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Novel metabolic biomarkers linked to CHD
ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
BiomarCaRE and other studies offer us a unique opportunity to integrate metabolomics with genetic and other biomarkers to really understand the systems biology of disease.
But there are many questions to answer before we start measuring phosphatidylcholines. How do these biomarkers add to clinical risk prediction in our patients? While the magnitude of effect was good for a biomarker, it did not meet the strength of strong cardiovascular risk factors, including total cholesterol. Also, the investigators were careful to adjust for confounders and were able to show independent association, but they did not address incremental risk prediction.
And would measuring these metabolites change what we do for our patients? Are these pathways modifiable? In the absence of something to modify the pathway, risk prediction may be less significant.
Even so, metabolomics holds great promise in identifying biological pathways and understanding heterogeneity in medication and other effects, and advancing our efforts in precision medicine and patient care.
Svati Shah, MD , is with the department of cardiology at Duke University, Durham, N.C. She holds a patent on an unrelated metabolomics finding, and a research grant from Bristol-Myers Squibb. She also is an adviser for Biosense Webster. Dr. Shah was the discussant for the study presentation.
ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.
The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.
The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).
A total of 141 metabolites were detected by mass spectrometry using the Biocrates Absolute IDQ p180 assay. After adjustment for body mass index, blood pressure, cholesterol level, hypertension, and other known coronary heart disease (CHD) risk factors, four metabolites – all phosphatidylcholines (PCs) – showed independent predictive value for incident CHD, with low levels associated with higher CHD risk. The effect was greatest among women.
Phosphatidylcholines are a class of phospholipids derived from egg yolks, soybeans, and other foods that play an essential role in cell membrane function, among other things. They are thought to have anti-inflammatory effects, Dr. Zeller said.
The investigators found that lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with statistically significant hazard ratios ranging from 1.09 to 1.13, similar to body mass index, but lower than for diabetes and total cholesterol level.
Dr. Zeller said the team couldn’t adjust for lipid-lowering medications and diet, both of which might have affected levels, because information was not available for the subjects. There have been suggestions in the literature that higher levels of PCs are associated with a lower risk of Alzheimer’s disease, cognitive impairment, diabetes, and other diseases, but supplementation trials have been mostly negative.
BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
AT THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Lower levels of four in particular – PC ae C40:6; PC ae C38:6; PC aa C38:5; and PC aa C38:6 – increase the risk of incident CHD, with hazard ratios ranging from 1.09 to 1.13.
Data source: More than 10,000 subjects in the BiomarCaRE consortium.
Disclosures: BiomarCaRE is funded by the European Union. The investigators had no relevant financial disclosures.
FDA approves first follow-on short-acting insulin product using abbreviated approval pathway
aged 3 years and older with type 1 and type 2 diabetes mellitus, according to a news release from the FDA.
Insulin lispro injections are to be administered subcutaneously by injection, infusion via an insulin pump, or intravenously. Doses should be individualized based on route of administration and patients’ individual metabolic needs. All diabetes patients should regularly monitor their blood sugar levels and insulin regimens should be exclusively modified under medical supervision.
“With today’s approval, we are providing an important short-acting insulin option for patients that meets our standards for safety and effectiveness,” Mary T. Thanh Hai, MD, deputy director of the Office of New Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research, said in a statement.
Admelog, a biosimilar to Eli Lilly’s Humalog, was approved as a follow-on product based on the prior approval of Humalog. This allowed insulin lispro injections to be passed through the abbreviated approval pathway under the Federal Food, Drug, and Cosmetic Act, formally known as the 505(b)(2) pathway. The makers of insulin lispro found it was scientifically justified to use the previous safety and effectiveness data from the approval of Humalog to support the approval of insulin lispro injections. In addition to the Humalog data, the insulin lispro injection data included findings from two phase 3 clinical trials, each of which comprised about 500 diabetes patients. Using this abbreviated pathway can reduce the costs of drug development significantly, allowing new products to be offered to patients at lower prices.
“One of my key policy efforts is increasing competition in the market for prescription drugs and helping facilitate the entry of lower-cost alternatives. This is particularly important for drugs like insulin that are taken by millions of Americans every day for a patient’s lifetime to manage a chronic disease,” FDA Commissioner Scott Gottlieb, MD, said in a statement “In the coming months, we’ll be taking additional policy steps to help to make sure patients continue to benefit from improved access to lower cost, safe and effective alternatives to brand name drugs approved through the agency’s abbreviated pathways.”
Insulin lispro injections are short-acting insulin products that can help improve blood sugar levels in diabetes patients. This can be useful in controlling blood sugar levels after eating. This contrasts with long-acting insulin products, which are intended to control background insulin levels between meals. The blood sugar control needs of type 1 and type 2 diabetes patients are unique. Type 1 patients require both short- and long-term controls, while some type 2 patients may never need a short-acting insulin product. Because of these differences, providing insulin lispro injections as a blood sugar control method may be particularly useful to type 1 diabetes patients who need to control mealtime blood sugar levels.
aged 3 years and older with type 1 and type 2 diabetes mellitus, according to a news release from the FDA.
Insulin lispro injections are to be administered subcutaneously by injection, infusion via an insulin pump, or intravenously. Doses should be individualized based on route of administration and patients’ individual metabolic needs. All diabetes patients should regularly monitor their blood sugar levels and insulin regimens should be exclusively modified under medical supervision.
“With today’s approval, we are providing an important short-acting insulin option for patients that meets our standards for safety and effectiveness,” Mary T. Thanh Hai, MD, deputy director of the Office of New Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research, said in a statement.
Admelog, a biosimilar to Eli Lilly’s Humalog, was approved as a follow-on product based on the prior approval of Humalog. This allowed insulin lispro injections to be passed through the abbreviated approval pathway under the Federal Food, Drug, and Cosmetic Act, formally known as the 505(b)(2) pathway. The makers of insulin lispro found it was scientifically justified to use the previous safety and effectiveness data from the approval of Humalog to support the approval of insulin lispro injections. In addition to the Humalog data, the insulin lispro injection data included findings from two phase 3 clinical trials, each of which comprised about 500 diabetes patients. Using this abbreviated pathway can reduce the costs of drug development significantly, allowing new products to be offered to patients at lower prices.
“One of my key policy efforts is increasing competition in the market for prescription drugs and helping facilitate the entry of lower-cost alternatives. This is particularly important for drugs like insulin that are taken by millions of Americans every day for a patient’s lifetime to manage a chronic disease,” FDA Commissioner Scott Gottlieb, MD, said in a statement “In the coming months, we’ll be taking additional policy steps to help to make sure patients continue to benefit from improved access to lower cost, safe and effective alternatives to brand name drugs approved through the agency’s abbreviated pathways.”
Insulin lispro injections are short-acting insulin products that can help improve blood sugar levels in diabetes patients. This can be useful in controlling blood sugar levels after eating. This contrasts with long-acting insulin products, which are intended to control background insulin levels between meals. The blood sugar control needs of type 1 and type 2 diabetes patients are unique. Type 1 patients require both short- and long-term controls, while some type 2 patients may never need a short-acting insulin product. Because of these differences, providing insulin lispro injections as a blood sugar control method may be particularly useful to type 1 diabetes patients who need to control mealtime blood sugar levels.
aged 3 years and older with type 1 and type 2 diabetes mellitus, according to a news release from the FDA.
Insulin lispro injections are to be administered subcutaneously by injection, infusion via an insulin pump, or intravenously. Doses should be individualized based on route of administration and patients’ individual metabolic needs. All diabetes patients should regularly monitor their blood sugar levels and insulin regimens should be exclusively modified under medical supervision.
“With today’s approval, we are providing an important short-acting insulin option for patients that meets our standards for safety and effectiveness,” Mary T. Thanh Hai, MD, deputy director of the Office of New Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research, said in a statement.
Admelog, a biosimilar to Eli Lilly’s Humalog, was approved as a follow-on product based on the prior approval of Humalog. This allowed insulin lispro injections to be passed through the abbreviated approval pathway under the Federal Food, Drug, and Cosmetic Act, formally known as the 505(b)(2) pathway. The makers of insulin lispro found it was scientifically justified to use the previous safety and effectiveness data from the approval of Humalog to support the approval of insulin lispro injections. In addition to the Humalog data, the insulin lispro injection data included findings from two phase 3 clinical trials, each of which comprised about 500 diabetes patients. Using this abbreviated pathway can reduce the costs of drug development significantly, allowing new products to be offered to patients at lower prices.
