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Brodalumab raced past ustekinumab to PASI 100
PARIS – The interleukin-17 receptor inhibitor
That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.
“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.
Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.
“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”
His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.
It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.
This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.
Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.
The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.
Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.
SOURCE: Reich K. EADV Congress, Abstract #FC03.06.
PARIS – The interleukin-17 receptor inhibitor
That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.
“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.
Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.
“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”
His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.
It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.
This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.
Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.
The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.
Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.
SOURCE: Reich K. EADV Congress, Abstract #FC03.06.
PARIS – The interleukin-17 receptor inhibitor
That’s according to a post hoc pooled analysis of the phase 3 randomized AMAGINE-1 and -3 trials that Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Other interleukin-17 inhibitors have also outperformed ustekinumab (Stelara) in head-to-head, randomized trials. What’s unique about this new secondary analysis of the AMAGINE trials is the demonstration that the complete clearance rate – that is, 100% improvement in Psoriasis Area and Severity Index (PASI) – with brodalumab (Siliq) was consistent, regardless of a psoriasis patient’s prior treatment history, according to Dr. Reich, professor of dermatology at Georg-August-University in Göttingen, Germany, and a partner at the Dermatologikum Hamburg.
“I don’t want to niche brodalumab as a rescue drug; but if you need a response in a patient who has failed a biologic, then obviously, this is a pretty good choice,” he said.
Typically, psoriasis patients who have previously failed to respond favorably to a biologic agent have a substantially lower complete clearance rate when placed on another biologic than do those who are biologic naive or haven’t been on a nonbiologic systemic therapy.
“I think it’s interesting that there is very little impact of previous treatment response with regard to this analysis when it comes to brodalumab,” the dermatologist observed. “It goes down a little bit, but if you compare it to ustekinumab, you see a very good robustness despite previous therapy.”
His presentation focused on the 339 AMAGINE-2 or AMAGINE-3 participants randomized to brodalumab at the approved dose of 210 mg by subcutaneous injection every 2 weeks, or to subcutaneous ustekinumab at the approved dose of 45 mg or 90 mg, depending upon body weight, on day 1, week 4, and then every 12 weeks in the 52-week trials.
It took 14 weeks for 50% of patients assigned to brodalumab to achieve a PASI 100 response, and 44 weeks to accomplish the same in the ustekinumab group. At 52 weeks, the PASI 100 response rate was 76% for brodalumab and 52% for ustekinumab.
This was a competing-risk analysis – a methodology relatively new to dermatology – in which the coprimary endpoint was inadequate response to treatment, as defined by a static Physician’s Global Assessment score of 3 or more or two consecutive sPGAs of at least 2 over a 4-week interval at any point from week 16 on. The inadequate response rate was 20% in the brodalumab group and 40% with ustekinumab.
Looking in the brodalumab group at PASI 100 response rates in relation to prior treatments, the complete clearance rate at week 52 was 76% in those with no prior systemic treatment at study entry, 78% in those with a history of nonbiologic systemic treatment, 75% in patients who hadn’t experienced treatment failure when previously on another biologic agent, and 70% in those with a baseline history of failure on a different biologic.
The corresponding PASI 100 rates in the ustekinumab group were strikingly lower, at 58%, 55%, 41%, and 30%.
Leo Pharma funded Dr. Reich’s post hoc analysis; Leo markets brodalumab in Europe. Dr. Reich reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.
SOURCE: Reich K. EADV Congress, Abstract #FC03.06.
REPORTING FROM THE EADV CONGRESS
Key clinical point: Complete clearance rates in psoriasis patients on brodalumab were similar regardless of treatment history.
Major finding: Half of brodalumab-treated patients with moderate-to-severe psoriasis experienced complete clearance at 14 weeks; it took 44 weeks in patients assigned to ustekinumab.
Study details: This was a post hoc analysis of 52-week outcomes in more than 900 participants in the phase 3 AMAGINE-2 and AMAGINE-3 randomized head-to-head comparisons of brodalumab and ustekinumab.
Disclosures: Leo Pharma funded the post hoc analysis. The presenter reported receiving research funding from and serving as a consultant to that pharmaceutical company and numerous others involved in developing new drugs for psoriasis and atopic dermatitis.
Source: Reich K. EADV Congress, Abstract #FC03.06.
New hypopnea criteria ID unique OSA patient subset
The latest recommended criteria for hypopnea define a distinct group of patients who report substantial daytime sleepiness but with no significant cardiovascular risk, investigators reported in a retrospective, cross-sectional analysis.
The number of obstructive sleep apnea (OSA) diagnoses increased by nearly 13% when using the 2012 American Academy of Sleep Medicine (AASM) criteria of ≥ 3% desaturation or arousal, instead of the 2007 criteria of ≥ 4% desaturation, according to investigators.
While cardiovascular disease risk did not appear to be elevated in those with an OSA diagnosis based on the newer, more inclusive criteria, reported lead author Christine H.J. Won, MD, of Yale University, New Haven, Conn., and her coinvestigators.
“Our findings suggest [that] a more inclusive hypopnea definition alters OSA severity categorization, identifies a new symptomatic group of patients with predominantly mild OSA without increased cardiovascular odds, and does not ameliorate the increased odds predicted by severe OSA for arrhythmias,” the investigators wrote in the Journal of Clinical Sleep Medicine.
The analysis by Dr. Won and her colleagues included 1,400 veterans who had polysomnography for suspected sleep-disordered breathing. Of those veterans, two-thirds (932; 66%) had an OSA diagnosis based on the ≥ 4% desaturation criteria.
With the newer criteria of ≥ 3% desaturation or arousal, another 175 OSA diagnoses were captured out of the remaining 468 previously negative studies, meaning that more than 37% of those patients would be recategorized as having OSA, Dr. Won and her coauthors said.
Compared with individuals with OSA classified by the older, more restrictive criteria, the 175 individuals in this “new OSA” group were younger and less likely to be obese, though they were still more likely to be obese, compared with individuals with no OSA diagnosis, according to the authors.
The new OSA group had more disrupted sleep architecture, significantly worse oxygen saturations, and more self-reported sleepiness on the Epworth Sleepiness Scale as compared with those with no OSA, they added.
Adding in the new OSA group redistributed disease severity, with a relative increase of 21.4% for mild and 21.3% for moderate OSA, but just 15.3% for severe OSA. “Most of the [new OSA] category consisted of mild sleep-disordered breathing,” said Dr. Won and her coauthors in the report.
While there was a statistically significant increase in odds ratio for arrhythmias using the older criteria, reclassifying OSA severity using the newer definition meant that mild and moderate disease lost predictive value. However, severe OSA by the new criteria remained a significant predictor of arrhythmias, the authors said.
Odds ratios for ischemic heart disease and heart failure were numerically higher in the new OSA group versus the no OSA group, though no statistically significant differences were found, according to investigators.
This is thought to be the first study to describe a unique group of patients who escape OSA diagnosis based on the ≥ 4% desaturation criteria but are captured ≥ 3% desaturation or arousal criteria, Dr. Won and her coauthors said.
Further studies would be helpful to evaluate other polysomnographic features in this group to see how they affect cardiovascular or other health risks, they added.
“It would also be important to assess whether treatment in any of these groups leads to improved cardiovascular health, or whether treatment of the [new OSA] group leads to improved daytime sleepiness or quality of life,” they said in the report.
The researchers reported no conflicts of interest related to their work, which was performed at the Veterans Affairs Healthcare System in West Haven, Conn.; Indianapolis; and Cleveland.
SOURCE: Won CHJ et al. J Clin Sleep Med. 2018 Dec 15;14[12]:1987-94.
The study by Won and colleagues provides a “useful perspective” on how hypopnea is defined by including outcome data based on the two different scoring criteria, according to Kenneth R. Casey, MD, MPH, and Rachna Tiwari, MBBS.
Results of the study suggest a rationale for using both the 2007 American Academy of Sleep Medicine hypopnea criteria based on ≥ 4% desaturation, and the updated 2012 AASM criteria based on ≥ 3% desaturation or arousal in the evaluation of polysomnography results, Dr. Casey and Dr. Tiwari said in a commentary accompanying the study.
“This perspective may ultimately be the solution to the confusion caused by competing functional definitions of hypopnea,” they said in the commentary published in the Journal of Clinical Sleep Medicine.
The 2007 recommended criteria of ≥ 4% desaturation seemed reasonable based on available evidence at the time, but was not rigorously based by today’s standards, the authors said.
At that time, they also proposed the new alternative criteria based on ≥ 3% desaturation or an arousal, which in 2012 became elevated to a recommended rule. However, the previous recommended rule was kept to accommodate patients who required Centers for Medicare & Medicaid Services reimbursement, according to Dr. Casey and Dr. Tiwari.
Subsequent studies demonstrated “significant differences” in apnea-hypopnea index results, depending on which scoring criteria were used, they added.
“This confusing, vacillating definition has created a rather bizarre, and perhaps unsettling, situation wherein the severity of the diagnosis of sleep-disordered breathing, and perhaps its presence or absence, is determined by the patient’s insurance coverage,” they said in the commentary.
Dr. Casey and Dr. Tiwari are with the University of Wisconsin and William S. Middleton Memorial Veterans Hospital, both in Madison. They reported no conflicts of interest related to their editorial, which appears in the Journal of Clinical Sleep Medicine.
The study by Won and colleagues provides a “useful perspective” on how hypopnea is defined by including outcome data based on the two different scoring criteria, according to Kenneth R. Casey, MD, MPH, and Rachna Tiwari, MBBS.
