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Romosozumab gets FDA approval for treating osteoporosis
“These are women who have a history of osteoporotic fracture or multiple risk factors or have failed other treatments for osteoporosis,” according to a news release from the agency.
The monthly treatment of two injections (given one after the other at one visit) mainly works by increasing new bone formation, but these effects wane after 12 doses. If patients still need osteoporosis therapy after that maximum of 12 doses, it’s recommended they are put on treatments that reduce bone breakdown. Romosozumab-aqqg is “a monoclonal antibody that blocks the effects of the protein sclerostin,” according to the news release.
The treatment’s efficacy and safety was evaluated in two clinical trials of more than 11,000 women with postmenopausal osteoporosis. In one trial, women received 12 months of either romosozumab-aqqg or placebo. The treatment arm had a 73% lower risk of vertebral fracture than did the placebo arm, and this benefit was maintained over a second year when both groups were switched to denosumab, another osteoporosis therapy. In the second trial, one group received romosozumab-aqqg for 1 year and then a year of alendronate, and the other group received 2 years of alendronate, another osteoporosis therapy, according to the news release. In this trial, the romosozumab-aqqg arm had 50% less risk of vertebral fractures than did the alendronate-only arm, as well as reduced risk of nonvertebral fractures.
Romosozumab-aqqg was associated with higher risks of cardiovascular death, heart attack, and stroke in the alendronate trial, so the treatment comes with a boxed warning regarding those risks and recommends that the drug not be used in patients who have had a heart attack or stroke within the previous year, according to the news release. Common side effects include joint pain and headache, as well as injection-site reactions.
“These are women who have a history of osteoporotic fracture or multiple risk factors or have failed other treatments for osteoporosis,” according to a news release from the agency.
The monthly treatment of two injections (given one after the other at one visit) mainly works by increasing new bone formation, but these effects wane after 12 doses. If patients still need osteoporosis therapy after that maximum of 12 doses, it’s recommended they are put on treatments that reduce bone breakdown. Romosozumab-aqqg is “a monoclonal antibody that blocks the effects of the protein sclerostin,” according to the news release.
The treatment’s efficacy and safety was evaluated in two clinical trials of more than 11,000 women with postmenopausal osteoporosis. In one trial, women received 12 months of either romosozumab-aqqg or placebo. The treatment arm had a 73% lower risk of vertebral fracture than did the placebo arm, and this benefit was maintained over a second year when both groups were switched to denosumab, another osteoporosis therapy. In the second trial, one group received romosozumab-aqqg for 1 year and then a year of alendronate, and the other group received 2 years of alendronate, another osteoporosis therapy, according to the news release. In this trial, the romosozumab-aqqg arm had 50% less risk of vertebral fractures than did the alendronate-only arm, as well as reduced risk of nonvertebral fractures.
Romosozumab-aqqg was associated with higher risks of cardiovascular death, heart attack, and stroke in the alendronate trial, so the treatment comes with a boxed warning regarding those risks and recommends that the drug not be used in patients who have had a heart attack or stroke within the previous year, according to the news release. Common side effects include joint pain and headache, as well as injection-site reactions.
“These are women who have a history of osteoporotic fracture or multiple risk factors or have failed other treatments for osteoporosis,” according to a news release from the agency.
The monthly treatment of two injections (given one after the other at one visit) mainly works by increasing new bone formation, but these effects wane after 12 doses. If patients still need osteoporosis therapy after that maximum of 12 doses, it’s recommended they are put on treatments that reduce bone breakdown. Romosozumab-aqqg is “a monoclonal antibody that blocks the effects of the protein sclerostin,” according to the news release.
The treatment’s efficacy and safety was evaluated in two clinical trials of more than 11,000 women with postmenopausal osteoporosis. In one trial, women received 12 months of either romosozumab-aqqg or placebo. The treatment arm had a 73% lower risk of vertebral fracture than did the placebo arm, and this benefit was maintained over a second year when both groups were switched to denosumab, another osteoporosis therapy. In the second trial, one group received romosozumab-aqqg for 1 year and then a year of alendronate, and the other group received 2 years of alendronate, another osteoporosis therapy, according to the news release. In this trial, the romosozumab-aqqg arm had 50% less risk of vertebral fractures than did the alendronate-only arm, as well as reduced risk of nonvertebral fractures.
Romosozumab-aqqg was associated with higher risks of cardiovascular death, heart attack, and stroke in the alendronate trial, so the treatment comes with a boxed warning regarding those risks and recommends that the drug not be used in patients who have had a heart attack or stroke within the previous year, according to the news release. Common side effects include joint pain and headache, as well as injection-site reactions.
Expert gives tips on timing, managing lupus pregnancies
SAN FRANCISCO – Not that many years ago, women with systemic lupus erythematosus were told not to get pregnant. It was just one more lupus heartbreak.
Times have changed, according to Lisa Sammaritano, MD, a lupus specialist and associate professor of clinical medicine at Weill Cornell Medical College, New York.
While lupus certainly complicates pregnancy, it by no means rules it out these days. With careful management, the dream of motherhood can become a reality for many women. Dr. Sammaritano shared her insights about timing and treatment at an international congress on systemic lupus erythematosus.
It’s important that the disease is under control as much as possible; that means that timing – and contraception – are key. Antiphospholipid antibodies, common in lupus, complicate matters, but there are workarounds, she said.
SAN FRANCISCO – Not that many years ago, women with systemic lupus erythematosus were told not to get pregnant. It was just one more lupus heartbreak.
Times have changed, according to Lisa Sammaritano, MD, a lupus specialist and associate professor of clinical medicine at Weill Cornell Medical College, New York.
While lupus certainly complicates pregnancy, it by no means rules it out these days. With careful management, the dream of motherhood can become a reality for many women. Dr. Sammaritano shared her insights about timing and treatment at an international congress on systemic lupus erythematosus.
It’s important that the disease is under control as much as possible; that means that timing – and contraception – are key. Antiphospholipid antibodies, common in lupus, complicate matters, but there are workarounds, she said.
SAN FRANCISCO – Not that many years ago, women with systemic lupus erythematosus were told not to get pregnant. It was just one more lupus heartbreak.
Times have changed, according to Lisa Sammaritano, MD, a lupus specialist and associate professor of clinical medicine at Weill Cornell Medical College, New York.
While lupus certainly complicates pregnancy, it by no means rules it out these days. With careful management, the dream of motherhood can become a reality for many women. Dr. Sammaritano shared her insights about timing and treatment at an international congress on systemic lupus erythematosus.
It’s important that the disease is under control as much as possible; that means that timing – and contraception – are key. Antiphospholipid antibodies, common in lupus, complicate matters, but there are workarounds, she said.
AT LUPUS 2019
Oxytocin dampens the brain’s food-related reward circuitry
NEW ORLEANS – Oxytocin shows promise as a weight-loss medication, with encouraging results in animal models and small human studies. Now, in a calorie-rich environment.
“It is clear by now that obesity is a very serious health concern,” Liya Kerem, MD, said in a video interview at the annual meeting of the Endocrine Society. “The most adopted strategy, which is lifestyle modification, does not help [with losing or maintaining] weight in many cases, so we really need to find new treatments for obesity.”
Functional magnetic resonance imaging (fMRI) is a good tool for investigating the neurobiologic basis of overeating, said Dr. Kerem, a pediatric endocrinology fellow at Massachusetts General Hospital, Boston. In previous studies, fMRI has shown that “individuals with obesity have hyperactivation of the reward circuitry in the brain.”
Oxytocin is produced in the hypothalamus and is active in many brain areas associated with reward processing, said Dr. Kerem. Animal studies have shown a decrease in food intake and weight gain with oxytocin administration.
The hormone, which is generally seen as very safe, has had limited study in humans as a weight-loss strategy. Findings from one small study have shown that in men, a single intranasal dose of 24 IU of oxytocin resulted in less hunger-driven eating as well as lower consumption of a postmeal palatable snack, with the latter representing hedonic eating, said Dr. Kerem. A second small pilot study showed that significant weight loss occurred in obese humans after 8 weeks of daily oxytocin administration.
Findings from another study showed that participants who were overweight or obese, unlike their normal-weight counterparts, had reduced activation in the ventral tegmental area (VTA) after oxytocin administration. The VTA is an important region in the brain’s reward network, explained Dr. Kerem.
She and her colleagues used fMRI to probe dynamic changes in brain reward circuitry under the effect of oxytocin. They wanted to understand how oxytocin would “change the dialog between the VTA and the key brain areas involved in processing visual food stimuli.”
The hypothesis was that oxytocin would reduce functional connectivity between the VTA and other brain areas that are important for food reward and sensory processing when the participants were exposed to pictures of high-calorie food.
To test that hypothesis, the researchers showed the participants 100 each of four different kinds of images: high-calorie foods, low-calorie foods, nonfood images, and “fixation” images, used for calibration. The 10 participants had a mean body mass index of 29 kg/m2, and the mean age was 31 years.
Oxytocin did indeed attenuate functional connectivity between the VTA and several brain regions that are “key food motivation areas,” said Dr. Kerem. In particular, connections between the VTA and the insula were reduced with oxytocin. The insula is the “gustatory hub of the brain, key to subjective perception of food stimuli,” she explained.
Other attenuated associations included the oral area of the somatosensory cortex; the operculum, which shows fMRI activation to taste; the temporal gyrus, which is important for sensory processing; and, importantly, both the amygdala and hippocampus, known to be important for stimulus-reward learning, said Dr. Kerem. “We found that oxytocin targets exactly that hyperactivation in an overweight and obese population.”
It “reduced the functional connectivity between the VTA, a key hedonic brain region that drives efforts to obtain desired foods, and multiple brain areas involved in the cognitive, sensory, and emotional processing of food cues in men with overweight and obesity,” she said at a press conference highlighting the research. She emphasized that the effect was seen only with exposure to high-calorie food images. “Targeting hyperactivation of reward areas with oxytocin may inhibit overeating behavior,” she added.
