternating regimen if the alternating therapy had led to a significantly improved quality of life, but the authors found none, a outcome that they characterized as unexpected. They concluded that there are no apparent advantages for the alternating regimen of pazopanib and everolimus relative to pazopanib alone.
FROM JAMA ONCOLOGY
Key clinical point:
Major finding: The median time to progression or death was 7.4 months for the combination versus 9.4 months for pazopanib alone (P = .37).
Data source: Randomized, multicenter controlled trial.
Disclosures: The principal investigator Dr. Cirkel reports travel expenses from Novartis, which, along with GlaxoSmithKline, provided funding for this study.
More early-stage cancer diagnosis since ACA implementation
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: The proportion of cancers that were stage I when diagnosed increased by about 1% after ACA implementation for breast, cervical, lung, and colorectal cancer, while it decreased by 1% for prostate cancer.
Data source: A cohort study of 272,656 patients with these five cancers from the National Cancer Database.
Disclosures: Dr. Han reported that she had no disclosures.
Mepolizumab proves effective for eosinophilic granulomatosis with polyangiitis
Adding mepolizumab to standard-of-care glucocorticoids with or without immunosuppressive agents can induce remission in many patients who have eosinophilic granulomatosis with polyangiitis (EGPA), according to a report published online May 18 in the New England Journal of Medicine.
EGPA, a rare disorder characterized by asthma, sinusitis, pulmonary infiltrates, neuropathy, and eosinophilic vasculitis in at least one end-organ, frequently relapses despite glucocorticoid therapy or fails to respond adequately to the treatment. Patients have elevated levels of the cytokine interleukin-5, which regulates eosinophil maturation, differentiation, and proliferation. Neutralizing this cytokine is thought to be a potential therapeutic approach, said Michael E. Wechsler, MD, of National Jewish Health, Denver, and his associates.
Proof-of-concept studies have demonstrated the efficacy of subcutaneous mepolizumab, an anti–interleukin-5 monoclonal antibody, in EGPA, so Dr. Wechsler and his colleagues assessed the safety and efficacy of a 1-year course of mepolizumab (300 mg) as add-on therapy in a double-blind, randomized, phase III trial, which involved 136 adults treated at 31 academic medical centers in nine countries. The study was sponsored by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases.
The first of two primary efficacy endpoints was the total accrued weeks of remission. A total of 28% of the mepolizumab group achieved remission for at least 24 weeks, compared with only 3% of the placebo group, for an odds ratio of 5.91.
The second primary efficacy endpoint was the proportion of patients in remission at both week 36 and week 48. Again, significantly more patients in the mepolizumab group (32%) than in the placebo group (3%) met this end point (OR, 16.74).
Mepolizumab also proved superior to placebo regarding numerous secondary endpoints, the investigators said (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1702079). More patients who received active treatment achieved remission within the first 6 months of treatment and remained in remission for a full year (19% vs. 1%; OR, 19.65). The time to first relapse was significantly longer for mepolizumab, with only 56% of that group experiencing a relapse within 1 year, compared with 82% of the placebo group. The annualized relapse rate was half as high with mepolizumab (1.14) as with placebo (2.27).
In addition, patients in the mepolizumab group were more likely to reduce their doses of glucocorticoids (OR, 0.20) or discontinue the drugs altogether (18% vs. 3% taking placebo).
Mepolizumab was most effective among the 79 patients who had a high absolute eosinophil count (150 or more cells per cubic millimeter) at baseline. In this subgroup, 33% of patients taking mepolizumab achieved remission for 6 months or more, compared with none of the patients taking placebo (OR, 26.1).
Although the effectiveness of mepolizumab in this difficult-to-treat population was noteworthy, only about half of the patients given the active treatment achieved remission as defined by the study protocol. It is unclear why the drug was not effective in the other half of patients. One possible reason is that some manifestations of the disorder are not driven by eosinophils. Another is that nonresponsive patients may have sustained longstanding, irreversible vasculitic damage that is no longer amenable to anti–interleukin-5 therapy.
Alternatively, it’s possible that mepolizumab reduced eosinophils in the blood but not those in the body tissues of nonresponsive patients or that the patients who didn’t respond well simply required a higher dose of the drug, Dr. Wechsler and his associates said.
The NIAID is now supporting a study of blood, urine, sputum, and tissue samples from some of these participants “to address questions related to disease risk and pathological features, as well as response to treatment,” they added.
Many authors reported receiving payments from pharmaceutical companies, including several from GlaxoSmithKline. Four authors are employees of the company.
The study by Michael E. Wechsler, MD, and his associates can be considered proof of concept. Now, researchers must turn to identifying biomarkers that predict the success or failure of mepolizumab in patients.
Researchers must also elucidate the fate of eosinophils in the tissues, especially in vasculitic lesions, after treatment with mepolizumab. And they should address possible synergistic activity when the drug is given together with immunosuppressants such as azathioprine and cyclophosphamide.
In addition, future studies should include patients who have organ-threatening or life-threatening eosinophilic granulomatosis with polyangiitis, who were excluded from this trial but who are most in need of novel treatments.
Ratko Djukanovic, MD, is with the University of Southampton (England) and the National Institute for Health Research Southampton Biomedical Research Centre. Paul M. O’Byrne, MD, is with the Firestone Institute for Respiratory Health within St. Joseph’s Healthcare and McMaster University in Hamilton, Ont. Dr. Djukanovic and Dr. O’Byrne both reported financial relationships with pharmaceutical companies outside their editorial. They made these remarks in an editorial accompanying Dr. Wechsler and colleagues’ report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1704402).
The study by Michael E. Wechsler, MD, and his associates can be considered proof of concept. Now, researchers must turn to identifying biomarkers that predict the success or failure of mepolizumab in patients.
Researchers must also elucidate the fate of eosinophils in the tissues, especially in vasculitic lesions, after treatment with mepolizumab. And they should address possible synergistic activity when the drug is given together with immunosuppressants such as azathioprine and cyclophosphamide.
In addition, future studies should include patients who have organ-threatening or life-threatening eosinophilic granulomatosis with polyangiitis, who were excluded from this trial but who are most in need of novel treatments.
Ratko Djukanovic, MD, is with the University of Southampton (England) and the National Institute for Health Research Southampton Biomedical Research Centre. Paul M. O’Byrne, MD, is with the Firestone Institute for Respiratory Health within St. Joseph’s Healthcare and McMaster University in Hamilton, Ont. Dr. Djukanovic and Dr. O’Byrne both reported financial relationships with pharmaceutical companies outside their editorial. They made these remarks in an editorial accompanying Dr. Wechsler and colleagues’ report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1704402).
The study by Michael E. Wechsler, MD, and his associates can be considered proof of concept. Now, researchers must turn to identifying biomarkers that predict the success or failure of mepolizumab in patients.
Researchers must also elucidate the fate of eosinophils in the tissues, especially in vasculitic lesions, after treatment with mepolizumab. And they should address possible synergistic activity when the drug is given together with immunosuppressants such as azathioprine and cyclophosphamide.
In addition, future studies should include patients who have organ-threatening or life-threatening eosinophilic granulomatosis with polyangiitis, who were excluded from this trial but who are most in need of novel treatments.
Ratko Djukanovic, MD, is with the University of Southampton (England) and the National Institute for Health Research Southampton Biomedical Research Centre. Paul M. O’Byrne, MD, is with the Firestone Institute for Respiratory Health within St. Joseph’s Healthcare and McMaster University in Hamilton, Ont. Dr. Djukanovic and Dr. O’Byrne both reported financial relationships with pharmaceutical companies outside their editorial. They made these remarks in an editorial accompanying Dr. Wechsler and colleagues’ report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1704402).
Adding mepolizumab to standard-of-care glucocorticoids with or without immunosuppressive agents can induce remission in many patients who have eosinophilic granulomatosis with polyangiitis (EGPA), according to a report published online May 18 in the New England Journal of Medicine.
EGPA, a rare disorder characterized by asthma, sinusitis, pulmonary infiltrates, neuropathy, and eosinophilic vasculitis in at least one end-organ, frequently relapses despite glucocorticoid therapy or fails to respond adequately to the treatment. Patients have elevated levels of the cytokine interleukin-5, which regulates eosinophil maturation, differentiation, and proliferation. Neutralizing this cytokine is thought to be a potential therapeutic approach, said Michael E. Wechsler, MD, of National Jewish Health, Denver, and his associates.
Proof-of-concept studies have demonstrated the efficacy of subcutaneous mepolizumab, an anti–interleukin-5 monoclonal antibody, in EGPA, so Dr. Wechsler and his colleagues assessed the safety and efficacy of a 1-year course of mepolizumab (300 mg) as add-on therapy in a double-blind, randomized, phase III trial, which involved 136 adults treated at 31 academic medical centers in nine countries. The study was sponsored by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases.
The first of two primary efficacy endpoints was the total accrued weeks of remission. A total of 28% of the mepolizumab group achieved remission for at least 24 weeks, compared with only 3% of the placebo group, for an odds ratio of 5.91.
The second primary efficacy endpoint was the proportion of patients in remission at both week 36 and week 48. Again, significantly more patients in the mepolizumab group (32%) than in the placebo group (3%) met this end point (OR, 16.74).
Mepolizumab also proved superior to placebo regarding numerous secondary endpoints, the investigators said (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1702079). More patients who received active treatment achieved remission within the first 6 months of treatment and remained in remission for a full year (19% vs. 1%; OR, 19.65). The time to first relapse was significantly longer for mepolizumab, with only 56% of that group experiencing a relapse within 1 year, compared with 82% of the placebo group. The annualized relapse rate was half as high with mepolizumab (1.14) as with placebo (2.27).
In addition, patients in the mepolizumab group were more likely to reduce their doses of glucocorticoids (OR, 0.20) or discontinue the drugs altogether (18% vs. 3% taking placebo).
Mepolizumab was most effective among the 79 patients who had a high absolute eosinophil count (150 or more cells per cubic millimeter) at baseline. In this subgroup, 33% of patients taking mepolizumab achieved remission for 6 months or more, compared with none of the patients taking placebo (OR, 26.1).