Results of the study suggest a rationale for using both the 2007 American Academy of Sleep Medicine hypopnea criteria based on ≥ 4% desaturation, and the updated 2012 AASM criteria based on ≥ 3% desaturation or arousal in the evaluation of polysomnography results, Dr. Casey and Dr. Tiwari said in a commentary accompanying the study.
“This perspective may ultimately be the solution to the confusion caused by competing functional definitions of hypopnea,” they said in the commentary published in the Journal of Clinical Sleep Medicine.
The 2007 recommended criteria of ≥ 4% desaturation seemed reasonable based on available evidence at the time, but was not rigorously based by today’s standards, the authors said.
At that time, they also proposed the new alternative criteria based on ≥ 3% desaturation or an arousal, which in 2012 became elevated to a recommended rule. However, the previous recommended rule was kept to accommodate patients who required Centers for Medicare & Medicaid Services reimbursement, according to Dr. Casey and Dr. Tiwari.
Subsequent studies demonstrated “significant differences” in apnea-hypopnea index results, depending on which scoring criteria were used, they added.
“This confusing, vacillating definition has created a rather bizarre, and perhaps unsettling, situation wherein the severity of the diagnosis of sleep-disordered breathing, and perhaps its presence or absence, is determined by the patient’s insurance coverage,” they said in the commentary.
Dr. Casey and Dr. Tiwari are with the University of Wisconsin and William S. Middleton Memorial Veterans Hospital, both in Madison. They reported no conflicts of interest related to their editorial, which appears in the Journal of Clinical Sleep Medicine.
The study by Won and colleagues provides a “useful perspective” on how hypopnea is defined by including outcome data based on the two different scoring criteria, according to Kenneth R. Casey, MD, MPH, and Rachna Tiwari, MBBS.
Results of the study suggest a rationale for using both the 2007 American Academy of Sleep Medicine hypopnea criteria based on ≥ 4% desaturation, and the updated 2012 AASM criteria based on ≥ 3% desaturation or arousal in the evaluation of polysomnography results, Dr. Casey and Dr. Tiwari said in a commentary accompanying the study.
“This perspective may ultimately be the solution to the confusion caused by competing functional definitions of hypopnea,” they said in the commentary published in the Journal of Clinical Sleep Medicine.
The 2007 recommended criteria of ≥ 4% desaturation seemed reasonable based on available evidence at the time, but was not rigorously based by today’s standards, the authors said.
At that time, they also proposed the new alternative criteria based on ≥ 3% desaturation or an arousal, which in 2012 became elevated to a recommended rule. However, the previous recommended rule was kept to accommodate patients who required Centers for Medicare & Medicaid Services reimbursement, according to Dr. Casey and Dr. Tiwari.
Subsequent studies demonstrated “significant differences” in apnea-hypopnea index results, depending on which scoring criteria were used, they added.
“This confusing, vacillating definition has created a rather bizarre, and perhaps unsettling, situation wherein the severity of the diagnosis of sleep-disordered breathing, and perhaps its presence or absence, is determined by the patient’s insurance coverage,” they said in the commentary.
Dr. Casey and Dr. Tiwari are with the University of Wisconsin and William S. Middleton Memorial Veterans Hospital, both in Madison. They reported no conflicts of interest related to their editorial, which appears in the Journal of Clinical Sleep Medicine.
The latest recommended criteria for hypopnea define a distinct group of patients who report substantial daytime sleepiness but with no significant cardiovascular risk, investigators reported in a retrospective, cross-sectional analysis.
The number of obstructive sleep apnea (OSA) diagnoses increased by nearly 13% when using the 2012 American Academy of Sleep Medicine (AASM) criteria of ≥ 3% desaturation or arousal, instead of the 2007 criteria of ≥ 4% desaturation, according to investigators.
While cardiovascular disease risk did not appear to be elevated in those with an OSA diagnosis based on the newer, more inclusive criteria, reported lead author Christine H.J. Won, MD, of Yale University, New Haven, Conn., and her coinvestigators.
“Our findings suggest [that] a more inclusive hypopnea definition alters OSA severity categorization, identifies a new symptomatic group of patients with predominantly mild OSA without increased cardiovascular odds, and does not ameliorate the increased odds predicted by severe OSA for arrhythmias,” the investigators wrote in the Journal of Clinical Sleep Medicine.
The analysis by Dr. Won and her colleagues included 1,400 veterans who had polysomnography for suspected sleep-disordered breathing. Of those veterans, two-thirds (932; 66%) had an OSA diagnosis based on the ≥ 4% desaturation criteria.
With the newer criteria of ≥ 3% desaturation or arousal, another 175 OSA diagnoses were captured out of the remaining 468 previously negative studies, meaning that more than 37% of those patients would be recategorized as having OSA, Dr. Won and her coauthors said.
Compared with individuals with OSA classified by the older, more restrictive criteria, the 175 individuals in this “new OSA” group were younger and less likely to be obese, though they were still more likely to be obese, compared with individuals with no OSA diagnosis, according to the authors.
The new OSA group had more disrupted sleep architecture, significantly worse oxygen saturations, and more self-reported sleepiness on the Epworth Sleepiness Scale as compared with those with no OSA, they added.
Adding in the new OSA group redistributed disease severity, with a relative increase of 21.4% for mild and 21.3% for moderate OSA, but just 15.3% for severe OSA. “Most of the [new OSA] category consisted of mild sleep-disordered breathing,” said Dr. Won and her coauthors in the report.
While there was a statistically significant increase in odds ratio for arrhythmias using the older criteria, reclassifying OSA severity using the newer definition meant that mild and moderate disease lost predictive value. However, severe OSA by the new criteria remained a significant predictor of arrhythmias, the authors said.
Odds ratios for ischemic heart disease and heart failure were numerically higher in the new OSA group versus the no OSA group, though no statistically significant differences were found, according to investigators.
This is thought to be the first study to describe a unique group of patients who escape OSA diagnosis based on the ≥ 4% desaturation criteria but are captured ≥ 3% desaturation or arousal criteria, Dr. Won and her coauthors said.
Further studies would be helpful to evaluate other polysomnographic features in this group to see how they affect cardiovascular or other health risks, they added.
“It would also be important to assess whether treatment in any of these groups leads to improved cardiovascular health, or whether treatment of the [new OSA] group leads to improved daytime sleepiness or quality of life,” they said in the report.
The researchers reported no conflicts of interest related to their work, which was performed at the Veterans Affairs Healthcare System in West Haven, Conn.; Indianapolis; and Cleveland.
SOURCE: Won CHJ et al. J Clin Sleep Med. 2018 Dec 15;14[12]:1987-94.
The latest recommended criteria for hypopnea define a distinct group of patients who report substantial daytime sleepiness but with no significant cardiovascular risk, investigators reported in a retrospective, cross-sectional analysis.
The number of obstructive sleep apnea (OSA) diagnoses increased by nearly 13% when using the 2012 American Academy of Sleep Medicine (AASM) criteria of ≥ 3% desaturation or arousal, instead of the 2007 criteria of ≥ 4% desaturation, according to investigators.
While cardiovascular disease risk did not appear to be elevated in those with an OSA diagnosis based on the newer, more inclusive criteria, reported lead author Christine H.J. Won, MD, of Yale University, New Haven, Conn., and her coinvestigators.
“Our findings suggest [that] a more inclusive hypopnea definition alters OSA severity categorization, identifies a new symptomatic group of patients with predominantly mild OSA without increased cardiovascular odds, and does not ameliorate the increased odds predicted by severe OSA for arrhythmias,” the investigators wrote in the Journal of Clinical Sleep Medicine.
The analysis by Dr. Won and her colleagues included 1,400 veterans who had polysomnography for suspected sleep-disordered breathing. Of those veterans, two-thirds (932; 66%) had an OSA diagnosis based on the ≥ 4% desaturation criteria.
With the newer criteria of ≥ 3% desaturation or arousal, another 175 OSA diagnoses were captured out of the remaining 468 previously negative studies, meaning that more than 37% of those patients would be recategorized as having OSA, Dr. Won and her coauthors said.
Compared with individuals with OSA classified by the older, more restrictive criteria, the 175 individuals in this “new OSA” group were younger and less likely to be obese, though they were still more likely to be obese, compared with individuals with no OSA diagnosis, according to the authors.
The new OSA group had more disrupted sleep architecture, significantly worse oxygen saturations, and more self-reported sleepiness on the Epworth Sleepiness Scale as compared with those with no OSA, they added.
Adding in the new OSA group redistributed disease severity, with a relative increase of 21.4% for mild and 21.3% for moderate OSA, but just 15.3% for severe OSA. “Most of the [new OSA] category consisted of mild sleep-disordered breathing,” said Dr. Won and her coauthors in the report.
While there was a statistically significant increase in odds ratio for arrhythmias using the older criteria, reclassifying OSA severity using the newer definition meant that mild and moderate disease lost predictive value. However, severe OSA by the new criteria remained a significant predictor of arrhythmias, the authors said.
Odds ratios for ischemic heart disease and heart failure were numerically higher in the new OSA group versus the no OSA group, though no statistically significant differences were found, according to investigators.
This is thought to be the first study to describe a unique group of patients who escape OSA diagnosis based on the ≥ 4% desaturation criteria but are captured ≥ 3% desaturation or arousal criteria, Dr. Won and her coauthors said.
Further studies would be helpful to evaluate other polysomnographic features in this group to see how they affect cardiovascular or other health risks, they added.
“It would also be important to assess whether treatment in any of these groups leads to improved cardiovascular health, or whether treatment of the [new OSA] group leads to improved daytime sleepiness or quality of life,” they said in the report.