Dr. Kerem and her colleagues are currently enrolling men and women for a larger clinical trial of oxytocin for weight loss.
Dr. Kerem reported no conflicts of interest. One of the study’s coauthors is a consultant for OXT Therapeutics, which is investigating obesity-related uses for oxytocin.
NEW ORLEANS – Oxytocin shows promise as a weight-loss medication, with encouraging results in animal models and small human studies. Now, in a calorie-rich environment.
“It is clear by now that obesity is a very serious health concern,” Liya Kerem, MD, said in a video interview at the annual meeting of the Endocrine Society. “The most adopted strategy, which is lifestyle modification, does not help [with losing or maintaining] weight in many cases, so we really need to find new treatments for obesity.”
Functional magnetic resonance imaging (fMRI) is a good tool for investigating the neurobiologic basis of overeating, said Dr. Kerem, a pediatric endocrinology fellow at Massachusetts General Hospital, Boston. In previous studies, fMRI has shown that “individuals with obesity have hyperactivation of the reward circuitry in the brain.”
Oxytocin is produced in the hypothalamus and is active in many brain areas associated with reward processing, said Dr. Kerem. Animal studies have shown a decrease in food intake and weight gain with oxytocin administration.
The hormone, which is generally seen as very safe, has had limited study in humans as a weight-loss strategy. Findings from one small study have shown that in men, a single intranasal dose of 24 IU of oxytocin resulted in less hunger-driven eating as well as lower consumption of a postmeal palatable snack, with the latter representing hedonic eating, said Dr. Kerem. A second small pilot study showed that significant weight loss occurred in obese humans after 8 weeks of daily oxytocin administration.
Findings from another study showed that participants who were overweight or obese, unlike their normal-weight counterparts, had reduced activation in the ventral tegmental area (VTA) after oxytocin administration. The VTA is an important region in the brain’s reward network, explained Dr. Kerem.
She and her colleagues used fMRI to probe dynamic changes in brain reward circuitry under the effect of oxytocin. They wanted to understand how oxytocin would “change the dialog between the VTA and the key brain areas involved in processing visual food stimuli.”
The hypothesis was that oxytocin would reduce functional connectivity between the VTA and other brain areas that are important for food reward and sensory processing when the participants were exposed to pictures of high-calorie food.
To test that hypothesis, the researchers showed the participants 100 each of four different kinds of images: high-calorie foods, low-calorie foods, nonfood images, and “fixation” images, used for calibration. The 10 participants had a mean body mass index of 29 kg/m2, and the mean age was 31 years.
Oxytocin did indeed attenuate functional connectivity between the VTA and several brain regions that are “key food motivation areas,” said Dr. Kerem. In particular, connections between the VTA and the insula were reduced with oxytocin. The insula is the “gustatory hub of the brain, key to subjective perception of food stimuli,” she explained.
Other attenuated associations included the oral area of the somatosensory cortex; the operculum, which shows fMRI activation to taste; the temporal gyrus, which is important for sensory processing; and, importantly, both the amygdala and hippocampus, known to be important for stimulus-reward learning, said Dr. Kerem. “We found that oxytocin targets exactly that hyperactivation in an overweight and obese population.”
It “reduced the functional connectivity between the VTA, a key hedonic brain region that drives efforts to obtain desired foods, and multiple brain areas involved in the cognitive, sensory, and emotional processing of food cues in men with overweight and obesity,” she said at a press conference highlighting the research. She emphasized that the effect was seen only with exposure to high-calorie food images. “Targeting hyperactivation of reward areas with oxytocin may inhibit overeating behavior,” she added.
Dr. Kerem and her colleagues are currently enrolling men and women for a larger clinical trial of oxytocin for weight loss.
Dr. Kerem reported no conflicts of interest. One of the study’s coauthors is a consultant for OXT Therapeutics, which is investigating obesity-related uses for oxytocin.
NEW ORLEANS – Oxytocin shows promise as a weight-loss medication, with encouraging results in animal models and small human studies. Now, in a calorie-rich environment.
“It is clear by now that obesity is a very serious health concern,” Liya Kerem, MD, said in a video interview at the annual meeting of the Endocrine Society. “The most adopted strategy, which is lifestyle modification, does not help [with losing or maintaining] weight in many cases, so we really need to find new treatments for obesity.”
Functional magnetic resonance imaging (fMRI) is a good tool for investigating the neurobiologic basis of overeating, said Dr. Kerem, a pediatric endocrinology fellow at Massachusetts General Hospital, Boston. In previous studies, fMRI has shown that “individuals with obesity have hyperactivation of the reward circuitry in the brain.”
Oxytocin is produced in the hypothalamus and is active in many brain areas associated with reward processing, said Dr. Kerem. Animal studies have shown a decrease in food intake and weight gain with oxytocin administration.
The hormone, which is generally seen as very safe, has had limited study in humans as a weight-loss strategy. Findings from one small study have shown that in men, a single intranasal dose of 24 IU of oxytocin resulted in less hunger-driven eating as well as lower consumption of a postmeal palatable snack, with the latter representing hedonic eating, said Dr. Kerem. A second small pilot study showed that significant weight loss occurred in obese humans after 8 weeks of daily oxytocin administration.
Findings from another study showed that participants who were overweight or obese, unlike their normal-weight counterparts, had reduced activation in the ventral tegmental area (VTA) after oxytocin administration. The VTA is an important region in the brain’s reward network, explained Dr. Kerem.
She and her colleagues used fMRI to probe dynamic changes in brain reward circuitry under the effect of oxytocin. They wanted to understand how oxytocin would “change the dialog between the VTA and the key brain areas involved in processing visual food stimuli.”
The hypothesis was that oxytocin would reduce functional connectivity between the VTA and other brain areas that are important for food reward and sensory processing when the participants were exposed to pictures of high-calorie food.
To test that hypothesis, the researchers showed the participants 100 each of four different kinds of images: high-calorie foods, low-calorie foods, nonfood images, and “fixation” images, used for calibration. The 10 participants had a mean body mass index of 29 kg/m2, and the mean age was 31 years.
Oxytocin did indeed attenuate functional connectivity between the VTA and several brain regions that are “key food motivation areas,” said Dr. Kerem. In particular, connections between the VTA and the insula were reduced with oxytocin. The insula is the “gustatory hub of the brain, key to subjective perception of food stimuli,” she explained.
Other attenuated associations included the oral area of the somatosensory cortex; the operculum, which shows fMRI activation to taste; the temporal gyrus, which is important for sensory processing; and, importantly, both the amygdala and hippocampus, known to be important for stimulus-reward learning, said Dr. Kerem. “We found that oxytocin targets exactly that hyperactivation in an overweight and obese population.”
It “reduced the functional connectivity between the VTA, a key hedonic brain region that drives efforts to obtain desired foods, and multiple brain areas involved in the cognitive, sensory, and emotional processing of food cues in men with overweight and obesity,” she said at a press conference highlighting the research. She emphasized that the effect was seen only with exposure to high-calorie food images. “Targeting hyperactivation of reward areas with oxytocin may inhibit overeating behavior,” she added.
Dr. Kerem and her colleagues are currently enrolling men and women for a larger clinical trial of oxytocin for weight loss.
Dr. Kerem reported no conflicts of interest. One of the study’s coauthors is a consultant for OXT Therapeutics, which is investigating obesity-related uses for oxytocin.
REPORTING FROM ENDO 2019
Older women have good functional recovery after POP surgery
TUCSON, ARIZ. – according to a new study.
Functional status was defined as the ability to perform activities essential to self-care, independent living, and recreation.
Patients with the highest level of function at baseline actually had a slight decrease in functionality scores, although this difference was not clinically meaningful.
“We can tell patients: You’re high functioning, your prolapse is bothering you in other ways, but we’re going to keep you as high functioning as you are now. I think that’s really important for older women who are retired and want to stay active. They want to make sure they don’t have a surgery that’s going to make them less so,” Daniel Lee, MD, of the University of Pennsylvania, Philadelphia, said in an interview. Dr. Lee presented the study at the annual scientific meeting of the Society of Gynecologic Surgeons.
The study used data from multiple centers across the United States and a range of patient ethnicities. “That helped strengthen the conclusions,” Dr. Lee said. Most previous studies used generalized questionnaires rather than functional outcome questionnaires to determine patient outcomes.
One confounder is the potential presence of cognitive dysfunction, which can occur sometimes in older women following surgery. The study relied on surveys and excluded patients who weren’t able to understand them. Two patients were much worse after the surgery, and Dr. Lee speculated that cognitive dysfunction could have been the cause, although the team could not confirm that. “There’s a possibility that preexisting dementia or cognitive dysfunction could be unmasked by the surgery,” he said. The team is working to incorporate accelerometers to more objectively measure outcomes and will soon publish a feasibility study of their use in older women with cognitive dysfunction.
One limitation of the study was that it excluded women who were considered poor candidates for surgery. But that also suggests that patient selection is working as intended. “I think it just shows that surgeons do a very good job of figuring out who is a good surgical candidate, that they turn out to be better off [functionally] or that their prolapse gets improved,” Dr. Lee said.
The researchers analyzed questionnaire data from 176 women. The mean age was 72 years, and mean body mass index was 27 kg/m2; 87% of the women were Caucasian and 10% were black. Using the Activities Assessment Scale (AAS), which covers sedentary, ambulatory, and work/exercise domains, as well as the Patient Health Questionnaire to measure depression, the researchers found that, by 3 months, 59% of patients had an improved functional status, 35% had returned to within one standard deviation of baseline, and 6% had worsened, compared with their baseline scores.