Although the effectiveness of mepolizumab in this difficult-to-treat population was noteworthy, only about half of the patients given the active treatment achieved remission as defined by the study protocol. It is unclear why the drug was not effective in the other half of patients. One possible reason is that some manifestations of the disorder are not driven by eosinophils. Another is that nonresponsive patients may have sustained longstanding, irreversible vasculitic damage that is no longer amenable to anti–interleukin-5 therapy.
Alternatively, it’s possible that mepolizumab reduced eosinophils in the blood but not those in the body tissues of nonresponsive patients or that the patients who didn’t respond well simply required a higher dose of the drug, Dr. Wechsler and his associates said.
The NIAID is now supporting a study of blood, urine, sputum, and tissue samples from some of these participants “to address questions related to disease risk and pathological features, as well as response to treatment,” they added.
Many authors reported receiving payments from pharmaceutical companies, including several from GlaxoSmithKline. Four authors are employees of the company.
Adding mepolizumab to standard-of-care glucocorticoids with or without immunosuppressive agents can induce remission in many patients who have eosinophilic granulomatosis with polyangiitis (EGPA), according to a report published online May 18 in the New England Journal of Medicine.
EGPA, a rare disorder characterized by asthma, sinusitis, pulmonary infiltrates, neuropathy, and eosinophilic vasculitis in at least one end-organ, frequently relapses despite glucocorticoid therapy or fails to respond adequately to the treatment. Patients have elevated levels of the cytokine interleukin-5, which regulates eosinophil maturation, differentiation, and proliferation. Neutralizing this cytokine is thought to be a potential therapeutic approach, said Michael E. Wechsler, MD, of National Jewish Health, Denver, and his associates.
Proof-of-concept studies have demonstrated the efficacy of subcutaneous mepolizumab, an anti–interleukin-5 monoclonal antibody, in EGPA, so Dr. Wechsler and his colleagues assessed the safety and efficacy of a 1-year course of mepolizumab (300 mg) as add-on therapy in a double-blind, randomized, phase III trial, which involved 136 adults treated at 31 academic medical centers in nine countries. The study was sponsored by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases.
The first of two primary efficacy endpoints was the total accrued weeks of remission. A total of 28% of the mepolizumab group achieved remission for at least 24 weeks, compared with only 3% of the placebo group, for an odds ratio of 5.91.
The second primary efficacy endpoint was the proportion of patients in remission at both week 36 and week 48. Again, significantly more patients in the mepolizumab group (32%) than in the placebo group (3%) met this end point (OR, 16.74).
Mepolizumab also proved superior to placebo regarding numerous secondary endpoints, the investigators said (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1702079). More patients who received active treatment achieved remission within the first 6 months of treatment and remained in remission for a full year (19% vs. 1%; OR, 19.65). The time to first relapse was significantly longer for mepolizumab, with only 56% of that group experiencing a relapse within 1 year, compared with 82% of the placebo group. The annualized relapse rate was half as high with mepolizumab (1.14) as with placebo (2.27).
In addition, patients in the mepolizumab group were more likely to reduce their doses of glucocorticoids (OR, 0.20) or discontinue the drugs altogether (18% vs. 3% taking placebo).
Mepolizumab was most effective among the 79 patients who had a high absolute eosinophil count (150 or more cells per cubic millimeter) at baseline. In this subgroup, 33% of patients taking mepolizumab achieved remission for 6 months or more, compared with none of the patients taking placebo (OR, 26.1).
Although the effectiveness of mepolizumab in this difficult-to-treat population was noteworthy, only about half of the patients given the active treatment achieved remission as defined by the study protocol. It is unclear why the drug was not effective in the other half of patients. One possible reason is that some manifestations of the disorder are not driven by eosinophils. Another is that nonresponsive patients may have sustained longstanding, irreversible vasculitic damage that is no longer amenable to anti–interleukin-5 therapy.
Alternatively, it’s possible that mepolizumab reduced eosinophils in the blood but not those in the body tissues of nonresponsive patients or that the patients who didn’t respond well simply required a higher dose of the drug, Dr. Wechsler and his associates said.
The NIAID is now supporting a study of blood, urine, sputum, and tissue samples from some of these participants “to address questions related to disease risk and pathological features, as well as response to treatment,” they added.
Many authors reported receiving payments from pharmaceutical companies, including several from GlaxoSmithKline. Four authors are employees of the company.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Of the mepolizumab group, 28% achieved remission for at least 24 weeks, compared with only 3% of the placebo group (OR, 5.91).
Data source: An international double-blind randomized placebo-controlled phase III trial involving 136 adults treated for 1 year.
Disclosures: This study was supported by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases. Many authors reported receiving payments from pharmaceutical companies, including several from GlaxoSmithKline. Four authors are employees of the company.
Imatinib cuts mast cells in severe asthma
Imatinib decreased airway mast-cell counts and airway hyperresponsiveness in adults with asthma, who were not responding well to maximal therapy, according to a report published online May 17 in the New England Journal of Medicine.
Imatinib is an inhibitor of the stem-cell factor receptor KIT, which is essential for mast-cell development and survival in bodily tissues. This study’s findings suggest that KIT-dependent processes and mast cells contribute to the pathobiology of severe asthma.
The researchers undertook this study because imatinib is known to reduce bone-marrow mast cells and tryptase levels in chronic myeloid leukemia and to reduce serum tryptase in patients with pulmonary hypertension. Tryptase is a marker of mast-cell burden and activation when detected in extracellular fluids, and it is elevated in the bronchoalveolar lavage fluid from patients with uncontrolled asthma.
To examine whether imatinib would decrease mast-cell counts and activation in the airways of adults with severe, refractory asthma, the investigators performed the randomized double-blind proof-of-principle trial at seven academic centers across the United States over the course of 5 years. A total of 62 patients were assigned to 24 weeks of either oral imatinib (32 participants) or a matching placebo (30 participants). Fifty patients, 24 in the imatinib group and 26 in the placebo group, completed the trial.
The primary outcome measure was the change in airway hyperresponsiveness at 6 months, as measured by the increase in the concentration of methacholine that causes significant bronchoconstriction (PC20). Imatinib decreased airway hyperresponsiveness to a greater degree than did placebo. Imatinib increased PC20 by a mean of 1.20 doubling doses at 3 months and by a mean of 1.73 doubling doses at 6 months, compared with 0.03 and 1.07, respectively, for placebo.
The small improvement in the placebo group is consistent with a phenomenon reported in other studies, in which patients show a delayed improvement in airway hyperresponsiveness for several months after they started inhaled glucocorticoids, Dr. Cahill and her associates noted (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1613125).
Imatinib also reduced mast-cell activity as measured by serum and airway levels of tryptase. Serum tryptase decreased by 43% in the imatinib group, compared with a 12% decline in the placebo group. And tryptase levels in bronchoalveolar lavage fluid tended to decrease in the imatinib group but to increase in the placebo group.
Imatinib also increased mean forced expiratory volume in 1 second (FEV1).
“Although the increase in FEV1 may not seem substantial, it suggests that mast-cell–dependent processes contribute to airway obstruction in these patients despite high-dose, anti-inflammatory glucocorticoid therapy. The near–50-mL difference in the change in baseline FEV1 between the imatinib and placebo groups is small, but it is likely to be important in light of the population we studied,” Dr. Cahill and her associates wrote.
In addition, exploratory analyses showed that the reduction in airway hyperresponsiveness with imatinib “negatively correlated with baseline blood eosinophil counts, and baseline numbers of neutrophils in bronchoalveolar lavage fluid were strongly correlated with increases in FEV1. Together, these findings support a role for mast cells in noneosinophilic asthma. Since almost half of the patients with severe asthma have neutrophilic airway inflammation, we speculate that KIT inhibition might represent an important approach to treatment for this group,” they said.
This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Vinik family, and the Kaye family; Novartis provided imatinib free of charge. The authors’ financial disclosures are available at www.nejm.org.
As Cahill et al. noted, these data suggest that the role of mast cells should be studied further, but cautiously.
It is not yet time to target mast cells in patients with asthma. Evolution has given us these cells for a reason. They appear to assist in host defense against parasites and play a role in other innate and adaptive immune responses. And they likely have other beneficial effects that haven’t been discovered yet.
However, in the unfortunate patients in whom mast cells can be strongly implicated as contributing to disease, either reducing their numbers or suppressing their function may confer more benefit than harm. This is particularly true in the case of asthma, where mast cells can be targeted locally, in the airways.
Stephen J. Galli, MD, is the Mary Hewitt Loveless, MD, Professor in the school of medicine, and is at the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University. His financial disclosures are available at www.nejm.org. Dr. Galli made these remarks in an editorial accompanying Dr. Cahill’s report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1702653).
As Cahill et al. noted, these data suggest that the role of mast cells should be studied further, but cautiously.
It is not yet time to target mast cells in patients with asthma. Evolution has given us these cells for a reason. They appear to assist in host defense against parasites and play a role in other innate and adaptive immune responses. And they likely have other beneficial effects that haven’t been discovered yet.
However, in the unfortunate patients in whom mast cells can be strongly implicated as contributing to disease, either reducing their numbers or suppressing their function may confer more benefit than harm. This is particularly true in the case of asthma, where mast cells can be targeted locally, in the airways.
Stephen J. Galli, MD, is the Mary Hewitt Loveless, MD, Professor in the school of medicine, and is at the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University. His financial disclosures are available at www.nejm.org. Dr. Galli made these remarks in an editorial accompanying Dr. Cahill’s report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1702653).
As Cahill et al. noted, these data suggest that the role of mast cells should be studied further, but cautiously.
It is not yet time to target mast cells in patients with asthma. Evolution has given us these cells for a reason. They appear to assist in host defense against parasites and play a role in other innate and adaptive immune responses. And they likely have other beneficial effects that haven’t been discovered yet.
However, in the unfortunate patients in whom mast cells can be strongly implicated as contributing to disease, either reducing their numbers or suppressing their function may confer more benefit than harm. This is particularly true in the case of asthma, where mast cells can be targeted locally, in the airways.
Stephen J. Galli, MD, is the Mary Hewitt Loveless, MD, Professor in the school of medicine, and is at the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University. His financial disclosures are available at www.nejm.org. Dr. Galli made these remarks in an editorial accompanying Dr. Cahill’s report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1702653).