The researchers reported no conflicts of interest related to their work, which was performed at the Veterans Affairs Healthcare System in West Haven, Conn.; Indianapolis; and Cleveland.
SOURCE: Won CHJ et al. J Clin Sleep Med. 2018 Dec 15;14[12]:1987-94.
FROM THE CLINICAL JOURNAL OF SLEEP MEDICINE
Key clinical point: The latest AASM criteria for hypopnea identify a subset of obstructive sleep apnea patients with substantial daytime sleepiness but no apparent significant increase in cardiovascular risk.
Major finding: The number of obstructive sleep apnea (OSA) diagnoses increased by nearly 13% when using the 2012 AASM criteria of ≥ 3% desaturation or an arousal, instead of the 2007 criteria of ≥ 4% desaturation.
Study details: Retrospective, cross-sectional, observational study that includes 1,400 veterans evaluated for suspected sleep-disordered breathing.
Disclosures: Authors reported no conflicts of interest.
Source: Won CHJ et al. J Clin Sleep Med. 2018 Dec 15;14(12):1987-94.
SGLT-2 inhibitors promising for heart failure prevention, not treatment
LOS ANGELES –
They also may play a role in the treatment of patients with known heart failure (HF), but further studies are required to prove definite treatment benefit.
“These trials enrolled a minority of patients with known heart failure, and, in those subgroups, the drugs seems to reduce the risk for hospitalization, opening the possibility of treatment benefit,” Javed Butler, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But there were not enough patients to conclude this. If you are treating diabetes with these agents in patients with heart failure, more power to you. But don’t think you are treating heart failure per se until the results of the dedicated heart failure trials come out.”
Good glycemic control has not been shown to affect heart failure outcomes per se, said Dr. Butler, professor and chairman of the department of medicine at the University of Mississippi Medical Center, Jackson.
“People seem to mix the concepts of prevention and treatment together,” he said. “We have now very good evidence across all trials with SGLT-2 inhibitors for prevention of heart failure. But for treatment, we need more data despite favorable early signals.
“Also, these trials include most patients with ischemic heart disease, but we don’t have data on nonischemic etiology for the development of heart failure from these trials,” Dr. Butler added.
The best available data from clinical trials suggest that patients with American College of Cardiology Foundation/American Heart Association heart failure classification stages A and B benefit the most from aggressive treatment to prevent HF.
“Either they have diseases like high blood pressure or diabetes, but their hearts are normal, or, perhaps, their hearts are abnormal, and they develop left ventricular hypertrophy or atrial fibrillation,” he said. “However, if someone is stage C – manifest heart failure – or stage D – advanced heart failure – we need further data on novel therapies to improve their outcomes.”
Dr. Butler emphasized that not all heart failure is associated with atherosclerotic vascular disease. In fact, the Health, Aging, and Body Composition Study showed that the incidence of heart failure increased progressively across age groups, both for those with and without a preceding vascular event (P = .03 and P less than .001, respectively; Eur J Heart Fail. 2014 May;16[5]:526-34). “There’s a whole other world of nonischemic heart failure that we also need to worry about,” he said. “There is a lot of microvascular endothelial dysfunction.”
The combination of heart failure and diabetes is especially lethal. “If you put them together, you’re looking at about a 10-fold higher risk of mortality, which is a horrible prognosis,” Dr. Butler said. “That means that we need to think about prevention and treatment separately.”
Data from the SAVOR-TIMI 53, EXAMINE, and TECOS trials show there is no protective effect of dipeptidyl peptidase–4 inhibitors when it comes to hospitalization for heart failure.
“The other classes of drugs either increase the risk, or we don’t have very good data,” Dr. Butler said. “So far, across the spectrum of therapies for diabetes, the effect on heart failure is neutral and perhaps confers some risk.”
SGLT-2 inhibitors convey a different story.
In the EMPA-REG OUTCOME Trial, one inclusion criterion was established cardiovascular disease (CVD) in the form of a prior MI, coronary artery disease, stroke, unstable angina, or occlusive peripheral artery disease, but not heart failure alone (N Engl J Med. 2015 Nov 26; 373[22]:2117-28). “This was not a heart failure study, so we don’t know what their New York Heart Association class was, or the details of their baseline HF treatment in the minority of patients who were enrolled who had a history of HF,” Dr. Butler cautioned.
However, the trial found that empagliflozin conferred an overall cardiovascular death risk reduction of 38%, compared with placebo. When the researchers assessed the impact of treatment on all modes of cardiovascular death, they found that death from heart failure benefited the most (hazard ratio, 0.32; P = .0008), while sudden death benefited as well. Empagliflozin also had a significant impact on reduced hospitalization for heart failure, compared with placebo (HR, 0.65).
“This is a large enough cohort that you should feel comfortable that this drug is preventing heart failure in those with HF at baseline,” said Dr. Butler, who was not involved with the study. “We can have a debate about whether this is a treatment for heart failure or not, but for prevention of heart failure, I feel comfortable that these drugs do that.”
A subsequent study of canagliflozin and cardiovascular and renal events in type 2 diabetes showed the same result (N Engl J Med. 2017 Aug 17; 377[7]:644-57). It reduced hospitalization for heart failure by 33% (HR, 0.67).
Then came the CVD-REAL study, which found low rates of hospitalization for heart failure and all-cause death in new users of SGLT-2 inhibitors. More recently, DECLARE-TIMI 58 yielded similar results.
“One of the criticisms of these findings is that heart failure characteristics were not well phenotyped in these studies,” Dr. Butler said. “I say it really does not matter. Heart failure hospitalizations are associated with a poor prognosis irrespective of whether the hospitalization occurred in patients without heart failure or in a patient with previously diagnosed heart failure, or whether the patient has reduced or preserved ejection fraction.
“Framingham and other classic studies show us that 5-year mortality for heart failure is about 50%,” he noted. “If you can prevent a disease that has a 5-year mortality of 50%, doesn’t that sound like a really good deal?”
A contemporary appraisal of the heart failure epidemic in Olmstead County, Minn., during 2000-2010 found that the mortality was 20.2% at 1 year after diagnosis, and 52.6% at 5 years after diagnosis. The data include new-onset HF in both inpatient and outpatient settings.
Specifically, new-onset HF hospitalization was associated with a 1-year post discharge mortality of 21.1% (JAMA Intern Med. 2015;175[6]:996-1004). “We cannot ignore prevention of heart failure,” Dr. Butler said. “Also, for treatment, once you get hospitalized for heart failure, the fundamental natural history of the disease changes. There is a 30% cumulative incremental death risk between the second and third hospitalizations.”
Dr. Butler concluded his presentation by noting that five randomized, controlled trials evaluating SGLT-2 inhibitors in HF have been launched, and should help elucidate any effects the drugs may have in treating the condition. They include EMPEROR-Preserved (NCT03057951), EMPEROR-Reduced (NCT03057977), Dapa-HF (NCT03036124), and SOLOIST-WHF (NCT03521934) and DELIVER (NCT03619213).
Dr. Butler disclosed that he has received research support from the National Institutes of Health, the European Union, and the Patient-Centered Outcomes Research Institute. He has also been a consultant for numerous pharmaceutical companies, including Boehringer Ingelheim, Janssen, and AstraZeneca, which sponsored the EMPA-REG, CANVAS, and DECLARE TIMI 58 trials.
LOS ANGELES –
They also may play a role in the treatment of patients with known heart failure (HF), but further studies are required to prove definite treatment benefit.
“These trials enrolled a minority of patients with known heart failure, and, in those subgroups, the drugs seems to reduce the risk for hospitalization, opening the possibility of treatment benefit,” Javed Butler, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But there were not enough patients to conclude this. If you are treating diabetes with these agents in patients with heart failure, more power to you. But don’t think you are treating heart failure per se until the results of the dedicated heart failure trials come out.”
Good glycemic control has not been shown to affect heart failure outcomes per se, said Dr. Butler, professor and chairman of the department of medicine at the University of Mississippi Medical Center, Jackson.
“People seem to mix the concepts of prevention and treatment together,” he said. “We have now very good evidence across all trials with SGLT-2 inhibitors for prevention of heart failure. But for treatment, we need more data despite favorable early signals.
“Also, these trials include most patients with ischemic heart disease, but we don’t have data on nonischemic etiology for the development of heart failure from these trials,” Dr. Butler added.
The best available data from clinical trials suggest that patients with American College of Cardiology Foundation/American Heart Association heart failure classification stages A and B benefit the most from aggressive treatment to prevent HF.
“Either they have diseases like high blood pressure or diabetes, but their hearts are normal, or, perhaps, their hearts are abnormal, and they develop left ventricular hypertrophy or atrial fibrillation,” he said. “However, if someone is stage C – manifest heart failure – or stage D – advanced heart failure – we need further data on novel therapies to improve their outcomes.”
Dr. Butler emphasized that not all heart failure is associated with atherosclerotic vascular disease. In fact, the Health, Aging, and Body Composition Study showed that the incidence of heart failure increased progressively across age groups, both for those with and without a preceding vascular event (P = .03 and P less than .001, respectively; Eur J Heart Fail. 2014 May;16[5]:526-34). “There’s a whole other world of nonischemic heart failure that we also need to worry about,” he said. “There is a lot of microvascular endothelial dysfunction.”
The combination of heart failure and diabetes is especially lethal. “If you put them together, you’re looking at about a 10-fold higher risk of mortality, which is a horrible prognosis,” Dr. Butler said. “That means that we need to think about prevention and treatment separately.”
Data from the SAVOR-TIMI 53, EXAMINE, and TECOS trials show there is no protective effect of dipeptidyl peptidase–4 inhibitors when it comes to hospitalization for heart failure.