Patients in the improved group started at a mean baseline total AAS score of 85 and improved to 100 at 3 months. Those who returned to baseline started at 100 on average and returned to 100 at 3 months, while those in the worsened group had a mean baseline score of 100 and a mean score of 93 at 3 months (P less than .001 for all comparisons).
The study was funded by the Fellows Pelvic Research Network. The investigators reported no relevant financial disclosures.
SOURCE: Lee D et al. SGS 2019, Abstract 09.
TUCSON, ARIZ. – according to a new study.
Functional status was defined as the ability to perform activities essential to self-care, independent living, and recreation.
Patients with the highest level of function at baseline actually had a slight decrease in functionality scores, although this difference was not clinically meaningful.
“We can tell patients: You’re high functioning, your prolapse is bothering you in other ways, but we’re going to keep you as high functioning as you are now. I think that’s really important for older women who are retired and want to stay active. They want to make sure they don’t have a surgery that’s going to make them less so,” Daniel Lee, MD, of the University of Pennsylvania, Philadelphia, said in an interview. Dr. Lee presented the study at the annual scientific meeting of the Society of Gynecologic Surgeons.
The study used data from multiple centers across the United States and a range of patient ethnicities. “That helped strengthen the conclusions,” Dr. Lee said. Most previous studies used generalized questionnaires rather than functional outcome questionnaires to determine patient outcomes.
One confounder is the potential presence of cognitive dysfunction, which can occur sometimes in older women following surgery. The study relied on surveys and excluded patients who weren’t able to understand them. Two patients were much worse after the surgery, and Dr. Lee speculated that cognitive dysfunction could have been the cause, although the team could not confirm that. “There’s a possibility that preexisting dementia or cognitive dysfunction could be unmasked by the surgery,” he said. The team is working to incorporate accelerometers to more objectively measure outcomes and will soon publish a feasibility study of their use in older women with cognitive dysfunction.
One limitation of the study was that it excluded women who were considered poor candidates for surgery. But that also suggests that patient selection is working as intended. “I think it just shows that surgeons do a very good job of figuring out who is a good surgical candidate, that they turn out to be better off [functionally] or that their prolapse gets improved,” Dr. Lee said.
The researchers analyzed questionnaire data from 176 women. The mean age was 72 years, and mean body mass index was 27 kg/m2; 87% of the women were Caucasian and 10% were black. Using the Activities Assessment Scale (AAS), which covers sedentary, ambulatory, and work/exercise domains, as well as the Patient Health Questionnaire to measure depression, the researchers found that, by 3 months, 59% of patients had an improved functional status, 35% had returned to within one standard deviation of baseline, and 6% had worsened, compared with their baseline scores.
Patients in the improved group started at a mean baseline total AAS score of 85 and improved to 100 at 3 months. Those who returned to baseline started at 100 on average and returned to 100 at 3 months, while those in the worsened group had a mean baseline score of 100 and a mean score of 93 at 3 months (P less than .001 for all comparisons).
The study was funded by the Fellows Pelvic Research Network. The investigators reported no relevant financial disclosures.
SOURCE: Lee D et al. SGS 2019, Abstract 09.
TUCSON, ARIZ. – according to a new study.
Functional status was defined as the ability to perform activities essential to self-care, independent living, and recreation.
Patients with the highest level of function at baseline actually had a slight decrease in functionality scores, although this difference was not clinically meaningful.
“We can tell patients: You’re high functioning, your prolapse is bothering you in other ways, but we’re going to keep you as high functioning as you are now. I think that’s really important for older women who are retired and want to stay active. They want to make sure they don’t have a surgery that’s going to make them less so,” Daniel Lee, MD, of the University of Pennsylvania, Philadelphia, said in an interview. Dr. Lee presented the study at the annual scientific meeting of the Society of Gynecologic Surgeons.
The study used data from multiple centers across the United States and a range of patient ethnicities. “That helped strengthen the conclusions,” Dr. Lee said. Most previous studies used generalized questionnaires rather than functional outcome questionnaires to determine patient outcomes.
One confounder is the potential presence of cognitive dysfunction, which can occur sometimes in older women following surgery. The study relied on surveys and excluded patients who weren’t able to understand them. Two patients were much worse after the surgery, and Dr. Lee speculated that cognitive dysfunction could have been the cause, although the team could not confirm that. “There’s a possibility that preexisting dementia or cognitive dysfunction could be unmasked by the surgery,” he said. The team is working to incorporate accelerometers to more objectively measure outcomes and will soon publish a feasibility study of their use in older women with cognitive dysfunction.
One limitation of the study was that it excluded women who were considered poor candidates for surgery. But that also suggests that patient selection is working as intended. “I think it just shows that surgeons do a very good job of figuring out who is a good surgical candidate, that they turn out to be better off [functionally] or that their prolapse gets improved,” Dr. Lee said.
The researchers analyzed questionnaire data from 176 women. The mean age was 72 years, and mean body mass index was 27 kg/m2; 87% of the women were Caucasian and 10% were black. Using the Activities Assessment Scale (AAS), which covers sedentary, ambulatory, and work/exercise domains, as well as the Patient Health Questionnaire to measure depression, the researchers found that, by 3 months, 59% of patients had an improved functional status, 35% had returned to within one standard deviation of baseline, and 6% had worsened, compared with their baseline scores.
Patients in the improved group started at a mean baseline total AAS score of 85 and improved to 100 at 3 months. Those who returned to baseline started at 100 on average and returned to 100 at 3 months, while those in the worsened group had a mean baseline score of 100 and a mean score of 93 at 3 months (P less than .001 for all comparisons).
The study was funded by the Fellows Pelvic Research Network. The investigators reported no relevant financial disclosures.
SOURCE: Lee D et al. SGS 2019, Abstract 09.
REPORTING FROM SGS 2019
Ligelizumab maintains urticaria control for up to 1 year
WASHINGTON – in an open-label extension study, Diane Baker, MD, said at the annual meeting of the American Academy of Dermatology.
About 75% of the cohort experienced complete disease control at least once during the study. Novartis is developing ligelizumab (QGE031) as a treatment option for patients with spontaneous chronic urticaria (CSU) whose symptoms are inadequately controlled by H1-antihistamines. Like omalizumab (Xolair), which is approved in the United States and Europe for treatment of CSU, ligelizumab is a humanized anti-IgE monoclonal antibody. But the investigational agent binds to IgE with greater affinity than omalizumab, said Dr. Baker, a dermatologist who practices in Portland, Ore.
The extension study was a follow-up to a 12-week, phase 2, dose-finding trial of 382 CSU patients. In the study, which was not powered for efficacy endpoints, 51% of those who received 72 mg subcutaneously every 4 weeks had a Hives Severity Score of 0 by week 12, compared with 42% of those who received 240 mg every 4 weeks and 26% of those taking the omalizumab comparator. Additionally, 47% of those in the 72-mg group and 46% of the 240-mg group achieved a score of 0 on another indicator, the Urticaria Activity Score, which measures symptoms over 7 days (UAS7).
The extension study, which evaluated the 240-mg dose, showed the durability of that response, with 52% of those in the 240-mg group maintained a UAS7 of 0 at 1 year, according to Dr. Baker. By the end of the year, most patients (75.8%) had experienced at least one period of complete symptom control, and 84.0% experienced a UAS of 6 or lower at least once.
Adverse events were common in the cohort, with 84% experiencing at least one. But most (78%) were mild or moderate, and there was no clear side effect pattern, Dr. Baker said. Eight patients discontinued treatment because of an adverse event, and another eight dropped out because of lack of efficacy. Other reasons for discontinuation were pregnancy, protocol deviation, and physician or patient decision.
Novartis has launched two 1-year, phase 3 trials randomizing patients to 72 mg or 240 mg of ligelizumab or 300 mg of omalizumab every 4 weeks in a similar patient population, Dr. Baker said. PEARL 1 and PEARL 2, the largest pivotal trials to date in CSU, will enroll more than 2,000 patients, according to a company press release.
Dr. Baker is a clinical trials investigator for Novartis.
SOURCE: Baker D et al. AAD 2019, Session S034.
WASHINGTON – in an open-label extension study, Diane Baker, MD, said at the annual meeting of the American Academy of Dermatology.
About 75% of the cohort experienced complete disease control at least once during the study. Novartis is developing ligelizumab (QGE031) as a treatment option for patients with spontaneous chronic urticaria (CSU) whose symptoms are inadequately controlled by H1-antihistamines. Like omalizumab (Xolair), which is approved in the United States and Europe for treatment of CSU, ligelizumab is a humanized anti-IgE monoclonal antibody. But the investigational agent binds to IgE with greater affinity than omalizumab, said Dr. Baker, a dermatologist who practices in Portland, Ore.
The extension study was a follow-up to a 12-week, phase 2, dose-finding trial of 382 CSU patients. In the study, which was not powered for efficacy endpoints, 51% of those who received 72 mg subcutaneously every 4 weeks had a Hives Severity Score of 0 by week 12, compared with 42% of those who received 240 mg every 4 weeks and 26% of those taking the omalizumab comparator. Additionally, 47% of those in the 72-mg group and 46% of the 240-mg group achieved a score of 0 on another indicator, the Urticaria Activity Score, which measures symptoms over 7 days (UAS7).
The extension study, which evaluated the 240-mg dose, showed the durability of that response, with 52% of those in the 240-mg group maintained a UAS7 of 0 at 1 year, according to Dr. Baker. By the end of the year, most patients (75.8%) had experienced at least one period of complete symptom control, and 84.0% experienced a UAS of 6 or lower at least once.
Adverse events were common in the cohort, with 84% experiencing at least one. But most (78%) were mild or moderate, and there was no clear side effect pattern, Dr. Baker said. Eight patients discontinued treatment because of an adverse event, and another eight dropped out because of lack of efficacy. Other reasons for discontinuation were pregnancy, protocol deviation, and physician or patient decision.