Imatinib decreased airway mast-cell counts and airway hyperresponsiveness in adults with asthma, who were not responding well to maximal therapy, according to a report published online May 17 in the New England Journal of Medicine.
Imatinib is an inhibitor of the stem-cell factor receptor KIT, which is essential for mast-cell development and survival in bodily tissues. This study’s findings suggest that KIT-dependent processes and mast cells contribute to the pathobiology of severe asthma.
The researchers undertook this study because imatinib is known to reduce bone-marrow mast cells and tryptase levels in chronic myeloid leukemia and to reduce serum tryptase in patients with pulmonary hypertension. Tryptase is a marker of mast-cell burden and activation when detected in extracellular fluids, and it is elevated in the bronchoalveolar lavage fluid from patients with uncontrolled asthma.
To examine whether imatinib would decrease mast-cell counts and activation in the airways of adults with severe, refractory asthma, the investigators performed the randomized double-blind proof-of-principle trial at seven academic centers across the United States over the course of 5 years. A total of 62 patients were assigned to 24 weeks of either oral imatinib (32 participants) or a matching placebo (30 participants). Fifty patients, 24 in the imatinib group and 26 in the placebo group, completed the trial.
The primary outcome measure was the change in airway hyperresponsiveness at 6 months, as measured by the increase in the concentration of methacholine that causes significant bronchoconstriction (PC20). Imatinib decreased airway hyperresponsiveness to a greater degree than did placebo. Imatinib increased PC20 by a mean of 1.20 doubling doses at 3 months and by a mean of 1.73 doubling doses at 6 months, compared with 0.03 and 1.07, respectively, for placebo.
The small improvement in the placebo group is consistent with a phenomenon reported in other studies, in which patients show a delayed improvement in airway hyperresponsiveness for several months after they started inhaled glucocorticoids, Dr. Cahill and her associates noted (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1613125).
Imatinib also reduced mast-cell activity as measured by serum and airway levels of tryptase. Serum tryptase decreased by 43% in the imatinib group, compared with a 12% decline in the placebo group. And tryptase levels in bronchoalveolar lavage fluid tended to decrease in the imatinib group but to increase in the placebo group.
Imatinib also increased mean forced expiratory volume in 1 second (FEV1).
“Although the increase in FEV1 may not seem substantial, it suggests that mast-cell–dependent processes contribute to airway obstruction in these patients despite high-dose, anti-inflammatory glucocorticoid therapy. The near–50-mL difference in the change in baseline FEV1 between the imatinib and placebo groups is small, but it is likely to be important in light of the population we studied,” Dr. Cahill and her associates wrote.
In addition, exploratory analyses showed that the reduction in airway hyperresponsiveness with imatinib “negatively correlated with baseline blood eosinophil counts, and baseline numbers of neutrophils in bronchoalveolar lavage fluid were strongly correlated with increases in FEV1. Together, these findings support a role for mast cells in noneosinophilic asthma. Since almost half of the patients with severe asthma have neutrophilic airway inflammation, we speculate that KIT inhibition might represent an important approach to treatment for this group,” they said.
This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Vinik family, and the Kaye family; Novartis provided imatinib free of charge. The authors’ financial disclosures are available at www.nejm.org.
Imatinib decreased airway mast-cell counts and airway hyperresponsiveness in adults with asthma, who were not responding well to maximal therapy, according to a report published online May 17 in the New England Journal of Medicine.
Imatinib is an inhibitor of the stem-cell factor receptor KIT, which is essential for mast-cell development and survival in bodily tissues. This study’s findings suggest that KIT-dependent processes and mast cells contribute to the pathobiology of severe asthma.
The researchers undertook this study because imatinib is known to reduce bone-marrow mast cells and tryptase levels in chronic myeloid leukemia and to reduce serum tryptase in patients with pulmonary hypertension. Tryptase is a marker of mast-cell burden and activation when detected in extracellular fluids, and it is elevated in the bronchoalveolar lavage fluid from patients with uncontrolled asthma.
To examine whether imatinib would decrease mast-cell counts and activation in the airways of adults with severe, refractory asthma, the investigators performed the randomized double-blind proof-of-principle trial at seven academic centers across the United States over the course of 5 years. A total of 62 patients were assigned to 24 weeks of either oral imatinib (32 participants) or a matching placebo (30 participants). Fifty patients, 24 in the imatinib group and 26 in the placebo group, completed the trial.
The primary outcome measure was the change in airway hyperresponsiveness at 6 months, as measured by the increase in the concentration of methacholine that causes significant bronchoconstriction (PC20). Imatinib decreased airway hyperresponsiveness to a greater degree than did placebo. Imatinib increased PC20 by a mean of 1.20 doubling doses at 3 months and by a mean of 1.73 doubling doses at 6 months, compared with 0.03 and 1.07, respectively, for placebo.
The small improvement in the placebo group is consistent with a phenomenon reported in other studies, in which patients show a delayed improvement in airway hyperresponsiveness for several months after they started inhaled glucocorticoids, Dr. Cahill and her associates noted (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1613125).
Imatinib also reduced mast-cell activity as measured by serum and airway levels of tryptase. Serum tryptase decreased by 43% in the imatinib group, compared with a 12% decline in the placebo group. And tryptase levels in bronchoalveolar lavage fluid tended to decrease in the imatinib group but to increase in the placebo group.
Imatinib also increased mean forced expiratory volume in 1 second (FEV1).
“Although the increase in FEV1 may not seem substantial, it suggests that mast-cell–dependent processes contribute to airway obstruction in these patients despite high-dose, anti-inflammatory glucocorticoid therapy. The near–50-mL difference in the change in baseline FEV1 between the imatinib and placebo groups is small, but it is likely to be important in light of the population we studied,” Dr. Cahill and her associates wrote.
In addition, exploratory analyses showed that the reduction in airway hyperresponsiveness with imatinib “negatively correlated with baseline blood eosinophil counts, and baseline numbers of neutrophils in bronchoalveolar lavage fluid were strongly correlated with increases in FEV1. Together, these findings support a role for mast cells in noneosinophilic asthma. Since almost half of the patients with severe asthma have neutrophilic airway inflammation, we speculate that KIT inhibition might represent an important approach to treatment for this group,” they said.
This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Vinik family, and the Kaye family; Novartis provided imatinib free of charge. The authors’ financial disclosures are available at www.nejm.org.
Key clinical point: Imatinib, a KIT inhibitor, reduced mast cell counts and airway hyperresponsiveness in severe asthma.
Major finding: Imatinib increased PC20 by a mean of 1.20 doubling doses at 3 months and by a mean of 1.73 doubling doses at 6 months, compared with 0.03 and 1.07, respectively, for placebo.
Data source: A randomized, double-blind, placebo-controlled proof-of-principle trial involving 62 adults treated for 24 weeks.
Disclosures: This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Vinik family, and the Kaye family; Novartis provided imatinib free of charge. The researchers’ financial disclosures are available at www.nejm.org.
Strength plus aerobics equals fitness for obese older adults
Physical performance measures increased by 21% in obese older adults who followed a combination aerobic and resistance exercise routine for weight management, based on data form 141 participants. The findings were published May 17 in the New England Journal of Medicine.
The combination plan scores improved significantly more than either an aerobic exercise or resistance exercise plan (14%), wrote Dennis T. Villareal, MD, professor in the division of diabetes, endocrinology and metabolism at Baylor College of Medicine, Houston, and his colleagues (N Engl J Med. 2017 May 18;376[20]:1943-55).
The researchers randomized 40 adults to each of four interventions: aerobic exercise, resistance exercise, combination aerobic/resistance, and control. A total of 141 participants completed the study, and baseline demographic characteristics were similar among the groups.
Overall, among members of the combination group, scores on the Physical Performance Test showed the greatest increase from baseline to 6 months (from 28 to 33 points), compared with the aerobic group (29 to 33 points) and the resistance group (29 to 33 points).
Peak oxygen consumption was significantly higher at the end of the training period than at baseline in the combination and aerobic groups, compared with the resistance group (with increases of 17%, 18%, and 8% increase, respectively). Strength was significantly higher in the combination and resistance groups than in the aerobic group (18%, 19%, and 4% increase, respectively). Both decreases in both lean body mass and bone mineral density were significantly less in the combination and resistance groups, compared with the aerobic group.
Body weight decreased by approximately 9% from baseline in all three exercise groups, but no significant change was noted in the control group.
Adverse events “were relatively few and consistent with coexisting medical conditions,” the researchers said. Exercise-related adverse events included knee, back, and hip pain in the combination group; falling, shoulder pain, and back pain in the aerobic group; and shoulder pain, knee pain, and atrial fibrillation in the resistance group.
The study was limited in part by factors including the physical ability of the study population, which may not represent obese older adults in general, the researchers said. However, “our findings support that the recommendation by the American Heart Association and American College of Sports Medicine to combine aerobic exercise with resistance exercise for overall health extends to obese older adults undertaking weight loss,” they noted.
The study was supported by grants from the National Institutes of Health. The researchers had no financial conflicts to disclose.
Physical performance measures increased by 21% in obese older adults who followed a combination aerobic and resistance exercise routine for weight management, based on data form 141 participants. The findings were published May 17 in the New England Journal of Medicine.
The combination plan scores improved significantly more than either an aerobic exercise or resistance exercise plan (14%), wrote Dennis T. Villareal, MD, professor in the division of diabetes, endocrinology and metabolism at Baylor College of Medicine, Houston, and his colleagues (N Engl J Med. 2017 May 18;376[20]:1943-55).
The researchers randomized 40 adults to each of four interventions: aerobic exercise, resistance exercise, combination aerobic/resistance, and control. A total of 141 participants completed the study, and baseline demographic characteristics were similar among the groups.
Overall, among members of the combination group, scores on the Physical Performance Test showed the greatest increase from baseline to 6 months (from 28 to 33 points), compared with the aerobic group (29 to 33 points) and the resistance group (29 to 33 points).