“The other classes of drugs either increase the risk, or we don’t have very good data,” Dr. Butler said. “So far, across the spectrum of therapies for diabetes, the effect on heart failure is neutral and perhaps confers some risk.”
SGLT-2 inhibitors convey a different story.
In the EMPA-REG OUTCOME Trial, one inclusion criterion was established cardiovascular disease (CVD) in the form of a prior MI, coronary artery disease, stroke, unstable angina, or occlusive peripheral artery disease, but not heart failure alone (N Engl J Med. 2015 Nov 26; 373[22]:2117-28). “This was not a heart failure study, so we don’t know what their New York Heart Association class was, or the details of their baseline HF treatment in the minority of patients who were enrolled who had a history of HF,” Dr. Butler cautioned.
However, the trial found that empagliflozin conferred an overall cardiovascular death risk reduction of 38%, compared with placebo. When the researchers assessed the impact of treatment on all modes of cardiovascular death, they found that death from heart failure benefited the most (hazard ratio, 0.32; P = .0008), while sudden death benefited as well. Empagliflozin also had a significant impact on reduced hospitalization for heart failure, compared with placebo (HR, 0.65).
“This is a large enough cohort that you should feel comfortable that this drug is preventing heart failure in those with HF at baseline,” said Dr. Butler, who was not involved with the study. “We can have a debate about whether this is a treatment for heart failure or not, but for prevention of heart failure, I feel comfortable that these drugs do that.”
A subsequent study of canagliflozin and cardiovascular and renal events in type 2 diabetes showed the same result (N Engl J Med. 2017 Aug 17; 377[7]:644-57). It reduced hospitalization for heart failure by 33% (HR, 0.67).
Then came the CVD-REAL study, which found low rates of hospitalization for heart failure and all-cause death in new users of SGLT-2 inhibitors. More recently, DECLARE-TIMI 58 yielded similar results.
“One of the criticisms of these findings is that heart failure characteristics were not well phenotyped in these studies,” Dr. Butler said. “I say it really does not matter. Heart failure hospitalizations are associated with a poor prognosis irrespective of whether the hospitalization occurred in patients without heart failure or in a patient with previously diagnosed heart failure, or whether the patient has reduced or preserved ejection fraction.
“Framingham and other classic studies show us that 5-year mortality for heart failure is about 50%,” he noted. “If you can prevent a disease that has a 5-year mortality of 50%, doesn’t that sound like a really good deal?”
A contemporary appraisal of the heart failure epidemic in Olmstead County, Minn., during 2000-2010 found that the mortality was 20.2% at 1 year after diagnosis, and 52.6% at 5 years after diagnosis. The data include new-onset HF in both inpatient and outpatient settings.
Specifically, new-onset HF hospitalization was associated with a 1-year post discharge mortality of 21.1% (JAMA Intern Med. 2015;175[6]:996-1004). “We cannot ignore prevention of heart failure,” Dr. Butler said. “Also, for treatment, once you get hospitalized for heart failure, the fundamental natural history of the disease changes. There is a 30% cumulative incremental death risk between the second and third hospitalizations.”
Dr. Butler concluded his presentation by noting that five randomized, controlled trials evaluating SGLT-2 inhibitors in HF have been launched, and should help elucidate any effects the drugs may have in treating the condition. They include EMPEROR-Preserved (NCT03057951), EMPEROR-Reduced (NCT03057977), Dapa-HF (NCT03036124), and SOLOIST-WHF (NCT03521934) and DELIVER (NCT03619213).
Dr. Butler disclosed that he has received research support from the National Institutes of Health, the European Union, and the Patient-Centered Outcomes Research Institute. He has also been a consultant for numerous pharmaceutical companies, including Boehringer Ingelheim, Janssen, and AstraZeneca, which sponsored the EMPA-REG, CANVAS, and DECLARE TIMI 58 trials.
LOS ANGELES –
They also may play a role in the treatment of patients with known heart failure (HF), but further studies are required to prove definite treatment benefit.
“These trials enrolled a minority of patients with known heart failure, and, in those subgroups, the drugs seems to reduce the risk for hospitalization, opening the possibility of treatment benefit,” Javed Butler, MD, said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “But there were not enough patients to conclude this. If you are treating diabetes with these agents in patients with heart failure, more power to you. But don’t think you are treating heart failure per se until the results of the dedicated heart failure trials come out.”
Good glycemic control has not been shown to affect heart failure outcomes per se, said Dr. Butler, professor and chairman of the department of medicine at the University of Mississippi Medical Center, Jackson.
“People seem to mix the concepts of prevention and treatment together,” he said. “We have now very good evidence across all trials with SGLT-2 inhibitors for prevention of heart failure. But for treatment, we need more data despite favorable early signals.
“Also, these trials include most patients with ischemic heart disease, but we don’t have data on nonischemic etiology for the development of heart failure from these trials,” Dr. Butler added.
The best available data from clinical trials suggest that patients with American College of Cardiology Foundation/American Heart Association heart failure classification stages A and B benefit the most from aggressive treatment to prevent HF.
“Either they have diseases like high blood pressure or diabetes, but their hearts are normal, or, perhaps, their hearts are abnormal, and they develop left ventricular hypertrophy or atrial fibrillation,” he said. “However, if someone is stage C – manifest heart failure – or stage D – advanced heart failure – we need further data on novel therapies to improve their outcomes.”
Dr. Butler emphasized that not all heart failure is associated with atherosclerotic vascular disease. In fact, the Health, Aging, and Body Composition Study showed that the incidence of heart failure increased progressively across age groups, both for those with and without a preceding vascular event (P = .03 and P less than .001, respectively; Eur J Heart Fail. 2014 May;16[5]:526-34). “There’s a whole other world of nonischemic heart failure that we also need to worry about,” he said. “There is a lot of microvascular endothelial dysfunction.”
The combination of heart failure and diabetes is especially lethal. “If you put them together, you’re looking at about a 10-fold higher risk of mortality, which is a horrible prognosis,” Dr. Butler said. “That means that we need to think about prevention and treatment separately.”
Data from the SAVOR-TIMI 53, EXAMINE, and TECOS trials show there is no protective effect of dipeptidyl peptidase–4 inhibitors when it comes to hospitalization for heart failure.
“The other classes of drugs either increase the risk, or we don’t have very good data,” Dr. Butler said. “So far, across the spectrum of therapies for diabetes, the effect on heart failure is neutral and perhaps confers some risk.”
SGLT-2 inhibitors convey a different story.
In the EMPA-REG OUTCOME Trial, one inclusion criterion was established cardiovascular disease (CVD) in the form of a prior MI, coronary artery disease, stroke, unstable angina, or occlusive peripheral artery disease, but not heart failure alone (N Engl J Med. 2015 Nov 26; 373[22]:2117-28). “This was not a heart failure study, so we don’t know what their New York Heart Association class was, or the details of their baseline HF treatment in the minority of patients who were enrolled who had a history of HF,” Dr. Butler cautioned.
However, the trial found that empagliflozin conferred an overall cardiovascular death risk reduction of 38%, compared with placebo. When the researchers assessed the impact of treatment on all modes of cardiovascular death, they found that death from heart failure benefited the most (hazard ratio, 0.32; P = .0008), while sudden death benefited as well. Empagliflozin also had a significant impact on reduced hospitalization for heart failure, compared with placebo (HR, 0.65).
“This is a large enough cohort that you should feel comfortable that this drug is preventing heart failure in those with HF at baseline,” said Dr. Butler, who was not involved with the study. “We can have a debate about whether this is a treatment for heart failure or not, but for prevention of heart failure, I feel comfortable that these drugs do that.”
A subsequent study of canagliflozin and cardiovascular and renal events in type 2 diabetes showed the same result (N Engl J Med. 2017 Aug 17; 377[7]:644-57). It reduced hospitalization for heart failure by 33% (HR, 0.67).
Then came the CVD-REAL study, which found low rates of hospitalization for heart failure and all-cause death in new users of SGLT-2 inhibitors. More recently, DECLARE-TIMI 58 yielded similar results.
“One of the criticisms of these findings is that heart failure characteristics were not well phenotyped in these studies,” Dr. Butler said. “I say it really does not matter. Heart failure hospitalizations are associated with a poor prognosis irrespective of whether the hospitalization occurred in patients without heart failure or in a patient with previously diagnosed heart failure, or whether the patient has reduced or preserved ejection fraction.
“Framingham and other classic studies show us that 5-year mortality for heart failure is about 50%,” he noted. “If you can prevent a disease that has a 5-year mortality of 50%, doesn’t that sound like a really good deal?”
A contemporary appraisal of the heart failure epidemic in Olmstead County, Minn., during 2000-2010 found that the mortality was 20.2% at 1 year after diagnosis, and 52.6% at 5 years after diagnosis. The data include new-onset HF in both inpatient and outpatient settings.
Specifically, new-onset HF hospitalization was associated with a 1-year post discharge mortality of 21.1% (JAMA Intern Med. 2015;175[6]:996-1004). “We cannot ignore prevention of heart failure,” Dr. Butler said. “Also, for treatment, once you get hospitalized for heart failure, the fundamental natural history of the disease changes. There is a 30% cumulative incremental death risk between the second and third hospitalizations.”
Dr. Butler concluded his presentation by noting that five randomized, controlled trials evaluating SGLT-2 inhibitors in HF have been launched, and should help elucidate any effects the drugs may have in treating the condition. They include EMPEROR-Preserved (NCT03057951), EMPEROR-Reduced (NCT03057977), Dapa-HF (NCT03036124), and SOLOIST-WHF (NCT03521934) and DELIVER (NCT03619213).
