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Helping patients with addictions get, stay clean
Roughly 6 months ago, a primary care physician referred a patient to our clinic for an assessment for opioid use disorder and a recommendation for treatment. The patient estimated, likely underestimated, his daily heroin use to five bags and dropped positive, in addition to heroin, for benzodiazepines, amphetamines, and cannabis. He was in a profession in which public safety was a critical concern, and he refused to notify his employer’s employee assistance program. He also declined to voluntarily admit himself for detox and treatment at the local, fully accredited addiction program, which was affiliated with a major university medical center. Instead, after an Internet search, the patient opted for an opioid treatment center featuring massage therapy, acupuncture, a stable, a sweat lodge – and a magnificent view of the Pacific Ocean.
Mental health professionals and lay people alike are aware of the “opioid crisis” – the derailment of lives, the devastation to communities, the death toll. But despite proposals to increase research funding, policies aimed at tightening the prescribing of opioids, and pledges to ramp up interdiction of heroin traffic, there is often an ignorance and confusion regarding the best, evidence-based approaches to getting patients with substance use disorders clean and keeping them clean.
Unfortunately, as with any crisis, there will be opportunists preying on vulnerable patients and their families. And this travesty has reportedly escalated, as outpatient treatment centers take advantage of laws guaranteeing mental health parity and insurance companies paying out tens of thousands of dollars for residential and outpatient opioid treatment. The potential for significant profit is plainly illustrated by the influx of private equity firms, such as Bain Capital, that are investing heavily in treatment centers.
Reports of malfeasance and misconduct, by owners, operators, staff, and others connected with the industry are beginning to get the attention of authorities. There have been reports of outpatient treatment centers that spend lavishly on furnishing, on BMWs and signed art, yet are understaffed, leading to inadequate one-on-one counseling and even sexual transgressions between residents. There are centers that have been investigated for insurance fraud, such as illegally waiving a copay or a deductible or for charging up to $5,000 for a simple urine five drug screen, often multiple times a day. And there is evidence of “junkie hunters” who cruise for people with addictions and brokers who provide such people with fake addresses in order to qualify for insurance plans with excellent benefits for addiction treatment.
Probably the best means to find a suitable outpatient treatment center is by way of a local, experienced, and respected chemical dependency counselor or physician certified in addiction medicine. If people with substance use disorders and their families want to independently conduct a search, as a good rule of thumb, they should be advised to consider programs affiliated with major medical centers and hospitals or outpatient treatment centers that have been established in good standing for years, in contrast to the rash of pop-up, for-profit programs. Of equal, or even greater importance, is that the prospective center ought to be accredited by a national organization, for example, The Joint Commission, and its staff ought to be licensed and credentialed as well.
In addition, there is merit if the staff has been educated, trained, and supervised under the direction of a respected institution. Needless to add, an outpatient treatment center must use evidence-based practices as the bedrock of treatment; this includes pharmacotherapies such as Suboxone and naltrexone (Vivitrol), and behavioral therapies such as cognitive-behavioral therapy, contingency management, and motivational enhancement. To date, massage and essential oils might be relaxing and pleasurable, but they are not considered accepted standard of care.
It is crucial, too, that an outpatient treatment center have both the resources to reliably handle acute medical detox, which can be a potentially life-threatening emergency, and the medical personnel who can assess and treat such medical conditions as hypertension as well as psychiatric illnesses such as bipolar and generalized anxiety disorders. A prospective patient also should inquire whether any of the staff has been the subject of disciplinary action by a licensing board or whether the center has been investigated by the state or a national accrediting organization.
Because addiction so often has facets rooted in the family system, and recovery so often depends on family support, an outpatient treatment center should provide a structured family program integrated into the patient’s treatment and emphasize the importance of continued family involvement after discharge.
Lastly, the best treatment centers often regularly update a patient’s local therapist and physician, spell out the elements of successful aftercare (12-step programs, and so on), and provide amenities, such as calls to a recently discharged patient and an alumni support network.
Dr. Marseille is a psychiatrist who works on the staff of a clinic in Wheaton, Ill. His special interests include adolescent and addiction medicine, eating disorders, trauma, bipolar disorder, and the psychiatric manifestations of acute and chronic medical conditions.
This article was updated 12/15/17.
Roughly 6 months ago, a primary care physician referred a patient to our clinic for an assessment for opioid use disorder and a recommendation for treatment. The patient estimated, likely underestimated, his daily heroin use to five bags and dropped positive, in addition to heroin, for benzodiazepines, amphetamines, and cannabis. He was in a profession in which public safety was a critical concern, and he refused to notify his employer’s employee assistance program. He also declined to voluntarily admit himself for detox and treatment at the local, fully accredited addiction program, which was affiliated with a major university medical center. Instead, after an Internet search, the patient opted for an opioid treatment center featuring massage therapy, acupuncture, a stable, a sweat lodge – and a magnificent view of the Pacific Ocean.
Mental health professionals and lay people alike are aware of the “opioid crisis” – the derailment of lives, the devastation to communities, the death toll. But despite proposals to increase research funding, policies aimed at tightening the prescribing of opioids, and pledges to ramp up interdiction of heroin traffic, there is often an ignorance and confusion regarding the best, evidence-based approaches to getting patients with substance use disorders clean and keeping them clean.
Unfortunately, as with any crisis, there will be opportunists preying on vulnerable patients and their families. And this travesty has reportedly escalated, as outpatient treatment centers take advantage of laws guaranteeing mental health parity and insurance companies paying out tens of thousands of dollars for residential and outpatient opioid treatment. The potential for significant profit is plainly illustrated by the influx of private equity firms, such as Bain Capital, that are investing heavily in treatment centers.
Reports of malfeasance and misconduct, by owners, operators, staff, and others connected with the industry are beginning to get the attention of authorities. There have been reports of outpatient treatment centers that spend lavishly on furnishing, on BMWs and signed art, yet are understaffed, leading to inadequate one-on-one counseling and even sexual transgressions between residents. There are centers that have been investigated for insurance fraud, such as illegally waiving a copay or a deductible or for charging up to $5,000 for a simple urine five drug screen, often multiple times a day. And there is evidence of “junkie hunters” who cruise for people with addictions and brokers who provide such people with fake addresses in order to qualify for insurance plans with excellent benefits for addiction treatment.
Probably the best means to find a suitable outpatient treatment center is by way of a local, experienced, and respected chemical dependency counselor or physician certified in addiction medicine. If people with substance use disorders and their families want to independently conduct a search, as a good rule of thumb, they should be advised to consider programs affiliated with major medical centers and hospitals or outpatient treatment centers that have been established in good standing for years, in contrast to the rash of pop-up, for-profit programs. Of equal, or even greater importance, is that the prospective center ought to be accredited by a national organization, for example, The Joint Commission, and its staff ought to be licensed and credentialed as well.
In addition, there is merit if the staff has been educated, trained, and supervised under the direction of a respected institution. Needless to add, an outpatient treatment center must use evidence-based practices as the bedrock of treatment; this includes pharmacotherapies such as Suboxone and naltrexone (Vivitrol), and behavioral therapies such as cognitive-behavioral therapy, contingency management, and motivational enhancement. To date, massage and essential oils might be relaxing and pleasurable, but they are not considered accepted standard of care.
It is crucial, too, that an outpatient treatment center have both the resources to reliably handle acute medical detox, which can be a potentially life-threatening emergency, and the medical personnel who can assess and treat such medical conditions as hypertension as well as psychiatric illnesses such as bipolar and generalized anxiety disorders. A prospective patient also should inquire whether any of the staff has been the subject of disciplinary action by a licensing board or whether the center has been investigated by the state or a national accrediting organization.
Because addiction so often has facets rooted in the family system, and recovery so often depends on family support, an outpatient treatment center should provide a structured family program integrated into the patient’s treatment and emphasize the importance of continued family involvement after discharge.
Lastly, the best treatment centers often regularly update a patient’s local therapist and physician, spell out the elements of successful aftercare (12-step programs, and so on), and provide amenities, such as calls to a recently discharged patient and an alumni support network.
Dr. Marseille is a psychiatrist who works on the staff of a clinic in Wheaton, Ill. His special interests include adolescent and addiction medicine, eating disorders, trauma, bipolar disorder, and the psychiatric manifestations of acute and chronic medical conditions.
This article was updated 12/15/17.
Roughly 6 months ago, a primary care physician referred a patient to our clinic for an assessment for opioid use disorder and a recommendation for treatment. The patient estimated, likely underestimated, his daily heroin use to five bags and dropped positive, in addition to heroin, for benzodiazepines, amphetamines, and cannabis. He was in a profession in which public safety was a critical concern, and he refused to notify his employer’s employee assistance program. He also declined to voluntarily admit himself for detox and treatment at the local, fully accredited addiction program, which was affiliated with a major university medical center. Instead, after an Internet search, the patient opted for an opioid treatment center featuring massage therapy, acupuncture, a stable, a sweat lodge – and a magnificent view of the Pacific Ocean.
Mental health professionals and lay people alike are aware of the “opioid crisis” – the derailment of lives, the devastation to communities, the death toll. But despite proposals to increase research funding, policies aimed at tightening the prescribing of opioids, and pledges to ramp up interdiction of heroin traffic, there is often an ignorance and confusion regarding the best, evidence-based approaches to getting patients with substance use disorders clean and keeping them clean.
Unfortunately, as with any crisis, there will be opportunists preying on vulnerable patients and their families. And this travesty has reportedly escalated, as outpatient treatment centers take advantage of laws guaranteeing mental health parity and insurance companies paying out tens of thousands of dollars for residential and outpatient opioid treatment. The potential for significant profit is plainly illustrated by the influx of private equity firms, such as Bain Capital, that are investing heavily in treatment centers.
Reports of malfeasance and misconduct, by owners, operators, staff, and others connected with the industry are beginning to get the attention of authorities. There have been reports of outpatient treatment centers that spend lavishly on furnishing, on BMWs and signed art, yet are understaffed, leading to inadequate one-on-one counseling and even sexual transgressions between residents. There are centers that have been investigated for insurance fraud, such as illegally waiving a copay or a deductible or for charging up to $5,000 for a simple urine five drug screen, often multiple times a day. And there is evidence of “junkie hunters” who cruise for people with addictions and brokers who provide such people with fake addresses in order to qualify for insurance plans with excellent benefits for addiction treatment.
Probably the best means to find a suitable outpatient treatment center is by way of a local, experienced, and respected chemical dependency counselor or physician certified in addiction medicine. If people with substance use disorders and their families want to independently conduct a search, as a good rule of thumb, they should be advised to consider programs affiliated with major medical centers and hospitals or outpatient treatment centers that have been established in good standing for years, in contrast to the rash of pop-up, for-profit programs. Of equal, or even greater importance, is that the prospective center ought to be accredited by a national organization, for example, The Joint Commission, and its staff ought to be licensed and credentialed as well.