Peak oxygen consumption was significantly higher at the end of the training period than at baseline in the combination and aerobic groups, compared with the resistance group (with increases of 17%, 18%, and 8% increase, respectively). Strength was significantly higher in the combination and resistance groups than in the aerobic group (18%, 19%, and 4% increase, respectively). Both decreases in both lean body mass and bone mineral density were significantly less in the combination and resistance groups, compared with the aerobic group.
Body weight decreased by approximately 9% from baseline in all three exercise groups, but no significant change was noted in the control group.
Adverse events “were relatively few and consistent with coexisting medical conditions,” the researchers said. Exercise-related adverse events included knee, back, and hip pain in the combination group; falling, shoulder pain, and back pain in the aerobic group; and shoulder pain, knee pain, and atrial fibrillation in the resistance group.
The study was limited in part by factors including the physical ability of the study population, which may not represent obese older adults in general, the researchers said. However, “our findings support that the recommendation by the American Heart Association and American College of Sports Medicine to combine aerobic exercise with resistance exercise for overall health extends to obese older adults undertaking weight loss,” they noted.
The study was supported by grants from the National Institutes of Health. The researchers had no financial conflicts to disclose.
Physical performance measures increased by 21% in obese older adults who followed a combination aerobic and resistance exercise routine for weight management, based on data form 141 participants. The findings were published May 17 in the New England Journal of Medicine.
The combination plan scores improved significantly more than either an aerobic exercise or resistance exercise plan (14%), wrote Dennis T. Villareal, MD, professor in the division of diabetes, endocrinology and metabolism at Baylor College of Medicine, Houston, and his colleagues (N Engl J Med. 2017 May 18;376[20]:1943-55).
The researchers randomized 40 adults to each of four interventions: aerobic exercise, resistance exercise, combination aerobic/resistance, and control. A total of 141 participants completed the study, and baseline demographic characteristics were similar among the groups.
Overall, among members of the combination group, scores on the Physical Performance Test showed the greatest increase from baseline to 6 months (from 28 to 33 points), compared with the aerobic group (29 to 33 points) and the resistance group (29 to 33 points).
Peak oxygen consumption was significantly higher at the end of the training period than at baseline in the combination and aerobic groups, compared with the resistance group (with increases of 17%, 18%, and 8% increase, respectively). Strength was significantly higher in the combination and resistance groups than in the aerobic group (18%, 19%, and 4% increase, respectively). Both decreases in both lean body mass and bone mineral density were significantly less in the combination and resistance groups, compared with the aerobic group.
Body weight decreased by approximately 9% from baseline in all three exercise groups, but no significant change was noted in the control group.
Adverse events “were relatively few and consistent with coexisting medical conditions,” the researchers said. Exercise-related adverse events included knee, back, and hip pain in the combination group; falling, shoulder pain, and back pain in the aerobic group; and shoulder pain, knee pain, and atrial fibrillation in the resistance group.
The study was limited in part by factors including the physical ability of the study population, which may not represent obese older adults in general, the researchers said. However, “our findings support that the recommendation by the American Heart Association and American College of Sports Medicine to combine aerobic exercise with resistance exercise for overall health extends to obese older adults undertaking weight loss,” they noted.
The study was supported by grants from the National Institutes of Health. The researchers had no financial conflicts to disclose.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Combining aerobic and resistance exercise was significantly more effective for improving physical function in obese older adults.
Major finding: Physical performance test scores improved by 21% from baseline for obese adults in a combination exercise program vs. 14% for those in either an aerobic-only or resistance-only exercise program.
Data source: The data came from a randomized trial of 141 obese adults aged 65 years and older.
Disclosures: The study was supported by grants from the National Institutes of Health. The researchers had no financial conflicts to disclose.
Adalimumab outperforms methotrexate in treating severe pediatric plaque psoriasis
Adalimumab appears to be a safe and effective treatment option for severe plaque psoriasis in children, outperforming methotrexate, based on the results of a phase III study, said Kim Papp, MD, PhD, of Probity Medical Research, Waterloo, Ont., and his associates.
“To our knowledge, this is the first randomized controlled study of either adalimumab or methotrexate in children and adolescents with psoriasis,” the researchers said, noting that the study did not include a placebo group because of ethical issues related to treating children with a severe chronic disorder.
At week 16 of the initial treatment period, an improvement of at least 75% in the Psoriasis Area and Severity Index (PASI75) score was reached by significantly more of the patients in the 0.8 mg/kg adalimumab group – 22 (58%) – than in the methotrexate group – 12 (32%). In the 0.4-mg/kg adalimumab group, 17 (44%) of patients reached a PASI75. The PASI75 response was rapid in the 0.8 mg/kg adalimumab group, a significant difference, compared with the methotrexate group. It was reached by week 4 (P = .002).
“At week 16, the 26% difference between adalimumab 0.8 mg/kg and methotrexate in the proportion of patients who achieved PASI75 was significant and clinically relevant,” Dr. Papp and his associates concluded.
At week 16 of treatment, the proportion of patients who achieved a physician global assessment (PGA) score of 0 or 1 (clear or minimal) was higher in the adalimumab 0.8 mg/kg group (23 of 38 [61%]) than in the methotrexate group (15 of 37 [41%]) or in the adalimumab 0.4-mg/kg group (16 of 39 [41%]) (P = .083). At week 16, the difference between the adalimumab 0.8-mg/kg and methotrexate groups was not significant, the investigators said (Lancet. 2017. doi: 10.1016/ S0140-6736[17]31189-3).
After the withdrawal period, PASI75 was achieved in 15 of 19 (79%) patients who were initial responders to adalimumab 0.8 mg/kg and 6 of 11 (55%) patients who were initial responders to adalimumab 0.4 mg/kg. PASI75 was achieved in six of eight (75%) patients who had responded to methotrexate treatment in the initial treatment period and who had loss of disease control in the withdrawal period.
During the initial treatment period, adverse events were reported by 26 of 38 (68%) in the adalimumab 0.8-mg/kg group, 30 of 39 (77%) in the adalimumab 0.4-mg/kg group, and 28 of 37 (76%) in the methotrexate group. Infections were the most frequently reported adverse events. Serious adverse events were infrequent, reported by three patients in the adalimumab 0.4-mg/kg group, and were not considered to be related to the study drug, the researchers said. Eleven severe adverse events were reported by 8 of the 114 (7%) children. Of these, headache was the most common. A case of urticaria during retreatment that led to discontinuation of adalimumab in the patient (who had received methotrexate in the first treatment period), was considered by the investigator as “probably related” to adalimumab.
“No new safety risks were identified in our study; however, longer-term data are needed to fully assess the safety profile of adalimumab in the pediatric population,” Dr. Papp and his associates commented.
“Our results showed better quality of life outcomes in children and adolescents treated with adalimumab compared with methotrexate. The mean 10.8-point change in PedsQL [pediatric quality of life inventory] from baseline to week 16 in the adalimumab 0.8-mg/kg group exceeded the minimal clinically important difference of 4.36, whereas the 1.9-point change in the methotrexate group did not,” they noted.
The study was funded by AbbVie, the manufacturer of adalimumab (Humira). Dr. Papp has served as a consultant for AbbVie and a number of other pharmaceutical companies, for which he has served as consultant or speaker or on advisory boards. His associates listed numerous similar disclosures. Two authors were AbbVie employees.
The initial treatment response to adalimumab was quick with “significant clinical difference compared with methotrexate seen as early as 4 weeks.” Improvement in the pediatric quality of life inventory (PedsQL) score from baseline “was significantly greater” in children in the adalimumab 0.8-mg/kg group than in children in the methotrexate group. Adalimumab provided “several clinically and statistically significant improvements” in children with severe plaque psoriasis, compared with methotrexate.
However, further studies are needed to determine both the short-term and long-term effectiveness and the safety of systemic treatments in children and adolescents with psoriasis.
Dario Kivelevitch, MD, is a third year dermatology resident, and Alan Menter, MD, is chief of dermatology at Baylor University Medical Center, Dallas. These comments are from an editorial that accompanied the study (Lancet. 2017. doi: 10.1016/ S0140-6736[17]31190-X). Dr. Kivelevitch said he had no relevant financial disclosures. Dr. Menter disclosed grants and personal fees from AbbVie and other pharmaceutical companies, all outside the submitted work.
The initial treatment response to adalimumab was quick with “significant clinical difference compared with methotrexate seen as early as 4 weeks.” Improvement in the pediatric quality of life inventory (PedsQL) score from baseline “was significantly greater” in children in the adalimumab 0.8-mg/kg group than in children in the methotrexate group. Adalimumab provided “several clinically and statistically significant improvements” in children with severe plaque psoriasis, compared with methotrexate.
However, further studies are needed to determine both the short-term and long-term effectiveness and the safety of systemic treatments in children and adolescents with psoriasis.
Dario Kivelevitch, MD, is a third year dermatology resident, and Alan Menter, MD, is chief of dermatology at Baylor University Medical Center, Dallas. These comments are from an editorial that accompanied the study (Lancet. 2017. doi: 10.1016/ S0140-6736[17]31190-X). Dr. Kivelevitch said he had no relevant financial disclosures. Dr. Menter disclosed grants and personal fees from AbbVie and other pharmaceutical companies, all outside the submitted work.
The initial treatment response to adalimumab was quick with “significant clinical difference compared with methotrexate seen as early as 4 weeks.” Improvement in the pediatric quality of life inventory (PedsQL) score from baseline “was significantly greater” in children in the adalimumab 0.8-mg/kg group than in children in the methotrexate group. Adalimumab provided “several clinically and statistically significant improvements” in children with severe plaque psoriasis, compared with methotrexate.
However, further studies are needed to determine both the short-term and long-term effectiveness and the safety of systemic treatments in children and adolescents with psoriasis.
Dario Kivelevitch, MD, is a third year dermatology resident, and Alan Menter, MD, is chief of dermatology at Baylor University Medical Center, Dallas. These comments are from an editorial that accompanied the study (Lancet. 2017. doi: 10.1016/ S0140-6736[17]31190-X). Dr. Kivelevitch said he had no relevant financial disclosures. Dr. Menter disclosed grants and personal fees from AbbVie and other pharmaceutical companies, all outside the submitted work.