Novartis has launched two 1-year, phase 3 trials randomizing patients to 72 mg or 240 mg of ligelizumab or 300 mg of omalizumab every 4 weeks in a similar patient population, Dr. Baker said. PEARL 1 and PEARL 2, the largest pivotal trials to date in CSU, will enroll more than 2,000 patients, according to a company press release.
Dr. Baker is a clinical trials investigator for Novartis.
SOURCE: Baker D et al. AAD 2019, Session S034.
WASHINGTON – in an open-label extension study, Diane Baker, MD, said at the annual meeting of the American Academy of Dermatology.
About 75% of the cohort experienced complete disease control at least once during the study. Novartis is developing ligelizumab (QGE031) as a treatment option for patients with spontaneous chronic urticaria (CSU) whose symptoms are inadequately controlled by H1-antihistamines. Like omalizumab (Xolair), which is approved in the United States and Europe for treatment of CSU, ligelizumab is a humanized anti-IgE monoclonal antibody. But the investigational agent binds to IgE with greater affinity than omalizumab, said Dr. Baker, a dermatologist who practices in Portland, Ore.
The extension study was a follow-up to a 12-week, phase 2, dose-finding trial of 382 CSU patients. In the study, which was not powered for efficacy endpoints, 51% of those who received 72 mg subcutaneously every 4 weeks had a Hives Severity Score of 0 by week 12, compared with 42% of those who received 240 mg every 4 weeks and 26% of those taking the omalizumab comparator. Additionally, 47% of those in the 72-mg group and 46% of the 240-mg group achieved a score of 0 on another indicator, the Urticaria Activity Score, which measures symptoms over 7 days (UAS7).
The extension study, which evaluated the 240-mg dose, showed the durability of that response, with 52% of those in the 240-mg group maintained a UAS7 of 0 at 1 year, according to Dr. Baker. By the end of the year, most patients (75.8%) had experienced at least one period of complete symptom control, and 84.0% experienced a UAS of 6 or lower at least once.
Adverse events were common in the cohort, with 84% experiencing at least one. But most (78%) were mild or moderate, and there was no clear side effect pattern, Dr. Baker said. Eight patients discontinued treatment because of an adverse event, and another eight dropped out because of lack of efficacy. Other reasons for discontinuation were pregnancy, protocol deviation, and physician or patient decision.
Novartis has launched two 1-year, phase 3 trials randomizing patients to 72 mg or 240 mg of ligelizumab or 300 mg of omalizumab every 4 weeks in a similar patient population, Dr. Baker said. PEARL 1 and PEARL 2, the largest pivotal trials to date in CSU, will enroll more than 2,000 patients, according to a company press release.
Dr. Baker is a clinical trials investigator for Novartis.
SOURCE: Baker D et al. AAD 2019, Session S034.
REPORTING FROM AAD 2019
SB-525 gene therapy looks viable for hemophilia A
Interim data suggest SB-525, an investigational gene therapy, may be safe and effective for patients with severe hemophilia A.
In the phase 1/2 Alta trial, SB-525 produced dose-dependent increases in factor VIII activity, with two of eight patients achieving normal factor VIII levels.
In addition, SB-525 was considered well tolerated. One patient did experience treatment-related serious adverse events – hypotension and fever – but these resolved within 24 hours.
Sangamo Therapeutics and Pfizer recently released these data in a press release and conference call.
The data include eight patients with severe hemophilia A who received SB-525 at 9e11 vg/kg, 2e12 vg/kg, 1e13 vg/kg, and 3e13 vg/kg.
Patient 1 (9e11 vg/kg), Patient 2 (9e11 vg/kg), and Patient 3 (2e12 vg/kg) did not experience clinically relevant increases in factor VIII levels and still require prophylactic recombinant factor VIII therapy.
Patient 4 (2e12 vg/kg) and Patient 5 (1e13 vg/kg) discontinued factor VIII therapy but have experienced spontaneous bleeds. Patient 4 had three bleeds in 48 weeks of follow-up, and Patient 5 had two bleeds in 40 weeks of follow-up.
Patient 6 (1e13 vg/kg), Patient 7 (3e13 vg/kg), and Patient 8 (3e13 vg/kg) have stopped factor VIII therapy and remain free of spontaneous bleeds at 28 weeks, 12 weeks, and 6 weeks of follow-up, respectively.
Patients 7 and 8 have achieved normal factor VIII levels. At 6 weeks, their factor VIII levels reached 140% and 94% of normal, respectively, according to a one-stage clotting assay, and 93% and 65%, respectively, according to a chromogenic assay.
“It appears the patients achieve their peak factor level at week 5 to 7 and maintain that level,” Edward Conner, MD, chief medical officer of Sangamo, said during the conference call.
The adverse events observed in this trial include grade 1 tachycardia (n = 1), grade 1 fatigue (n = 1), grade 1 alanine aminotransferase increase (n = 3), grade 1 myalgia (n = 1), grade 2 pyrexia (n = 2), and grade 3 hypotension (n = 1).
“These interim results indicate that SB-525 has the potential to comprise a well-tolerated, reliable, and predictable treatment, features that we believe will be a hallmark of the future gene therapy treatment of hemophilia A,” Dr. Conner said during the call.
Sangamo and Pfizer are enrolling additional patients in this trial, with the goal of expanding the 3e13 vg/kg cohort by up to five patients. The companies plan to present longer-term follow-up data at an upcoming scientific meeting.
The Alta trial is sponsored by Sangamo Therapeutics in collaboration with Pfizer.
Interim data suggest SB-525, an investigational gene therapy, may be safe and effective for patients with severe hemophilia A.
In the phase 1/2 Alta trial, SB-525 produced dose-dependent increases in factor VIII activity, with two of eight patients achieving normal factor VIII levels.
In addition, SB-525 was considered well tolerated. One patient did experience treatment-related serious adverse events – hypotension and fever – but these resolved within 24 hours.
Sangamo Therapeutics and Pfizer recently released these data in a press release and conference call.
The data include eight patients with severe hemophilia A who received SB-525 at 9e11 vg/kg, 2e12 vg/kg, 1e13 vg/kg, and 3e13 vg/kg.
Patient 1 (9e11 vg/kg), Patient 2 (9e11 vg/kg), and Patient 3 (2e12 vg/kg) did not experience clinically relevant increases in factor VIII levels and still require prophylactic recombinant factor VIII therapy.
Patient 4 (2e12 vg/kg) and Patient 5 (1e13 vg/kg) discontinued factor VIII therapy but have experienced spontaneous bleeds. Patient 4 had three bleeds in 48 weeks of follow-up, and Patient 5 had two bleeds in 40 weeks of follow-up.
Patient 6 (1e13 vg/kg), Patient 7 (3e13 vg/kg), and Patient 8 (3e13 vg/kg) have stopped factor VIII therapy and remain free of spontaneous bleeds at 28 weeks, 12 weeks, and 6 weeks of follow-up, respectively.
Patients 7 and 8 have achieved normal factor VIII levels. At 6 weeks, their factor VIII levels reached 140% and 94% of normal, respectively, according to a one-stage clotting assay, and 93% and 65%, respectively, according to a chromogenic assay.
“It appears the patients achieve their peak factor level at week 5 to 7 and maintain that level,” Edward Conner, MD, chief medical officer of Sangamo, said during the conference call.
The adverse events observed in this trial include grade 1 tachycardia (n = 1), grade 1 fatigue (n = 1), grade 1 alanine aminotransferase increase (n = 3), grade 1 myalgia (n = 1), grade 2 pyrexia (n = 2), and grade 3 hypotension (n = 1).
“These interim results indicate that SB-525 has the potential to comprise a well-tolerated, reliable, and predictable treatment, features that we believe will be a hallmark of the future gene therapy treatment of hemophilia A,” Dr. Conner said during the call.
Sangamo and Pfizer are enrolling additional patients in this trial, with the goal of expanding the 3e13 vg/kg cohort by up to five patients. The companies plan to present longer-term follow-up data at an upcoming scientific meeting.
The Alta trial is sponsored by Sangamo Therapeutics in collaboration with Pfizer.
Interim data suggest SB-525, an investigational gene therapy, may be safe and effective for patients with severe hemophilia A.
In the phase 1/2 Alta trial, SB-525 produced dose-dependent increases in factor VIII activity, with two of eight patients achieving normal factor VIII levels.
In addition, SB-525 was considered well tolerated. One patient did experience treatment-related serious adverse events – hypotension and fever – but these resolved within 24 hours.
Sangamo Therapeutics and Pfizer recently released these data in a press release and conference call.
The data include eight patients with severe hemophilia A who received SB-525 at 9e11 vg/kg, 2e12 vg/kg, 1e13 vg/kg, and 3e13 vg/kg.
Patient 1 (9e11 vg/kg), Patient 2 (9e11 vg/kg), and Patient 3 (2e12 vg/kg) did not experience clinically relevant increases in factor VIII levels and still require prophylactic recombinant factor VIII therapy.
Patient 4 (2e12 vg/kg) and Patient 5 (1e13 vg/kg) discontinued factor VIII therapy but have experienced spontaneous bleeds. Patient 4 had three bleeds in 48 weeks of follow-up, and Patient 5 had two bleeds in 40 weeks of follow-up.
Patient 6 (1e13 vg/kg), Patient 7 (3e13 vg/kg), and Patient 8 (3e13 vg/kg) have stopped factor VIII therapy and remain free of spontaneous bleeds at 28 weeks, 12 weeks, and 6 weeks of follow-up, respectively.
Patients 7 and 8 have achieved normal factor VIII levels. At 6 weeks, their factor VIII levels reached 140% and 94% of normal, respectively, according to a one-stage clotting assay, and 93% and 65%, respectively, according to a chromogenic assay.