Dr. Butler disclosed that he has received research support from the National Institutes of Health, the European Union, and the Patient-Centered Outcomes Research Institute. He has also been a consultant for numerous pharmaceutical companies, including Boehringer Ingelheim, Janssen, and AstraZeneca, which sponsored the EMPA-REG, CANVAS, and DECLARE TIMI 58 trials.
EXPERT ANALYSIS FROM WCIRDC 2018
Novel atopic dermatitis cream shows promise in phase 2 study
Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.
“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.
In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.
After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.
In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.
The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.
The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.
The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.
However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.
AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.
SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.
Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.
“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.
In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.
After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.
In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.
The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.
The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.
The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.
However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.
AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.
SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.
Adults with mild to moderate atopic dermatitis showed significant improvement after 8 weeks of treatment with a novel topical cream, compared with a placebo group, based on data from 194 patients.
“Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is expressed not only on sensory nerves, but also on keratinocytes, dendritic cells and sebocytes in the skin,” wrote Y.W. Lee, MD, of Konkuk University, Seoul, South Korea, and colleagues. Previous research suggests that TRPV1 may play a role in the inflammation and itching associated with atopic dermatitis, but use of a TRPV antagonist as treatment has not been well studied, the researchers said.
In a phase 2b trial published in the British Journal of Dermatology, the researchers randomized 194 adults with atopic dermatitis to one of three concentrations of a topical cream containing the selective TRPV1 antagonist PAC‐14028, or a placebo vehicle. The patients had baseline scores of 2 or 3 (mild to moderate) on the Investigator’s Global Assessment (IGA) scale. Patients were instructed to apply the cream twice daily to AD-affected areas.
After 8 weeks, treatment success (defined as a score of 0 or 1 on the IGA) occurred in 57% of patients given 1% cream, 38% of those given 0.3% cream, 43% of those given 0.1% cream, and 15% of those given a placebo cream.
In addition, other measures of improvement including the Scoring of Atopic Dermatitis (SCORAD) index, EASI 75/90, sleep disturbance score, and pruritus visual analogue scale (VAS) trended toward improvement in patients who received the treatment cream.
The mean change in the SCORAD index was significantly greater in the 0.1% and 1.0% groups, compared with the placebo group. Also of note, patients in the 1.0% cream group showed significant improvements in both sleep disturbance and VAS scores, compared with the placebo patients, the researchers said.
The incidence of adverse events was similar among the groups, and no treatment-related serious adverse events were reported. A total of 18 patients discontinued the study, but 193 received at least one dose of treatment cream.
The study findings were limited by several factors, including the small size and lack of comparison to treatment with topical corticosteroids and topical calcineurin inhibitors, the researchers noted.
However, the results support the safety and efficacy of PAC‐14028, they added. And “based on these results, a phase III program is underway to assess the efficacy and safety of PAC-14028 topical cream 10% in adolescent and adult patients with mild to moderate AD,” they said.
AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.
SOURCE: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.
FROM THE BRITISH JOURNAL OF DERMATOLOGY
Key clinical point: Significantly more atopic dermatitis patients improved when treated with PAC-14028 cream, compared with those treated with a placebo vehicle.
Major finding: After 8 weeks, 58% of patients given the 1.0 cream achieved scores of 0 or 1 on the Investigator’s Global Assessment scale, compared with 15% for placebo patients.
Study details: The data come from a phase 2b randomized, double-blind trial including 194 atopic dermatitis patients.
Disclosures: AmorePacific funded the study. Dr. Lee disclosed relationships with AmorePacific, as well as LG Household & Health Care and Medytox.
Source: Lee YW et al. Br J Dermatol. 2019 Jan 8. doi: 10.1111/bjd.17455.
New or existing drugs? Both fuel price inflation
Inflation in existing drugs’ prices and the debut of new drugs are both contributing to the overall rising costs of pharmaceuticals.
.
For oral and injectable specialty drugs, costs increased 20.6% and 12.5%, respectively, with 71.1% and 52.4% attributable to new drugs. Costs of oral and injectable generic drugs grew by 4.4% and 7.3%, also driven by entrants into the market.
Researchers looked at monthly wholesale acquisition costs of 24,877 National Drug Codes for oral drugs and 3,049 injectable drugs from 2005 to 2016. They compared them with pharmacy claims from the UPMC Health Plan, which offers insurance products to more than 3.2 million members across the spectrum of private and public arenas.
“Our analyses yielded three main findings,” explained Inmaculada Hernandez, PharmD, PhD, University of Pittsburgh, and her colleagues in a report published in the January 2019 issue of Health Affairs.
“First, costs increased considerably faster than inflation across all drug classes, and increases were highest for oral specialty drugs and lowest for oral generics,” Dr. Hernandez and her colleagues wrote.
“Second, rising costs of brand-name drugs were driven by inflation in the prices of widely used existing drugs,” they added. A combination of new products and price inflation in existing drugs drove the rising costs of specialty drugs, with new drugs accounting for a larger share of the price increases.
Third, “existing generics tended to decrease the average cost of generic drugs,” Dr. Hernandez noted. However, new generic products cost more than those already on the market, which fueled the annual increases in average costs.
The authors noted that their estimates demonstrate the role of inflation on pharmaceutical cost increases and support policy efforts to control that inflation.
“In the current value-based landscape, increasing drug costs attributable to new products can sometimes be justified on the basis of improved outcomes,” Dr. Hernandez and colleagues stated. “However, rising costs due to inflation do not reflect improved value for patients.”
The researchers noted that the data are limited by the lack of rebate information, which is generally proprietary. Thus, “the contribution of existing drugs may have been lower than we estimated,” they noted. In addition, “because the magnitude of rebates has increased in the past decade, our findings likely overestimated cost increases for brand-name drugs.” The researchers also didn’t examine the effect of drugs transitioning from brand to generic offerings.
The authors provided no disclosures.
gtwachtman@mdedge.com
SOURCE: Hernandez I et al. Health Aff (Millwood). 2019 Jan 2019. doi: 10.1377/hlthaff.2018.05147.
Inflation in existing drugs’ prices and the debut of new drugs are both contributing to the overall rising costs of pharmaceuticals.
.
For oral and injectable specialty drugs, costs increased 20.6% and 12.5%, respectively, with 71.1% and 52.4% attributable to new drugs. Costs of oral and injectable generic drugs grew by 4.4% and 7.3%, also driven by entrants into the market.
Researchers looked at monthly wholesale acquisition costs of 24,877 National Drug Codes for oral drugs and 3,049 injectable drugs from 2005 to 2016. They compared them with pharmacy claims from the UPMC Health Plan, which offers insurance products to more than 3.2 million members across the spectrum of private and public arenas.
“Our analyses yielded three main findings,” explained Inmaculada Hernandez, PharmD, PhD, University of Pittsburgh, and her colleagues in a report published in the January 2019 issue of Health Affairs.
“First, costs increased considerably faster than inflation across all drug classes, and increases were highest for oral specialty drugs and lowest for oral generics,” Dr. Hernandez and her colleagues wrote.
“Second, rising costs of brand-name drugs were driven by inflation in the prices of widely used existing drugs,” they added. A combination of new products and price inflation in existing drugs drove the rising costs of specialty drugs, with new drugs accounting for a larger share of the price increases.
Third, “existing generics tended to decrease the average cost of generic drugs,” Dr. Hernandez noted. However, new generic products cost more than those already on the market, which fueled the annual increases in average costs.
The authors noted that their estimates demonstrate the role of inflation on pharmaceutical cost increases and support policy efforts to control that inflation.
“In the current value-based landscape, increasing drug costs attributable to new products can sometimes be justified on the basis of improved outcomes,” Dr. Hernandez and colleagues stated. “However, rising costs due to inflation do not reflect improved value for patients.”
The researchers noted that the data are limited by the lack of rebate information, which is generally proprietary. Thus, “the contribution of existing drugs may have been lower than we estimated,” they noted. In addition, “because the magnitude of rebates has increased in the past decade, our findings likely overestimated cost increases for brand-name drugs.” The researchers also didn’t examine the effect of drugs transitioning from brand to generic offerings.
The authors provided no disclosures.
gtwachtman@mdedge.com
SOURCE: Hernandez I et al. Health Aff (Millwood). 2019 Jan 2019. doi: 10.1377/hlthaff.2018.05147.
Inflation in existing drugs’ prices and the debut of new drugs are both contributing to the overall rising costs of pharmaceuticals.
.
For oral and injectable specialty drugs, costs increased 20.6% and 12.5%, respectively, with 71.1% and 52.4% attributable to new drugs. Costs of oral and injectable generic drugs grew by 4.4% and 7.3%, also driven by entrants into the market.
Researchers looked at monthly wholesale acquisition costs of 24,877 National Drug Codes for oral drugs and 3,049 injectable drugs from 2005 to 2016. They compared them with pharmacy claims from the UPMC Health Plan, which offers insurance products to more than 3.2 million members across the spectrum of private and public arenas.
“Our analyses yielded three main findings,” explained Inmaculada Hernandez, PharmD, PhD, University of Pittsburgh, and her colleagues in a report published in the January 2019 issue of Health Affairs.
“First, costs increased considerably faster than inflation across all drug classes, and increases were highest for oral specialty drugs and lowest for oral generics,” Dr. Hernandez and her colleagues wrote.
“Second, rising costs of brand-name drugs were driven by inflation in the prices of widely used existing drugs,” they added. A combination of new products and price inflation in existing drugs drove the rising costs of specialty drugs, with new drugs accounting for a larger share of the price increases.