Adalimumab appears to be a safe and effective treatment option for severe plaque psoriasis in children, outperforming methotrexate, based on the results of a phase III study, said Kim Papp, MD, PhD, of Probity Medical Research, Waterloo, Ont., and his associates.
“To our knowledge, this is the first randomized controlled study of either adalimumab or methotrexate in children and adolescents with psoriasis,” the researchers said, noting that the study did not include a placebo group because of ethical issues related to treating children with a severe chronic disorder.
At week 16 of the initial treatment period, an improvement of at least 75% in the Psoriasis Area and Severity Index (PASI75) score was reached by significantly more of the patients in the 0.8 mg/kg adalimumab group – 22 (58%) – than in the methotrexate group – 12 (32%). In the 0.4-mg/kg adalimumab group, 17 (44%) of patients reached a PASI75. The PASI75 response was rapid in the 0.8 mg/kg adalimumab group, a significant difference, compared with the methotrexate group. It was reached by week 4 (P = .002).
“At week 16, the 26% difference between adalimumab 0.8 mg/kg and methotrexate in the proportion of patients who achieved PASI75 was significant and clinically relevant,” Dr. Papp and his associates concluded.
At week 16 of treatment, the proportion of patients who achieved a physician global assessment (PGA) score of 0 or 1 (clear or minimal) was higher in the adalimumab 0.8 mg/kg group (23 of 38 [61%]) than in the methotrexate group (15 of 37 [41%]) or in the adalimumab 0.4-mg/kg group (16 of 39 [41%]) (P = .083). At week 16, the difference between the adalimumab 0.8-mg/kg and methotrexate groups was not significant, the investigators said (Lancet. 2017. doi: 10.1016/ S0140-6736[17]31189-3).
After the withdrawal period, PASI75 was achieved in 15 of 19 (79%) patients who were initial responders to adalimumab 0.8 mg/kg and 6 of 11 (55%) patients who were initial responders to adalimumab 0.4 mg/kg. PASI75 was achieved in six of eight (75%) patients who had responded to methotrexate treatment in the initial treatment period and who had loss of disease control in the withdrawal period.
During the initial treatment period, adverse events were reported by 26 of 38 (68%) in the adalimumab 0.8-mg/kg group, 30 of 39 (77%) in the adalimumab 0.4-mg/kg group, and 28 of 37 (76%) in the methotrexate group. Infections were the most frequently reported adverse events. Serious adverse events were infrequent, reported by three patients in the adalimumab 0.4-mg/kg group, and were not considered to be related to the study drug, the researchers said. Eleven severe adverse events were reported by 8 of the 114 (7%) children. Of these, headache was the most common. A case of urticaria during retreatment that led to discontinuation of adalimumab in the patient (who had received methotrexate in the first treatment period), was considered by the investigator as “probably related” to adalimumab.
“No new safety risks were identified in our study; however, longer-term data are needed to fully assess the safety profile of adalimumab in the pediatric population,” Dr. Papp and his associates commented.
“Our results showed better quality of life outcomes in children and adolescents treated with adalimumab compared with methotrexate. The mean 10.8-point change in PedsQL [pediatric quality of life inventory] from baseline to week 16 in the adalimumab 0.8-mg/kg group exceeded the minimal clinically important difference of 4.36, whereas the 1.9-point change in the methotrexate group did not,” they noted.
The study was funded by AbbVie, the manufacturer of adalimumab (Humira). Dr. Papp has served as a consultant for AbbVie and a number of other pharmaceutical companies, for which he has served as consultant or speaker or on advisory boards. His associates listed numerous similar disclosures. Two authors were AbbVie employees.
Adalimumab appears to be a safe and effective treatment option for severe plaque psoriasis in children, outperforming methotrexate, based on the results of a phase III study, said Kim Papp, MD, PhD, of Probity Medical Research, Waterloo, Ont., and his associates.
“To our knowledge, this is the first randomized controlled study of either adalimumab or methotrexate in children and adolescents with psoriasis,” the researchers said, noting that the study did not include a placebo group because of ethical issues related to treating children with a severe chronic disorder.
At week 16 of the initial treatment period, an improvement of at least 75% in the Psoriasis Area and Severity Index (PASI75) score was reached by significantly more of the patients in the 0.8 mg/kg adalimumab group – 22 (58%) – than in the methotrexate group – 12 (32%). In the 0.4-mg/kg adalimumab group, 17 (44%) of patients reached a PASI75. The PASI75 response was rapid in the 0.8 mg/kg adalimumab group, a significant difference, compared with the methotrexate group. It was reached by week 4 (P = .002).
“At week 16, the 26% difference between adalimumab 0.8 mg/kg and methotrexate in the proportion of patients who achieved PASI75 was significant and clinically relevant,” Dr. Papp and his associates concluded.
At week 16 of treatment, the proportion of patients who achieved a physician global assessment (PGA) score of 0 or 1 (clear or minimal) was higher in the adalimumab 0.8 mg/kg group (23 of 38 [61%]) than in the methotrexate group (15 of 37 [41%]) or in the adalimumab 0.4-mg/kg group (16 of 39 [41%]) (P = .083). At week 16, the difference between the adalimumab 0.8-mg/kg and methotrexate groups was not significant, the investigators said (Lancet. 2017. doi: 10.1016/ S0140-6736[17]31189-3).
After the withdrawal period, PASI75 was achieved in 15 of 19 (79%) patients who were initial responders to adalimumab 0.8 mg/kg and 6 of 11 (55%) patients who were initial responders to adalimumab 0.4 mg/kg. PASI75 was achieved in six of eight (75%) patients who had responded to methotrexate treatment in the initial treatment period and who had loss of disease control in the withdrawal period.
During the initial treatment period, adverse events were reported by 26 of 38 (68%) in the adalimumab 0.8-mg/kg group, 30 of 39 (77%) in the adalimumab 0.4-mg/kg group, and 28 of 37 (76%) in the methotrexate group. Infections were the most frequently reported adverse events. Serious adverse events were infrequent, reported by three patients in the adalimumab 0.4-mg/kg group, and were not considered to be related to the study drug, the researchers said. Eleven severe adverse events were reported by 8 of the 114 (7%) children. Of these, headache was the most common. A case of urticaria during retreatment that led to discontinuation of adalimumab in the patient (who had received methotrexate in the first treatment period), was considered by the investigator as “probably related” to adalimumab.
“No new safety risks were identified in our study; however, longer-term data are needed to fully assess the safety profile of adalimumab in the pediatric population,” Dr. Papp and his associates commented.
“Our results showed better quality of life outcomes in children and adolescents treated with adalimumab compared with methotrexate. The mean 10.8-point change in PedsQL [pediatric quality of life inventory] from baseline to week 16 in the adalimumab 0.8-mg/kg group exceeded the minimal clinically important difference of 4.36, whereas the 1.9-point change in the methotrexate group did not,” they noted.
The study was funded by AbbVie, the manufacturer of adalimumab (Humira). Dr. Papp has served as a consultant for AbbVie and a number of other pharmaceutical companies, for which he has served as consultant or speaker or on advisory boards. His associates listed numerous similar disclosures. Two authors were AbbVie employees.
FROM THE LANCET
Key clinical point:
Major finding: At week 16 of the initial treatment period, Psoriasis Area and Severity Index (PASI)175 was reached by significantly more of the patients in the 0.8 mg/kg adalimumab group (22 of 38 [58%]) than in the methotrexate group (12 of 37 [32%]).
Data source: A double-blind, phase III trial was done at 38 clinics in 13 countries with 114 children aged 4-17 years, with severe plaque psoriasis that had not responded to topical therapy.
Disclosures: The study was funded by AbbVie. Dr. Papp has served as a consultant for adalimumab manufacturer AbbVie and a number of other pharmaceutical companies for which he has served as consultant or speaker or on advisory boards. His associates listed numerous similar disclosures. Two authors were AbbVie employees.
HPV vaccine training video improved provider knowledge, confidence
SAN FRANCISCO – Showing pediatric providers a 22-minute online training video about the human papillomavirus (HPV) vaccine and how to counsel families on it improved the providers’ knowledge, attitudes, and confidence in recommending the vaccine, according to a study.
“This video may be a cost-effective way to train providers across the nation to strongly recommend the HPV vaccine, which may ultimately impact vaccination rates,” lead author Maya Kumar, MD, of the University of California, San Diego, said at the Pediatric Academic Societies meeting.
Previous research has shown that one of the biggest obstacles to uptake of the HPV vaccine is the lack of a strong provider recommendation.
“Common reasons for this include inadequate knowledge of the impact of HPV-related disease, perceptions that the vaccine is less important for preteens or less important for boys, and discomfort with addressing parental concerns about the vaccine,” explained Dr. Kumar.
She therefore wanted to see whether a video addressing these concerns and knowledge gaps would improve providers’ knowledge, confidence, and their likelihood of strongly recommending the HPV vaccine to their clients.
The AAP California Chapter 3 created a 22-minute video that explains the burden of HPV-related disease, provides general information about the vaccine, and reviews common provider-related obstacles to vaccination (although not patient-related or systemic barriers). Then the video provides counseling strategies to help providers in improving HPV vaccine uptake at their clinic. Following the discussion of those strategies are eight clinical vignettes in which experienced pediatricians model those techniques with “patients” and “parents” played by actors.
The researchers then showed the video to 109 providers from four large pediatric practices in San Diego and the San Diego Immunization Coalition. The group included 47% of pediatricians and nurse practitioners, 25% of allied health professionals, 20% nurses and 7% of trainees.
Before viewing, the providers filled out a questionnaire assessing their knowledge and attitude toward the HPV vaccine and how they perceived their skill in recommending the vaccine. Then they filled out the same questionnaire after viewing the video.
Providers’ correct answers to questions on their knowledge about the vaccine all increased substantially after viewing the video. The biggest improvement was seen in response to the question about whether the vaccine’s efficacy changes with age. Before viewing the video, 49% of the providers knew that the immune response to the vaccine was stronger among younger recipients and that its efficacy dropped off as people reach their mid-20s. After seeing the video, 89% of providers correctly answered that question (P less than .01).