In addition, there is merit if the staff has been educated, trained, and supervised under the direction of a respected institution. Needless to add, an outpatient treatment center must use evidence-based practices as the bedrock of treatment; this includes pharmacotherapies such as Suboxone and naltrexone (Vivitrol), and behavioral therapies such as cognitive-behavioral therapy, contingency management, and motivational enhancement. To date, massage and essential oils might be relaxing and pleasurable, but they are not considered accepted standard of care.
It is crucial, too, that an outpatient treatment center have both the resources to reliably handle acute medical detox, which can be a potentially life-threatening emergency, and the medical personnel who can assess and treat such medical conditions as hypertension as well as psychiatric illnesses such as bipolar and generalized anxiety disorders. A prospective patient also should inquire whether any of the staff has been the subject of disciplinary action by a licensing board or whether the center has been investigated by the state or a national accrediting organization.
Because addiction so often has facets rooted in the family system, and recovery so often depends on family support, an outpatient treatment center should provide a structured family program integrated into the patient’s treatment and emphasize the importance of continued family involvement after discharge.
Lastly, the best treatment centers often regularly update a patient’s local therapist and physician, spell out the elements of successful aftercare (12-step programs, and so on), and provide amenities, such as calls to a recently discharged patient and an alumni support network.
Dr. Marseille is a psychiatrist who works on the staff of a clinic in Wheaton, Ill. His special interests include adolescent and addiction medicine, eating disorders, trauma, bipolar disorder, and the psychiatric manifestations of acute and chronic medical conditions.
This article was updated 12/15/17.
FDA approves premixed, low-volume colon-cleansing solution
in adults preparing to undergo colonoscopy, according to Ferring Pharmaceuticals.
The sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution is a relatively low-volume, premixed, cranberry-flavored solution, making it easier to use and more palatable for patients.
The oral solution is approved with two dosing options: split dose, one dose the evening prior and one dose the morning of the procedure, or the day before dose, which involves taking both doses the day prior to the procedure. Day before dosing is an alternative and should be used when split dosing is not appropriate. After each dose of sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution, clear liquids should be consumed based on the dosing recommendation. The American College of Gastroenterology recommends the split-dose regimen because of its improved cleansing quality of the colon and better tolerability of the liquid volume by patients.
Patients with impaired renal function should exercise caution if using sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution as it may effect renal function. A more comprehensive list of safety information is available at www.clenpiq.com.
in adults preparing to undergo colonoscopy, according to Ferring Pharmaceuticals.
The sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution is a relatively low-volume, premixed, cranberry-flavored solution, making it easier to use and more palatable for patients.
The oral solution is approved with two dosing options: split dose, one dose the evening prior and one dose the morning of the procedure, or the day before dose, which involves taking both doses the day prior to the procedure. Day before dosing is an alternative and should be used when split dosing is not appropriate. After each dose of sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution, clear liquids should be consumed based on the dosing recommendation. The American College of Gastroenterology recommends the split-dose regimen because of its improved cleansing quality of the colon and better tolerability of the liquid volume by patients.
Patients with impaired renal function should exercise caution if using sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution as it may effect renal function. A more comprehensive list of safety information is available at www.clenpiq.com.
in adults preparing to undergo colonoscopy, according to Ferring Pharmaceuticals.
The sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution is a relatively low-volume, premixed, cranberry-flavored solution, making it easier to use and more palatable for patients.
The oral solution is approved with two dosing options: split dose, one dose the evening prior and one dose the morning of the procedure, or the day before dose, which involves taking both doses the day prior to the procedure. Day before dosing is an alternative and should be used when split dosing is not appropriate. After each dose of sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution, clear liquids should be consumed based on the dosing recommendation. The American College of Gastroenterology recommends the split-dose regimen because of its improved cleansing quality of the colon and better tolerability of the liquid volume by patients.
Patients with impaired renal function should exercise caution if using sodium picosulfate, magnesium oxide, and anhydrous citric acid oral solution as it may effect renal function. A more comprehensive list of safety information is available at www.clenpiq.com.
Sprifermin shows cartilage-building potential in knee OA patients
in the initial 2-year results of the ongoing FORWARD trial.
“Sprifermin appears to be the first investigational medicinal product to show dose-dependent prevention of cartilage loss and an increase in cartilage thickness, not only in the total tibiofemoral joint [TFJ] but also in both the medial and lateral compartments, including the central medial femorotibial region,” said Marc H. Hochberg, MD, primary investigator in the trial and division head of rheumatology and clinical immunology at the University of Maryland, Baltimore. “The recommendation is that these findings should be further evaluated in phase 3 clinical trials.”
He and his colleagues randomized 549 osteoarthritis (OA) patients to double-blind treatment with one of four different dosing regimens of sprifermin or placebo. These patients were aged 40-85 with symptomatic radiographic primary femorotibial knee OA measuring grade 2 or 3 on the Kellgren-Lawrence scale and a medial minimum joint space width (mJSW) 2.5 mm or greater.
At 2 years, researchers observed a significant dose-dependent relationship between the amount of sprifermin given and the increase in total TFJ cartilage thickness. Patients who received three 100-mcg intra-articular injections of sprifermin every 6 months (group 1) showed a gain in TFJ cartilage thickness of 0.03 mm as seen on MRI, while those who received three 100-mcg injections of sprifermin every 12 months (group 2) had a gain of 0.02 mm, Dr. Hochberg said during a late-breaking abstract session at the annual meeting of the American College of Rheumatology. By contrast, those who received placebo had a loss in TFJ cartilage thickness of 0.02 mm (P less than .001). The other two groups received 30 mcg of sprifermin in three weekly injections every 6 months (group 3) or every 12 months (group 4), and these had TFJ cartilage thickness losses of about 0.01 mm or less.
Similar dose-dependent relationships were observed for some of the secondary endpoints, which included changes in cartilage thickness seen in the medial and lateral compartments, changes in cartilage thickness in the compartments’ subregions, and changes in mJSW. Significant differences in cartilage thickness were observed between sprifermin treatment groups and placebo in the medial (group 1, gain of 0.02 mm vs. loss of 0.03 mm; P less than .001) and lateral (groups 1 and 2, gain of 0.04 mm vs. loss of 0.01 mm; P less than .001) TFJ compartments, and in central medial and lateral TFJ subregions.
Changes in mJSW as seen on x-ray between those in group 1 and those on placebo were significant for the lateral compartment, with an increase in mJSW at the higher doses and a decline in the placebo group, but not for the medial compartment.
There were no significant differences in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores among the treatment groups. Dr. Hochberg noted that patients were permitted to take pain medications during the study, which could have affected this result.
The most frequently reported adverse events were musculoskeletal and connective tissue disorders, specifically arthralgias and back pain, Dr. Hochberg said. The incidence of acute inflammatory reactions was higher with sprifermin, compared with placebo, but the increase was only significant after the first injection cycle, he said.
Merck KGaA and the EMD Serono Research Institute funded the study. Dr. Hochberg reported receiving consulting fees from numerous companies that market or are developing OA drugs, including EMD Serono.
in the initial 2-year results of the ongoing FORWARD trial.
“Sprifermin appears to be the first investigational medicinal product to show dose-dependent prevention of cartilage loss and an increase in cartilage thickness, not only in the total tibiofemoral joint [TFJ] but also in both the medial and lateral compartments, including the central medial femorotibial region,” said Marc H. Hochberg, MD, primary investigator in the trial and division head of rheumatology and clinical immunology at the University of Maryland, Baltimore. “The recommendation is that these findings should be further evaluated in phase 3 clinical trials.”
He and his colleagues randomized 549 osteoarthritis (OA) patients to double-blind treatment with one of four different dosing regimens of sprifermin or placebo. These patients were aged 40-85 with symptomatic radiographic primary femorotibial knee OA measuring grade 2 or 3 on the Kellgren-Lawrence scale and a medial minimum joint space width (mJSW) 2.5 mm or greater.
At 2 years, researchers observed a significant dose-dependent relationship between the amount of sprifermin given and the increase in total TFJ cartilage thickness. Patients who received three 100-mcg intra-articular injections of sprifermin every 6 months (group 1) showed a gain in TFJ cartilage thickness of 0.03 mm as seen on MRI, while those who received three 100-mcg injections of sprifermin every 12 months (group 2) had a gain of 0.02 mm, Dr. Hochberg said during a late-breaking abstract session at the annual meeting of the American College of Rheumatology. By contrast, those who received placebo had a loss in TFJ cartilage thickness of 0.02 mm (P less than .001). The other two groups received 30 mcg of sprifermin in three weekly injections every 6 months (group 3) or every 12 months (group 4), and these had TFJ cartilage thickness losses of about 0.01 mm or less.
Similar dose-dependent relationships were observed for some of the secondary endpoints, which included changes in cartilage thickness seen in the medial and lateral compartments, changes in cartilage thickness in the compartments’ subregions, and changes in mJSW. Significant differences in cartilage thickness were observed between sprifermin treatment groups and placebo in the medial (group 1, gain of 0.02 mm vs. loss of 0.03 mm; P less than .001) and lateral (groups 1 and 2, gain of 0.04 mm vs. loss of 0.01 mm; P less than .001) TFJ compartments, and in central medial and lateral TFJ subregions.
Changes in mJSW as seen on x-ray between those in group 1 and those on placebo were significant for the lateral compartment, with an increase in mJSW at the higher doses and a decline in the placebo group, but not for the medial compartment.
There were no significant differences in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores among the treatment groups. Dr. Hochberg noted that patients were permitted to take pain medications during the study, which could have affected this result.
The most frequently reported adverse events were musculoskeletal and connective tissue disorders, specifically arthralgias and back pain, Dr. Hochberg said. The incidence of acute inflammatory reactions was higher with sprifermin, compared with placebo, but the increase was only significant after the first injection cycle, he said.
Merck KGaA and the EMD Serono Research Institute funded the study. Dr. Hochberg reported receiving consulting fees from numerous companies that market or are developing OA drugs, including EMD Serono.
in the initial 2-year results of the ongoing FORWARD trial.
“Sprifermin appears to be the first investigational medicinal product to show dose-dependent prevention of cartilage loss and an increase in cartilage thickness, not only in the total tibiofemoral joint [TFJ] but also in both the medial and lateral compartments, including the central medial femorotibial region,” said Marc H. Hochberg, MD, primary investigator in the trial and division head of rheumatology and clinical immunology at the University of Maryland, Baltimore. “The recommendation is that these findings should be further evaluated in phase 3 clinical trials.”
He and his colleagues randomized 549 osteoarthritis (OA) patients to double-blind treatment with one of four different dosing regimens of sprifermin or placebo. These patients were aged 40-85 with symptomatic radiographic primary femorotibial knee OA measuring grade 2 or 3 on the Kellgren-Lawrence scale and a medial minimum joint space width (mJSW) 2.5 mm or greater.