“One of my key policy efforts is increasing competition in the market for prescription drugs and helping facilitate the entry of lower-cost alternatives. This is particularly important for drugs like insulin that are taken by millions of Americans every day for a patient’s lifetime to manage a chronic disease,” FDA Commissioner Scott Gottlieb, MD, said in a statement “In the coming months, we’ll be taking additional policy steps to help to make sure patients continue to benefit from improved access to lower cost, safe and effective alternatives to brand name drugs approved through the agency’s abbreviated pathways.”
Insulin lispro injections are short-acting insulin products that can help improve blood sugar levels in diabetes patients. This can be useful in controlling blood sugar levels after eating. This contrasts with long-acting insulin products, which are intended to control background insulin levels between meals. The blood sugar control needs of type 1 and type 2 diabetes patients are unique. Type 1 patients require both short- and long-term controls, while some type 2 patients may never need a short-acting insulin product. Because of these differences, providing insulin lispro injections as a blood sugar control method may be particularly useful to type 1 diabetes patients who need to control mealtime blood sugar levels.
Clinical trial: The Role of the Robotic Platform in Inguinal Hernia Repair Surgery
The Role of the Robotic Platform in Inguinal Hernia Repair Surgery is an interventional trial currently recruiting patients who require inguinal hernia repair surgery.
The trial will compare postoperative pain in patients undergoing laparoscopic inguinal hernia surgery repair or robotic inguinal hernia repair surgery. The laparoscopic approach has been used frequently and has several advantages. However, it has several disadvantages that the robotic approach may address. As such, the study investigators have hypothesized that the robotic approach will result in less postoperative pain than the laparoscopic approach.
The primary outcome measure is the difference in postoperative pain between patients who undergo robotic inguinal hernia repair and those who undergo laparoscopic inguinal hernia repair during the 2 years following surgery. Secondary outcome measures include differences in surgeon ergonomics between the two approaches, institution cost analysis, and long-term recurrence rate differences, all within 2 years of surgery.
The study will end in May 2019. About 100 people are expected to be included in the final analysis.
Find more information on the study page at Clinicaltrials.gov.
SOURCE: Clinicaltrials.gov. NCT02816658.
The Role of the Robotic Platform in Inguinal Hernia Repair Surgery is an interventional trial currently recruiting patients who require inguinal hernia repair surgery.
The trial will compare postoperative pain in patients undergoing laparoscopic inguinal hernia surgery repair or robotic inguinal hernia repair surgery. The laparoscopic approach has been used frequently and has several advantages. However, it has several disadvantages that the robotic approach may address. As such, the study investigators have hypothesized that the robotic approach will result in less postoperative pain than the laparoscopic approach.
The primary outcome measure is the difference in postoperative pain between patients who undergo robotic inguinal hernia repair and those who undergo laparoscopic inguinal hernia repair during the 2 years following surgery. Secondary outcome measures include differences in surgeon ergonomics between the two approaches, institution cost analysis, and long-term recurrence rate differences, all within 2 years of surgery.
The study will end in May 2019. About 100 people are expected to be included in the final analysis.
Find more information on the study page at Clinicaltrials.gov.
SOURCE: Clinicaltrials.gov. NCT02816658.
The Role of the Robotic Platform in Inguinal Hernia Repair Surgery is an interventional trial currently recruiting patients who require inguinal hernia repair surgery.
The trial will compare postoperative pain in patients undergoing laparoscopic inguinal hernia surgery repair or robotic inguinal hernia repair surgery. The laparoscopic approach has been used frequently and has several advantages. However, it has several disadvantages that the robotic approach may address. As such, the study investigators have hypothesized that the robotic approach will result in less postoperative pain than the laparoscopic approach.
The primary outcome measure is the difference in postoperative pain between patients who undergo robotic inguinal hernia repair and those who undergo laparoscopic inguinal hernia repair during the 2 years following surgery. Secondary outcome measures include differences in surgeon ergonomics between the two approaches, institution cost analysis, and long-term recurrence rate differences, all within 2 years of surgery.
The study will end in May 2019. About 100 people are expected to be included in the final analysis.
Find more information on the study page at Clinicaltrials.gov.
SOURCE: Clinicaltrials.gov. NCT02816658.
FROM CLINICALTRIALS.GOV
Quick Byte: Take a seat
A survey of 305 inpatients showed that patients who reported that at least one provider sat down while caring for them were more likely to feel that their provider spent appropriate time with them and that their provider kept them well informed. The authors concluded that sitting down at a patient’s bedside improves some aspects of patients’ and families’ experience of their hospital care, and should be included in hospital efforts to improve the patient experience.
Reference
1. Adebusuyi OA et al. Does sitting enhance patient satisfaction in the hospital? [abstract]. J Hosp Med. 2017; 12 (suppl 2). Accessed Aug. 7, 2017.
A survey of 305 inpatients showed that patients who reported that at least one provider sat down while caring for them were more likely to feel that their provider spent appropriate time with them and that their provider kept them well informed. The authors concluded that sitting down at a patient’s bedside improves some aspects of patients’ and families’ experience of their hospital care, and should be included in hospital efforts to improve the patient experience.
Reference
1. Adebusuyi OA et al. Does sitting enhance patient satisfaction in the hospital? [abstract]. J Hosp Med. 2017; 12 (suppl 2). Accessed Aug. 7, 2017.
A survey of 305 inpatients showed that patients who reported that at least one provider sat down while caring for them were more likely to feel that their provider spent appropriate time with them and that their provider kept them well informed. The authors concluded that sitting down at a patient’s bedside improves some aspects of patients’ and families’ experience of their hospital care, and should be included in hospital efforts to improve the patient experience.
Reference
1. Adebusuyi OA et al. Does sitting enhance patient satisfaction in the hospital? [abstract]. J Hosp Med. 2017; 12 (suppl 2). Accessed Aug. 7, 2017.
VIDEO: Venetoclax/rituximab prolongs PFS in relapsed/refractory CLL
ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.
The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.
In a video interview at the annual meeting of the American Society of Hematology, comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.
Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.
The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.
ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.
The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.
In a video interview at the annual meeting of the American Society of Hematology, comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.
Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.
The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.
ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.
The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.
In a video interview at the annual meeting of the American Society of Hematology, comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.
Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.
The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.
REPORTING FROM ASH 2017
Don’t choose hormones to protect postmenopausal women
Hormone therapy should not be used to prevent chronic conditions in postmenopausal women, according to updated recommendations from the U.S. Preventive Services Task Force. The recommendations were published online Dec. 12 in JAMA.
In the latest recommendation statement, the USPSTF issued D recommendations against using combination estrogen and progestin to prevent chronic conditions in postmenopausal women and against using estrogen only to prevent chronic conditions in postmenopausal women who have undergone hysterectomies (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.18261). A grade D recommendation is defined as “The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”
In response to public comments, the USPSTF team made several changes including adjusting the language to clarify that the recommendations apply only to postmenopausal women, and adding tables showing estimates of increased or decreased risk of various outcomes for postmenopausal women receiving different hormone therapies.
Approximately 40,000 women aged 53-79 years were included in an evidence report from Gerald Gartlehner, MD, of the University of North Carolina, Chapel Hill, and his colleagues that accompanied the recommendations (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.16952).
The researchers found that women taking estrogen alone had significantly lower risk of breast cancer, diabetes, and osteoporotic fractures, but significantly higher risk of gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo. In addition, women using a combination of estrogen and progestin had significantly lower risk of colorectal cancer, diabetes, and osteoporotic fractures, but significantly higher risk of breast cancer, probable dementia, gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo.
“Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms,” and the current evidence for the risks and benefits of hormone therapy is inconclusive, the researchers said.
The final recommendation remains consistent with the USPSTF draft statement issued earlier in 2017 and with the final recommendation statements issued in 2012.
The researchers had no relevant financial conflicts to disclose.
Twenty-five years ago, the U.S. Preventive Services Task Force advised clinicians to consider hormone therapy for the prevention of disease in all women, particularly those at risk for coronary heart disease, Deborah Grady, MD, wrote in an editorial (JAMA Intern Med. 2017 Dec 12. doi: 10.1001/jamainternmed.2017.7861). Dr. Grady was one of the coauthors of a literature review supporting the American College of Physicians’ recommendation to counsel asymptomatic postmenopausal women about hormone therapy based on data from observational studies. “No randomized trials with clinical outcomes had been conducted,” Dr. Grady said. By 2002, data from three large randomized trials told a different story, and the Task Force recommended against using estrogen alone as a strategy to prevent chronic conditions in postmenopausal women, she noted.