Another substantial improvement occurred for the question about HPV-related cancers’ prevalence in men. Before the video, 37% of providers answered correctly that a large proportion of these cancers do occur in men; after the video, 67% answered correctly (P less than .01).
The proportion of providers who correctly responded that HPV infects the majority of sexually active people increased from 85% to 90%. Similarly, those who knew HPV catch-up vaccination can be offered up until age 26 years increased from 88% to 96%, and those who knew HPV-related cancer is more prevalent than meningococcal disease increased from 91% to 97% (P less than .01 for all of these). The increase in providers who knew HPV infects the majority of sexually active people, from 85% to 97%, was the only one that didn’t reach statistical significance.
Similar improvements were seen in providers’ attitudes after viewing the video. On a Likert scale of 1 (strongly disagree) to 5 (strongly agree), statistically significant increases occurred for responding to whether it’s important to vaccinate girls against HPV (.07 increase) and the importance of the HPV vaccine for cancer protection rather than wart protection (.22 increase).
Likewise, statistically significant decreases occurred for whether it’s acceptable to delay the vaccine for a child before sexual debut (–0.38), whether it’s more important to give the Tdap and meningococcal vaccines than the HPV vaccines (–0.44), and whether the provider is concerned about short-term (–0.20) or long-term (–0.12) side effects of the vaccine.
Every one of the questions about providers’ skills improved statistically significantly, from increases of 0.19 to 0.66 points:
• Making a strong recommendation for the HPV vaccine.
• Discussing HPV vaccination again with a family who has previously declined it.
• Facilitating completion of a three-dose vaccine series once initiated.
• Presenting the HPV vaccine as a cancer-prevention vaccine.
• Addressing parental concerns about safety and side effects.
• Addressing parental concerns about HPV being sexually transmitted and the need to vaccinate before sexual debut.
• Counseling about the need to routinely vaccinate boys against HPV.
• Counseling about the rationale for routinely giving the HPV vaccine at age 11-12 years.
“There was positive feedback from the viewing providers, particularly about the use of clinical vignettes to model effective counseling strategies for recommending vaccination,” Dr. Kumar said.
She acknowledged that the results may not be generalizable to providers in other regions, and the study was unable to assess whether providers’ actual behavior or practice vaccination rates changed after viewing the video.
The study was funded by an American Academy of Pediatrics Adolescent Vaccinations and Wellness Education Grant, supported by Merck. Dr. Kumar had no relevant financial disclosures.
SAN FRANCISCO – Showing pediatric providers a 22-minute online training video about the human papillomavirus (HPV) vaccine and how to counsel families on it improved the providers’ knowledge, attitudes, and confidence in recommending the vaccine, according to a study.
“This video may be a cost-effective way to train providers across the nation to strongly recommend the HPV vaccine, which may ultimately impact vaccination rates,” lead author Maya Kumar, MD, of the University of California, San Diego, said at the Pediatric Academic Societies meeting.
Previous research has shown that one of the biggest obstacles to uptake of the HPV vaccine is the lack of a strong provider recommendation.
“Common reasons for this include inadequate knowledge of the impact of HPV-related disease, perceptions that the vaccine is less important for preteens or less important for boys, and discomfort with addressing parental concerns about the vaccine,” explained Dr. Kumar.
She therefore wanted to see whether a video addressing these concerns and knowledge gaps would improve providers’ knowledge, confidence, and their likelihood of strongly recommending the HPV vaccine to their clients.
The AAP California Chapter 3 created a 22-minute video that explains the burden of HPV-related disease, provides general information about the vaccine, and reviews common provider-related obstacles to vaccination (although not patient-related or systemic barriers). Then the video provides counseling strategies to help providers in improving HPV vaccine uptake at their clinic. Following the discussion of those strategies are eight clinical vignettes in which experienced pediatricians model those techniques with “patients” and “parents” played by actors.
The researchers then showed the video to 109 providers from four large pediatric practices in San Diego and the San Diego Immunization Coalition. The group included 47% of pediatricians and nurse practitioners, 25% of allied health professionals, 20% nurses and 7% of trainees.
Before viewing, the providers filled out a questionnaire assessing their knowledge and attitude toward the HPV vaccine and how they perceived their skill in recommending the vaccine. Then they filled out the same questionnaire after viewing the video.
Providers’ correct answers to questions on their knowledge about the vaccine all increased substantially after viewing the video. The biggest improvement was seen in response to the question about whether the vaccine’s efficacy changes with age. Before viewing the video, 49% of the providers knew that the immune response to the vaccine was stronger among younger recipients and that its efficacy dropped off as people reach their mid-20s. After seeing the video, 89% of providers correctly answered that question (P less than .01).
Another substantial improvement occurred for the question about HPV-related cancers’ prevalence in men. Before the video, 37% of providers answered correctly that a large proportion of these cancers do occur in men; after the video, 67% answered correctly (P less than .01).
The proportion of providers who correctly responded that HPV infects the majority of sexually active people increased from 85% to 90%. Similarly, those who knew HPV catch-up vaccination can be offered up until age 26 years increased from 88% to 96%, and those who knew HPV-related cancer is more prevalent than meningococcal disease increased from 91% to 97% (P less than .01 for all of these). The increase in providers who knew HPV infects the majority of sexually active people, from 85% to 97%, was the only one that didn’t reach statistical significance.
Similar improvements were seen in providers’ attitudes after viewing the video. On a Likert scale of 1 (strongly disagree) to 5 (strongly agree), statistically significant increases occurred for responding to whether it’s important to vaccinate girls against HPV (.07 increase) and the importance of the HPV vaccine for cancer protection rather than wart protection (.22 increase).
Likewise, statistically significant decreases occurred for whether it’s acceptable to delay the vaccine for a child before sexual debut (–0.38), whether it’s more important to give the Tdap and meningococcal vaccines than the HPV vaccines (–0.44), and whether the provider is concerned about short-term (–0.20) or long-term (–0.12) side effects of the vaccine.
Every one of the questions about providers’ skills improved statistically significantly, from increases of 0.19 to 0.66 points:
• Making a strong recommendation for the HPV vaccine.
• Discussing HPV vaccination again with a family who has previously declined it.
• Facilitating completion of a three-dose vaccine series once initiated.
• Presenting the HPV vaccine as a cancer-prevention vaccine.
• Addressing parental concerns about safety and side effects.
• Addressing parental concerns about HPV being sexually transmitted and the need to vaccinate before sexual debut.
• Counseling about the need to routinely vaccinate boys against HPV.
• Counseling about the rationale for routinely giving the HPV vaccine at age 11-12 years.
“There was positive feedback from the viewing providers, particularly about the use of clinical vignettes to model effective counseling strategies for recommending vaccination,” Dr. Kumar said.
She acknowledged that the results may not be generalizable to providers in other regions, and the study was unable to assess whether providers’ actual behavior or practice vaccination rates changed after viewing the video.
The study was funded by an American Academy of Pediatrics Adolescent Vaccinations and Wellness Education Grant, supported by Merck. Dr. Kumar had no relevant financial disclosures.
SAN FRANCISCO – Showing pediatric providers a 22-minute online training video about the human papillomavirus (HPV) vaccine and how to counsel families on it improved the providers’ knowledge, attitudes, and confidence in recommending the vaccine, according to a study.
“This video may be a cost-effective way to train providers across the nation to strongly recommend the HPV vaccine, which may ultimately impact vaccination rates,” lead author Maya Kumar, MD, of the University of California, San Diego, said at the Pediatric Academic Societies meeting.
Previous research has shown that one of the biggest obstacles to uptake of the HPV vaccine is the lack of a strong provider recommendation.
“Common reasons for this include inadequate knowledge of the impact of HPV-related disease, perceptions that the vaccine is less important for preteens or less important for boys, and discomfort with addressing parental concerns about the vaccine,” explained Dr. Kumar.
She therefore wanted to see whether a video addressing these concerns and knowledge gaps would improve providers’ knowledge, confidence, and their likelihood of strongly recommending the HPV vaccine to their clients.
The AAP California Chapter 3 created a 22-minute video that explains the burden of HPV-related disease, provides general information about the vaccine, and reviews common provider-related obstacles to vaccination (although not patient-related or systemic barriers). Then the video provides counseling strategies to help providers in improving HPV vaccine uptake at their clinic. Following the discussion of those strategies are eight clinical vignettes in which experienced pediatricians model those techniques with “patients” and “parents” played by actors.
The researchers then showed the video to 109 providers from four large pediatric practices in San Diego and the San Diego Immunization Coalition. The group included 47% of pediatricians and nurse practitioners, 25% of allied health professionals, 20% nurses and 7% of trainees.
Before viewing, the providers filled out a questionnaire assessing their knowledge and attitude toward the HPV vaccine and how they perceived their skill in recommending the vaccine. Then they filled out the same questionnaire after viewing the video.
Providers’ correct answers to questions on their knowledge about the vaccine all increased substantially after viewing the video. The biggest improvement was seen in response to the question about whether the vaccine’s efficacy changes with age. Before viewing the video, 49% of the providers knew that the immune response to the vaccine was stronger among younger recipients and that its efficacy dropped off as people reach their mid-20s. After seeing the video, 89% of providers correctly answered that question (P less than .01).
Another substantial improvement occurred for the question about HPV-related cancers’ prevalence in men. Before the video, 37% of providers answered correctly that a large proportion of these cancers do occur in men; after the video, 67% answered correctly (P less than .01).
The proportion of providers who correctly responded that HPV infects the majority of sexually active people increased from 85% to 90%. Similarly, those who knew HPV catch-up vaccination can be offered up until age 26 years increased from 88% to 96%, and those who knew HPV-related cancer is more prevalent than meningococcal disease increased from 91% to 97% (P less than .01 for all of these). The increase in providers who knew HPV infects the majority of sexually active people, from 85% to 97%, was the only one that didn’t reach statistical significance.
Similar improvements were seen in providers’ attitudes after viewing the video. On a Likert scale of 1 (strongly disagree) to 5 (strongly agree), statistically significant increases occurred for responding to whether it’s important to vaccinate girls against HPV (.07 increase) and the importance of the HPV vaccine for cancer protection rather than wart protection (.22 increase).