“It appears the patients achieve their peak factor level at week 5 to 7 and maintain that level,” Edward Conner, MD, chief medical officer of Sangamo, said during the conference call.
The adverse events observed in this trial include grade 1 tachycardia (n = 1), grade 1 fatigue (n = 1), grade 1 alanine aminotransferase increase (n = 3), grade 1 myalgia (n = 1), grade 2 pyrexia (n = 2), and grade 3 hypotension (n = 1).
“These interim results indicate that SB-525 has the potential to comprise a well-tolerated, reliable, and predictable treatment, features that we believe will be a hallmark of the future gene therapy treatment of hemophilia A,” Dr. Conner said during the call.
Sangamo and Pfizer are enrolling additional patients in this trial, with the goal of expanding the 3e13 vg/kg cohort by up to five patients. The companies plan to present longer-term follow-up data at an upcoming scientific meeting.
The Alta trial is sponsored by Sangamo Therapeutics in collaboration with Pfizer.
My patient will die
“You are the best doctor I ever had.” These were the words of my patient at our final session. I kissed Rosa on the cheek and embraced her as she left my office. And I said, “It is important to show the love.”
“This may be the last time I come to your office,” she said. When Rosa came through the door at the beginning of the session, I was taken aback. She had lost weight and was using a walker; her face was drawn and sallow. I knew she had a recent diagnosis of liver cancer and had been hospitalized. She told me: “I have 3 months to live.” The cancer was inoperable.
She sat in a chair close to me, and we reminisced about 20 years as doctor and patient. She also talked about the stents in her liver; when they blocked, the pain resulted in a revisit to the emergency department. She had help from home health aides for several hours a day. Rosa’s sister arrived from Puerto Rico to be here “for as long as it takes.”
When she started therapy, Rosa was a single mother who lived in the projects with her adolescent son, Wesley. Her husband had died of AIDS. Unemployed and depressed, she told me that an uncle had sexually abused her when she was a child. Over the years, she looked to me for support: When her son, Wesley, got shot in the leg on a basketball court; when Wesley married a woman who shunned her; when her nephew who stayed with her got arrested for selling drugs and she lost her apartment as a result. Rosa remained in New York, displaced and struggling to find a reasonable home. After Wesley married, he moved with his family to rural Pennsylvania.
Whenever Rosa called to set up a therapy session, we talked about her problems. I prescribed medication for her, and I directed her to proper medical care. Often, I encouraged her to improve her diet, lose weight, and exercise – but to no avail. Her health deteriorated. She had cardiac surgery, heart failure, diabetes, hypertension, and chronic obesity. All these illnesses became her concern. She attended clinics at the hospital.
Now she told me that she would miss her son and would not see her two young grandchildren grow up. Rosa took Wesley to a funeral home to select a coffin and a headstone. It was tough for both of them, but she wanted to spare Wesley the trouble of doing it alone. She reflected, “It was like hitting a concrete wall” when she discovered her terminal diagnosis.
Rosa is facing pain, saying goodbye, and death. During her meeting, her ordeal made me cry, but I tried to contain it. I have been her doctor for so long, not a member of her family, not a friend. Yet I love her.
“Just to be is a blessing. Just to live is holy.”
– Abraham Joshua Heschel
Dr. Cohen is in private practice and is a clinical assistant professor of psychiatry at Weill Cornell Medical Center of New York-Presbyterian Hospital, and psychiatric consultant at the Hospital for Special Surgery, also in New York. She made changes to the patient’s story to protect confidentiality.
“You are the best doctor I ever had.” These were the words of my patient at our final session. I kissed Rosa on the cheek and embraced her as she left my office. And I said, “It is important to show the love.”
“This may be the last time I come to your office,” she said. When Rosa came through the door at the beginning of the session, I was taken aback. She had lost weight and was using a walker; her face was drawn and sallow. I knew she had a recent diagnosis of liver cancer and had been hospitalized. She told me: “I have 3 months to live.” The cancer was inoperable.
She sat in a chair close to me, and we reminisced about 20 years as doctor and patient. She also talked about the stents in her liver; when they blocked, the pain resulted in a revisit to the emergency department. She had help from home health aides for several hours a day. Rosa’s sister arrived from Puerto Rico to be here “for as long as it takes.”
When she started therapy, Rosa was a single mother who lived in the projects with her adolescent son, Wesley. Her husband had died of AIDS. Unemployed and depressed, she told me that an uncle had sexually abused her when she was a child. Over the years, she looked to me for support: When her son, Wesley, got shot in the leg on a basketball court; when Wesley married a woman who shunned her; when her nephew who stayed with her got arrested for selling drugs and she lost her apartment as a result. Rosa remained in New York, displaced and struggling to find a reasonable home. After Wesley married, he moved with his family to rural Pennsylvania.
Whenever Rosa called to set up a therapy session, we talked about her problems. I prescribed medication for her, and I directed her to proper medical care. Often, I encouraged her to improve her diet, lose weight, and exercise – but to no avail. Her health deteriorated. She had cardiac surgery, heart failure, diabetes, hypertension, and chronic obesity. All these illnesses became her concern. She attended clinics at the hospital.
Now she told me that she would miss her son and would not see her two young grandchildren grow up. Rosa took Wesley to a funeral home to select a coffin and a headstone. It was tough for both of them, but she wanted to spare Wesley the trouble of doing it alone. She reflected, “It was like hitting a concrete wall” when she discovered her terminal diagnosis.
Rosa is facing pain, saying goodbye, and death. During her meeting, her ordeal made me cry, but I tried to contain it. I have been her doctor for so long, not a member of her family, not a friend. Yet I love her.
“Just to be is a blessing. Just to live is holy.”
– Abraham Joshua Heschel
Dr. Cohen is in private practice and is a clinical assistant professor of psychiatry at Weill Cornell Medical Center of New York-Presbyterian Hospital, and psychiatric consultant at the Hospital for Special Surgery, also in New York. She made changes to the patient’s story to protect confidentiality.
“You are the best doctor I ever had.” These were the words of my patient at our final session. I kissed Rosa on the cheek and embraced her as she left my office. And I said, “It is important to show the love.”
“This may be the last time I come to your office,” she said. When Rosa came through the door at the beginning of the session, I was taken aback. She had lost weight and was using a walker; her face was drawn and sallow. I knew she had a recent diagnosis of liver cancer and had been hospitalized. She told me: “I have 3 months to live.” The cancer was inoperable.
She sat in a chair close to me, and we reminisced about 20 years as doctor and patient. She also talked about the stents in her liver; when they blocked, the pain resulted in a revisit to the emergency department. She had help from home health aides for several hours a day. Rosa’s sister arrived from Puerto Rico to be here “for as long as it takes.”
When she started therapy, Rosa was a single mother who lived in the projects with her adolescent son, Wesley. Her husband had died of AIDS. Unemployed and depressed, she told me that an uncle had sexually abused her when she was a child. Over the years, she looked to me for support: When her son, Wesley, got shot in the leg on a basketball court; when Wesley married a woman who shunned her; when her nephew who stayed with her got arrested for selling drugs and she lost her apartment as a result. Rosa remained in New York, displaced and struggling to find a reasonable home. After Wesley married, he moved with his family to rural Pennsylvania.
Whenever Rosa called to set up a therapy session, we talked about her problems. I prescribed medication for her, and I directed her to proper medical care. Often, I encouraged her to improve her diet, lose weight, and exercise – but to no avail. Her health deteriorated. She had cardiac surgery, heart failure, diabetes, hypertension, and chronic obesity. All these illnesses became her concern. She attended clinics at the hospital.
Now she told me that she would miss her son and would not see her two young grandchildren grow up. Rosa took Wesley to a funeral home to select a coffin and a headstone. It was tough for both of them, but she wanted to spare Wesley the trouble of doing it alone. She reflected, “It was like hitting a concrete wall” when she discovered her terminal diagnosis.
Rosa is facing pain, saying goodbye, and death. During her meeting, her ordeal made me cry, but I tried to contain it. I have been her doctor for so long, not a member of her family, not a friend. Yet I love her.
“Just to be is a blessing. Just to live is holy.”
– Abraham Joshua Heschel
Dr. Cohen is in private practice and is a clinical assistant professor of psychiatry at Weill Cornell Medical Center of New York-Presbyterian Hospital, and psychiatric consultant at the Hospital for Special Surgery, also in New York. She made changes to the patient’s story to protect confidentiality.
In search of high-value care
Six steps that can help your team
U.S. spending on health care is growing rapidly and expected to reach 19.7% of gross domestic product by 2026.1 In response, the Centers for Medicare and Medicaid Services and national organizations such as the American Board of Internal Medicine (ABIM) and the American College of Physicians (ACP) have launched initiatives to ensure that the value being delivered to patients is on par with the escalating cost of care.
Over the past 10 years, I have led and advised hundreds of small- and large-scale projects that focused on improving patient care quality and cost. Below, I share what I, along with other leaders in high-value care, have observed that it takes to implement successful and lasting improvements – for the benefit of patients and hospitals.
A brief history of high-value care
When compared to other wealthy countries, the United States spends disproportionately more money on health care. In 2016, U.S. health care spending was $3.3 trillion1, or $10,348 per person.2 Hospital care alone was responsible for a third of health spending and amounted to $1.1 trillion in 20161. By 2026, national health spending is projected to reach $5.7 trillion1.
In response to escalating health care costs, CMS and other payers have shifted toward value-based reimbursements that tie payments to health care facilities and clinicians to their performance on selected quality, cost, and efficiency measures. For example, under the CMS Merit-based Incentive Payment System (MIPS), 5% of clinicians’ revenue in 2020 is tied to their 2018 performance in four categories: Quality, Cost, Improvement Activities, and Promoting Interoperability. The percentage of revenue at risk will increase to 9% in 2022, based on 2020 performance.