“I believe that the fear of hormone therapy is overblown,” Dr. Grady wrote. “When adequately informed, women with moderate to severe symptoms and without contraindications should be able to take such small risks if hormone therapy improves symptoms and quality of life,” she said.
In fact, professional societies, including the North American Menopause Society, the American College of Obstetricians and Gynecologists, and the Endocrine Society support hormone therapy for symptomatic women who are recently menopausal, said Dr. Grady. However, a key lesson learned from the ongoing research on hormone therapy is the importance of conducting clinical trials that are large enough to identify serious adverse effects, she added.
Dr. Grady is affiliated with the University of California, San Francisco. She had no financial conflicts to disclose.
Twenty-five years ago, the U.S. Preventive Services Task Force advised clinicians to consider hormone therapy for the prevention of disease in all women, particularly those at risk for coronary heart disease, Deborah Grady, MD, wrote in an editorial (JAMA Intern Med. 2017 Dec 12. doi: 10.1001/jamainternmed.2017.7861). Dr. Grady was one of the coauthors of a literature review supporting the American College of Physicians’ recommendation to counsel asymptomatic postmenopausal women about hormone therapy based on data from observational studies. “No randomized trials with clinical outcomes had been conducted,” Dr. Grady said. By 2002, data from three large randomized trials told a different story, and the Task Force recommended against using estrogen alone as a strategy to prevent chronic conditions in postmenopausal women, she noted.
“I believe that the fear of hormone therapy is overblown,” Dr. Grady wrote. “When adequately informed, women with moderate to severe symptoms and without contraindications should be able to take such small risks if hormone therapy improves symptoms and quality of life,” she said.
In fact, professional societies, including the North American Menopause Society, the American College of Obstetricians and Gynecologists, and the Endocrine Society support hormone therapy for symptomatic women who are recently menopausal, said Dr. Grady. However, a key lesson learned from the ongoing research on hormone therapy is the importance of conducting clinical trials that are large enough to identify serious adverse effects, she added.
Dr. Grady is affiliated with the University of California, San Francisco. She had no financial conflicts to disclose.
Twenty-five years ago, the U.S. Preventive Services Task Force advised clinicians to consider hormone therapy for the prevention of disease in all women, particularly those at risk for coronary heart disease, Deborah Grady, MD, wrote in an editorial (JAMA Intern Med. 2017 Dec 12. doi: 10.1001/jamainternmed.2017.7861). Dr. Grady was one of the coauthors of a literature review supporting the American College of Physicians’ recommendation to counsel asymptomatic postmenopausal women about hormone therapy based on data from observational studies. “No randomized trials with clinical outcomes had been conducted,” Dr. Grady said. By 2002, data from three large randomized trials told a different story, and the Task Force recommended against using estrogen alone as a strategy to prevent chronic conditions in postmenopausal women, she noted.
“I believe that the fear of hormone therapy is overblown,” Dr. Grady wrote. “When adequately informed, women with moderate to severe symptoms and without contraindications should be able to take such small risks if hormone therapy improves symptoms and quality of life,” she said.
In fact, professional societies, including the North American Menopause Society, the American College of Obstetricians and Gynecologists, and the Endocrine Society support hormone therapy for symptomatic women who are recently menopausal, said Dr. Grady. However, a key lesson learned from the ongoing research on hormone therapy is the importance of conducting clinical trials that are large enough to identify serious adverse effects, she added.
Dr. Grady is affiliated with the University of California, San Francisco. She had no financial conflicts to disclose.
Hormone therapy should not be used to prevent chronic conditions in postmenopausal women, according to updated recommendations from the U.S. Preventive Services Task Force. The recommendations were published online Dec. 12 in JAMA.
In the latest recommendation statement, the USPSTF issued D recommendations against using combination estrogen and progestin to prevent chronic conditions in postmenopausal women and against using estrogen only to prevent chronic conditions in postmenopausal women who have undergone hysterectomies (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.18261). A grade D recommendation is defined as “The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”
In response to public comments, the USPSTF team made several changes including adjusting the language to clarify that the recommendations apply only to postmenopausal women, and adding tables showing estimates of increased or decreased risk of various outcomes for postmenopausal women receiving different hormone therapies.
Approximately 40,000 women aged 53-79 years were included in an evidence report from Gerald Gartlehner, MD, of the University of North Carolina, Chapel Hill, and his colleagues that accompanied the recommendations (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.16952).
The researchers found that women taking estrogen alone had significantly lower risk of breast cancer, diabetes, and osteoporotic fractures, but significantly higher risk of gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo. In addition, women using a combination of estrogen and progestin had significantly lower risk of colorectal cancer, diabetes, and osteoporotic fractures, but significantly higher risk of breast cancer, probable dementia, gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo.
“Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms,” and the current evidence for the risks and benefits of hormone therapy is inconclusive, the researchers said.
The final recommendation remains consistent with the USPSTF draft statement issued earlier in 2017 and with the final recommendation statements issued in 2012.
The researchers had no relevant financial conflicts to disclose.
Hormone therapy should not be used to prevent chronic conditions in postmenopausal women, according to updated recommendations from the U.S. Preventive Services Task Force. The recommendations were published online Dec. 12 in JAMA.
In the latest recommendation statement, the USPSTF issued D recommendations against using combination estrogen and progestin to prevent chronic conditions in postmenopausal women and against using estrogen only to prevent chronic conditions in postmenopausal women who have undergone hysterectomies (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.18261). A grade D recommendation is defined as “The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”
In response to public comments, the USPSTF team made several changes including adjusting the language to clarify that the recommendations apply only to postmenopausal women, and adding tables showing estimates of increased or decreased risk of various outcomes for postmenopausal women receiving different hormone therapies.
Approximately 40,000 women aged 53-79 years were included in an evidence report from Gerald Gartlehner, MD, of the University of North Carolina, Chapel Hill, and his colleagues that accompanied the recommendations (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.16952).
The researchers found that women taking estrogen alone had significantly lower risk of breast cancer, diabetes, and osteoporotic fractures, but significantly higher risk of gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo. In addition, women using a combination of estrogen and progestin had significantly lower risk of colorectal cancer, diabetes, and osteoporotic fractures, but significantly higher risk of breast cancer, probable dementia, gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo.
“Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms,” and the current evidence for the risks and benefits of hormone therapy is inconclusive, the researchers said.
The final recommendation remains consistent with the USPSTF draft statement issued earlier in 2017 and with the final recommendation statements issued in 2012.
The researchers had no relevant financial conflicts to disclose.
FROM JAMA
Study supports methotrexate monotherapy with TNF inhibitor rescue for early RA treatment
For patients with early rheumatoid arthritis, starting with methotrexate and adding adalimumab after 26 weeks if needed led to clinical and functional outcomes similar to those of starting with a dual adalimumab-methotrexate regimen, according to a study published in Annals of the Rheumatic Diseases.
Although upfront adalimumab-methotrexate led to about a 14% decrease in the likelihood of radiographic progression, nearly one in four patients did well over more than a year of follow-up without ever needing to add a biologic disease-modifying antirheumatic drug (DMARD), said Arthur Kavanaugh, MD, of the University of California at San Diego, La Jolla, Calif., and his associates.
At week 26, patients who had achieved stable low disease activity (LDA; 28-joint modified Disease Activity Score of less than 3.2, based on C-reactive protein) on dual therapy were re-randomized to either stay on or withdraw from adalimumab. Patients who achieved stable LDA on methotrexate alone stayed on it. Patients who did not achieve stable LDA by week 26 either stayed on methotrexate-adalimumab or received adalimumab rescue. For the current post hoc study, Dr. Kavanaugh and his associates compared longer-term outcomes between patients who received adalimumab-methotrexate at baseline and patients who started with methotrexate only. In addition to stable LDA, the investigators assessed normal function (Health Assessment Questionnaire Disability Index less than 0.5) and radiographic nonprogression (no more than 0.5 change in modified total Sharp score).