At 2 years, researchers observed a significant dose-dependent relationship between the amount of sprifermin given and the increase in total TFJ cartilage thickness. Patients who received three 100-mcg intra-articular injections of sprifermin every 6 months (group 1) showed a gain in TFJ cartilage thickness of 0.03 mm as seen on MRI, while those who received three 100-mcg injections of sprifermin every 12 months (group 2) had a gain of 0.02 mm, Dr. Hochberg said during a late-breaking abstract session at the annual meeting of the American College of Rheumatology. By contrast, those who received placebo had a loss in TFJ cartilage thickness of 0.02 mm (P less than .001). The other two groups received 30 mcg of sprifermin in three weekly injections every 6 months (group 3) or every 12 months (group 4), and these had TFJ cartilage thickness losses of about 0.01 mm or less.
Similar dose-dependent relationships were observed for some of the secondary endpoints, which included changes in cartilage thickness seen in the medial and lateral compartments, changes in cartilage thickness in the compartments’ subregions, and changes in mJSW. Significant differences in cartilage thickness were observed between sprifermin treatment groups and placebo in the medial (group 1, gain of 0.02 mm vs. loss of 0.03 mm; P less than .001) and lateral (groups 1 and 2, gain of 0.04 mm vs. loss of 0.01 mm; P less than .001) TFJ compartments, and in central medial and lateral TFJ subregions.
Changes in mJSW as seen on x-ray between those in group 1 and those on placebo were significant for the lateral compartment, with an increase in mJSW at the higher doses and a decline in the placebo group, but not for the medial compartment.
There were no significant differences in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores among the treatment groups. Dr. Hochberg noted that patients were permitted to take pain medications during the study, which could have affected this result.
The most frequently reported adverse events were musculoskeletal and connective tissue disorders, specifically arthralgias and back pain, Dr. Hochberg said. The incidence of acute inflammatory reactions was higher with sprifermin, compared with placebo, but the increase was only significant after the first injection cycle, he said.
Merck KGaA and the EMD Serono Research Institute funded the study. Dr. Hochberg reported receiving consulting fees from numerous companies that market or are developing OA drugs, including EMD Serono.
REPORTING FROM ACR 2017
Key clinical point: Sprifermin may help build knee joint cartilage in patients with OA.
Major finding: Patients taking sprifermin 100 mcg three times a week every 6 months or every 12 months had gains in tibiofemoral joint cartilage thickness of 0.03 mm and 0.02 mm, respectively, over a 2-year period.
Study details: A study of 549 patients with symptomatic knee OA randomized to receive either 30 mcg or 100 mcg of sprifermin three times a week every 6 or every 12 months, or placebo.
Disclosures: Merck KGaA and the EMD Serono Research Institute funded the study. The presenter reported receiving consulting fees from numerous companies that market or are developing OA drugs, including EMD Serono.
Source: Hochberg M et al. ACR 2017 abstract 1L.
New HIV vaccine trial launched in Africa
The National Institutes of Health has partnered with Janssen Vaccines & Prevention B.V. to conduct the phase 2b proof-of-concept “Imbokodo” study of a quadrivalent HIV vaccine regimen using “mosaic” immunogens, which means the vaccine components are designed to trigger an immune response against a variety of HIV strains.
Preclinical studies in monkeys suggest this approach can protect against HIV infection, and two early-stage clinical trials in humans showed the vaccine was well tolerated and generated immune responses against HIV in healthy individuals.
The four doses of the vaccine will be spread out over a year, and the final two doses will be given together with doses of an HIV protein, clade C gp140, and an aluminum phosphate adjuvant to boost immune responses. The study has already begun to immunize some of the 2,600 HIV-negative sub-Saharan African women to be recruited for the study.
The study is sponsored by Janssen Vaccines & Prevention B.V. and cofunded by the Bill & Melinda Gates Foundation and the NIH.
SOURCE: National Institute of Allergy and Infectious Diseases News Releases Nov. 30, 2017.
The National Institutes of Health has partnered with Janssen Vaccines & Prevention B.V. to conduct the phase 2b proof-of-concept “Imbokodo” study of a quadrivalent HIV vaccine regimen using “mosaic” immunogens, which means the vaccine components are designed to trigger an immune response against a variety of HIV strains.
Preclinical studies in monkeys suggest this approach can protect against HIV infection, and two early-stage clinical trials in humans showed the vaccine was well tolerated and generated immune responses against HIV in healthy individuals.
The four doses of the vaccine will be spread out over a year, and the final two doses will be given together with doses of an HIV protein, clade C gp140, and an aluminum phosphate adjuvant to boost immune responses. The study has already begun to immunize some of the 2,600 HIV-negative sub-Saharan African women to be recruited for the study.
The study is sponsored by Janssen Vaccines & Prevention B.V. and cofunded by the Bill & Melinda Gates Foundation and the NIH.
SOURCE: National Institute of Allergy and Infectious Diseases News Releases Nov. 30, 2017.
The National Institutes of Health has partnered with Janssen Vaccines & Prevention B.V. to conduct the phase 2b proof-of-concept “Imbokodo” study of a quadrivalent HIV vaccine regimen using “mosaic” immunogens, which means the vaccine components are designed to trigger an immune response against a variety of HIV strains.
Preclinical studies in monkeys suggest this approach can protect against HIV infection, and two early-stage clinical trials in humans showed the vaccine was well tolerated and generated immune responses against HIV in healthy individuals.
The four doses of the vaccine will be spread out over a year, and the final two doses will be given together with doses of an HIV protein, clade C gp140, and an aluminum phosphate adjuvant to boost immune responses. The study has already begun to immunize some of the 2,600 HIV-negative sub-Saharan African women to be recruited for the study.
The study is sponsored by Janssen Vaccines & Prevention B.V. and cofunded by the Bill & Melinda Gates Foundation and the NIH.
SOURCE: National Institute of Allergy and Infectious Diseases News Releases Nov. 30, 2017.
VIDEO: Ibrutinib PFS is nearly 3 years in MCL patients who had one prior therapy
ATLANTA – Ibrutinib yielded a median progression-free survival (PFS) of nearly 3 years for patients with relapsed or refractory mantle cell lymphoma (MCL) treated with the agent after just one prior line of therapy, according to pooled long-term follow-up data presented at the annual meeting of the American Society of Hematology.
With a 3.5-year median follow-up, a median PFS of 33.6 months was reported for MCL patients with one prior line of therapy, compared to 8.4 months for patients who had two or more prior lines of therapy, reported lead study author Simon Rule, MD, of Plymouth (England) University Medical School.
“I think the take-home message from the ibrutinib data is the earlier you use the drug in the relapse setting, the better the outcomes you’re going to get,” Dr. Rule said in an interview. “It is quite dramatic, the difference between one prior line of therapy and subsequent lines of therapy.”
Response rates were also higher in MCL patients who had only one prior line of therapy, Dr. Rule said.
The overall and complete response rates for that group were 77.8% and 36.4%, respectively, according to data Dr. Rule presented in an oral presentation. For patients receiving more than one line of therapy prior to ibrutinib, overall and complete response rates were 66.8% and 22.9%.
The pooled analysis presented by Dr. Rule included 370 patients enrolled in ibrutinib trials between 2011 and 2013. Patients in those trials received oral ibrutinib 560 mg daily until progressive disease or unacceptable toxicity.
Patients achieving a CR had an “extraordinary” PFS of nearly 4 years and a median duration of response of 55 months, Dr. Rule said.
Atrial fibrillation (AF) rates were reported to be 5.7% (21/370 patients). A total of 53 patients in the analysis had ongoing controlled AF/arrhythmia or had a history of it. Over the course of follow-up, 70% of them (37 patients) had no recurrences, according to Dr. Rule and his colleagues.
No patients discontinued ibrutinib because of grade 3-4 AF, they reported. Moreover, less than 2% of the 370 patients discontinued or reduced dose of ibrutinib because of grade 3-4 bleeding or AF.
New onset grade 3-4 adverse events were more common in the first year of treatment and generally were less frequent over time, Dr. Rule said.
Patients with only one prior line of therapy were less likely to have grade 3-4 adverse events, suggesting again that “the earlier you use [ibrutinib], the fewer side effects you get, particularly with hematologic toxicity,” Dr. Rule said.
Sponsorship for the research came from Janssen, and funding for writing assistance came from Janssen Global Services. Dr. Rule reported financial relationships with Janssen and several other companies.
SOURCE: Rule S et al. ASH 2017 Abstract 151.
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ATLANTA – Ibrutinib yielded a median progression-free survival (PFS) of nearly 3 years for patients with relapsed or refractory mantle cell lymphoma (MCL) treated with the agent after just one prior line of therapy, according to pooled long-term follow-up data presented at the annual meeting of the American Society of Hematology.
With a 3.5-year median follow-up, a median PFS of 33.6 months was reported for MCL patients with one prior line of therapy, compared to 8.4 months for patients who had two or more prior lines of therapy, reported lead study author Simon Rule, MD, of Plymouth (England) University Medical School.
“I think the take-home message from the ibrutinib data is the earlier you use the drug in the relapse setting, the better the outcomes you’re going to get,” Dr. Rule said in an interview. “It is quite dramatic, the difference between one prior line of therapy and subsequent lines of therapy.”
Response rates were also higher in MCL patients who had only one prior line of therapy, Dr. Rule said.
The overall and complete response rates for that group were 77.8% and 36.4%, respectively, according to data Dr. Rule presented in an oral presentation. For patients receiving more than one line of therapy prior to ibrutinib, overall and complete response rates were 66.8% and 22.9%.
The pooled analysis presented by Dr. Rule included 370 patients enrolled in ibrutinib trials between 2011 and 2013. Patients in those trials received oral ibrutinib 560 mg daily until progressive disease or unacceptable toxicity.
Patients achieving a CR had an “extraordinary” PFS of nearly 4 years and a median duration of response of 55 months, Dr. Rule said.
Atrial fibrillation (AF) rates were reported to be 5.7% (21/370 patients). A total of 53 patients in the analysis had ongoing controlled AF/arrhythmia or had a history of it. Over the course of follow-up, 70% of them (37 patients) had no recurrences, according to Dr. Rule and his colleagues.
No patients discontinued ibrutinib because of grade 3-4 AF, they reported. Moreover, less than 2% of the 370 patients discontinued or reduced dose of ibrutinib because of grade 3-4 bleeding or AF.
New onset grade 3-4 adverse events were more common in the first year of treatment and generally were less frequent over time, Dr. Rule said.
Patients with only one prior line of therapy were less likely to have grade 3-4 adverse events, suggesting again that “the earlier you use [ibrutinib], the fewer side effects you get, particularly with hematologic toxicity,” Dr. Rule said.
Sponsorship for the research came from Janssen, and funding for writing assistance came from Janssen Global Services. Dr. Rule reported financial relationships with Janssen and several other companies.