Rising health care costs put a burden not just on the federal and state budgets, but on individual and family budgets as well. Out-of-pocket spending grew 3.9% in 2016 to $352.5 billion1 and is expected to increase in the future. High health care costs rightfully bring into question the value individual consumers of health care services are getting in return. If value is defined as the level of benefit achieved for a given cost, what is high-value care? The 2013 Institute of Medicine report3 defined high-value care as “the best care for the patient, with the optimal result for the circumstances, delivered at the right price.” It goes beyond a set of quality and cost measures used by payers to affect provider reimbursement and is driven by day-to-day individual providers’ decisions that affect individual patients’ outcomes and their cost of care.
High-value care has been embraced by national organizations. In 2012, the ABIM Foundation launched the Choosing Wisely initiative to support and promote conversations between clinicians and patients in choosing care that is truly necessary, supported by evidence, and free from harm. The result was an evidence-based list of recommendations from 540 specialty societies, including the Society of Hospital Medicine. The SHM – Adult Hospital Medicine list4 features the following “Five things physicians and patients should question”:
- Don’t place, or leave in place, urinary catheters for incontinence or convenience or monitoring of output for non–critically ill patients.
- Don’t prescribe medications for stress ulcer prophylaxis to medical inpatients unless at high risk for GI complications.
- Avoid transfusions of red blood cells for arbitrary hemoglobin or hematocrit thresholds and in the absence of symptoms of active coronary disease, heart failure, or stroke.
- Don’t order continuous telemetry monitoring outside of the ICU without using a protocol that governs continuation.
- Don’t perform repetitive CBC and chemistry testing in the face of clinical and lab stability.
The ACP launched a high-value care initiative that offers learning resources for clinicians and medical educators, clinical guidelines, and best practice advice. In 2012, a workgroup of internists convened by ACP developed a list of 37 clinical situations in which medical tests are commonly used but do not provide high value.5 Seven of those situations are applicable to adult hospital medicine.
High-value care today: What the experts say
More than 5 years later, what progress have hospitalists made in adopting high-value care practices? To answer this and other questions, I reached out to three national experts in high-value care in hospital medicine: Amit Pahwa, MD, assistant professor of medicine and pediatrics at Johns Hopkins University, Baltimore, and a course director of “Topics in interdisciplinary medicine: High-value health care”; Christopher Petrilli, MD, clinical assistant professor in the department of medicine at New York University Langone Health and clinical lead, Manhattan campus, value-based management; and Charlie Wray, DO, MS, assistant professor of medicine at the University of California in San Francisco and a coauthor of an article on high-value care in hospital medicine published recently in the Journal of General Internal Medicine6.
The experts agree that awareness of high-value care among practicing physicians and medical trainees has increased in the last few years. Major professional publications have highlighted the topic, including The Journal of Hospital Medicine’s “Things We Do For No Reason” series, JAMA’s “Teachable Moments,” and the American Journal of Medicine’s recurring column dedicated to high-value care practice. Leading teaching institutions have built high-value care curricula as a part of their medical student and resident training. However, widespread adoption has been slow and sometimes difficult.
The barriers to adoption of high-value practices among hospitalists are numerous and deep rooted in historical practices and culture. As Dr. Petrilli said, the “culture of overordering [diagnostic tests] is hard to break.” Hospitalists may not have well-developed relationships with patients, or time to explain why some tests or treatments are unnecessary. There is a lack of cost transparency, including the cost of the tests themselves and the downstream costs of additional tests and follow-ups. The best intended interventions fail to produce durable change unless they are seamlessly integrated into a hospitalist’s daily workflow.
Six steps to implementing a successful high-value care initiative
What can hospitalists do to improve the value of care they provide to their patients and hospital partners?
1. Identify high-value care opportunities at your hospital.
Dr. Wray pointed out that “all high-value care is local.” Start by looking at the national guidelines and talking to your senior clinical leaders and colleagues. Review your hospital data to identify opportunities and understand the root causes, including variability among providers.
If you choose to analyze and present provider-specific data, first be transparent on why you are doing that. Your goal is not to tell physicians how to practice or to score them, but instead, to promote adoption of evidence-based high-value care by identifying and discussing provider practice variations, and to generate possible solutions. Second, make sure that the data you present is credible and trustworthy by clearly outlining the data source, time frame, sample size per provider, any inclusion and exclusion criteria, attribution logic, and severity adjustment methodology. Third, expect initial pushback as transparency and change can be scary. But most doctors are inherently competitive and will want to be the best at caring for their patients.
2. Assemble the team.
Identify an executive sponsor – a senior clinical executive (for example, the chief medical officer or vice president of medical affairs) whose role is to help engage stakeholders, secure resources, and remove barriers. When assembling the rest of the team, include a representative from each major stakeholder group, but keep the team small enough to be effective. For example, if your project focuses on improving telemetry utilization, seek representation from hospitalists, cardiologists, nurses, utilization managers, and possibly IT. Look for people with the relevant knowledge and experience who are respected by their peers and can influence opinion.
3. Design a sustainable solution.
To be sustainable, a solution must be evidence based, well integrated in provider workflow, and have acceptable impact on daily workload (e.g., additional time per patient). If an estimated impact is significant, you need to discuss adding resources or negotiating trade-offs.
A great example of a sustainable solution, aimed to control overutilization of telemetry and urinary catheters, is the one implemented by Dr. Wray and his team.7 They designed an EHR-based “silent” indicator that clearly signaled an active telemetry or urinary catheter order for each patient. Clicking on the indicator directed a provider to a “manage order” screen where she could cancel the order, if necessary.
4. Engage providers.
You may design the best solution, but it will not succeed unless it is embraced by others. To engage providers, you must clearly communicate why the change is urgently needed for the benefit of their patients, hospital, or community, and appeal to their minds, hearts, and competitive nature.
For example, if you are focusing on overutilization of urinary catheters, you may share your hospital’s urinary catheter device utilization ratio (# of indwelling catheter days/# patient days) against national benchmarks, or the impact on hospital catheter–associated urinary tract infections (CAUTI) rates to appeal to the physicians’ minds. Often, data alone are not enough to move people to action. You must appeal to their hearts by sharing stories of real patients whose lives were affected by preventable CAUTI. Leverage physicians’ competitive nature by using provider-specific data to compare against their peers to spark a discussion.
5. Evaluate impact.
Even before you implement a solution, select metrics to measure impact and set SMART (specific, measurable, achievable, relevant, and time-bound) goals. As your implementation moves forward, do not let up or give up – continue to evaluate impact, remove barriers, refine your solution to get back on track if needed, and constantly communicate to share ongoing project results and lessons learned.
6. Sustain improvements.
Sustainable improvements require well-designed solutions integrated into provider workflow, but that is just the first step. Once you demonstrate the impact, consider including the metric (e.g., telemetry or urinary catheter utilization) in your team and/or individual provider performance dashboard, regularly reviewing and discussing performance during your team meetings to maintain engagement, and if needed, making improvements to get back on track.
Successful adoption of high-value care practices requires a disciplined approach to design and implement solutions that are patient-centric, evidence-based, data-driven and integrated in provider workflow.
Dr. Farah is a hospitalist, Physician Advisor, and Lean Six Sigma Black Belt. She is a performance improvement consultant based in Corvallis, Ore., and a member of The Hospitalist’s editorial advisory board.
References
1. From the Centers for Medicare & Medicaid Services: National Health Expenditure Projections 2018-2027.
2. Peterson-Kaiser Health System Tracker: How does health spending in the U.S. compare to other countries?
3. Creating a new culture of care, in “Best care at lower cost: The path to continuously learning health care in America.” (Washington: National Academies Press, 2013, pp. 255-80).
4. Choosing Wisely: SHM – Adult Hospital Medicine; Five things physicians and patients should question.
5. Qaseem A et al. Appropriate use of screening and diagnostic tests to foster high-value, cost-conscious care. Ann Intern Med. 2012 Jan 17;156(2):147-9.
6. Cho HJ et al. Right care in hospital medicine: Co-creation of ten opportunities in overuse and underuse for improving value in hospital medicine. J Gen Intern Med. 2018 Jun;33(6):804-6.
7. Wray CM et al. Improving value by reducing unnecessary telemetry and urinary catheter utilization in hospitalized patients. Am J Med. 2017 Sep;130(9):1037-41.
Six steps that can help your team
Six steps that can help your team
U.S. spending on health care is growing rapidly and expected to reach 19.7% of gross domestic product by 2026.1 In response, the Centers for Medicare and Medicaid Services and national organizations such as the American Board of Internal Medicine (ABIM) and the American College of Physicians (ACP) have launched initiatives to ensure that the value being delivered to patients is on par with the escalating cost of care.
Over the past 10 years, I have led and advised hundreds of small- and large-scale projects that focused on improving patient care quality and cost. Below, I share what I, along with other leaders in high-value care, have observed that it takes to implement successful and lasting improvements – for the benefit of patients and hospitals.
A brief history of high-value care
When compared to other wealthy countries, the United States spends disproportionately more money on health care. In 2016, U.S. health care spending was $3.3 trillion1, or $10,348 per person.2 Hospital care alone was responsible for a third of health spending and amounted to $1.1 trillion in 20161. By 2026, national health spending is projected to reach $5.7 trillion1.
In response to escalating health care costs, CMS and other payers have shifted toward value-based reimbursements that tie payments to health care facilities and clinicians to their performance on selected quality, cost, and efficiency measures. For example, under the CMS Merit-based Incentive Payment System (MIPS), 5% of clinicians’ revenue in 2020 is tied to their 2018 performance in four categories: Quality, Cost, Improvement Activities, and Promoting Interoperability. The percentage of revenue at risk will increase to 9% in 2022, based on 2020 performance.