Patients who started on adalimumab-methotrexate instead of methotrexate monotherapy were significantly more likely to achieve stable LDA (53% vs. 30%), good function (45% vs. 33%), and radiographic nonprogression (87% vs. 72%) at week 26 (Ann Rheum Dis. 2013;72:64-71). However, as-needed rescue treatment with adalimumab at week 26 achieved very similar clinical and functional outcomes compared with initial treatment with methotrexate-adalimumab. At week 52, 62% and 65% of patients in these two groups had stable LDA, and 44% and 47% had normal function, respectively. At week 78, 65% of patients in both groups had stable LDA and 45% and 48% had normal function, respectively. However, initial therapy with adalimumab-methotrexate was associated with lower chances of radiographic progression compared with methotrexate monotherapy (86% and 72% at both time points, respectively).
This is the first study to assess whether rapidly adding a TNFi improves disease outcomes compared with starting treatment with both adalimumab and methotrexate in patients with early RA, the researchers said. Importantly, 24% of patients who started on methotrexate alone never needed to add a biological DMARD, experiencing “little to no radiographic progression and mostly good physical function thereafter,” they reported. The study supports current guidelines and a stepwise treat-to-target strategy can prevent overtreatment in about one in four patients with early RA, they concluded.
AbbVie makes adalimumab, sponsored the study, and was involved in its design, analysis, writeup, and review. Dr. Kavanaugh disclosed ties to AbbVie through his institution. Nine coinvestigators disclosed ties to AbbVie; five of the nine reported current or former employment with the company.
SOURCE: Ann Rheum Dis. 2017 Nov 16. doi: 10.1136/annrheumdis-2017-211871
This study is of general interest and its design is complex, with double-blind, open re-randomization, and open-label extension arms.
There are a number of points to highlight:
1. Both methotrexate-adalimumab arms eventuate in a small advantage with respect to radiographs, with less accrued damage than with methotrexate alone. As in multiple other studies, the radiographic differences, although statistically significant, are not clinically important during this short study. However, if extended over a number of years, they could become clinically important, and that should not be ignored.
2. The authors state that methotrexate monotherapy patients who later added adalimumab achieved symptomatic and functional relief equivalent to starting on methotrexate-adalimumab – which I fully agree with – but the authors pointed out that there may well be some bias in that conclusion because the “add-on” patients did so during an open-label phase of the study. The complex design of the study makes this a bit hard to dissect.
4. Also, this study design did not allow corticosteroids. While I am a staunch advocate of minimizing steroids, some clinicians would have used steroids early on to improve early response, thus mitigating the early differential effect of methotrexate monotherapy.
So what is the bottom line? In my mind, this study supports that methotrexate-adalimumab decreases the rate of bony damage (not a new finding among biologics plus methotrexate in RA) and gently advocates that using methotrexate alone as the first DMARD is appropriate.
The data actually do not clarify the potentially important symptomatic/functional differences during the early months between the group that went from methotrexate monotherapy to methotrexate-adalimumab vs. the group that received immediate methotrexate-adalimumab, where the “immediate” methotrexate-adalimumab patients probably felt better faster. Still, one needs to consider potential toxicity and cost of the immediate methotrexate-adalimumab group, and that is not well addressed here.
When faced with a patient, I always ask how bad are the symptoms (worse leaning me toward immediate methotrexate-adalimumab) vs. how frail is the patient (more frail leaning me toward first using methotrexate) and how good is their insurance (sadly a consideration in the United States, with better insurance leaning me toward the “immediate” combo because I think other data show this yields a faster response).
Daniel E. Furst, MD, is professor of rheumatology at the University of California, Los Angeles (emeritus), at the University of Washington, Seattle, and at the University of Florence (Italy). He reported receiving grant/research support from Bristol-Myers-Squibb, Pfizer, and Roche/Genentech. He is also a consultant to AbbVie, Novartis, Pfizer, and Roche/Genentech.
This study is of general interest and its design is complex, with double-blind, open re-randomization, and open-label extension arms.
There are a number of points to highlight:
1. Both methotrexate-adalimumab arms eventuate in a small advantage with respect to radiographs, with less accrued damage than with methotrexate alone. As in multiple other studies, the radiographic differences, although statistically significant, are not clinically important during this short study. However, if extended over a number of years, they could become clinically important, and that should not be ignored.
2. The authors state that methotrexate monotherapy patients who later added adalimumab achieved symptomatic and functional relief equivalent to starting on methotrexate-adalimumab – which I fully agree with – but the authors pointed out that there may well be some bias in that conclusion because the “add-on” patients did so during an open-label phase of the study. The complex design of the study makes this a bit hard to dissect.
4. Also, this study design did not allow corticosteroids. While I am a staunch advocate of minimizing steroids, some clinicians would have used steroids early on to improve early response, thus mitigating the early differential effect of methotrexate monotherapy.
So what is the bottom line? In my mind, this study supports that methotrexate-adalimumab decreases the rate of bony damage (not a new finding among biologics plus methotrexate in RA) and gently advocates that using methotrexate alone as the first DMARD is appropriate.
The data actually do not clarify the potentially important symptomatic/functional differences during the early months between the group that went from methotrexate monotherapy to methotrexate-adalimumab vs. the group that received immediate methotrexate-adalimumab, where the “immediate” methotrexate-adalimumab patients probably felt better faster. Still, one needs to consider potential toxicity and cost of the immediate methotrexate-adalimumab group, and that is not well addressed here.
When faced with a patient, I always ask how bad are the symptoms (worse leaning me toward immediate methotrexate-adalimumab) vs. how frail is the patient (more frail leaning me toward first using methotrexate) and how good is their insurance (sadly a consideration in the United States, with better insurance leaning me toward the “immediate” combo because I think other data show this yields a faster response).
Daniel E. Furst, MD, is professor of rheumatology at the University of California, Los Angeles (emeritus), at the University of Washington, Seattle, and at the University of Florence (Italy). He reported receiving grant/research support from Bristol-Myers-Squibb, Pfizer, and Roche/Genentech. He is also a consultant to AbbVie, Novartis, Pfizer, and Roche/Genentech.
This study is of general interest and its design is complex, with double-blind, open re-randomization, and open-label extension arms.
There are a number of points to highlight:
1. Both methotrexate-adalimumab arms eventuate in a small advantage with respect to radiographs, with less accrued damage than with methotrexate alone. As in multiple other studies, the radiographic differences, although statistically significant, are not clinically important during this short study. However, if extended over a number of years, they could become clinically important, and that should not be ignored.
2. The authors state that methotrexate monotherapy patients who later added adalimumab achieved symptomatic and functional relief equivalent to starting on methotrexate-adalimumab – which I fully agree with – but the authors pointed out that there may well be some bias in that conclusion because the “add-on” patients did so during an open-label phase of the study. The complex design of the study makes this a bit hard to dissect.
4. Also, this study design did not allow corticosteroids. While I am a staunch advocate of minimizing steroids, some clinicians would have used steroids early on to improve early response, thus mitigating the early differential effect of methotrexate monotherapy.
So what is the bottom line? In my mind, this study supports that methotrexate-adalimumab decreases the rate of bony damage (not a new finding among biologics plus methotrexate in RA) and gently advocates that using methotrexate alone as the first DMARD is appropriate.
The data actually do not clarify the potentially important symptomatic/functional differences during the early months between the group that went from methotrexate monotherapy to methotrexate-adalimumab vs. the group that received immediate methotrexate-adalimumab, where the “immediate” methotrexate-adalimumab patients probably felt better faster. Still, one needs to consider potential toxicity and cost of the immediate methotrexate-adalimumab group, and that is not well addressed here.
When faced with a patient, I always ask how bad are the symptoms (worse leaning me toward immediate methotrexate-adalimumab) vs. how frail is the patient (more frail leaning me toward first using methotrexate) and how good is their insurance (sadly a consideration in the United States, with better insurance leaning me toward the “immediate” combo because I think other data show this yields a faster response).
Daniel E. Furst, MD, is professor of rheumatology at the University of California, Los Angeles (emeritus), at the University of Washington, Seattle, and at the University of Florence (Italy). He reported receiving grant/research support from Bristol-Myers-Squibb, Pfizer, and Roche/Genentech. He is also a consultant to AbbVie, Novartis, Pfizer, and Roche/Genentech.
For patients with early rheumatoid arthritis, starting with methotrexate and adding adalimumab after 26 weeks if needed led to clinical and functional outcomes similar to those of starting with a dual adalimumab-methotrexate regimen, according to a study published in Annals of the Rheumatic Diseases.