Third, “existing generics tended to decrease the average cost of generic drugs,” Dr. Hernandez noted. However, new generic products cost more than those already on the market, which fueled the annual increases in average costs.
The authors noted that their estimates demonstrate the role of inflation on pharmaceutical cost increases and support policy efforts to control that inflation.
“In the current value-based landscape, increasing drug costs attributable to new products can sometimes be justified on the basis of improved outcomes,” Dr. Hernandez and colleagues stated. “However, rising costs due to inflation do not reflect improved value for patients.”
The researchers noted that the data are limited by the lack of rebate information, which is generally proprietary. Thus, “the contribution of existing drugs may have been lower than we estimated,” they noted. In addition, “because the magnitude of rebates has increased in the past decade, our findings likely overestimated cost increases for brand-name drugs.” The researchers also didn’t examine the effect of drugs transitioning from brand to generic offerings.
The authors provided no disclosures.
gtwachtman@mdedge.com
SOURCE: Hernandez I et al. Health Aff (Millwood). 2019 Jan 2019. doi: 10.1377/hlthaff.2018.05147.
FROM HEALTH AFFAIRS
Key clinical point: Price inflation in existing drugs and new product introductions are driving increases in pharmaceutical costs.
Major finding: 71% of oral specialty drug price increases during 2005-2019 are attributable to new products.
Study details: Researchers analyzed the wholesale acquisition prices of 24,877 oral drugs and 3,049 injectable drugs and compared them with pharmacy claims across all public and private insurance products offered by the UPMC Health Plan.
Disclosures: The authors provided no disclosures.
Source: Hernandez I et al. Health Aff (Millwood). 2019 Jan. doi: 10.1377/hlthaff.2018.05147.
Soy didn’t up all-cause mortality in breast cancer survivors
A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.
The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.
Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.
The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.
Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.
There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.
However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.
This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”
Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho
Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.
Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.
The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.
Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.
Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.
Patient, disease, and treatment characteristics did not differ significantly among the tertiles.
An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.
For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.
For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).
Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).
Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”
“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”
The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”
The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.
The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.
SOURCE: Ho S et al. NAMS 2018, Abstract S-23.
A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.
The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.
Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.
The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.
Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.
There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.
However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.
This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”
Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho
Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.
Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.
The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.
Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.
Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.
Patient, disease, and treatment characteristics did not differ significantly among the tertiles.
An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.
For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.
For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).
Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).
Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”
“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”
The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”
The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.
The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.
SOURCE: Ho S et al. NAMS 2018, Abstract S-23.
A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.
The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.
Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.
The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.
Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.
There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.
However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.
This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”
Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho
Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.
Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.
The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.
Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.
Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.
Patient, disease, and treatment characteristics did not differ significantly among the tertiles.
An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.
For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.
For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).
Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).
Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”
“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”
The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”
The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.
The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.
SOURCE: Ho S et al. NAMS 2018, Abstract S-23.
REPORTING FROM NAMS 2018
Key clinical point: Soy consumption did not increase mortality risk in breast cancer survivors.
Major finding: The hazard ratios for all-cause mortality were 0.63 and 0.95 for the two highest tertiles of soy consumption.
Study details: An ongoing prospective cohort study of 1,497 female breast cancer survivors in Hong Kong.
Disclosures: The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.
Source: Ho S et al. NAMS 2018, Abstract S-23.
Daily News Special: SABCS
Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.
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Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.
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Apple Podcasts
Google Podcasts
Spotify
Stories include: uUing low-dose tamoxifen, the latest findings from the KATHERINE trial, results of a meta-analysis of neoadjuvant chemotherapy, and capecitabine in early stage triple negative breast cancer.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Blood test shows potential as an early biomarker of methotrexate inefficacy
A newly developed gene expression classifier may be able to identify rheumatoid arthritis patients who are unlikely to benefit from methotrexate, according to an analysis of blood samples from patients who had just begun the drug.
“This study highlights the potential of early treatment biomarker monitoring in RA and raises important questions regarding acceptable levels of performance for complementary diagnostic testing,” wrote lead author Darren Plant, PhD, of the University of Manchester (England), and his coauthors. The study was published in Arthritis & Rheumatology.
The study analyzed 85 participants in the Rheumatoid Arthritis Medication Study, a U.K.-based longitudinal observational study of RA patients taking methotrexate for the first time, and classified them as either good responders (n = 42) or nonresponders (n = 43) after 6 months on the drug, based on European League Against Rheumatism response criteria. Dr. Plant and his colleagues then performed gene expression profiling on whole-blood samples from those participants, collected before treatment and after 4 weeks on methotrexate.
Ultimately, pathway analysis indicated an overrepresentation of type 1 interferon signaling pathway genes in nonresponsive patients at both pretreatment (P = 2.8 x 10-25) and 4 weeks (P = 4.9 x 10-28). As such, the coauthors “developed a gene expression classifier that could potentially provide an early response biomarker of methotrexate inefficacy” at 6 months based on the gene expression ratio between 4 weeks and pretreatment, which yielded an area under the receiver operating characteristic curve (ROC AUC) of 0.78. This was proven stable in cross validation and superior to models including clinical covariates (ROC AUC = 0.65).
The authors did not replicate the results in an independent cohort, but the authors noted that the “utility of a gene expression classifier of methotrexate nonresponse now requires validation, not only in independent samples but also using independent technology.”
The study was also potentially limited by the fact that the patients at baseline were atypical in having a long disease duration at a median of 6-9 years but relatively low disease activity, based on a mean 28-joint Disease Activity Score (DAS28) of 4.8 in good responders and 4.0 in nonresponders. The authors also acknowledged both the objective and subjective nature of the DAS28 and its components in approximating disease activity. The authors also did not include a negative predictive value in their analysis, which would have been useful in considering the value of the test.
The study was jointly funded by Pfizer, the Medical Research Council, and Arthritis Research UK. No conflicts of interest were reported.
SOURCE: Plant D et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40810.
A newly developed gene expression classifier may be able to identify rheumatoid arthritis patients who are unlikely to benefit from methotrexate, according to an analysis of blood samples from patients who had just begun the drug.
“This study highlights the potential of early treatment biomarker monitoring in RA and raises important questions regarding acceptable levels of performance for complementary diagnostic testing,” wrote lead author Darren Plant, PhD, of the University of Manchester (England), and his coauthors. The study was published in Arthritis & Rheumatology.
The study analyzed 85 participants in the Rheumatoid Arthritis Medication Study, a U.K.-based longitudinal observational study of RA patients taking methotrexate for the first time, and classified them as either good responders (n = 42) or nonresponders (n = 43) after 6 months on the drug, based on European League Against Rheumatism response criteria. Dr. Plant and his colleagues then performed gene expression profiling on whole-blood samples from those participants, collected before treatment and after 4 weeks on methotrexate.
Ultimately, pathway analysis indicated an overrepresentation of type 1 interferon signaling pathway genes in nonresponsive patients at both pretreatment (P = 2.8 x 10-25) and 4 weeks (P = 4.9 x 10-28). As such, the coauthors “developed a gene expression classifier that could potentially provide an early response biomarker of methotrexate inefficacy” at 6 months based on the gene expression ratio between 4 weeks and pretreatment, which yielded an area under the receiver operating characteristic curve (ROC AUC) of 0.78. This was proven stable in cross validation and superior to models including clinical covariates (ROC AUC = 0.65).
The authors did not replicate the results in an independent cohort, but the authors noted that the “utility of a gene expression classifier of methotrexate nonresponse now requires validation, not only in independent samples but also using independent technology.”
The study was also potentially limited by the fact that the patients at baseline were atypical in having a long disease duration at a median of 6-9 years but relatively low disease activity, based on a mean 28-joint Disease Activity Score (DAS28) of 4.8 in good responders and 4.0 in nonresponders. The authors also acknowledged both the objective and subjective nature of the DAS28 and its components in approximating disease activity. The authors also did not include a negative predictive value in their analysis, which would have been useful in considering the value of the test.
The study was jointly funded by Pfizer, the Medical Research Council, and Arthritis Research UK. No conflicts of interest were reported.
SOURCE: Plant D et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40810.
A newly developed gene expression classifier may be able to identify rheumatoid arthritis patients who are unlikely to benefit from methotrexate, according to an analysis of blood samples from patients who had just begun the drug.
“This study highlights the potential of early treatment biomarker monitoring in RA and raises important questions regarding acceptable levels of performance for complementary diagnostic testing,” wrote lead author Darren Plant, PhD, of the University of Manchester (England), and his coauthors. The study was published in Arthritis & Rheumatology.
The study analyzed 85 participants in the Rheumatoid Arthritis Medication Study, a U.K.-based longitudinal observational study of RA patients taking methotrexate for the first time, and classified them as either good responders (n = 42) or nonresponders (n = 43) after 6 months on the drug, based on European League Against Rheumatism response criteria. Dr. Plant and his colleagues then performed gene expression profiling on whole-blood samples from those participants, collected before treatment and after 4 weeks on methotrexate.
Ultimately, pathway analysis indicated an overrepresentation of type 1 interferon signaling pathway genes in nonresponsive patients at both pretreatment (P = 2.8 x 10-25) and 4 weeks (P = 4.9 x 10-28). As such, the coauthors “developed a gene expression classifier that could potentially provide an early response biomarker of methotrexate inefficacy” at 6 months based on the gene expression ratio between 4 weeks and pretreatment, which yielded an area under the receiver operating characteristic curve (ROC AUC) of 0.78. This was proven stable in cross validation and superior to models including clinical covariates (ROC AUC = 0.65).
The authors did not replicate the results in an independent cohort, but the authors noted that the “utility of a gene expression classifier of methotrexate nonresponse now requires validation, not only in independent samples but also using independent technology.”