Rising health care costs put a burden not just on the federal and state budgets, but on individual and family budgets as well. Out-of-pocket spending grew 3.9% in 2016 to $352.5 billion1 and is expected to increase in the future. High health care costs rightfully bring into question the value individual consumers of health care services are getting in return. If value is defined as the level of benefit achieved for a given cost, what is high-value care? The 2013 Institute of Medicine report3 defined high-value care as “the best care for the patient, with the optimal result for the circumstances, delivered at the right price.” It goes beyond a set of quality and cost measures used by payers to affect provider reimbursement and is driven by day-to-day individual providers’ decisions that affect individual patients’ outcomes and their cost of care.
High-value care has been embraced by national organizations. In 2012, the ABIM Foundation launched the Choosing Wisely initiative to support and promote conversations between clinicians and patients in choosing care that is truly necessary, supported by evidence, and free from harm. The result was an evidence-based list of recommendations from 540 specialty societies, including the Society of Hospital Medicine. The SHM – Adult Hospital Medicine list4 features the following “Five things physicians and patients should question”:
- Don’t place, or leave in place, urinary catheters for incontinence or convenience or monitoring of output for non–critically ill patients.
- Don’t prescribe medications for stress ulcer prophylaxis to medical inpatients unless at high risk for GI complications.
- Avoid transfusions of red blood cells for arbitrary hemoglobin or hematocrit thresholds and in the absence of symptoms of active coronary disease, heart failure, or stroke.
- Don’t order continuous telemetry monitoring outside of the ICU without using a protocol that governs continuation.
- Don’t perform repetitive CBC and chemistry testing in the face of clinical and lab stability.
The ACP launched a high-value care initiative that offers learning resources for clinicians and medical educators, clinical guidelines, and best practice advice. In 2012, a workgroup of internists convened by ACP developed a list of 37 clinical situations in which medical tests are commonly used but do not provide high value.5 Seven of those situations are applicable to adult hospital medicine.
High-value care today: What the experts say
More than 5 years later, what progress have hospitalists made in adopting high-value care practices? To answer this and other questions, I reached out to three national experts in high-value care in hospital medicine: Amit Pahwa, MD, assistant professor of medicine and pediatrics at Johns Hopkins University, Baltimore, and a course director of “Topics in interdisciplinary medicine: High-value health care”; Christopher Petrilli, MD, clinical assistant professor in the department of medicine at New York University Langone Health and clinical lead, Manhattan campus, value-based management; and Charlie Wray, DO, MS, assistant professor of medicine at the University of California in San Francisco and a coauthor of an article on high-value care in hospital medicine published recently in the Journal of General Internal Medicine6.
The experts agree that awareness of high-value care among practicing physicians and medical trainees has increased in the last few years. Major professional publications have highlighted the topic, including The Journal of Hospital Medicine’s “Things We Do For No Reason” series, JAMA’s “Teachable Moments,” and the American Journal of Medicine’s recurring column dedicated to high-value care practice. Leading teaching institutions have built high-value care curricula as a part of their medical student and resident training. However, widespread adoption has been slow and sometimes difficult.
The barriers to adoption of high-value practices among hospitalists are numerous and deep rooted in historical practices and culture. As Dr. Petrilli said, the “culture of overordering [diagnostic tests] is hard to break.” Hospitalists may not have well-developed relationships with patients, or time to explain why some tests or treatments are unnecessary. There is a lack of cost transparency, including the cost of the tests themselves and the downstream costs of additional tests and follow-ups. The best intended interventions fail to produce durable change unless they are seamlessly integrated into a hospitalist’s daily workflow.
Six steps to implementing a successful high-value care initiative
What can hospitalists do to improve the value of care they provide to their patients and hospital partners?
1. Identify high-value care opportunities at your hospital.
Dr. Wray pointed out that “all high-value care is local.” Start by looking at the national guidelines and talking to your senior clinical leaders and colleagues. Review your hospital data to identify opportunities and understand the root causes, including variability among providers.
If you choose to analyze and present provider-specific data, first be transparent on why you are doing that. Your goal is not to tell physicians how to practice or to score them, but instead, to promote adoption of evidence-based high-value care by identifying and discussing provider practice variations, and to generate possible solutions. Second, make sure that the data you present is credible and trustworthy by clearly outlining the data source, time frame, sample size per provider, any inclusion and exclusion criteria, attribution logic, and severity adjustment methodology. Third, expect initial pushback as transparency and change can be scary. But most doctors are inherently competitive and will want to be the best at caring for their patients.
2. Assemble the team.
Identify an executive sponsor – a senior clinical executive (for example, the chief medical officer or vice president of medical affairs) whose role is to help engage stakeholders, secure resources, and remove barriers. When assembling the rest of the team, include a representative from each major stakeholder group, but keep the team small enough to be effective. For example, if your project focuses on improving telemetry utilization, seek representation from hospitalists, cardiologists, nurses, utilization managers, and possibly IT. Look for people with the relevant knowledge and experience who are respected by their peers and can influence opinion.
3. Design a sustainable solution.
To be sustainable, a solution must be evidence based, well integrated in provider workflow, and have acceptable impact on daily workload (e.g., additional time per patient). If an estimated impact is significant, you need to discuss adding resources or negotiating trade-offs.
A great example of a sustainable solution, aimed to control overutilization of telemetry and urinary catheters, is the one implemented by Dr. Wray and his team.7 They designed an EHR-based “silent” indicator that clearly signaled an active telemetry or urinary catheter order for each patient. Clicking on the indicator directed a provider to a “manage order” screen where she could cancel the order, if necessary.
4. Engage providers.
You may design the best solution, but it will not succeed unless it is embraced by others. To engage providers, you must clearly communicate why the change is urgently needed for the benefit of their patients, hospital, or community, and appeal to their minds, hearts, and competitive nature.
For example, if you are focusing on overutilization of urinary catheters, you may share your hospital’s urinary catheter device utilization ratio (# of indwelling catheter days/# patient days) against national benchmarks, or the impact on hospital catheter–associated urinary tract infections (CAUTI) rates to appeal to the physicians’ minds. Often, data alone are not enough to move people to action. You must appeal to their hearts by sharing stories of real patients whose lives were affected by preventable CAUTI. Leverage physicians’ competitive nature by using provider-specific data to compare against their peers to spark a discussion.
5. Evaluate impact.
Even before you implement a solution, select metrics to measure impact and set SMART (specific, measurable, achievable, relevant, and time-bound) goals. As your implementation moves forward, do not let up or give up – continue to evaluate impact, remove barriers, refine your solution to get back on track if needed, and constantly communicate to share ongoing project results and lessons learned.
6. Sustain improvements.
Sustainable improvements require well-designed solutions integrated into provider workflow, but that is just the first step. Once you demonstrate the impact, consider including the metric (e.g., telemetry or urinary catheter utilization) in your team and/or individual provider performance dashboard, regularly reviewing and discussing performance during your team meetings to maintain engagement, and if needed, making improvements to get back on track.
Successful adoption of high-value care practices requires a disciplined approach to design and implement solutions that are patient-centric, evidence-based, data-driven and integrated in provider workflow.
Dr. Farah is a hospitalist, Physician Advisor, and Lean Six Sigma Black Belt. She is a performance improvement consultant based in Corvallis, Ore., and a member of The Hospitalist’s editorial advisory board.
References
1. From the Centers for Medicare & Medicaid Services: National Health Expenditure Projections 2018-2027.
2. Peterson-Kaiser Health System Tracker: How does health spending in the U.S. compare to other countries?
3. Creating a new culture of care, in “Best care at lower cost: The path to continuously learning health care in America.” (Washington: National Academies Press, 2013, pp. 255-80).
4. Choosing Wisely: SHM – Adult Hospital Medicine; Five things physicians and patients should question.
5. Qaseem A et al. Appropriate use of screening and diagnostic tests to foster high-value, cost-conscious care. Ann Intern Med. 2012 Jan 17;156(2):147-9.
6. Cho HJ et al. Right care in hospital medicine: Co-creation of ten opportunities in overuse and underuse for improving value in hospital medicine. J Gen Intern Med. 2018 Jun;33(6):804-6.
7. Wray CM et al. Improving value by reducing unnecessary telemetry and urinary catheter utilization in hospitalized patients. Am J Med. 2017 Sep;130(9):1037-41.
U.S. spending on health care is growing rapidly and expected to reach 19.7% of gross domestic product by 2026.1 In response, the Centers for Medicare and Medicaid Services and national organizations such as the American Board of Internal Medicine (ABIM) and the American College of Physicians (ACP) have launched initiatives to ensure that the value being delivered to patients is on par with the escalating cost of care.
Over the past 10 years, I have led and advised hundreds of small- and large-scale projects that focused on improving patient care quality and cost. Below, I share what I, along with other leaders in high-value care, have observed that it takes to implement successful and lasting improvements – for the benefit of patients and hospitals.
A brief history of high-value care
When compared to other wealthy countries, the United States spends disproportionately more money on health care. In 2016, U.S. health care spending was $3.3 trillion1, or $10,348 per person.2 Hospital care alone was responsible for a third of health spending and amounted to $1.1 trillion in 20161. By 2026, national health spending is projected to reach $5.7 trillion1.
In response to escalating health care costs, CMS and other payers have shifted toward value-based reimbursements that tie payments to health care facilities and clinicians to their performance on selected quality, cost, and efficiency measures. For example, under the CMS Merit-based Incentive Payment System (MIPS), 5% of clinicians’ revenue in 2020 is tied to their 2018 performance in four categories: Quality, Cost, Improvement Activities, and Promoting Interoperability. The percentage of revenue at risk will increase to 9% in 2022, based on 2020 performance.