Although upfront adalimumab-methotrexate led to about a 14% decrease in the likelihood of radiographic progression, nearly one in four patients did well over more than a year of follow-up without ever needing to add a biologic disease-modifying antirheumatic drug (DMARD), said Arthur Kavanaugh, MD, of the University of California at San Diego, La Jolla, Calif., and his associates.
At week 26, patients who had achieved stable low disease activity (LDA; 28-joint modified Disease Activity Score of less than 3.2, based on C-reactive protein) on dual therapy were re-randomized to either stay on or withdraw from adalimumab. Patients who achieved stable LDA on methotrexate alone stayed on it. Patients who did not achieve stable LDA by week 26 either stayed on methotrexate-adalimumab or received adalimumab rescue. For the current post hoc study, Dr. Kavanaugh and his associates compared longer-term outcomes between patients who received adalimumab-methotrexate at baseline and patients who started with methotrexate only. In addition to stable LDA, the investigators assessed normal function (Health Assessment Questionnaire Disability Index less than 0.5) and radiographic nonprogression (no more than 0.5 change in modified total Sharp score).
Patients who started on adalimumab-methotrexate instead of methotrexate monotherapy were significantly more likely to achieve stable LDA (53% vs. 30%), good function (45% vs. 33%), and radiographic nonprogression (87% vs. 72%) at week 26 (Ann Rheum Dis. 2013;72:64-71). However, as-needed rescue treatment with adalimumab at week 26 achieved very similar clinical and functional outcomes compared with initial treatment with methotrexate-adalimumab. At week 52, 62% and 65% of patients in these two groups had stable LDA, and 44% and 47% had normal function, respectively. At week 78, 65% of patients in both groups had stable LDA and 45% and 48% had normal function, respectively. However, initial therapy with adalimumab-methotrexate was associated with lower chances of radiographic progression compared with methotrexate monotherapy (86% and 72% at both time points, respectively).
This is the first study to assess whether rapidly adding a TNFi improves disease outcomes compared with starting treatment with both adalimumab and methotrexate in patients with early RA, the researchers said. Importantly, 24% of patients who started on methotrexate alone never needed to add a biological DMARD, experiencing “little to no radiographic progression and mostly good physical function thereafter,” they reported. The study supports current guidelines and a stepwise treat-to-target strategy can prevent overtreatment in about one in four patients with early RA, they concluded.
AbbVie makes adalimumab, sponsored the study, and was involved in its design, analysis, writeup, and review. Dr. Kavanaugh disclosed ties to AbbVie through his institution. Nine coinvestigators disclosed ties to AbbVie; five of the nine reported current or former employment with the company.
SOURCE: Ann Rheum Dis. 2017 Nov 16. doi: 10.1136/annrheumdis-2017-211871
For patients with early rheumatoid arthritis, starting with methotrexate and adding adalimumab after 26 weeks if needed led to clinical and functional outcomes similar to those of starting with a dual adalimumab-methotrexate regimen, according to a study published in Annals of the Rheumatic Diseases.
Although upfront adalimumab-methotrexate led to about a 14% decrease in the likelihood of radiographic progression, nearly one in four patients did well over more than a year of follow-up without ever needing to add a biologic disease-modifying antirheumatic drug (DMARD), said Arthur Kavanaugh, MD, of the University of California at San Diego, La Jolla, Calif., and his associates.
At week 26, patients who had achieved stable low disease activity (LDA; 28-joint modified Disease Activity Score of less than 3.2, based on C-reactive protein) on dual therapy were re-randomized to either stay on or withdraw from adalimumab. Patients who achieved stable LDA on methotrexate alone stayed on it. Patients who did not achieve stable LDA by week 26 either stayed on methotrexate-adalimumab or received adalimumab rescue. For the current post hoc study, Dr. Kavanaugh and his associates compared longer-term outcomes between patients who received adalimumab-methotrexate at baseline and patients who started with methotrexate only. In addition to stable LDA, the investigators assessed normal function (Health Assessment Questionnaire Disability Index less than 0.5) and radiographic nonprogression (no more than 0.5 change in modified total Sharp score).
Patients who started on adalimumab-methotrexate instead of methotrexate monotherapy were significantly more likely to achieve stable LDA (53% vs. 30%), good function (45% vs. 33%), and radiographic nonprogression (87% vs. 72%) at week 26 (Ann Rheum Dis. 2013;72:64-71). However, as-needed rescue treatment with adalimumab at week 26 achieved very similar clinical and functional outcomes compared with initial treatment with methotrexate-adalimumab. At week 52, 62% and 65% of patients in these two groups had stable LDA, and 44% and 47% had normal function, respectively. At week 78, 65% of patients in both groups had stable LDA and 45% and 48% had normal function, respectively. However, initial therapy with adalimumab-methotrexate was associated with lower chances of radiographic progression compared with methotrexate monotherapy (86% and 72% at both time points, respectively).
This is the first study to assess whether rapidly adding a TNFi improves disease outcomes compared with starting treatment with both adalimumab and methotrexate in patients with early RA, the researchers said. Importantly, 24% of patients who started on methotrexate alone never needed to add a biological DMARD, experiencing “little to no radiographic progression and mostly good physical function thereafter,” they reported. The study supports current guidelines and a stepwise treat-to-target strategy can prevent overtreatment in about one in four patients with early RA, they concluded.
AbbVie makes adalimumab, sponsored the study, and was involved in its design, analysis, writeup, and review. Dr. Kavanaugh disclosed ties to AbbVie through his institution. Nine coinvestigators disclosed ties to AbbVie; five of the nine reported current or former employment with the company.
SOURCE: Ann Rheum Dis. 2017 Nov 16. doi: 10.1136/annrheumdis-2017-211871
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: Adding adalimumab as rescue therapy at 26 weeks achieved outcomes at 78 weeks similar to those of starting treatment with adalimumab-methotrexate.
Data source: A post hoc analysis of a 78-week, randomized, double-blind, phase 4 study of 926 methotrexate-naive patients with a less than 1-year history of active RA.
Disclosures: AbbVie makes adalimumab, sponsored the study, and was involved in its design, analysis, writeup, and review. Dr. Kavanaugh disclosed ties to AbbVie through his institution. Nine coinvestigators disclosed ties to AbbVie; five of the nine reported current or former employment with the company.
Source: Ann Rheum Dis. 2017 Nov 16. doi: 10.1136/annrheumdis-2017-211871
Gene silencer reduces mutant huntingtin protein in early-stage Huntington’s patients
An investigational gene-silencing molecule safely and dose-dependently reduced production of the mutant huntingtin protein in people with early-stage Huntington’s disease in a small, early-phase study, according to an announcement from the drug’s developer, Ionis Pharmaceuticals.
The antisense oligonucleotide IONIS-HTTRx – the first potentially disease-modifying drug for Huntington’s – will now go forward in a larger study to determine whether lowering mutant huntingtin protein (mHTT) confers any clinical benefits upon patients with the fatal neurodegenerative disease.
IONIS-HTTRx reduced mHTT by fractions that “exceeded expectations” set for the 46-person trial, C. Frank Bennett, PhD, senior vice president of research at Ionis, said in a press statement.
“The results of this trial are of groundbreaking importance for Huntington’s disease patients and families,” said Dr. Tabrizi, director of the Huntington’s Disease Centre at University College London. “For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well tolerated. The key now is to move quickly to a larger trial to test whether the drug slows disease progression.”
Upon receiving the positive data, Roche Pharma exercised its $45 million option to license the molecule. Roche now takes all regulatory and clinical development responsibility for IONIS-HTTRx.
There are few publicly available data on the IONIS-HTTRx study. It enrolled 46 patients with early-stage Huntington’s who were recruited from nine sites in the United Kingdom, Germany, and Canada. They were randomized to placebo or to four ascending doses of IONIS-HTTRx. The primary outcomes were mHTT levels in spinal fluid, safety, and tolerability. It produced significant, dose-dependent reductions of mHTT without concerning or dose-limiting safety signals, the press statement noted.
A larger study with clinical endpoints is next up, according to a statement Ionis and Roche jointly issued to the Huntington’s Disease Society of America.
“The next step for this program will be to conduct a safety and efficacy study to investigate if decreasing mutant huntingtin protein with IONIS-HTTRx can benefit people with Huntington’s disease,” the statement noted. “Future studies for the program will be conducted globally, including in the U.S. Roche will announce details about future studies, including eligibility criteria and planned start dates, as this information becomes available. All relevant information on upcoming studies will also be posted on HDTrialFinder.org and ClinicalTrials.gov.”