The study was also potentially limited by the fact that the patients at baseline were atypical in having a long disease duration at a median of 6-9 years but relatively low disease activity, based on a mean 28-joint Disease Activity Score (DAS28) of 4.8 in good responders and 4.0 in nonresponders. The authors also acknowledged both the objective and subjective nature of the DAS28 and its components in approximating disease activity. The authors also did not include a negative predictive value in their analysis, which would have been useful in considering the value of the test.
The study was jointly funded by Pfizer, the Medical Research Council, and Arthritis Research UK. No conflicts of interest were reported.
SOURCE: Plant D et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40810.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: A blood test that uses a gene expression ratio between 4 weeks and pretreatment yielded a ROC AUC of 0.78 for predicting methotrexate inefficacy at 6 months.
Study details: An analysis of blood samples from 85 participants in a U.K.-based longitudinal observational study of RA patients starting methotrexate for the first time.
Disclosures: The study was jointly funded by Pfizer, the Medical Research Council, and Arthritis Research UK. No conflicts of interest were reported.
Source: Plant D et al. Arthritis Rheumatol. 2019 Jan 7. doi: 10.1002/art.40810.
Product News January 2019
Ducray Densiage Redensifying Hair Care to Launch in March
Ducray Laboratoires Dermatologiques introduces the Densiage Redensifying hair care line for patients with thin and brittle hair. This line consists of 4 products: the Densiage Redensifying Shampoo to noticeably improve hair quality; the Densiage Redensifying Conditioner to provide detangling benefits and leave hair softer; the Densiage Redensifying Serum to promote development of thicker denser hair with more volume; and the Densiage Dietary Supplement for Aging Hair to provide nutrients to maintain hair density and protect against signs of aging. The line will be available in March 2019. For more information, visit www.ducray.com.
Revance Announces Phase 3 Results for Neuromodulator DaxibotulinumtoxinA
Revance Therapeutics, Inc, works to submit a Biologics License Application with the US Food and Drug Administration in the first half of 2019 for its injectable neuromodulator axibotulinumtoxinA (RT002) following results from a phase 3 open-label, longterm safety study on treating moderate to severe glabellar (frown) lines. Participants received up to 3 treatments of RT002 and were followed for more than 1.5 years. Overall, the safety findings were consistent with the known safety profiles for currently available neuromodulators in aesthetics. Measuring duration of effect, the median time to return to baseline glabellar line severity was 28 weeks. The median time to loss of none or mild wrinkle severity was 24 weeks. The results demonstrate that RT002, utilizing proprietary stabilizing excipient peptide technology in its formulation, produces long duration and high response rates and is well tolerated over successive treatments. For more information, visit www.revance.com.
SNA-120 Demonstrates Potential for Psoriasis in Phase 2b Trial
Sienna Biopharmaceuticals announces results of a phase 2b study of the tropomyosin receptor kinase A (TrkA) inhibitor SNA-120 (pegcantratinib) for mild to moderate psoriasis, with itch as the primary end point. SNA-120 blocks nerve growth factor signaling, which plays an important role in the pathogenesis of psoriasis and itch. Participants (N=208) achieved 58% improvement in itch from baseline; efficacy results indicated 75% reduction in psoriasis area and severity index score from baseline in 27% of participants versus 13% with vehicle, and 29% of participants achieved 2-grade improvement in investigator global assessment versus 13% with vehicle. These results demonstrate the potential of SNA-120 as a topical nonsteroidal treatment of psoriasis. Phase 3 studies for psoriasis will begin in the second half of 2019. For more information, visit www.siennabio.com.
If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@mdedge.com.
Ducray Densiage Redensifying Hair Care to Launch in March
Ducray Laboratoires Dermatologiques introduces the Densiage Redensifying hair care line for patients with thin and brittle hair. This line consists of 4 products: the Densiage Redensifying Shampoo to noticeably improve hair quality; the Densiage Redensifying Conditioner to provide detangling benefits and leave hair softer; the Densiage Redensifying Serum to promote development of thicker denser hair with more volume; and the Densiage Dietary Supplement for Aging Hair to provide nutrients to maintain hair density and protect against signs of aging. The line will be available in March 2019. For more information, visit www.ducray.com.
Revance Announces Phase 3 Results for Neuromodulator DaxibotulinumtoxinA
Revance Therapeutics, Inc, works to submit a Biologics License Application with the US Food and Drug Administration in the first half of 2019 for its injectable neuromodulator axibotulinumtoxinA (RT002) following results from a phase 3 open-label, longterm safety study on treating moderate to severe glabellar (frown) lines. Participants received up to 3 treatments of RT002 and were followed for more than 1.5 years. Overall, the safety findings were consistent with the known safety profiles for currently available neuromodulators in aesthetics. Measuring duration of effect, the median time to return to baseline glabellar line severity was 28 weeks. The median time to loss of none or mild wrinkle severity was 24 weeks. The results demonstrate that RT002, utilizing proprietary stabilizing excipient peptide technology in its formulation, produces long duration and high response rates and is well tolerated over successive treatments. For more information, visit www.revance.com.
SNA-120 Demonstrates Potential for Psoriasis in Phase 2b Trial
Sienna Biopharmaceuticals announces results of a phase 2b study of the tropomyosin receptor kinase A (TrkA) inhibitor SNA-120 (pegcantratinib) for mild to moderate psoriasis, with itch as the primary end point. SNA-120 blocks nerve growth factor signaling, which plays an important role in the pathogenesis of psoriasis and itch. Participants (N=208) achieved 58% improvement in itch from baseline; efficacy results indicated 75% reduction in psoriasis area and severity index score from baseline in 27% of participants versus 13% with vehicle, and 29% of participants achieved 2-grade improvement in investigator global assessment versus 13% with vehicle. These results demonstrate the potential of SNA-120 as a topical nonsteroidal treatment of psoriasis. Phase 3 studies for psoriasis will begin in the second half of 2019. For more information, visit www.siennabio.com.
If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@mdedge.com.
Ducray Densiage Redensifying Hair Care to Launch in March
Ducray Laboratoires Dermatologiques introduces the Densiage Redensifying hair care line for patients with thin and brittle hair. This line consists of 4 products: the Densiage Redensifying Shampoo to noticeably improve hair quality; the Densiage Redensifying Conditioner to provide detangling benefits and leave hair softer; the Densiage Redensifying Serum to promote development of thicker denser hair with more volume; and the Densiage Dietary Supplement for Aging Hair to provide nutrients to maintain hair density and protect against signs of aging. The line will be available in March 2019. For more information, visit www.ducray.com.
Revance Announces Phase 3 Results for Neuromodulator DaxibotulinumtoxinA
Revance Therapeutics, Inc, works to submit a Biologics License Application with the US Food and Drug Administration in the first half of 2019 for its injectable neuromodulator axibotulinumtoxinA (RT002) following results from a phase 3 open-label, longterm safety study on treating moderate to severe glabellar (frown) lines. Participants received up to 3 treatments of RT002 and were followed for more than 1.5 years. Overall, the safety findings were consistent with the known safety profiles for currently available neuromodulators in aesthetics. Measuring duration of effect, the median time to return to baseline glabellar line severity was 28 weeks. The median time to loss of none or mild wrinkle severity was 24 weeks. The results demonstrate that RT002, utilizing proprietary stabilizing excipient peptide technology in its formulation, produces long duration and high response rates and is well tolerated over successive treatments. For more information, visit www.revance.com.
SNA-120 Demonstrates Potential for Psoriasis in Phase 2b Trial
Sienna Biopharmaceuticals announces results of a phase 2b study of the tropomyosin receptor kinase A (TrkA) inhibitor SNA-120 (pegcantratinib) for mild to moderate psoriasis, with itch as the primary end point. SNA-120 blocks nerve growth factor signaling, which plays an important role in the pathogenesis of psoriasis and itch. Participants (N=208) achieved 58% improvement in itch from baseline; efficacy results indicated 75% reduction in psoriasis area and severity index score from baseline in 27% of participants versus 13% with vehicle, and 29% of participants achieved 2-grade improvement in investigator global assessment versus 13% with vehicle. These results demonstrate the potential of SNA-120 as a topical nonsteroidal treatment of psoriasis. Phase 3 studies for psoriasis will begin in the second half of 2019. For more information, visit www.siennabio.com.
If you would like your product included in Product News, please email a press release to the Editorial Office at cutis@mdedge.com.
Population-level rate of SUDEP may have decreased
NEW ORLEANS – according to data described at the annual meeting of the American Epilepsy Society. Whether this decrease resulted from an improved understanding of SUDEP risk or a focus on risk-reduction strategies is unknown, said Daniel Friedman, MD, associate professor of neurology at the New York University Langone Health.
In addition, the rates of SUDEP in various populations differ according to their socioeconomic status. Differences in access to care are a potential, but unconfirmed, explanation for this association, said Dr. Friedman. Another possible explanation is that confounders such as mental health disorders, substance abuse, and insufficient social support affect individuals’ ability to manage their disorder.
Dr. Friedman and colleagues initially examined SUDEP rates over time in a cohort of patients who received vagus nerve stimulator (VNS) implantation for drug-resistant epilepsy. They analyzed data for 40,443 patients who underwent surgery during 1988-2012. The age-adjusted SUDEP rate per 1,000 person-years of follow-up decreased significantly from 2.47 in years 1-2 to 1.68 in years 3-10. “There was no control group, so we couldn’t necessarily attribute the SUDEP rate reduction to the intervention,” said Dr. Friedman. A study by Tomson et al of patients with epilepsy who received VNS implantation had similar findings.