SOURCE: Rule S et al. ASH 2017 Abstract 151.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
ATLANTA – Ibrutinib yielded a median progression-free survival (PFS) of nearly 3 years for patients with relapsed or refractory mantle cell lymphoma (MCL) treated with the agent after just one prior line of therapy, according to pooled long-term follow-up data presented at the annual meeting of the American Society of Hematology.
With a 3.5-year median follow-up, a median PFS of 33.6 months was reported for MCL patients with one prior line of therapy, compared to 8.4 months for patients who had two or more prior lines of therapy, reported lead study author Simon Rule, MD, of Plymouth (England) University Medical School.
“I think the take-home message from the ibrutinib data is the earlier you use the drug in the relapse setting, the better the outcomes you’re going to get,” Dr. Rule said in an interview. “It is quite dramatic, the difference between one prior line of therapy and subsequent lines of therapy.”
Response rates were also higher in MCL patients who had only one prior line of therapy, Dr. Rule said.
The overall and complete response rates for that group were 77.8% and 36.4%, respectively, according to data Dr. Rule presented in an oral presentation. For patients receiving more than one line of therapy prior to ibrutinib, overall and complete response rates were 66.8% and 22.9%.
The pooled analysis presented by Dr. Rule included 370 patients enrolled in ibrutinib trials between 2011 and 2013. Patients in those trials received oral ibrutinib 560 mg daily until progressive disease or unacceptable toxicity.
Patients achieving a CR had an “extraordinary” PFS of nearly 4 years and a median duration of response of 55 months, Dr. Rule said.
Atrial fibrillation (AF) rates were reported to be 5.7% (21/370 patients). A total of 53 patients in the analysis had ongoing controlled AF/arrhythmia or had a history of it. Over the course of follow-up, 70% of them (37 patients) had no recurrences, according to Dr. Rule and his colleagues.
No patients discontinued ibrutinib because of grade 3-4 AF, they reported. Moreover, less than 2% of the 370 patients discontinued or reduced dose of ibrutinib because of grade 3-4 bleeding or AF.
New onset grade 3-4 adverse events were more common in the first year of treatment and generally were less frequent over time, Dr. Rule said.
Patients with only one prior line of therapy were less likely to have grade 3-4 adverse events, suggesting again that “the earlier you use [ibrutinib], the fewer side effects you get, particularly with hematologic toxicity,” Dr. Rule said.
Sponsorship for the research came from Janssen, and funding for writing assistance came from Janssen Global Services. Dr. Rule reported financial relationships with Janssen and several other companies.
SOURCE: Rule S et al. ASH 2017 Abstract 151.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
REPORTING FROM ASH 2017
Key clinical point:
Major finding: Median PFS was 33.6 months for MCL patients with one prior line of therapy, versus 8.4 months for patients who had two or more prior lines of therapy.
Study details: A pooled analysis of 370 patients enrolled in ibrutinib clinical trials with a median 3.5-year follow-up.
Disclosures: Janssen sponsored the research and Janssen Global Services funded writing assistance. Lead author Simon Rule, MD, reported financial relationships with Janssen and several other companies.
Source: Rule S et al. ASH 2017 Abstract 151.
Intrauterine exposure to methylphenidate tied to increased cardiac risk
The use of methylphenidate by pregnant women is associated with a small increased risk of congenital cardiac malformations in newborns. However, a comparable increased risk is not found with intrauterine exposure to stimulants, according to a population-based cohort study published Dec. 13.
Krista F. Huybrechts, PhD, and her associates analyzed data from more than 1 million pregnancies in the United States. They found that the overall incidence of congenital malformations among the 1,813,894 pregnancies was 35 per 1,000 control infants, compared with 45.9 per 1,000 infants whose mothers used methylphenidate and 45.4 per 1,000 infants whose mothers used amphetamines. 
For the subset of infants with cardiac malformations, the risk per 1,000 infants was 12.7 for controls, 18.8 for methylphenidate exposure, and 15.4 for amphetamine exposure. The researchers identified an adjusted relative risk of 1.11 for overall congenital abnormalities and 1.28 for cardiac abnormalities with methylphenidate exposure, compared with a relative risk of 1.05 for overall congenital abnormalities and 0.96 for cardiac abnormalities with stimulant exposure.
An analysis among 2,560,069 pregnancies in Denmark, Finland, Iceland, Norway, and Sweden yielded a similarly significant relative risk of 1.28 for cardiac malformations associated with methylphenidate exposure (JAMA Psychiatry 2017. doi: 10.1001/jamapsychiatry.2017.3644).
“We found a 28% increased prevalence of cardiac malformations after first-trimester exposure to methylphenidate,” wrote Dr. Huybrechts of Brigham and Women’s Hospital, Boston, and her associates. “Although the absolute risk is small, it is nevertheless important evidence to consider when weighing the potential risks and benefits of different treatment strategies for [attention-deficit/hyperactivity disorder] in young women of reproductive age and in pregnant women.”
The researchers had no financial conflicts to disclose. The study was supported in part by grants from the National Institutes of Mental Health, the Eunice Kennedy Shriver National Institute for Child Health & Human Development, and the Söderström König Foundation.
The use of methylphenidate by pregnant women is associated with a small increased risk of congenital cardiac malformations in newborns. However, a comparable increased risk is not found with intrauterine exposure to stimulants, according to a population-based cohort study published Dec. 13.
Krista F. Huybrechts, PhD, and her associates analyzed data from more than 1 million pregnancies in the United States. They found that the overall incidence of congenital malformations among the 1,813,894 pregnancies was 35 per 1,000 control infants, compared with 45.9 per 1,000 infants whose mothers used methylphenidate and 45.4 per 1,000 infants whose mothers used amphetamines.
For the subset of infants with cardiac malformations, the risk per 1,000 infants was 12.7 for controls, 18.8 for methylphenidate exposure, and 15.4 for amphetamine exposure. The researchers identified an adjusted relative risk of 1.11 for overall congenital abnormalities and 1.28 for cardiac abnormalities with methylphenidate exposure, compared with a relative risk of 1.05 for overall congenital abnormalities and 0.96 for cardiac abnormalities with stimulant exposure.
An analysis among 2,560,069 pregnancies in Denmark, Finland, Iceland, Norway, and Sweden yielded a similarly significant relative risk of 1.28 for cardiac malformations associated with methylphenidate exposure (JAMA Psychiatry 2017. doi: 10.1001/jamapsychiatry.2017.3644).
“We found a 28% increased prevalence of cardiac malformations after first-trimester exposure to methylphenidate,” wrote Dr. Huybrechts of Brigham and Women’s Hospital, Boston, and her associates. “Although the absolute risk is small, it is nevertheless important evidence to consider when weighing the potential risks and benefits of different treatment strategies for [attention-deficit/hyperactivity disorder] in young women of reproductive age and in pregnant women.”
The researchers had no financial conflicts to disclose. The study was supported in part by grants from the National Institutes of Mental Health, the Eunice Kennedy Shriver National Institute for Child Health & Human Development, and the Söderström König Foundation.
The use of methylphenidate by pregnant women is associated with a small increased risk of congenital cardiac malformations in newborns. However, a comparable increased risk is not found with intrauterine exposure to stimulants, according to a population-based cohort study published Dec. 13.
Krista F. Huybrechts, PhD, and her associates analyzed data from more than 1 million pregnancies in the United States. They found that the overall incidence of congenital malformations among the 1,813,894 pregnancies was 35 per 1,000 control infants, compared with 45.9 per 1,000 infants whose mothers used methylphenidate and 45.4 per 1,000 infants whose mothers used amphetamines.
For the subset of infants with cardiac malformations, the risk per 1,000 infants was 12.7 for controls, 18.8 for methylphenidate exposure, and 15.4 for amphetamine exposure. The researchers identified an adjusted relative risk of 1.11 for overall congenital abnormalities and 1.28 for cardiac abnormalities with methylphenidate exposure, compared with a relative risk of 1.05 for overall congenital abnormalities and 0.96 for cardiac abnormalities with stimulant exposure.
An analysis among 2,560,069 pregnancies in Denmark, Finland, Iceland, Norway, and Sweden yielded a similarly significant relative risk of 1.28 for cardiac malformations associated with methylphenidate exposure (JAMA Psychiatry 2017. doi: 10.1001/jamapsychiatry.2017.3644).
“We found a 28% increased prevalence of cardiac malformations after first-trimester exposure to methylphenidate,” wrote Dr. Huybrechts of Brigham and Women’s Hospital, Boston, and her associates. “Although the absolute risk is small, it is nevertheless important evidence to consider when weighing the potential risks and benefits of different treatment strategies for [attention-deficit/hyperactivity disorder] in young women of reproductive age and in pregnant women.”
The researchers had no financial conflicts to disclose. The study was supported in part by grants from the National Institutes of Mental Health, the Eunice Kennedy Shriver National Institute for Child Health & Human Development, and the Söderström König Foundation.
FROM JAMA PSYCHIATRY
Social Media Creates Anxiety for Teenagers With Acne
Adolescents with acne experience anxiety over using social media, according to a recent online survey of teenagers in the United States. The results of the survey, conducted by Harris Poll on behalf of Cutanea Life Sciences, Inc, demonstrate the negative impact of acne on body image and self-esteem.
Of 1010 teens surveyed (age range, 15–19 years), 86% said they have had acne, and a majority of respondents said that acne has a negative effect on their body image and attractiveness (71%) as well as their self-esteem (67%). Fifty-one percent of respondents who use social media said it makes having acne harder and 72% agreed most teenagers with acne are self-conscious about showing their acne on social media. As a result, 68% reported that most of their peers with acne edit or alter their photographs on social media, and 58% have offered to take a photograph to avoid being in a picture. Half of the respondents have taken at least 1 of the following actions to avoid displaying their acne on social media:
- Chose not to include a photograph on social media
- Deleted or untagged a photograph that showed their acne
- Asked someone else to take down a photograph because it showed their acne
- Altered, edited, retouched, or cropped a photograph to try and hide their acne
- Avoided having their picture taken with someone who had clearer skin
- Stayed off social media so they would not have to post or see photographs of themselves
Dermatologists should be aware of the psychosocial impact of acne in teenagers to provide effective management strategies. Although the majority of teens (61%) said they were doing everything possible to manage their acne, 1 in 3 respondents admitted to having difficulty managing their condition. To effectively treat acne, more than three-quarters said that it was at least very important to use a therapy that worked quickly (83%) and was affordable (80%) and easy to use (78%). Be sure to address the psychosocial impact of acne with your teenaged patients, especially pertaining to social media.
Adolescents with acne experience anxiety over using social media, according to a recent online survey of teenagers in the United States. The results of the survey, conducted by Harris Poll on behalf of Cutanea Life Sciences, Inc, demonstrate the negative impact of acne on body image and self-esteem.