Huntington’s disease is caused by an expansion of at least 36 repeats of the CAG trinucleotide sequence in the huntingtin gene. The resulting mHTT is toxic and gradually damages neurons. IONIS-HTTRx interrupts the messenger RNA that fuels this toxic protein buildup, and it is the only drug that has ever attacked the disease at this level. This development is “a historic moment in the fight against Huntington’s, as it represents the successful completion of the first trial to treat the underlying cause of Huntington’s disease, the genetic mutation itself,” according to a statement by Louise Vetter, president of the Huntington’s Disease Society of America.
“The fact that levels of mutant huntingtin were reduced in correlation to the dose of IONIS-HTTRx that was given is significant, and the fact that participants in this first Phase 1/2a study are able to continue on the drug through an open-label extension gives us optimism regarding its safety,” Ms. Vetter said.
In January 2016, the Food and Drug Administration granted orphan drug status to IONIS-HTTRX; the European Medicines Agency had previously granted it similar status.
The press release from Ionis Pharmaceuticals sounds very promising. There is reason to believe that lowering mHTT protein might prevent or delay Huntington’s disease, and this antisense molecule appears to be safe and to lower mHTT in cerebrospinal fluid. However, there are several caveats.
First, it is unclear whether lowering mHTT protein might help those who already have clinical Huntington’s disease.
Third, no information is given in the press release about the degree of reduction of mHTT observed and whether there is evidence that this lowering might be sufficient for a therapeutic effect.
Fourth, neurotoxicity may not only result from the mHTT protein but also directly from the mRNA itself. The contribution of mutant mRNA to pathogenesis is a key open question in the study of Huntington’s disease and other related “repeat disorders.”
Michael Wolfe, PhD , is the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. He has no relevant disclosures.
The press release from Ionis Pharmaceuticals sounds very promising. There is reason to believe that lowering mHTT protein might prevent or delay Huntington’s disease, and this antisense molecule appears to be safe and to lower mHTT in cerebrospinal fluid. However, there are several caveats.
First, it is unclear whether lowering mHTT protein might help those who already have clinical Huntington’s disease.
Third, no information is given in the press release about the degree of reduction of mHTT observed and whether there is evidence that this lowering might be sufficient for a therapeutic effect.
Fourth, neurotoxicity may not only result from the mHTT protein but also directly from the mRNA itself. The contribution of mutant mRNA to pathogenesis is a key open question in the study of Huntington’s disease and other related “repeat disorders.”
Michael Wolfe, PhD , is the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. He has no relevant disclosures.
The press release from Ionis Pharmaceuticals sounds very promising. There is reason to believe that lowering mHTT protein might prevent or delay Huntington’s disease, and this antisense molecule appears to be safe and to lower mHTT in cerebrospinal fluid. However, there are several caveats.
First, it is unclear whether lowering mHTT protein might help those who already have clinical Huntington’s disease.
Third, no information is given in the press release about the degree of reduction of mHTT observed and whether there is evidence that this lowering might be sufficient for a therapeutic effect.
Fourth, neurotoxicity may not only result from the mHTT protein but also directly from the mRNA itself. The contribution of mutant mRNA to pathogenesis is a key open question in the study of Huntington’s disease and other related “repeat disorders.”
Michael Wolfe, PhD , is the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. He has no relevant disclosures.
An investigational gene-silencing molecule safely and dose-dependently reduced production of the mutant huntingtin protein in people with early-stage Huntington’s disease in a small, early-phase study, according to an announcement from the drug’s developer, Ionis Pharmaceuticals.
The antisense oligonucleotide IONIS-HTTRx – the first potentially disease-modifying drug for Huntington’s – will now go forward in a larger study to determine whether lowering mutant huntingtin protein (mHTT) confers any clinical benefits upon patients with the fatal neurodegenerative disease.
IONIS-HTTRx reduced mHTT by fractions that “exceeded expectations” set for the 46-person trial, C. Frank Bennett, PhD, senior vice president of research at Ionis, said in a press statement.
“The results of this trial are of groundbreaking importance for Huntington’s disease patients and families,” said Dr. Tabrizi, director of the Huntington’s Disease Centre at University College London. “For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well tolerated. The key now is to move quickly to a larger trial to test whether the drug slows disease progression.”
Upon receiving the positive data, Roche Pharma exercised its $45 million option to license the molecule. Roche now takes all regulatory and clinical development responsibility for IONIS-HTTRx.
There are few publicly available data on the IONIS-HTTRx study. It enrolled 46 patients with early-stage Huntington’s who were recruited from nine sites in the United Kingdom, Germany, and Canada. They were randomized to placebo or to four ascending doses of IONIS-HTTRx. The primary outcomes were mHTT levels in spinal fluid, safety, and tolerability. It produced significant, dose-dependent reductions of mHTT without concerning or dose-limiting safety signals, the press statement noted.
A larger study with clinical endpoints is next up, according to a statement Ionis and Roche jointly issued to the Huntington’s Disease Society of America.
“The next step for this program will be to conduct a safety and efficacy study to investigate if decreasing mutant huntingtin protein with IONIS-HTTRx can benefit people with Huntington’s disease,” the statement noted. “Future studies for the program will be conducted globally, including in the U.S. Roche will announce details about future studies, including eligibility criteria and planned start dates, as this information becomes available. All relevant information on upcoming studies will also be posted on HDTrialFinder.org and ClinicalTrials.gov.”
Huntington’s disease is caused by an expansion of at least 36 repeats of the CAG trinucleotide sequence in the huntingtin gene. The resulting mHTT is toxic and gradually damages neurons. IONIS-HTTRx interrupts the messenger RNA that fuels this toxic protein buildup, and it is the only drug that has ever attacked the disease at this level. This development is “a historic moment in the fight against Huntington’s, as it represents the successful completion of the first trial to treat the underlying cause of Huntington’s disease, the genetic mutation itself,” according to a statement by Louise Vetter, president of the Huntington’s Disease Society of America.
“The fact that levels of mutant huntingtin were reduced in correlation to the dose of IONIS-HTTRx that was given is significant, and the fact that participants in this first Phase 1/2a study are able to continue on the drug through an open-label extension gives us optimism regarding its safety,” Ms. Vetter said.
In January 2016, the Food and Drug Administration granted orphan drug status to IONIS-HTTRX; the European Medicines Agency had previously granted it similar status.
An investigational gene-silencing molecule safely and dose-dependently reduced production of the mutant huntingtin protein in people with early-stage Huntington’s disease in a small, early-phase study, according to an announcement from the drug’s developer, Ionis Pharmaceuticals.
The antisense oligonucleotide IONIS-HTTRx – the first potentially disease-modifying drug for Huntington’s – will now go forward in a larger study to determine whether lowering mutant huntingtin protein (mHTT) confers any clinical benefits upon patients with the fatal neurodegenerative disease.
IONIS-HTTRx reduced mHTT by fractions that “exceeded expectations” set for the 46-person trial, C. Frank Bennett, PhD, senior vice president of research at Ionis, said in a press statement.
“The results of this trial are of groundbreaking importance for Huntington’s disease patients and families,” said Dr. Tabrizi, director of the Huntington’s Disease Centre at University College London. “For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well tolerated. The key now is to move quickly to a larger trial to test whether the drug slows disease progression.”
Upon receiving the positive data, Roche Pharma exercised its $45 million option to license the molecule. Roche now takes all regulatory and clinical development responsibility for IONIS-HTTRx.
There are few publicly available data on the IONIS-HTTRx study. It enrolled 46 patients with early-stage Huntington’s who were recruited from nine sites in the United Kingdom, Germany, and Canada. They were randomized to placebo or to four ascending doses of IONIS-HTTRx. The primary outcomes were mHTT levels in spinal fluid, safety, and tolerability. It produced significant, dose-dependent reductions of mHTT without concerning or dose-limiting safety signals, the press statement noted.
A larger study with clinical endpoints is next up, according to a statement Ionis and Roche jointly issued to the Huntington’s Disease Society of America.
“The next step for this program will be to conduct a safety and efficacy study to investigate if decreasing mutant huntingtin protein with IONIS-HTTRx can benefit people with Huntington’s disease,” the statement noted. “Future studies for the program will be conducted globally, including in the U.S. Roche will announce details about future studies, including eligibility criteria and planned start dates, as this information becomes available. All relevant information on upcoming studies will also be posted on HDTrialFinder.org and ClinicalTrials.gov.”