The literature about the mechanisms of SUDEP and reduction of SUDEP risk has increased in recent years. Neurologists have advocated for greater disclosure to patients of SUDEP risk, as well as better risk counseling. Dr. Friedman and his colleagues decided to investigate whether these factors have affected the risk of SUDEP during the past decade.
They retrospectively examined data for people whose deaths had been investigated at medical examiner’s offices in New York City, San Diego County, and Maryland. They focused on decedents for whom epilepsy or seizure was listed as a cause or contributor to death or as a comorbid condition on the death certificate. They reviewed all available reports, including investigator notes, autopsy reports, and medical records. Next, Dr. Friedman and his colleagues calculated the annual SUDEP rate as a proportion of the general population, estimated using annual Census and American Community Survey data. They used the Mann-Kendall test to analyze the trends in SUDEP rate during 2009-2015.
Of 1,466 deaths in people with epilepsy during this period, 1,124 were classified as definite SUDEP, probable SUDEP, or near SUDEP. Approximately 63% of SUDEP cases were male, and 45% were African-American. The mean age at death was 38 years.
Dr. Friedman’s group found a significant decrease in the overall incidence of SUDEP in the total population during 2009-2015. When they examined the three regions separately, they found decreases in SUDEP incidence in New York City and Maryland, but not in San Diego County. They found no difference in SUDEP rates by season or by day of the week.
In a subsequent analysis, Dr. Friedman and his colleagues adjudicated all deaths related to seizure and epilepsy in the three regions during 2009-2010 and 2014-2015 and identified all cases of definite and probable SUDEP. The estimated rate of SUDEP decreased by about 36% from the first period to the second period. SUDEP rates as a proportion of the total population in those regions also declined.
The investigators also examined differences in estimated SUDEP rates in the United States according to median household income. In New York, the zip codes with the highest SUDEP rates tended to have the lowest median household incomes. The zip codes in the lowest quartile of family household income had a SUDEP rate more than twice as high as that in the zip codes in the highest income quartile. This association held true for the period from 2009-2010 and for 2014-2015.
Dr. Friedman and colleagues received funding from Finding a Cure for Epilepsy and Seizures, which is affiliated with the NYU Comprehensive Epilepsy Center and NYU Langone Health.
SOURCE: Cihan E et al. AES 2018, Abstract 2.419.
NEW ORLEANS – according to data described at the annual meeting of the American Epilepsy Society. Whether this decrease resulted from an improved understanding of SUDEP risk or a focus on risk-reduction strategies is unknown, said Daniel Friedman, MD, associate professor of neurology at the New York University Langone Health.
In addition, the rates of SUDEP in various populations differ according to their socioeconomic status. Differences in access to care are a potential, but unconfirmed, explanation for this association, said Dr. Friedman. Another possible explanation is that confounders such as mental health disorders, substance abuse, and insufficient social support affect individuals’ ability to manage their disorder.
Dr. Friedman and colleagues initially examined SUDEP rates over time in a cohort of patients who received vagus nerve stimulator (VNS) implantation for drug-resistant epilepsy. They analyzed data for 40,443 patients who underwent surgery during 1988-2012. The age-adjusted SUDEP rate per 1,000 person-years of follow-up decreased significantly from 2.47 in years 1-2 to 1.68 in years 3-10. “There was no control group, so we couldn’t necessarily attribute the SUDEP rate reduction to the intervention,” said Dr. Friedman. A study by Tomson et al of patients with epilepsy who received VNS implantation had similar findings.
The literature about the mechanisms of SUDEP and reduction of SUDEP risk has increased in recent years. Neurologists have advocated for greater disclosure to patients of SUDEP risk, as well as better risk counseling. Dr. Friedman and his colleagues decided to investigate whether these factors have affected the risk of SUDEP during the past decade.
They retrospectively examined data for people whose deaths had been investigated at medical examiner’s offices in New York City, San Diego County, and Maryland. They focused on decedents for whom epilepsy or seizure was listed as a cause or contributor to death or as a comorbid condition on the death certificate. They reviewed all available reports, including investigator notes, autopsy reports, and medical records. Next, Dr. Friedman and his colleagues calculated the annual SUDEP rate as a proportion of the general population, estimated using annual Census and American Community Survey data. They used the Mann-Kendall test to analyze the trends in SUDEP rate during 2009-2015.
Of 1,466 deaths in people with epilepsy during this period, 1,124 were classified as definite SUDEP, probable SUDEP, or near SUDEP. Approximately 63% of SUDEP cases were male, and 45% were African-American. The mean age at death was 38 years.
Dr. Friedman’s group found a significant decrease in the overall incidence of SUDEP in the total population during 2009-2015. When they examined the three regions separately, they found decreases in SUDEP incidence in New York City and Maryland, but not in San Diego County. They found no difference in SUDEP rates by season or by day of the week.
In a subsequent analysis, Dr. Friedman and his colleagues adjudicated all deaths related to seizure and epilepsy in the three regions during 2009-2010 and 2014-2015 and identified all cases of definite and probable SUDEP. The estimated rate of SUDEP decreased by about 36% from the first period to the second period. SUDEP rates as a proportion of the total population in those regions also declined.
The investigators also examined differences in estimated SUDEP rates in the United States according to median household income. In New York, the zip codes with the highest SUDEP rates tended to have the lowest median household incomes. The zip codes in the lowest quartile of family household income had a SUDEP rate more than twice as high as that in the zip codes in the highest income quartile. This association held true for the period from 2009-2010 and for 2014-2015.
Dr. Friedman and colleagues received funding from Finding a Cure for Epilepsy and Seizures, which is affiliated with the NYU Comprehensive Epilepsy Center and NYU Langone Health.
SOURCE: Cihan E et al. AES 2018, Abstract 2.419.
NEW ORLEANS – according to data described at the annual meeting of the American Epilepsy Society. Whether this decrease resulted from an improved understanding of SUDEP risk or a focus on risk-reduction strategies is unknown, said Daniel Friedman, MD, associate professor of neurology at the New York University Langone Health.
In addition, the rates of SUDEP in various populations differ according to their socioeconomic status. Differences in access to care are a potential, but unconfirmed, explanation for this association, said Dr. Friedman. Another possible explanation is that confounders such as mental health disorders, substance abuse, and insufficient social support affect individuals’ ability to manage their disorder.
Dr. Friedman and colleagues initially examined SUDEP rates over time in a cohort of patients who received vagus nerve stimulator (VNS) implantation for drug-resistant epilepsy. They analyzed data for 40,443 patients who underwent surgery during 1988-2012. The age-adjusted SUDEP rate per 1,000 person-years of follow-up decreased significantly from 2.47 in years 1-2 to 1.68 in years 3-10. “There was no control group, so we couldn’t necessarily attribute the SUDEP rate reduction to the intervention,” said Dr. Friedman. A study by Tomson et al of patients with epilepsy who received VNS implantation had similar findings.
The literature about the mechanisms of SUDEP and reduction of SUDEP risk has increased in recent years. Neurologists have advocated for greater disclosure to patients of SUDEP risk, as well as better risk counseling. Dr. Friedman and his colleagues decided to investigate whether these factors have affected the risk of SUDEP during the past decade.
They retrospectively examined data for people whose deaths had been investigated at medical examiner’s offices in New York City, San Diego County, and Maryland. They focused on decedents for whom epilepsy or seizure was listed as a cause or contributor to death or as a comorbid condition on the death certificate. They reviewed all available reports, including investigator notes, autopsy reports, and medical records. Next, Dr. Friedman and his colleagues calculated the annual SUDEP rate as a proportion of the general population, estimated using annual Census and American Community Survey data. They used the Mann-Kendall test to analyze the trends in SUDEP rate during 2009-2015.
Of 1,466 deaths in people with epilepsy during this period, 1,124 were classified as definite SUDEP, probable SUDEP, or near SUDEP. Approximately 63% of SUDEP cases were male, and 45% were African-American. The mean age at death was 38 years.
Dr. Friedman’s group found a significant decrease in the overall incidence of SUDEP in the total population during 2009-2015. When they examined the three regions separately, they found decreases in SUDEP incidence in New York City and Maryland, but not in San Diego County. They found no difference in SUDEP rates by season or by day of the week.
In a subsequent analysis, Dr. Friedman and his colleagues adjudicated all deaths related to seizure and epilepsy in the three regions during 2009-2010 and 2014-2015 and identified all cases of definite and probable SUDEP. The estimated rate of SUDEP decreased by about 36% from the first period to the second period. SUDEP rates as a proportion of the total population in those regions also declined.
The investigators also examined differences in estimated SUDEP rates in the United States according to median household income. In New York, the zip codes with the highest SUDEP rates tended to have the lowest median household incomes. The zip codes in the lowest quartile of family household income had a SUDEP rate more than twice as high as that in the zip codes in the highest income quartile. This association held true for the period from 2009-2010 and for 2014-2015.
Dr. Friedman and colleagues received funding from Finding a Cure for Epilepsy and Seizures, which is affiliated with the NYU Comprehensive Epilepsy Center and NYU Langone Health.
SOURCE: Cihan E et al. AES 2018, Abstract 2.419.
REPORTING FROM AES 2018
Key clinical point: Data indicate a decline over time in the incidence of SUDEP.
Major finding: The incidence of SUDEP declined by 36% from 2009-2010 to 2014-2015.
Study details: A retrospective analysis of medical examiner data on 1,466 deaths in people with epilepsy.
Disclosures: Finding a Cure for Epilepsy and Seizures provided funding for the study.
Source: Cihan E et al. AES 2018, Abstract 2.419.