Of 1010 teens surveyed (age range, 15–19 years), 86% said they have had acne, and a majority of respondents said that acne has a negative effect on their body image and attractiveness (71%) as well as their self-esteem (67%). Fifty-one percent of respondents who use social media said it makes having acne harder and 72% agreed most teenagers with acne are self-conscious about showing their acne on social media. As a result, 68% reported that most of their peers with acne edit or alter their photographs on social media, and 58% have offered to take a photograph to avoid being in a picture. Half of the respondents have taken at least 1 of the following actions to avoid displaying their acne on social media:
- Chose not to include a photograph on social media
- Deleted or untagged a photograph that showed their acne
- Asked someone else to take down a photograph because it showed their acne
- Altered, edited, retouched, or cropped a photograph to try and hide their acne
- Avoided having their picture taken with someone who had clearer skin
- Stayed off social media so they would not have to post or see photographs of themselves
Dermatologists should be aware of the psychosocial impact of acne in teenagers to provide effective management strategies. Although the majority of teens (61%) said they were doing everything possible to manage their acne, 1 in 3 respondents admitted to having difficulty managing their condition. To effectively treat acne, more than three-quarters said that it was at least very important to use a therapy that worked quickly (83%) and was affordable (80%) and easy to use (78%). Be sure to address the psychosocial impact of acne with your teenaged patients, especially pertaining to social media.
Adolescents with acne experience anxiety over using social media, according to a recent online survey of teenagers in the United States. The results of the survey, conducted by Harris Poll on behalf of Cutanea Life Sciences, Inc, demonstrate the negative impact of acne on body image and self-esteem.
Of 1010 teens surveyed (age range, 15–19 years), 86% said they have had acne, and a majority of respondents said that acne has a negative effect on their body image and attractiveness (71%) as well as their self-esteem (67%). Fifty-one percent of respondents who use social media said it makes having acne harder and 72% agreed most teenagers with acne are self-conscious about showing their acne on social media. As a result, 68% reported that most of their peers with acne edit or alter their photographs on social media, and 58% have offered to take a photograph to avoid being in a picture. Half of the respondents have taken at least 1 of the following actions to avoid displaying their acne on social media:
- Chose not to include a photograph on social media
- Deleted or untagged a photograph that showed their acne
- Asked someone else to take down a photograph because it showed their acne
- Altered, edited, retouched, or cropped a photograph to try and hide their acne
- Avoided having their picture taken with someone who had clearer skin
- Stayed off social media so they would not have to post or see photographs of themselves
Dermatologists should be aware of the psychosocial impact of acne in teenagers to provide effective management strategies. Although the majority of teens (61%) said they were doing everything possible to manage their acne, 1 in 3 respondents admitted to having difficulty managing their condition. To effectively treat acne, more than three-quarters said that it was at least very important to use a therapy that worked quickly (83%) and was affordable (80%) and easy to use (78%). Be sure to address the psychosocial impact of acne with your teenaged patients, especially pertaining to social media.
Studies looking at pravastatin for preeclampsia prevention
In the United States, preeclampsia affects 3%-5% of all pregnancies and 10%-20% of pregnancies complicated by diabetes. Up to 20% of maternal deaths in the United States – and a much larger percentage of maternal deaths worldwide – occur in women with the condition, as do numerous maternal and fetal comorbidities. These include severe hypertension, pulmonary edema, stroke, and kidney and liver injury in the mother, and stillbirth, placental abruption, growth restriction, and premature delivery of the fetus.
Longer-term complications for the offspring include chronic lung disease, hearing and vision disorders, cerebral palsy and other neurodevelopmental disorders, and – as shown by more recent research – poor cardiovascular and metabolic outcomes.
Preeclampsia predisposes the mother to at least a twofold increased risk of future heart disease, compared with a woman who does not have the condition. In addition, women with preeclampsia who deliver at term are approximately two times more likely to die prematurely from heart disease than women without a history of preeclampsia, and those who deliver before 34 weeks’ gestation have been shown to have a ninefold greater risk of premature death. The American Heart Association, in fact, now includes preeclampsia in its list of heart disease risk factors.
Much attention now is focused on statins (inhibitors of HMG-CoA reductase), which have been used for more than 30 years for the primary and secondary prevention of heart disease. The properties and mechanisms of this class of drugs – and the similarities in the pathophysiology of cardiovascular disease and preeclampsia – make statins a plausible candidate for preeclampsia prevention. Thus far, data from preclinical work and subsequent pilot studies have been encouraging.
The commonalities
Preeclampsia is unique to pregnancy, but its pathophysiology and risk factors largely overlap with those of adult atherosclerotic cardiovascular disease. The exact pathophysiology of preeclampsia is unknown, but it is generally agreed that angiogenic imbalance and endothelial dysfunction play key roles, as do associated inflammation and oxidative stress.
Women with preeclampsia have been shown, for instance, to have had increased levels of antiangiogenic factors (soluble FMS-like tyrosine kinase 1 and soluble endoglin) and decreased levels of angiogenic factors (vascular endothelial growth factor and placental growth factor) prior to developing the condition clinically. Risk factors common to both preeclampsia and heart disease include chronic hypertension, dyslipidemia, diabetes or insulin resistance, obesity, and a family history of the condition.
Statins, meanwhile, have been shown to prevent or reverse angiogenic imbalance by promoting the release of vascular endothelial growth factor and placental growth factor and by suppressing the production of soluble FMS-like tyrosine kinase 1 and soluble endoglin. The drugs also improve vascular relaxation and exhibit anti-inflammatory and antioxidative effects, thereby broadly improving endovascular health. In the cardiovascular arena, notably, men and women who have elevated inflammatory markers even without hypercholesterolemia have been shown to have improved cardiovascular outcomes with statin treatment.
In various mouse models of preeclampsia studied in the past decade, pravastatin, a hydrophilic statin, has had beneficial effects. Mice with the angiogenic imbalance characteristic of preeclampsia that received this statin have shown a reversal of the imbalance, as well as reduced blood pressure, increased levels of nitric oxide synthase production, decreased oxidative stress, improved vascular reactivity, decreased kidney damage and proteinuria, and other positive effects. These effects occurred without detrimental outcomes to the mice or any increase in the rates of anomalies or resorption in offspring (Clin Obstet Gynecol. 2017 Mar;60:161-8).
Moreover, in addition to ameliorating the preeclampsia phenotype, pravastatin use in these animal models has improved pregnancy outcomes and reduced rates of pregnancy losses.
Safety issues
So, can we use statins in pregnancy? When statins were originally marketed in the 1980s, they were labeled pregnancy category X, which means 1) that there is evidence of fetal abnormalities or risk and 2) that these risks clearly outweigh potential benefits.
This designation for statins was based largely on the second half of the definition (no benefit to outweigh any risk). In addition, there were theoretical concerns about the inhibition of cholesterol synthesis during embryologic development and about a small case series of the original lipophilic statins suggesting an increased risk of malformations. While pregnancy category X does not exist anymore, statins are still labeled as contraindicated in pregnancy.
Pravastatin is one of the safest statins to consider in pregnancy for several reasons: It is one of the most hydrophilic statins and is a substrate of the placental efflux transporters, such as P-glycoprotein; both of those properties limit its ability to cross the placenta. It also has a short-elimination half-life, is cleared through both hepatic and renal routes, and is among the most hepatoselective statins available (one of the weakest inhibitors of HMG-CoA reductase). Indeed, in vitro placental transfer studies suggest that pravastatin transfer is limited and slow and that clearance is significantly higher in the fetal-to-maternal direction than in the maternal-to-fetal direction.
Animal studies have demonstrated that pravastatin is not teratogenic and has no effect on placental weight, pup birth weight, and pup adult weight. Moreover, at least six published cohort studies of women with first-trimester exposure to statins (women who had been prescribed the drugs before becoming pregnant and who received the drugs in the first trimester before realizing they were pregnant) showed no patterns or increased rates of congenital anomalies, compared with women without exposure to known teratogens. Additionally, these cohorts did not show any associations with miscarriage or fetal growth restriction (Obstet Gynecol. 2013 Feb;121:349-53).
A more recent cohort study of close to 900,000 women – of which 1,152 women used a statin (pravastatin or other statins) during their first trimester – similarly found no significant increases in any type of congenital malformation, compared with other completed pregnancies in the larger cohort. Notably, the analysis of this cohort was done using propensity score–based methods to control for potential confounders, including prepregnancy conditions that prompted use of a statin (BMJ. 2015;350:h1035).
A drawback to this body of research is that, with the exception of the BMJ study, the cohorts have been generally small; furthermore, in keeping with current recommendations, most of the statin-exposed patients discontinued use of the drugs upon confirmation of their pregnancies, thereby leaving the effects of long-term use unknown.
A promising pilot
Daily pravastatin use in pregnancy, starting in the second trimester, got its first major test of safety and pharmacokinetics in a pilot randomized, controlled trial undertaken by the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s (NICHD’s) Obstetric-Fetal Pharmacology Research Units Network. Women with singleton pregnancies and a history of severe preeclampsia requiring delivery prior to 34 weeks’ gestation were randomized between 12 and 16 weeks’ gestation to receive pravastatin or placebo until delivery.
This pilot is the first of three cohorts of women who were or will be randomized in separate pilot trials to escalating doses of pravastatin: 10 mg, 20 mg, and 40 mg (the last of which is the usual dose for lipid lowering in adults). Results of the first cohort, in which 20 patients were randomized to 10 mg pravastatin or placebo, were reported in 2016, and those from the second cohort will be reported soon. The third pilot is currently enrolling women.
In this first pilot we found no differences in rates of congenital anomalies or other identifiable maternal or fetal/neonatal safety risks, no differences in adverse events, and no maternal, fetal, or neonatal deaths. There were also no reports of myopathy/rhabdomyolysis or liver injury; the most common adverse events were heartburn (reported by four patients in the pravastatin group and three in the placebo group) and musculoskeletal pain (reported by four patients and one patient, respectively).
Although not statistically significant, a 10-mg dose of pravastatin was associated with favorable outcomes. None of the women receiving pravastatin developed preeclampsia, while four in the placebo group developed the disorder (with three of these four having severe preeclampsia).
Women in the pravastatin group also were less likely to have an indicated preterm delivery (one vs. five in the placebo group), and their neonates were less likely to be admitted to intermediate nurseries or the neonatal ICU. In addition, their angiogenic profiles were improved (higher placental growth factor and lower FMS-like tyrosine kinase 1 and soluble endoglin).
Importantly, while pravastatin reduced maternal cholesterol concentrations, there were no differences in birth weight or umbilical cord cholesterol concentrations (total cholesterol or LDL) between the two groups (Am J Obstet Gynecol. 2016;214[6]:720.e1-17).