Huntington’s disease is caused by an expansion of at least 36 repeats of the CAG trinucleotide sequence in the huntingtin gene. The resulting mHTT is toxic and gradually damages neurons. IONIS-HTTRx interrupts the messenger RNA that fuels this toxic protein buildup, and it is the only drug that has ever attacked the disease at this level. This development is “a historic moment in the fight against Huntington’s, as it represents the successful completion of the first trial to treat the underlying cause of Huntington’s disease, the genetic mutation itself,” according to a statement by Louise Vetter, president of the Huntington’s Disease Society of America.
“The fact that levels of mutant huntingtin were reduced in correlation to the dose of IONIS-HTTRx that was given is significant, and the fact that participants in this first Phase 1/2a study are able to continue on the drug through an open-label extension gives us optimism regarding its safety,” Ms. Vetter said.
In January 2016, the Food and Drug Administration granted orphan drug status to IONIS-HTTRX; the European Medicines Agency had previously granted it similar status.
Using “design thinking” to improve health care
Health care workers creating innovations by applying “design thinking” – “a human-centered approach to innovation” that comes from the business world – is a growing trend, according to a recent New York Times article.
“With design thinking, the innovations come from those who actually work there, providing feedback to designers to improve the final product,” wrote author Amitha Kalaichandran, MD, MHS.
“Health providers ... are uniquely positioned to come up with fresh solutions to health care problems,” Dr. Kalaichandran wrote. An example at her own hospital: The leader of the trauma team now wears an orange vest, clearly identifying who’s in charge in a potentially chaotic situation. It was an idea created by a hospital nurse.
“A 2016 report that looked at ways in which a health system can implement design thinking identified three principles behind the approach: empathy for the user, in this case a patient, doctor or other health care provider; the involvement of an interdisciplinary team; and rapid prototyping of the idea,” she wrote. “To develop a truly useful product, a comprehensive understanding of the problem the innovation aims to solve is paramount.”
In design thinking, described as creative, multidisciplinary thinking around a problem, groups naturally coalesce to find such solutions. The article cites examples such as Clinicians for Design, an international group of providers focused on improving hospital layouts, and Health Design by Us, a collaborative group that supports health care innovations such as a mobile system for diabetes management, designed by a patient.
Reference
Kalaichandran A. Design thinking for doctors and nurses. The New York Times. Aug. 3, 2017. Accessed Aug. 7, 2017.
Health care workers creating innovations by applying “design thinking” – “a human-centered approach to innovation” that comes from the business world – is a growing trend, according to a recent New York Times article.
“With design thinking, the innovations come from those who actually work there, providing feedback to designers to improve the final product,” wrote author Amitha Kalaichandran, MD, MHS.
“Health providers ... are uniquely positioned to come up with fresh solutions to health care problems,” Dr. Kalaichandran wrote. An example at her own hospital: The leader of the trauma team now wears an orange vest, clearly identifying who’s in charge in a potentially chaotic situation. It was an idea created by a hospital nurse.
“A 2016 report that looked at ways in which a health system can implement design thinking identified three principles behind the approach: empathy for the user, in this case a patient, doctor or other health care provider; the involvement of an interdisciplinary team; and rapid prototyping of the idea,” she wrote. “To develop a truly useful product, a comprehensive understanding of the problem the innovation aims to solve is paramount.”
In design thinking, described as creative, multidisciplinary thinking around a problem, groups naturally coalesce to find such solutions. The article cites examples such as Clinicians for Design, an international group of providers focused on improving hospital layouts, and Health Design by Us, a collaborative group that supports health care innovations such as a mobile system for diabetes management, designed by a patient.
Reference
Kalaichandran A. Design thinking for doctors and nurses. The New York Times. Aug. 3, 2017. Accessed Aug. 7, 2017.
Health care workers creating innovations by applying “design thinking” – “a human-centered approach to innovation” that comes from the business world – is a growing trend, according to a recent New York Times article.
“With design thinking, the innovations come from those who actually work there, providing feedback to designers to improve the final product,” wrote author Amitha Kalaichandran, MD, MHS.
“Health providers ... are uniquely positioned to come up with fresh solutions to health care problems,” Dr. Kalaichandran wrote. An example at her own hospital: The leader of the trauma team now wears an orange vest, clearly identifying who’s in charge in a potentially chaotic situation. It was an idea created by a hospital nurse.
“A 2016 report that looked at ways in which a health system can implement design thinking identified three principles behind the approach: empathy for the user, in this case a patient, doctor or other health care provider; the involvement of an interdisciplinary team; and rapid prototyping of the idea,” she wrote. “To develop a truly useful product, a comprehensive understanding of the problem the innovation aims to solve is paramount.”
In design thinking, described as creative, multidisciplinary thinking around a problem, groups naturally coalesce to find such solutions. The article cites examples such as Clinicians for Design, an international group of providers focused on improving hospital layouts, and Health Design by Us, a collaborative group that supports health care innovations such as a mobile system for diabetes management, designed by a patient.
Reference
Kalaichandran A. Design thinking for doctors and nurses. The New York Times. Aug. 3, 2017. Accessed Aug. 7, 2017.
Early weight change has no special effect on mortality in RA
Weight loss at the time of rheumatoid arthritis diagnosis had the same impact on mortality in patients with and without RA, according to research trying to solve the so-called obesity paradox in RA, which has been related to prior observations of a protective effect of obesity on mortality in RA patients.
The finding indicates that clinicians can continue to encourage patients with rheumatoid arthritis to follow healthy weight-loss strategies, according to first author of the study, Jeffrey Sparks, MD, of Brigham and Women’s Hospital in Boston.
Dr. Sparks and his colleagues examined the impact of weight change and mortality in RA patients based on data from the Nurses’ Health Study.
“Our study is the first to focus on weight change around RA diagnosis and risk of death, rather than weight change in patients who had RA for many years,” Dr. Sparks noted.
By examining changes in weight near the time of RA diagnosis, Dr. Sparks and his colleagues said that they hoped to extract information about RA-specific processes rather than the underlying pathologies that might cause weight changes near the end of life.
In the study published in Arthritis & Rheumatology, the researchers compared women diagnosed with RA during follow-up to women without RA during the same index time period of 1976-2016. The study population included 121,701 women. Of these, 902 developed incident RA and were matched with 7,884 non-RA controls.
During an average of 18 years of follow-up, 41% of the RA cohort and 29% of the controls died. The risk of death was approximately twice as high (hazard ratio, 2.78; 95% confidence interval, 1.58-4.89) among those with weight loss greater than 30 pounds at the time of RA diagnosis, compared with those whose weight remained stable. However, the risk for mortality was similarly increased (HR, 2.16; 95% CI, 1.61-2.88) among the controls with weight loss greater than 30 pounds, compared with those with stable weight. No association with mortality was noted in either group among women who gained more than 30 pounds at the time of RA diagnosis.
Dr. Sparks said he was somewhat surprised by the findings.
“We expected severe, pathologic weight loss to be associated with increased risk of death among patients with RA and comparators. It was somewhat surprising that the risks in both groups were similar,” he said. “Conversely, prior studies suggested that weight gain might have been associated with increased risk of death. However, we found no association of weight gain with risk of death,” he noted.
In addition, “Our findings argue that there is not an RA-specific mortality risk based on either weight loss or gain,” he said. “While we found that weight loss was associated with increased mortality, this was most pronounced in the severe weight loss group, so was likely due to unintentional weight loss.”
Joshua F. Baker, MD, of the University of Pennsylvania, Philadelphia, and his colleagues identified an association between weight change and risk of death in RA patients in a study first published online in Arthritis & Rheumatology in 2015 (Arthritis Rheumatol. 2015 Jul;67[7]:1711-17). That study addressed the so-called obesity paradox in RA, and Dr. Baker and his colleagues noted that weight loss associated with the development of chronic illness is a significant confounder that may explain the observed protective effect of obesity on mortality.
“It is not clear how best to monitor changes in weight, when exactly to become concerned, and what to do when changes are observed,” Dr. Baker noted. “RA patients may lose weight for a number of reasons, not all related to their arthritis, and it is unlikely that there is a ‘one size fits all’ approach,” he said.