Likewise, statistically significant decreases occurred for whether it’s acceptable to delay the vaccine for a child before sexual debut (–0.38), whether it’s more important to give the Tdap and meningococcal vaccines than the HPV vaccines (–0.44), and whether the provider is concerned about short-term (–0.20) or long-term (–0.12) side effects of the vaccine.
Every one of the questions about providers’ skills improved statistically significantly, from increases of 0.19 to 0.66 points:
• Making a strong recommendation for the HPV vaccine.
• Discussing HPV vaccination again with a family who has previously declined it.
• Facilitating completion of a three-dose vaccine series once initiated.
• Presenting the HPV vaccine as a cancer-prevention vaccine.
• Addressing parental concerns about safety and side effects.
• Addressing parental concerns about HPV being sexually transmitted and the need to vaccinate before sexual debut.
• Counseling about the need to routinely vaccinate boys against HPV.
• Counseling about the rationale for routinely giving the HPV vaccine at age 11-12 years.
“There was positive feedback from the viewing providers, particularly about the use of clinical vignettes to model effective counseling strategies for recommending vaccination,” Dr. Kumar said.
She acknowledged that the results may not be generalizable to providers in other regions, and the study was unable to assess whether providers’ actual behavior or practice vaccination rates changed after viewing the video.
The study was funded by an American Academy of Pediatrics Adolescent Vaccinations and Wellness Education Grant, supported by Merck. Dr. Kumar had no relevant financial disclosures.
Key clinical point:
Major finding: Statistically significant improvements occurred among providers for five questions on HPV vaccine knowledge, six questions about attitudes toward the vaccine, and all eight questions concerning self-assessed skills in counseling families about the vaccine.
Data source: The findings are based on a cohort of 109 California pediatric providers whose knowledge, attitudes, and self-reported skills were assessed before and after the intervention.
Disclosures: The study was funded by an American Academy of Pediatrics Adolescent Vaccinations and Wellness Education Grant, supported by Merck. Dr. Kumar had no relevant financial disclosures.
FDA: Some blood lead tests have reported falsely low levels since 2014
The Food and Drug Administration is recommending repeat lead testing of young children and at-risk women who were tested via a venous blood sample. The recommendation was issued May 17 after the agency discovered a probable 3-year history of inaccurate tests by the nation’s largest lead test distributor.
The tests should be repeated with a capillary sample in children younger than 6 years of age as of May 17, and all pregnant or breastfeeding women who had a lead level of 10 mcg/dL or lower in a venous blood draw tested with any system made by Magellan Diagnostics, FDA representatives said during at a press briefing.
“We do have evidence of a problem with falsely lower lead reading with venous blood,” said Dr. Shuren, director of the FDA Center for Devices and Radiological Health. “Based on the information we have now, we don’t know how often we see this inaccuracy in samples, or how much lower it is. There is a wide variation and a small amount of data. We need to do further testing to see how big the problem is and the root cause. However, we do have enough data to be confident that we don’t have the problem in capillary blood.”
The warning includes all tests run on four of Magellan Diagnostics’ lead testing systems: LeadCare; LeadCare II; LeadCare Plus; and LeadCare Ultra. All LeadCare systems can be used with blood from a finger or heel stick, including the LeadCare II system – one found in many doctors’ offices and clinics. In addition, some laboratories offer other methods of lead testing, which are not now believed to be affected.
At this point, Magellan isn’t required to pay for any retesting. Tim Hill, acting director of the Center for Medicaid and CHIP Services, who was also on the call, confirmed that retesting will be covered for Medicaid and CHIP recipients. Patients with private insurance will have to contact their insurance companies to ascertain coverage, he said.
“Our first priority is to be sure folks get retested through our programs,” Mr. Hill said during the briefing. “We don’t want reimbursement to hold up the retesting. My understanding is that talks with Magellan with regard to their liability are ongoing.”
Regulators discovered the extent of the problem in March, after Magellan submitted a 510(k) premarket notification for a new iteration of its point-of-care test, FDA spokesperson Tara Goodin said in an interview. The new product was based on a kit approved in 2013, so all tests run on venous blood since then are in question.
During the data review, FDA discovered that customers began complaining to Magellan about inaccurate results on venous blood in 2014. Magellan issued three customer notifications letters (primarily to laboratories) alerting them to testing inaccuracies and recommending mitigations designed to address them. These customer notifications were issued on Nov. 24, 2014; Nov. 4, 2016; and April 28, 2017. In these, the company indicated that about 2.5% of patients whose tests were below the level of medical concern could actually have enough lead to warrant intervention. Magellan suggested that the problem could be solved by holding all samples for 24 hours before mixing them with the reagent – a step the company said would reduce risk of a misread to zero.
Regulators disagreed, Ms. Goodin said.
“Based on available information, the FDA believes that Magellan should have determined that the risk of an inaccurate test result and the number of people that could be adversely affected was much higher than they estimated and that their mitigation might not be adequate to address the increased risk. Instead, the company submitted a malfunction report in 2015 related to an observed increased frequency of falsely low test results in the LeadCare Ultra system that the firm indicated it first identified through the August 2014 complaint.”
In the malfunction report, the company characterized this issue as a Class III recall, which the FDA defines as a situation in which use of or exposure to a violative product is not likely to cause adverse health consequences.
The scope of the problem became apparent only after Magellan submitted its 510(k) paperwork in March, Ms. Goodin said.
“After reviewing initial data available from Magellan on these inaccuracies and their mitigations, the FDA was unable to identify the root cause of the inaccuracies, the frequency and extent of the inaccuracies, or to confirm that the mitigations are effective. While the FDA’s investigation is in its early stages, we did not want to delay warning health care professionals and laboratories about the risk of testing inaccuracies and encouraging parents and at-risk adults to follow the CDC’s recommendations.”
As soon as FDA identified the issue as a potential public health risk, it began working with the Centers for Medicare & Medicaid Services to issue recommendations for laboratories, health care professionals, and at-risk individuals.
“The FDA prioritized communicating to the public about this issue but is also aggressively investigating this issue to determine the cause of the inaccurate results and will provide updates as more is learned,” Ms. Goodin said. “This includes reviewing data provided by the company, requesting additional information from Magellan regarding the issue, and inspecting the company’s facility. The FDA has also requested an independent analysis of the test. We are aggressively investigating this issue and have already sent staff to inspect Magellan’s facility.”
Phone calls to Magellan for clarification on its mitigation procedures, the potential impact on customers, and the history of the LeadCare series’ approvals were not returned at press time, and the company had no prepared statement. A safety communication was posted to its website.
Since 2014, Magellan has run 8 million blood lead tests. Based on the company’s 2.5% estimate of misreads, 200,000 patients tested with the kit could have dangerously high blood lead levels. Currently, the FDA has no official estimate of how many tests were run on venous blood, how many of those returned inaccurate results, or even what caused the tests to read out with falsely low levels, Dr. Shuren said.
“We are investigating the cause, however when [Magellan’s prior test kits] came on the market, there was data supporting their accuracy. The root cause of this, we don’t know. It may not be specific to the test; it may have to do with the tubes, the reactions with chemicals, the way it’s processed. We are looking into all [of] these.”
On Twitter @Alz_gal
The Food and Drug Administration is recommending repeat lead testing of young children and at-risk women who were tested via a venous blood sample. The recommendation was issued May 17 after the agency discovered a probable 3-year history of inaccurate tests by the nation’s largest lead test distributor.
The tests should be repeated with a capillary sample in children younger than 6 years of age as of May 17, and all pregnant or breastfeeding women who had a lead level of 10 mcg/dL or lower in a venous blood draw tested with any system made by Magellan Diagnostics, FDA representatives said during at a press briefing.
“We do have evidence of a problem with falsely lower lead reading with venous blood,” said Dr. Shuren, director of the FDA Center for Devices and Radiological Health. “Based on the information we have now, we don’t know how often we see this inaccuracy in samples, or how much lower it is. There is a wide variation and a small amount of data. We need to do further testing to see how big the problem is and the root cause. However, we do have enough data to be confident that we don’t have the problem in capillary blood.”
The warning includes all tests run on four of Magellan Diagnostics’ lead testing systems: LeadCare; LeadCare II; LeadCare Plus; and LeadCare Ultra. All LeadCare systems can be used with blood from a finger or heel stick, including the LeadCare II system – one found in many doctors’ offices and clinics. In addition, some laboratories offer other methods of lead testing, which are not now believed to be affected.
At this point, Magellan isn’t required to pay for any retesting. Tim Hill, acting director of the Center for Medicaid and CHIP Services, who was also on the call, confirmed that retesting will be covered for Medicaid and CHIP recipients. Patients with private insurance will have to contact their insurance companies to ascertain coverage, he said.
“Our first priority is to be sure folks get retested through our programs,” Mr. Hill said during the briefing. “We don’t want reimbursement to hold up the retesting. My understanding is that talks with Magellan with regard to their liability are ongoing.”
Regulators discovered the extent of the problem in March, after Magellan submitted a 510(k) premarket notification for a new iteration of its point-of-care test, FDA spokesperson Tara Goodin said in an interview. The new product was based on a kit approved in 2013, so all tests run on venous blood since then are in question.
During the data review, FDA discovered that customers began complaining to Magellan about inaccurate results on venous blood in 2014. Magellan issued three customer notifications letters (primarily to laboratories) alerting them to testing inaccuracies and recommending mitigations designed to address them. These customer notifications were issued on Nov. 24, 2014; Nov. 4, 2016; and April 28, 2017. In these, the company indicated that about 2.5% of patients whose tests were below the level of medical concern could actually have enough lead to warrant intervention. Magellan suggested that the problem could be solved by holding all samples for 24 hours before mixing them with the reagent – a step the company said would reduce risk of a misread to zero.
Regulators disagreed, Ms. Goodin said.
“Based on available information, the FDA believes that Magellan should have determined that the risk of an inaccurate test result and the number of people that could be adversely affected was much higher than they estimated and that their mitigation might not be adequate to address the increased risk. Instead, the company submitted a malfunction report in 2015 related to an observed increased frequency of falsely low test results in the LeadCare Ultra system that the firm indicated it first identified through the August 2014 complaint.”