That cholesterol concentrations were not reduced in fetuses exposed to pravastatin is reassuring and aligns with findings from other studies showing that fetal cholesterol concentrations are largely independent from maternal cholesterol concentrations or diet. For instance, we know from studies of Smith-Lemli-Opitz syndrome, a multiple congenital anomaly/intellectual disability syndrome caused by a defect in cholesterol synthesis, that there is not any significant interaction between cholesterol concentrations of the mother and fetus. Only about 10% of the fetal absolute cholesterol requirement comes from the mother, research has demonstrated.
The future
Infant follow-up in the NICHD study is planned, and a large, randomized clinical trial powered to look at the efficacy of pravastatin for preventing preeclampsia in high-risk women has been approved by the NICHD. Once funded, the study is expected to enroll approximately 1,700 pregnant women who have a history of severe preeclampsia and delivery before 36 weeks’ gestation and who are between 10 and 16 weeks’ gestation.
With continued research, we face the question of whether pravastatin may potentiate the benefit of aspirin in pregnant women. In cardiovascular medicine, there is evidence for additive or synergistic effects of the combined use of aspirin and statins.
Interestingly, a recent prospective cohort study of women with antiphospholipid syndrome and poor outcomes in prior pregnancies showed dramatic improvement in both maternal and fetal/neonatal outcomes when pravastatin was administered after the onset of preeclampsia or intrauterine growth restriction. All 21 women in the cohort were treated with low-dose aspirin and low-molecular-weight heparin; after the development of preeclampsia or intrauterine growth restriction, 10 patients were maintained on aspirin and LMWH, and 11 were started on 20 mg daily pravastatin along with the aspirin and LMWH (J Clin Invest. 2016 Aug;126[8]:2933-40; and J Clin Invest. 2016 Aug;126[8]:2792-4).
Those who received the statin had improved uterine artery Doppler velocimetry, lower systemic blood pressure, and delivered infants with higher birth weights and at a more advanced gestational age (median, 36 weeks’ vs. 26.5 weeks’ gestation). The study did not randomly allocate the women and did not include a placebo arm. Still, it is another impressive proof-of-concept study.
Dr. Costantine is an associate professor of obstetrics and gynecology at the University of Texas Medical Branch in Galveston. He reported that he has no financial disclosures.
In the United States, preeclampsia affects 3%-5% of all pregnancies and 10%-20% of pregnancies complicated by diabetes. Up to 20% of maternal deaths in the United States – and a much larger percentage of maternal deaths worldwide – occur in women with the condition, as do numerous maternal and fetal comorbidities. These include severe hypertension, pulmonary edema, stroke, and kidney and liver injury in the mother, and stillbirth, placental abruption, growth restriction, and premature delivery of the fetus.
Longer-term complications for the offspring include chronic lung disease, hearing and vision disorders, cerebral palsy and other neurodevelopmental disorders, and – as shown by more recent research – poor cardiovascular and metabolic outcomes.
Preeclampsia predisposes the mother to at least a twofold increased risk of future heart disease, compared with a woman who does not have the condition. In addition, women with preeclampsia who deliver at term are approximately two times more likely to die prematurely from heart disease than women without a history of preeclampsia, and those who deliver before 34 weeks’ gestation have been shown to have a ninefold greater risk of premature death. The American Heart Association, in fact, now includes preeclampsia in its list of heart disease risk factors.
Much attention now is focused on statins (inhibitors of HMG-CoA reductase), which have been used for more than 30 years for the primary and secondary prevention of heart disease. The properties and mechanisms of this class of drugs – and the similarities in the pathophysiology of cardiovascular disease and preeclampsia – make statins a plausible candidate for preeclampsia prevention. Thus far, data from preclinical work and subsequent pilot studies have been encouraging.
The commonalities
Preeclampsia is unique to pregnancy, but its pathophysiology and risk factors largely overlap with those of adult atherosclerotic cardiovascular disease. The exact pathophysiology of preeclampsia is unknown, but it is generally agreed that angiogenic imbalance and endothelial dysfunction play key roles, as do associated inflammation and oxidative stress.
Women with preeclampsia have been shown, for instance, to have had increased levels of antiangiogenic factors (soluble FMS-like tyrosine kinase 1 and soluble endoglin) and decreased levels of angiogenic factors (vascular endothelial growth factor and placental growth factor) prior to developing the condition clinically. Risk factors common to both preeclampsia and heart disease include chronic hypertension, dyslipidemia, diabetes or insulin resistance, obesity, and a family history of the condition.
Statins, meanwhile, have been shown to prevent or reverse angiogenic imbalance by promoting the release of vascular endothelial growth factor and placental growth factor and by suppressing the production of soluble FMS-like tyrosine kinase 1 and soluble endoglin. The drugs also improve vascular relaxation and exhibit anti-inflammatory and antioxidative effects, thereby broadly improving endovascular health. In the cardiovascular arena, notably, men and women who have elevated inflammatory markers even without hypercholesterolemia have been shown to have improved cardiovascular outcomes with statin treatment.
In various mouse models of preeclampsia studied in the past decade, pravastatin, a hydrophilic statin, has had beneficial effects. Mice with the angiogenic imbalance characteristic of preeclampsia that received this statin have shown a reversal of the imbalance, as well as reduced blood pressure, increased levels of nitric oxide synthase production, decreased oxidative stress, improved vascular reactivity, decreased kidney damage and proteinuria, and other positive effects. These effects occurred without detrimental outcomes to the mice or any increase in the rates of anomalies or resorption in offspring (Clin Obstet Gynecol. 2017 Mar;60:161-8).
Moreover, in addition to ameliorating the preeclampsia phenotype, pravastatin use in these animal models has improved pregnancy outcomes and reduced rates of pregnancy losses.
Safety issues
So, can we use statins in pregnancy? When statins were originally marketed in the 1980s, they were labeled pregnancy category X, which means 1) that there is evidence of fetal abnormalities or risk and 2) that these risks clearly outweigh potential benefits.
This designation for statins was based largely on the second half of the definition (no benefit to outweigh any risk). In addition, there were theoretical concerns about the inhibition of cholesterol synthesis during embryologic development and about a small case series of the original lipophilic statins suggesting an increased risk of malformations. While pregnancy category X does not exist anymore, statins are still labeled as contraindicated in pregnancy.
Pravastatin is one of the safest statins to consider in pregnancy for several reasons: It is one of the most hydrophilic statins and is a substrate of the placental efflux transporters, such as P-glycoprotein; both of those properties limit its ability to cross the placenta. It also has a short-elimination half-life, is cleared through both hepatic and renal routes, and is among the most hepatoselective statins available (one of the weakest inhibitors of HMG-CoA reductase). Indeed, in vitro placental transfer studies suggest that pravastatin transfer is limited and slow and that clearance is significantly higher in the fetal-to-maternal direction than in the maternal-to-fetal direction.
Animal studies have demonstrated that pravastatin is not teratogenic and has no effect on placental weight, pup birth weight, and pup adult weight. Moreover, at least six published cohort studies of women with first-trimester exposure to statins (women who had been prescribed the drugs before becoming pregnant and who received the drugs in the first trimester before realizing they were pregnant) showed no patterns or increased rates of congenital anomalies, compared with women without exposure to known teratogens. Additionally, these cohorts did not show any associations with miscarriage or fetal growth restriction (Obstet Gynecol. 2013 Feb;121:349-53).
A more recent cohort study of close to 900,000 women – of which 1,152 women used a statin (pravastatin or other statins) during their first trimester – similarly found no significant increases in any type of congenital malformation, compared with other completed pregnancies in the larger cohort. Notably, the analysis of this cohort was done using propensity score–based methods to control for potential confounders, including prepregnancy conditions that prompted use of a statin (BMJ. 2015;350:h1035).
A drawback to this body of research is that, with the exception of the BMJ study, the cohorts have been generally small; furthermore, in keeping with current recommendations, most of the statin-exposed patients discontinued use of the drugs upon confirmation of their pregnancies, thereby leaving the effects of long-term use unknown.
A promising pilot
Daily pravastatin use in pregnancy, starting in the second trimester, got its first major test of safety and pharmacokinetics in a pilot randomized, controlled trial undertaken by the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s (NICHD’s) Obstetric-Fetal Pharmacology Research Units Network. Women with singleton pregnancies and a history of severe preeclampsia requiring delivery prior to 34 weeks’ gestation were randomized between 12 and 16 weeks’ gestation to receive pravastatin or placebo until delivery.
This pilot is the first of three cohorts of women who were or will be randomized in separate pilot trials to escalating doses of pravastatin: 10 mg, 20 mg, and 40 mg (the last of which is the usual dose for lipid lowering in adults). Results of the first cohort, in which 20 patients were randomized to 10 mg pravastatin or placebo, were reported in 2016, and those from the second cohort will be reported soon. The third pilot is currently enrolling women.
In this first pilot we found no differences in rates of congenital anomalies or other identifiable maternal or fetal/neonatal safety risks, no differences in adverse events, and no maternal, fetal, or neonatal deaths. There were also no reports of myopathy/rhabdomyolysis or liver injury; the most common adverse events were heartburn (reported by four patients in the pravastatin group and three in the placebo group) and musculoskeletal pain (reported by four patients and one patient, respectively).
Although not statistically significant, a 10-mg dose of pravastatin was associated with favorable outcomes. None of the women receiving pravastatin developed preeclampsia, while four in the placebo group developed the disorder (with three of these four having severe preeclampsia).
Women in the pravastatin group also were less likely to have an indicated preterm delivery (one vs. five in the placebo group), and their neonates were less likely to be admitted to intermediate nurseries or the neonatal ICU. In addition, their angiogenic profiles were improved (higher placental growth factor and lower FMS-like tyrosine kinase 1 and soluble endoglin).
Importantly, while pravastatin reduced maternal cholesterol concentrations, there were no differences in birth weight or umbilical cord cholesterol concentrations (total cholesterol or LDL) between the two groups (Am J Obstet Gynecol. 2016;214[6]:720.e1-17).
That cholesterol concentrations were not reduced in fetuses exposed to pravastatin is reassuring and aligns with findings from other studies showing that fetal cholesterol concentrations are largely independent from maternal cholesterol concentrations or diet. For instance, we know from studies of Smith-Lemli-Opitz syndrome, a multiple congenital anomaly/intellectual disability syndrome caused by a defect in cholesterol synthesis, that there is not any significant interaction between cholesterol concentrations of the mother and fetus. Only about 10% of the fetal absolute cholesterol requirement comes from the mother, research has demonstrated.
The future
Infant follow-up in the NICHD study is planned, and a large, randomized clinical trial powered to look at the efficacy of pravastatin for preventing preeclampsia in high-risk women has been approved by the NICHD. Once funded, the study is expected to enroll approximately 1,700 pregnant women who have a history of severe preeclampsia and delivery before 36 weeks’ gestation and who are between 10 and 16 weeks’ gestation.
With continued research, we face the question of whether pravastatin may potentiate the benefit of aspirin in pregnant women. In cardiovascular medicine, there is evidence for additive or synergistic effects of the combined use of aspirin and statins.