The study was limited in part by the women-only study population, so the results might not be generalizable to men, Dr. Sparks said. “The reason for weight change was unavailable,” he added. Directions for further research include investigation of how factors such as physical activity, diet, and weight loss may affect the risk of death among individuals with and without RA, he said.
Dr. Sparks had no financial conflicts to disclose. The study was supported in part by the National Institutes of Health and the Rheumatology Research Foundation’s Disease-Targeted Innovative Award and Scientist Development Awards.
SOURCE: Sparks J et al. Arthritis Rheumatol. 2017 Nov 30. doi: 10.1002/art.40346.
Weight loss at the time of rheumatoid arthritis diagnosis had the same impact on mortality in patients with and without RA, according to research trying to solve the so-called obesity paradox in RA, which has been related to prior observations of a protective effect of obesity on mortality in RA patients.
The finding indicates that clinicians can continue to encourage patients with rheumatoid arthritis to follow healthy weight-loss strategies, according to first author of the study, Jeffrey Sparks, MD, of Brigham and Women’s Hospital in Boston.
Dr. Sparks and his colleagues examined the impact of weight change and mortality in RA patients based on data from the Nurses’ Health Study.
“Our study is the first to focus on weight change around RA diagnosis and risk of death, rather than weight change in patients who had RA for many years,” Dr. Sparks noted.
By examining changes in weight near the time of RA diagnosis, Dr. Sparks and his colleagues said that they hoped to extract information about RA-specific processes rather than the underlying pathologies that might cause weight changes near the end of life.
In the study published in Arthritis & Rheumatology, the researchers compared women diagnosed with RA during follow-up to women without RA during the same index time period of 1976-2016. The study population included 121,701 women. Of these, 902 developed incident RA and were matched with 7,884 non-RA controls.
During an average of 18 years of follow-up, 41% of the RA cohort and 29% of the controls died. The risk of death was approximately twice as high (hazard ratio, 2.78; 95% confidence interval, 1.58-4.89) among those with weight loss greater than 30 pounds at the time of RA diagnosis, compared with those whose weight remained stable. However, the risk for mortality was similarly increased (HR, 2.16; 95% CI, 1.61-2.88) among the controls with weight loss greater than 30 pounds, compared with those with stable weight. No association with mortality was noted in either group among women who gained more than 30 pounds at the time of RA diagnosis.
Dr. Sparks said he was somewhat surprised by the findings.
“We expected severe, pathologic weight loss to be associated with increased risk of death among patients with RA and comparators. It was somewhat surprising that the risks in both groups were similar,” he said. “Conversely, prior studies suggested that weight gain might have been associated with increased risk of death. However, we found no association of weight gain with risk of death,” he noted.
In addition, “Our findings argue that there is not an RA-specific mortality risk based on either weight loss or gain,” he said. “While we found that weight loss was associated with increased mortality, this was most pronounced in the severe weight loss group, so was likely due to unintentional weight loss.”
Joshua F. Baker, MD, of the University of Pennsylvania, Philadelphia, and his colleagues identified an association between weight change and risk of death in RA patients in a study first published online in Arthritis & Rheumatology in 2015 (Arthritis Rheumatol. 2015 Jul;67[7]:1711-17). That study addressed the so-called obesity paradox in RA, and Dr. Baker and his colleagues noted that weight loss associated with the development of chronic illness is a significant confounder that may explain the observed protective effect of obesity on mortality.
“It is not clear how best to monitor changes in weight, when exactly to become concerned, and what to do when changes are observed,” Dr. Baker noted. “RA patients may lose weight for a number of reasons, not all related to their arthritis, and it is unlikely that there is a ‘one size fits all’ approach,” he said.
The study was limited in part by the women-only study population, so the results might not be generalizable to men, Dr. Sparks said. “The reason for weight change was unavailable,” he added. Directions for further research include investigation of how factors such as physical activity, diet, and weight loss may affect the risk of death among individuals with and without RA, he said.
Dr. Sparks had no financial conflicts to disclose. The study was supported in part by the National Institutes of Health and the Rheumatology Research Foundation’s Disease-Targeted Innovative Award and Scientist Development Awards.
SOURCE: Sparks J et al. Arthritis Rheumatol. 2017 Nov 30. doi: 10.1002/art.40346.
Weight loss at the time of rheumatoid arthritis diagnosis had the same impact on mortality in patients with and without RA, according to research trying to solve the so-called obesity paradox in RA, which has been related to prior observations of a protective effect of obesity on mortality in RA patients.
The finding indicates that clinicians can continue to encourage patients with rheumatoid arthritis to follow healthy weight-loss strategies, according to first author of the study, Jeffrey Sparks, MD, of Brigham and Women’s Hospital in Boston.
Dr. Sparks and his colleagues examined the impact of weight change and mortality in RA patients based on data from the Nurses’ Health Study.
“Our study is the first to focus on weight change around RA diagnosis and risk of death, rather than weight change in patients who had RA for many years,” Dr. Sparks noted.
By examining changes in weight near the time of RA diagnosis, Dr. Sparks and his colleagues said that they hoped to extract information about RA-specific processes rather than the underlying pathologies that might cause weight changes near the end of life.
In the study published in Arthritis & Rheumatology, the researchers compared women diagnosed with RA during follow-up to women without RA during the same index time period of 1976-2016. The study population included 121,701 women. Of these, 902 developed incident RA and were matched with 7,884 non-RA controls.
During an average of 18 years of follow-up, 41% of the RA cohort and 29% of the controls died. The risk of death was approximately twice as high (hazard ratio, 2.78; 95% confidence interval, 1.58-4.89) among those with weight loss greater than 30 pounds at the time of RA diagnosis, compared with those whose weight remained stable. However, the risk for mortality was similarly increased (HR, 2.16; 95% CI, 1.61-2.88) among the controls with weight loss greater than 30 pounds, compared with those with stable weight. No association with mortality was noted in either group among women who gained more than 30 pounds at the time of RA diagnosis.
Dr. Sparks said he was somewhat surprised by the findings.
“We expected severe, pathologic weight loss to be associated with increased risk of death among patients with RA and comparators. It was somewhat surprising that the risks in both groups were similar,” he said. “Conversely, prior studies suggested that weight gain might have been associated with increased risk of death. However, we found no association of weight gain with risk of death,” he noted.
In addition, “Our findings argue that there is not an RA-specific mortality risk based on either weight loss or gain,” he said. “While we found that weight loss was associated with increased mortality, this was most pronounced in the severe weight loss group, so was likely due to unintentional weight loss.”
Joshua F. Baker, MD, of the University of Pennsylvania, Philadelphia, and his colleagues identified an association between weight change and risk of death in RA patients in a study first published online in Arthritis & Rheumatology in 2015 (Arthritis Rheumatol. 2015 Jul;67[7]:1711-17). That study addressed the so-called obesity paradox in RA, and Dr. Baker and his colleagues noted that weight loss associated with the development of chronic illness is a significant confounder that may explain the observed protective effect of obesity on mortality.
“It is not clear how best to monitor changes in weight, when exactly to become concerned, and what to do when changes are observed,” Dr. Baker noted. “RA patients may lose weight for a number of reasons, not all related to their arthritis, and it is unlikely that there is a ‘one size fits all’ approach,” he said.
The study was limited in part by the women-only study population, so the results might not be generalizable to men, Dr. Sparks said. “The reason for weight change was unavailable,” he added. Directions for further research include investigation of how factors such as physical activity, diet, and weight loss may affect the risk of death among individuals with and without RA, he said.
Dr. Sparks had no financial conflicts to disclose. The study was supported in part by the National Institutes of Health and the Rheumatology Research Foundation’s Disease-Targeted Innovative Award and Scientist Development Awards.
SOURCE: Sparks J et al. Arthritis Rheumatol. 2017 Nov 30. doi: 10.1002/art.40346.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: The risk of death was approximately twice as high among women with weight loss greater than 30 pounds both for those diagnosed around the same time with RA (hazard ratio, 2.78) and for controls (HR, 2.16), compared with those whose weight remained stable.
Study details: A case-control study of 8,786 participants in the Nurses’ Health Study during 1976-2016.
Disclosures: Dr. Sparks had no financial conflicts to disclose. The study was supported in part by the National Institutes of Health and the Rheumatology Research Foundation’s Disease-Targeted Innovative Award and Scientist Development Awards.
Source: Sparks J et al. Arthritis Rheumatol. 2017 Nov 30. doi: 10.1002/art.40346.