In the malfunction report, the company characterized this issue as a Class III recall, which the FDA defines as a situation in which use of or exposure to a violative product is not likely to cause adverse health consequences.
The scope of the problem became apparent only after Magellan submitted its 510(k) paperwork in March, Ms. Goodin said.
“After reviewing initial data available from Magellan on these inaccuracies and their mitigations, the FDA was unable to identify the root cause of the inaccuracies, the frequency and extent of the inaccuracies, or to confirm that the mitigations are effective. While the FDA’s investigation is in its early stages, we did not want to delay warning health care professionals and laboratories about the risk of testing inaccuracies and encouraging parents and at-risk adults to follow the CDC’s recommendations.”
As soon as FDA identified the issue as a potential public health risk, it began working with the Centers for Medicare & Medicaid Services to issue recommendations for laboratories, health care professionals, and at-risk individuals.
“The FDA prioritized communicating to the public about this issue but is also aggressively investigating this issue to determine the cause of the inaccurate results and will provide updates as more is learned,” Ms. Goodin said. “This includes reviewing data provided by the company, requesting additional information from Magellan regarding the issue, and inspecting the company’s facility. The FDA has also requested an independent analysis of the test. We are aggressively investigating this issue and have already sent staff to inspect Magellan’s facility.”
Phone calls to Magellan for clarification on its mitigation procedures, the potential impact on customers, and the history of the LeadCare series’ approvals were not returned at press time, and the company had no prepared statement. A safety communication was posted to its website.
Since 2014, Magellan has run 8 million blood lead tests. Based on the company’s 2.5% estimate of misreads, 200,000 patients tested with the kit could have dangerously high blood lead levels. Currently, the FDA has no official estimate of how many tests were run on venous blood, how many of those returned inaccurate results, or even what caused the tests to read out with falsely low levels, Dr. Shuren said.
“We are investigating the cause, however when [Magellan’s prior test kits] came on the market, there was data supporting their accuracy. The root cause of this, we don’t know. It may not be specific to the test; it may have to do with the tubes, the reactions with chemicals, the way it’s processed. We are looking into all [of] these.”
On Twitter @Alz_gal
The Food and Drug Administration is recommending repeat lead testing of young children and at-risk women who were tested via a venous blood sample. The recommendation was issued May 17 after the agency discovered a probable 3-year history of inaccurate tests by the nation’s largest lead test distributor.
The tests should be repeated with a capillary sample in children younger than 6 years of age as of May 17, and all pregnant or breastfeeding women who had a lead level of 10 mcg/dL or lower in a venous blood draw tested with any system made by Magellan Diagnostics, FDA representatives said during at a press briefing.
“We do have evidence of a problem with falsely lower lead reading with venous blood,” said Dr. Shuren, director of the FDA Center for Devices and Radiological Health. “Based on the information we have now, we don’t know how often we see this inaccuracy in samples, or how much lower it is. There is a wide variation and a small amount of data. We need to do further testing to see how big the problem is and the root cause. However, we do have enough data to be confident that we don’t have the problem in capillary blood.”
The warning includes all tests run on four of Magellan Diagnostics’ lead testing systems: LeadCare; LeadCare II; LeadCare Plus; and LeadCare Ultra. All LeadCare systems can be used with blood from a finger or heel stick, including the LeadCare II system – one found in many doctors’ offices and clinics. In addition, some laboratories offer other methods of lead testing, which are not now believed to be affected.
At this point, Magellan isn’t required to pay for any retesting. Tim Hill, acting director of the Center for Medicaid and CHIP Services, who was also on the call, confirmed that retesting will be covered for Medicaid and CHIP recipients. Patients with private insurance will have to contact their insurance companies to ascertain coverage, he said.
“Our first priority is to be sure folks get retested through our programs,” Mr. Hill said during the briefing. “We don’t want reimbursement to hold up the retesting. My understanding is that talks with Magellan with regard to their liability are ongoing.”
Regulators discovered the extent of the problem in March, after Magellan submitted a 510(k) premarket notification for a new iteration of its point-of-care test, FDA spokesperson Tara Goodin said in an interview. The new product was based on a kit approved in 2013, so all tests run on venous blood since then are in question.
During the data review, FDA discovered that customers began complaining to Magellan about inaccurate results on venous blood in 2014. Magellan issued three customer notifications letters (primarily to laboratories) alerting them to testing inaccuracies and recommending mitigations designed to address them. These customer notifications were issued on Nov. 24, 2014; Nov. 4, 2016; and April 28, 2017. In these, the company indicated that about 2.5% of patients whose tests were below the level of medical concern could actually have enough lead to warrant intervention. Magellan suggested that the problem could be solved by holding all samples for 24 hours before mixing them with the reagent – a step the company said would reduce risk of a misread to zero.
Regulators disagreed, Ms. Goodin said.
“Based on available information, the FDA believes that Magellan should have determined that the risk of an inaccurate test result and the number of people that could be adversely affected was much higher than they estimated and that their mitigation might not be adequate to address the increased risk. Instead, the company submitted a malfunction report in 2015 related to an observed increased frequency of falsely low test results in the LeadCare Ultra system that the firm indicated it first identified through the August 2014 complaint.”
In the malfunction report, the company characterized this issue as a Class III recall, which the FDA defines as a situation in which use of or exposure to a violative product is not likely to cause adverse health consequences.
The scope of the problem became apparent only after Magellan submitted its 510(k) paperwork in March, Ms. Goodin said.
“After reviewing initial data available from Magellan on these inaccuracies and their mitigations, the FDA was unable to identify the root cause of the inaccuracies, the frequency and extent of the inaccuracies, or to confirm that the mitigations are effective. While the FDA’s investigation is in its early stages, we did not want to delay warning health care professionals and laboratories about the risk of testing inaccuracies and encouraging parents and at-risk adults to follow the CDC’s recommendations.”
As soon as FDA identified the issue as a potential public health risk, it began working with the Centers for Medicare & Medicaid Services to issue recommendations for laboratories, health care professionals, and at-risk individuals.
“The FDA prioritized communicating to the public about this issue but is also aggressively investigating this issue to determine the cause of the inaccurate results and will provide updates as more is learned,” Ms. Goodin said. “This includes reviewing data provided by the company, requesting additional information from Magellan regarding the issue, and inspecting the company’s facility. The FDA has also requested an independent analysis of the test. We are aggressively investigating this issue and have already sent staff to inspect Magellan’s facility.”
Phone calls to Magellan for clarification on its mitigation procedures, the potential impact on customers, and the history of the LeadCare series’ approvals were not returned at press time, and the company had no prepared statement. A safety communication was posted to its website.
Since 2014, Magellan has run 8 million blood lead tests. Based on the company’s 2.5% estimate of misreads, 200,000 patients tested with the kit could have dangerously high blood lead levels. Currently, the FDA has no official estimate of how many tests were run on venous blood, how many of those returned inaccurate results, or even what caused the tests to read out with falsely low levels, Dr. Shuren said.
“We are investigating the cause, however when [Magellan’s prior test kits] came on the market, there was data supporting their accuracy. The root cause of this, we don’t know. It may not be specific to the test; it may have to do with the tubes, the reactions with chemicals, the way it’s processed. We are looking into all [of] these.”
On Twitter @Alz_gal
AGA recognizes 52 investigators with research funding
The AGA Research Foundation is thrilled to award 52 researchers with research funding in the 2017 award year.
“The AGA Research Foundation has a proven track record of funding young investigators who subsequently achieve great success in research. We are confident that the 2017 class will be no exception,” said Robert S. Sandler, MD, MPH, AGAF, chair, AGA Research Foundation. “AGA is honored to invest in this year’s award recipients and looks forward to seeing how each research project contributes to advancing the field of gastroenterology.”
The AGA Research Award Program serves to support talented investigators who are pursuing careers in digestive disease research. A grant from the AGA Research Foundation ensures that a major proportion of the recipient’s time is protected for research.
The awards program is made possible thanks to generous donors and funders contributing to the AGA Research Foundation. Show your support for GI research.
To learn about upcoming research funding opportunities, and to view the list of this years’ winners, visit www.gastro.org/awards.
This year’s honorees were recognized during several AGA Research Foundation events at Digestive Disease Week® 2017, which took place May 6-9 in Chicago, IL.
The AGA Research Foundation is thrilled to award 52 researchers with research funding in the 2017 award year.
“The AGA Research Foundation has a proven track record of funding young investigators who subsequently achieve great success in research. We are confident that the 2017 class will be no exception,” said Robert S. Sandler, MD, MPH, AGAF, chair, AGA Research Foundation. “AGA is honored to invest in this year’s award recipients and looks forward to seeing how each research project contributes to advancing the field of gastroenterology.”
The AGA Research Award Program serves to support talented investigators who are pursuing careers in digestive disease research. A grant from the AGA Research Foundation ensures that a major proportion of the recipient’s time is protected for research.
The awards program is made possible thanks to generous donors and funders contributing to the AGA Research Foundation. Show your support for GI research.
To learn about upcoming research funding opportunities, and to view the list of this years’ winners, visit www.gastro.org/awards.
This year’s honorees were recognized during several AGA Research Foundation events at Digestive Disease Week® 2017, which took place May 6-9 in Chicago, IL.
The AGA Research Foundation is thrilled to award 52 researchers with research funding in the 2017 award year.
“The AGA Research Foundation has a proven track record of funding young investigators who subsequently achieve great success in research. We are confident that the 2017 class will be no exception,” said Robert S. Sandler, MD, MPH, AGAF, chair, AGA Research Foundation. “AGA is honored to invest in this year’s award recipients and looks forward to seeing how each research project contributes to advancing the field of gastroenterology.”
The AGA Research Award Program serves to support talented investigators who are pursuing careers in digestive disease research. A grant from the AGA Research Foundation ensures that a major proportion of the recipient’s time is protected for research.
The awards program is made possible thanks to generous donors and funders contributing to the AGA Research Foundation. Show your support for GI research.
To learn about upcoming research funding opportunities, and to view the list of this years’ winners, visit www.gastro.org/awards.
This year’s honorees were recognized during several AGA Research Foundation events at Digestive Disease Week® 2017, which took place May 6-9 in Chicago, IL.