Interestingly, a recent prospective cohort study of women with antiphospholipid syndrome and poor outcomes in prior pregnancies showed dramatic improvement in both maternal and fetal/neonatal outcomes when pravastatin was administered after the onset of preeclampsia or intrauterine growth restriction. All 21 women in the cohort were treated with low-dose aspirin and low-molecular-weight heparin; after the development of preeclampsia or intrauterine growth restriction, 10 patients were maintained on aspirin and LMWH, and 11 were started on 20 mg daily pravastatin along with the aspirin and LMWH (J Clin Invest. 2016 Aug;126[8]:2933-40; and J Clin Invest. 2016 Aug;126[8]:2792-4).
Those who received the statin had improved uterine artery Doppler velocimetry, lower systemic blood pressure, and delivered infants with higher birth weights and at a more advanced gestational age (median, 36 weeks’ vs. 26.5 weeks’ gestation). The study did not randomly allocate the women and did not include a placebo arm. Still, it is another impressive proof-of-concept study.
Dr. Costantine is an associate professor of obstetrics and gynecology at the University of Texas Medical Branch in Galveston. He reported that he has no financial disclosures.
In the United States, preeclampsia affects 3%-5% of all pregnancies and 10%-20% of pregnancies complicated by diabetes. Up to 20% of maternal deaths in the United States – and a much larger percentage of maternal deaths worldwide – occur in women with the condition, as do numerous maternal and fetal comorbidities. These include severe hypertension, pulmonary edema, stroke, and kidney and liver injury in the mother, and stillbirth, placental abruption, growth restriction, and premature delivery of the fetus.
Longer-term complications for the offspring include chronic lung disease, hearing and vision disorders, cerebral palsy and other neurodevelopmental disorders, and – as shown by more recent research – poor cardiovascular and metabolic outcomes.
Preeclampsia predisposes the mother to at least a twofold increased risk of future heart disease, compared with a woman who does not have the condition. In addition, women with preeclampsia who deliver at term are approximately two times more likely to die prematurely from heart disease than women without a history of preeclampsia, and those who deliver before 34 weeks’ gestation have been shown to have a ninefold greater risk of premature death. The American Heart Association, in fact, now includes preeclampsia in its list of heart disease risk factors.
Much attention now is focused on statins (inhibitors of HMG-CoA reductase), which have been used for more than 30 years for the primary and secondary prevention of heart disease. The properties and mechanisms of this class of drugs – and the similarities in the pathophysiology of cardiovascular disease and preeclampsia – make statins a plausible candidate for preeclampsia prevention. Thus far, data from preclinical work and subsequent pilot studies have been encouraging.
The commonalities
Preeclampsia is unique to pregnancy, but its pathophysiology and risk factors largely overlap with those of adult atherosclerotic cardiovascular disease. The exact pathophysiology of preeclampsia is unknown, but it is generally agreed that angiogenic imbalance and endothelial dysfunction play key roles, as do associated inflammation and oxidative stress.
Women with preeclampsia have been shown, for instance, to have had increased levels of antiangiogenic factors (soluble FMS-like tyrosine kinase 1 and soluble endoglin) and decreased levels of angiogenic factors (vascular endothelial growth factor and placental growth factor) prior to developing the condition clinically. Risk factors common to both preeclampsia and heart disease include chronic hypertension, dyslipidemia, diabetes or insulin resistance, obesity, and a family history of the condition.
Statins, meanwhile, have been shown to prevent or reverse angiogenic imbalance by promoting the release of vascular endothelial growth factor and placental growth factor and by suppressing the production of soluble FMS-like tyrosine kinase 1 and soluble endoglin. The drugs also improve vascular relaxation and exhibit anti-inflammatory and antioxidative effects, thereby broadly improving endovascular health. In the cardiovascular arena, notably, men and women who have elevated inflammatory markers even without hypercholesterolemia have been shown to have improved cardiovascular outcomes with statin treatment.
In various mouse models of preeclampsia studied in the past decade, pravastatin, a hydrophilic statin, has had beneficial effects. Mice with the angiogenic imbalance characteristic of preeclampsia that received this statin have shown a reversal of the imbalance, as well as reduced blood pressure, increased levels of nitric oxide synthase production, decreased oxidative stress, improved vascular reactivity, decreased kidney damage and proteinuria, and other positive effects. These effects occurred without detrimental outcomes to the mice or any increase in the rates of anomalies or resorption in offspring (Clin Obstet Gynecol. 2017 Mar;60:161-8).
Moreover, in addition to ameliorating the preeclampsia phenotype, pravastatin use in these animal models has improved pregnancy outcomes and reduced rates of pregnancy losses.
Safety issues
So, can we use statins in pregnancy? When statins were originally marketed in the 1980s, they were labeled pregnancy category X, which means 1) that there is evidence of fetal abnormalities or risk and 2) that these risks clearly outweigh potential benefits.
This designation for statins was based largely on the second half of the definition (no benefit to outweigh any risk). In addition, there were theoretical concerns about the inhibition of cholesterol synthesis during embryologic development and about a small case series of the original lipophilic statins suggesting an increased risk of malformations. While pregnancy category X does not exist anymore, statins are still labeled as contraindicated in pregnancy.
Pravastatin is one of the safest statins to consider in pregnancy for several reasons: It is one of the most hydrophilic statins and is a substrate of the placental efflux transporters, such as P-glycoprotein; both of those properties limit its ability to cross the placenta. It also has a short-elimination half-life, is cleared through both hepatic and renal routes, and is among the most hepatoselective statins available (one of the weakest inhibitors of HMG-CoA reductase). Indeed, in vitro placental transfer studies suggest that pravastatin transfer is limited and slow and that clearance is significantly higher in the fetal-to-maternal direction than in the maternal-to-fetal direction.
Animal studies have demonstrated that pravastatin is not teratogenic and has no effect on placental weight, pup birth weight, and pup adult weight. Moreover, at least six published cohort studies of women with first-trimester exposure to statins (women who had been prescribed the drugs before becoming pregnant and who received the drugs in the first trimester before realizing they were pregnant) showed no patterns or increased rates of congenital anomalies, compared with women without exposure to known teratogens. Additionally, these cohorts did not show any associations with miscarriage or fetal growth restriction (Obstet Gynecol. 2013 Feb;121:349-53).
A more recent cohort study of close to 900,000 women – of which 1,152 women used a statin (pravastatin or other statins) during their first trimester – similarly found no significant increases in any type of congenital malformation, compared with other completed pregnancies in the larger cohort. Notably, the analysis of this cohort was done using propensity score–based methods to control for potential confounders, including prepregnancy conditions that prompted use of a statin (BMJ. 2015;350:h1035).
A drawback to this body of research is that, with the exception of the BMJ study, the cohorts have been generally small; furthermore, in keeping with current recommendations, most of the statin-exposed patients discontinued use of the drugs upon confirmation of their pregnancies, thereby leaving the effects of long-term use unknown.
A promising pilot
Daily pravastatin use in pregnancy, starting in the second trimester, got its first major test of safety and pharmacokinetics in a pilot randomized, controlled trial undertaken by the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s (NICHD’s) Obstetric-Fetal Pharmacology Research Units Network. Women with singleton pregnancies and a history of severe preeclampsia requiring delivery prior to 34 weeks’ gestation were randomized between 12 and 16 weeks’ gestation to receive pravastatin or placebo until delivery.
This pilot is the first of three cohorts of women who were or will be randomized in separate pilot trials to escalating doses of pravastatin: 10 mg, 20 mg, and 40 mg (the last of which is the usual dose for lipid lowering in adults). Results of the first cohort, in which 20 patients were randomized to 10 mg pravastatin or placebo, were reported in 2016, and those from the second cohort will be reported soon. The third pilot is currently enrolling women.
In this first pilot we found no differences in rates of congenital anomalies or other identifiable maternal or fetal/neonatal safety risks, no differences in adverse events, and no maternal, fetal, or neonatal deaths. There were also no reports of myopathy/rhabdomyolysis or liver injury; the most common adverse events were heartburn (reported by four patients in the pravastatin group and three in the placebo group) and musculoskeletal pain (reported by four patients and one patient, respectively).
Although not statistically significant, a 10-mg dose of pravastatin was associated with favorable outcomes. None of the women receiving pravastatin developed preeclampsia, while four in the placebo group developed the disorder (with three of these four having severe preeclampsia).
Women in the pravastatin group also were less likely to have an indicated preterm delivery (one vs. five in the placebo group), and their neonates were less likely to be admitted to intermediate nurseries or the neonatal ICU. In addition, their angiogenic profiles were improved (higher placental growth factor and lower FMS-like tyrosine kinase 1 and soluble endoglin).
Importantly, while pravastatin reduced maternal cholesterol concentrations, there were no differences in birth weight or umbilical cord cholesterol concentrations (total cholesterol or LDL) between the two groups (Am J Obstet Gynecol. 2016;214[6]:720.e1-17).
That cholesterol concentrations were not reduced in fetuses exposed to pravastatin is reassuring and aligns with findings from other studies showing that fetal cholesterol concentrations are largely independent from maternal cholesterol concentrations or diet. For instance, we know from studies of Smith-Lemli-Opitz syndrome, a multiple congenital anomaly/intellectual disability syndrome caused by a defect in cholesterol synthesis, that there is not any significant interaction between cholesterol concentrations of the mother and fetus. Only about 10% of the fetal absolute cholesterol requirement comes from the mother, research has demonstrated.
The future
Infant follow-up in the NICHD study is planned, and a large, randomized clinical trial powered to look at the efficacy of pravastatin for preventing preeclampsia in high-risk women has been approved by the NICHD. Once funded, the study is expected to enroll approximately 1,700 pregnant women who have a history of severe preeclampsia and delivery before 36 weeks’ gestation and who are between 10 and 16 weeks’ gestation.
With continued research, we face the question of whether pravastatin may potentiate the benefit of aspirin in pregnant women. In cardiovascular medicine, there is evidence for additive or synergistic effects of the combined use of aspirin and statins.
Interestingly, a recent prospective cohort study of women with antiphospholipid syndrome and poor outcomes in prior pregnancies showed dramatic improvement in both maternal and fetal/neonatal outcomes when pravastatin was administered after the onset of preeclampsia or intrauterine growth restriction. All 21 women in the cohort were treated with low-dose aspirin and low-molecular-weight heparin; after the development of preeclampsia or intrauterine growth restriction, 10 patients were maintained on aspirin and LMWH, and 11 were started on 20 mg daily pravastatin along with the aspirin and LMWH (J Clin Invest. 2016 Aug;126[8]:2933-40; and J Clin Invest. 2016 Aug;126[8]:2792-4).
Those who received the statin had improved uterine artery Doppler velocimetry, lower systemic blood pressure, and delivered infants with higher birth weights and at a more advanced gestational age (median, 36 weeks’ vs. 26.5 weeks’ gestation). The study did not randomly allocate the women and did not include a placebo arm. Still, it is another impressive proof-of-concept study.
Dr. Costantine is an associate professor of obstetrics and gynecology at the University of Texas Medical Branch in Galveston. He reported that he has no financial disclosures.
Hope for targeted management of preeclampsia
In medicine, there are many diseases and conditions that pose significant challenges to health care practitioners. For example, within brain science, there are patients with debilitating neurodegenerative diseases; within emergency medicine, there are patients who have suffered severe and acute trauma; within pediatrics, there are patients with terminal illnesses, such as cancer. In ob.gyn., one of the great obstetrical syndromes is preeclampsia.
Humans have known about preeclampsia for thousands of years, dating back to the 4th and 5th centuries B.C., since the time of Hippocrates. Ancient writings on medical conditions of women reflect a recognition of preeclampsia and eclampsia, although formal classification of the condition as a hypertensive disorder associated specifically with pregnancy did not occur until the late 1800s. Despite this, the pathology of preeclampsia is significantly underdefined, and because the underlying causes of preeclampsia are largely unknown, prevention and management continue to be hindered.
However, recent research indicating an association between statin use and prevention of preeclampsia has given us some hope that targeted management is possible. As ob.gyns. continue to grapple with the intricacies of managing patients with preeclampsia, a condition we increasingly see because of concurrent rises in being overweight, being obese, and having diabetes during pregnancy, so we are eager to see whether the research might confirm an effective role for statins in patient care. Although statins are still quite far from becoming a new standard of care, we are, as a specialty, hungry for a solution to this millennia-old problem.
Therefore, this month we have invited Maged Costantine, MD, an associate professor in the department of obstetrics and gynecology and division of maternal fetal medicine at the University of Texas Medical Branch in Galveston, to discuss this novel and exciting new area of research.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
In medicine, there are many diseases and conditions that pose significant challenges to health care practitioners. For example, within brain science, there are patients with debilitating neurodegenerative diseases; within emergency medicine, there are patients who have suffered severe and acute trauma; within pediatrics, there are patients with terminal illnesses, such as cancer. In ob.gyn., one of the great obstetrical syndromes is preeclampsia.
Humans have known about preeclampsia for thousands of years, dating back to the 4th and 5th centuries B.C., since the time of Hippocrates. Ancient writings on medical conditions of women reflect a recognition of preeclampsia and eclampsia, although formal classification of the condition as a hypertensive disorder associated specifically with pregnancy did not occur until the late 1800s. Despite this, the pathology of preeclampsia is significantly underdefined, and because the underlying causes of preeclampsia are largely unknown, prevention and management continue to be hindered.
However, recent research indicating an association between statin use and prevention of preeclampsia has given us some hope that targeted management is possible. As ob.gyns. continue to grapple with the intricacies of managing patients with preeclampsia, a condition we increasingly see because of concurrent rises in being overweight, being obese, and having diabetes during pregnancy, so we are eager to see whether the research might confirm an effective role for statins in patient care. Although statins are still quite far from becoming a new standard of care, we are, as a specialty, hungry for a solution to this millennia-old problem.
Therefore, this month we have invited Maged Costantine, MD, an associate professor in the department of obstetrics and gynecology and division of maternal fetal medicine at the University of Texas Medical Branch in Galveston, to discuss this novel and exciting new area of research.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
In medicine, there are many diseases and conditions that pose significant challenges to health care practitioners. For example, within brain science, there are patients with debilitating neurodegenerative diseases; within emergency medicine, there are patients who have suffered severe and acute trauma; within pediatrics, there are patients with terminal illnesses, such as cancer. In ob.gyn., one of the great obstetrical syndromes is preeclampsia.
Humans have known about preeclampsia for thousands of years, dating back to the 4th and 5th centuries B.C., since the time of Hippocrates. Ancient writings on medical conditions of women reflect a recognition of preeclampsia and eclampsia, although formal classification of the condition as a hypertensive disorder associated specifically with pregnancy did not occur until the late 1800s. Despite this, the pathology of preeclampsia is significantly underdefined, and because the underlying causes of preeclampsia are largely unknown, prevention and management continue to be hindered.
However, recent research indicating an association between statin use and prevention of preeclampsia has given us some hope that targeted management is possible. As ob.gyns. continue to grapple with the intricacies of managing patients with preeclampsia, a condition we increasingly see because of concurrent rises in being overweight, being obese, and having diabetes during pregnancy, so we are eager to see whether the research might confirm an effective role for statins in patient care. Although statins are still quite far from becoming a new standard of care, we are, as a specialty, hungry for a solution to this millennia-old problem.
Therefore, this month we have invited Maged Costantine, MD, an associate professor in the department of obstetrics and gynecology and division of maternal fetal medicine at the University of Texas Medical Branch in Galveston, to discuss this novel and exciting new area of research.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Reducing outpatient medication costs
For many patients, paying for medication presents a serious challenge. Studies show that up to 45% of Americans do not fill prescriptions secondary to cost, and medication nonadherence leads to morbidity and mortality, with costs from $100 billion to $300 billion annually.
One way to address the problem is by empowering clinicians to reduce patient outpatient medication costs – the goal described in a recent abstract.
Initial testing was promising. One patient, admitted for the fourth time in 14 months for hypertriglyceridemia-induced pancreatitis secondary to medication nonadherence, was able to reduce 90-day outpatient medication cost by 95%, from $1,287.00 to $61.79. By reducing his readmissions, the institution saved more than $20,000 a year.
The researchers secured internal grant funding to develop an automated version of the tool. “We currently have technology that can dramatically reduce the cost of many medications with early promising results for patient outcomes, readmissions rates and overall systemic cost,” Dr. Kubey said. “We are working rapidly to further develop and study our tool and, if prospective results confirm our initial findings, we will seek to provide this tool to clinicians broadly.”
Such tools are a true win-win. Hospitalists using them help ensure that discharged patients are able to afford the often life-saving medications that will keep them healthy and out of the hospital, improve readmission rates, patient satisfaction metrics, total system cost, and, most important, do right by our patients in need for whom we are charged to care, Dr. Kubey said.
“Hospitalists first must be aware that savings of 90% or more are possible for many medications and that medication nonadherence because of cost is a serious issue affecting nearly half the patients we see,” he said. “The first step is simply asking patients if medication cost is proving troublesome – we cannot address what we do not see. The second step is to use current discount tools such as GoodRx, NeedyMeds, and the like – and, we hope, in the not too distant future, our tool, which we plan to integrate into EHR prescribing to make it easy and nearly instantaneous for hospitalists to prescribe the most high-value, low-cost medication regimen for each individual patient at discharge.”
Reference
Kubey A et al. Expensive free hospitalizations – A novel approach to reducing outpatient medication cost [abstract]. J Hosp Med. 2017; 12 (suppl 2). Accessed Aug. 7, 2017.
For many patients, paying for medication presents a serious challenge. Studies show that up to 45% of Americans do not fill prescriptions secondary to cost, and medication nonadherence leads to morbidity and mortality, with costs from $100 billion to $300 billion annually.
One way to address the problem is by empowering clinicians to reduce patient outpatient medication costs – the goal described in a recent abstract.
Initial testing was promising. One patient, admitted for the fourth time in 14 months for hypertriglyceridemia-induced pancreatitis secondary to medication nonadherence, was able to reduce 90-day outpatient medication cost by 95%, from $1,287.00 to $61.79. By reducing his readmissions, the institution saved more than $20,000 a year.
The researchers secured internal grant funding to develop an automated version of the tool. “We currently have technology that can dramatically reduce the cost of many medications with early promising results for patient outcomes, readmissions rates and overall systemic cost,” Dr. Kubey said. “We are working rapidly to further develop and study our tool and, if prospective results confirm our initial findings, we will seek to provide this tool to clinicians broadly.”
Such tools are a true win-win. Hospitalists using them help ensure that discharged patients are able to afford the often life-saving medications that will keep them healthy and out of the hospital, improve readmission rates, patient satisfaction metrics, total system cost, and, most important, do right by our patients in need for whom we are charged to care, Dr. Kubey said.
“Hospitalists first must be aware that savings of 90% or more are possible for many medications and that medication nonadherence because of cost is a serious issue affecting nearly half the patients we see,” he said. “The first step is simply asking patients if medication cost is proving troublesome – we cannot address what we do not see. The second step is to use current discount tools such as GoodRx, NeedyMeds, and the like – and, we hope, in the not too distant future, our tool, which we plan to integrate into EHR prescribing to make it easy and nearly instantaneous for hospitalists to prescribe the most high-value, low-cost medication regimen for each individual patient at discharge.”
Reference
Kubey A et al. Expensive free hospitalizations – A novel approach to reducing outpatient medication cost [abstract]. J Hosp Med. 2017; 12 (suppl 2). Accessed Aug. 7, 2017.
For many patients, paying for medication presents a serious challenge. Studies show that up to 45% of Americans do not fill prescriptions secondary to cost, and medication nonadherence leads to morbidity and mortality, with costs from $100 billion to $300 billion annually.
One way to address the problem is by empowering clinicians to reduce patient outpatient medication costs – the goal described in a recent abstract.
Initial testing was promising. One patient, admitted for the fourth time in 14 months for hypertriglyceridemia-induced pancreatitis secondary to medication nonadherence, was able to reduce 90-day outpatient medication cost by 95%, from $1,287.00 to $61.79. By reducing his readmissions, the institution saved more than $20,000 a year.
The researchers secured internal grant funding to develop an automated version of the tool. “We currently have technology that can dramatically reduce the cost of many medications with early promising results for patient outcomes, readmissions rates and overall systemic cost,” Dr. Kubey said. “We are working rapidly to further develop and study our tool and, if prospective results confirm our initial findings, we will seek to provide this tool to clinicians broadly.”
Such tools are a true win-win. Hospitalists using them help ensure that discharged patients are able to afford the often life-saving medications that will keep them healthy and out of the hospital, improve readmission rates, patient satisfaction metrics, total system cost, and, most important, do right by our patients in need for whom we are charged to care, Dr. Kubey said.
“Hospitalists first must be aware that savings of 90% or more are possible for many medications and that medication nonadherence because of cost is a serious issue affecting nearly half the patients we see,” he said. “The first step is simply asking patients if medication cost is proving troublesome – we cannot address what we do not see. The second step is to use current discount tools such as GoodRx, NeedyMeds, and the like – and, we hope, in the not too distant future, our tool, which we plan to integrate into EHR prescribing to make it easy and nearly instantaneous for hospitalists to prescribe the most high-value, low-cost medication regimen for each individual patient at discharge.”
Reference
Kubey A et al. Expensive free hospitalizations – A novel approach to reducing outpatient medication cost [abstract]. J Hosp Med. 2017; 12 (suppl 2). Accessed Aug. 7, 2017.