Rising health care costs put a burden not just on the federal and state budgets, but on individual and family budgets as well. Out-of-pocket spending grew 3.9% in 2016 to $352.5 billion1 and is expected to increase in the future. High health care costs rightfully bring into question the value individual consumers of health care services are getting in return. If value is defined as the level of benefit achieved for a given cost, what is high-value care? The 2013 Institute of Medicine report3 defined high-value care as “the best care for the patient, with the optimal result for the circumstances, delivered at the right price.” It goes beyond a set of quality and cost measures used by payers to affect provider reimbursement and is driven by day-to-day individual providers’ decisions that affect individual patients’ outcomes and their cost of care.
High-value care has been embraced by national organizations. In 2012, the ABIM Foundation launched the Choosing Wisely initiative to support and promote conversations between clinicians and patients in choosing care that is truly necessary, supported by evidence, and free from harm. The result was an evidence-based list of recommendations from 540 specialty societies, including the Society of Hospital Medicine. The SHM – Adult Hospital Medicine list4 features the following “Five things physicians and patients should question”:
- Don’t place, or leave in place, urinary catheters for incontinence or convenience or monitoring of output for non–critically ill patients.
- Don’t prescribe medications for stress ulcer prophylaxis to medical inpatients unless at high risk for GI complications.
- Avoid transfusions of red blood cells for arbitrary hemoglobin or hematocrit thresholds and in the absence of symptoms of active coronary disease, heart failure, or stroke.
- Don’t order continuous telemetry monitoring outside of the ICU without using a protocol that governs continuation.
- Don’t perform repetitive CBC and chemistry testing in the face of clinical and lab stability.
The ACP launched a high-value care initiative that offers learning resources for clinicians and medical educators, clinical guidelines, and best practice advice. In 2012, a workgroup of internists convened by ACP developed a list of 37 clinical situations in which medical tests are commonly used but do not provide high value.5 Seven of those situations are applicable to adult hospital medicine.
High-value care today: What the experts say
More than 5 years later, what progress have hospitalists made in adopting high-value care practices? To answer this and other questions, I reached out to three national experts in high-value care in hospital medicine: Amit Pahwa, MD, assistant professor of medicine and pediatrics at Johns Hopkins University, Baltimore, and a course director of “Topics in interdisciplinary medicine: High-value health care”; Christopher Petrilli, MD, clinical assistant professor in the department of medicine at New York University Langone Health and clinical lead, Manhattan campus, value-based management; and Charlie Wray, DO, MS, assistant professor of medicine at the University of California in San Francisco and a coauthor of an article on high-value care in hospital medicine published recently in the Journal of General Internal Medicine6.
The experts agree that awareness of high-value care among practicing physicians and medical trainees has increased in the last few years. Major professional publications have highlighted the topic, including The Journal of Hospital Medicine’s “Things We Do For No Reason” series, JAMA’s “Teachable Moments,” and the American Journal of Medicine’s recurring column dedicated to high-value care practice. Leading teaching institutions have built high-value care curricula as a part of their medical student and resident training. However, widespread adoption has been slow and sometimes difficult.
The barriers to adoption of high-value practices among hospitalists are numerous and deep rooted in historical practices and culture. As Dr. Petrilli said, the “culture of overordering [diagnostic tests] is hard to break.” Hospitalists may not have well-developed relationships with patients, or time to explain why some tests or treatments are unnecessary. There is a lack of cost transparency, including the cost of the tests themselves and the downstream costs of additional tests and follow-ups. The best intended interventions fail to produce durable change unless they are seamlessly integrated into a hospitalist’s daily workflow.
Six steps to implementing a successful high-value care initiative
What can hospitalists do to improve the value of care they provide to their patients and hospital partners?
1. Identify high-value care opportunities at your hospital.
Dr. Wray pointed out that “all high-value care is local.” Start by looking at the national guidelines and talking to your senior clinical leaders and colleagues. Review your hospital data to identify opportunities and understand the root causes, including variability among providers.
If you choose to analyze and present provider-specific data, first be transparent on why you are doing that. Your goal is not to tell physicians how to practice or to score them, but instead, to promote adoption of evidence-based high-value care by identifying and discussing provider practice variations, and to generate possible solutions. Second, make sure that the data you present is credible and trustworthy by clearly outlining the data source, time frame, sample size per provider, any inclusion and exclusion criteria, attribution logic, and severity adjustment methodology. Third, expect initial pushback as transparency and change can be scary. But most doctors are inherently competitive and will want to be the best at caring for their patients.
2. Assemble the team.
Identify an executive sponsor – a senior clinical executive (for example, the chief medical officer or vice president of medical affairs) whose role is to help engage stakeholders, secure resources, and remove barriers. When assembling the rest of the team, include a representative from each major stakeholder group, but keep the team small enough to be effective. For example, if your project focuses on improving telemetry utilization, seek representation from hospitalists, cardiologists, nurses, utilization managers, and possibly IT. Look for people with the relevant knowledge and experience who are respected by their peers and can influence opinion.
3. Design a sustainable solution.
To be sustainable, a solution must be evidence based, well integrated in provider workflow, and have acceptable impact on daily workload (e.g., additional time per patient). If an estimated impact is significant, you need to discuss adding resources or negotiating trade-offs.
A great example of a sustainable solution, aimed to control overutilization of telemetry and urinary catheters, is the one implemented by Dr. Wray and his team.7 They designed an EHR-based “silent” indicator that clearly signaled an active telemetry or urinary catheter order for each patient. Clicking on the indicator directed a provider to a “manage order” screen where she could cancel the order, if necessary.
4. Engage providers.
You may design the best solution, but it will not succeed unless it is embraced by others. To engage providers, you must clearly communicate why the change is urgently needed for the benefit of their patients, hospital, or community, and appeal to their minds, hearts, and competitive nature.
For example, if you are focusing on overutilization of urinary catheters, you may share your hospital’s urinary catheter device utilization ratio (# of indwelling catheter days/# patient days) against national benchmarks, or the impact on hospital catheter–associated urinary tract infections (CAUTI) rates to appeal to the physicians’ minds. Often, data alone are not enough to move people to action. You must appeal to their hearts by sharing stories of real patients whose lives were affected by preventable CAUTI. Leverage physicians’ competitive nature by using provider-specific data to compare against their peers to spark a discussion.
5. Evaluate impact.
Even before you implement a solution, select metrics to measure impact and set SMART (specific, measurable, achievable, relevant, and time-bound) goals. As your implementation moves forward, do not let up or give up – continue to evaluate impact, remove barriers, refine your solution to get back on track if needed, and constantly communicate to share ongoing project results and lessons learned.
6. Sustain improvements.
Sustainable improvements require well-designed solutions integrated into provider workflow, but that is just the first step. Once you demonstrate the impact, consider including the metric (e.g., telemetry or urinary catheter utilization) in your team and/or individual provider performance dashboard, regularly reviewing and discussing performance during your team meetings to maintain engagement, and if needed, making improvements to get back on track.
Successful adoption of high-value care practices requires a disciplined approach to design and implement solutions that are patient-centric, evidence-based, data-driven and integrated in provider workflow.
Dr. Farah is a hospitalist, Physician Advisor, and Lean Six Sigma Black Belt. She is a performance improvement consultant based in Corvallis, Ore., and a member of The Hospitalist’s editorial advisory board.
References
1. From the Centers for Medicare & Medicaid Services: National Health Expenditure Projections 2018-2027.
2. Peterson-Kaiser Health System Tracker: How does health spending in the U.S. compare to other countries?
3. Creating a new culture of care, in “Best care at lower cost: The path to continuously learning health care in America.” (Washington: National Academies Press, 2013, pp. 255-80).
4. Choosing Wisely: SHM – Adult Hospital Medicine; Five things physicians and patients should question.
5. Qaseem A et al. Appropriate use of screening and diagnostic tests to foster high-value, cost-conscious care. Ann Intern Med. 2012 Jan 17;156(2):147-9.
6. Cho HJ et al. Right care in hospital medicine: Co-creation of ten opportunities in overuse and underuse for improving value in hospital medicine. J Gen Intern Med. 2018 Jun;33(6):804-6.
7. Wray CM et al. Improving value by reducing unnecessary telemetry and urinary catheter utilization in hospitalized patients. Am J Med. 2017 Sep;130(9):1037-41.
Dapagliflozin’s cardiovascular benefits bloom in T2D with prior MI
NEW ORLEANS – Dapagliflozin markedly reduces the risks of both major adverse cardiovascular events and heart failure hospitalization in the subset of patients with type 2 diabetes (T2D) and prior MI, according to a new subanalysis of the landmark DECLARE-TIMI 58 trial.
The effectiveness of dapagliflozin (Farxiga), an oral sodium glucose transporter-2 inhibitor (SGLT-2i), was particularly striking with regard to prevention of recurrent MI, Remo H.M. Furtado, MD, reported at the annual meeting of the American College of Cardiology.
“The 22% relative risk reduction in recurrent MI with dapagliflozin is comparable to other established therapies used in secondary prevention after MI, like DAPT [dual-antiplatelet therapy] and intensive lipid lowering,” observed Dr. Furtado of Brigham and Women’s Hospital, Boston.
Not bad for a drug developed as a glucose-lowering agent.
The new DECLARE-TIMI 58 subanalysis provides information that’s relevant to ACC guidelines issued in late 2018. The guidelines, in the form of an “expert consensus decision pathway,” emphatically recommend that all patients with T2D and known atherosclerotic cardiovascular disease (ASCVD) should have metformin as their first-line glucose-lowering agent, while at the same time giving serious consideration to the addition of either an oral SGLT-2i or a subcutaneously injected glucagonlike peptide–1 receptor agonist (GLP-1RA) with demonstrated cardiovascular benefit as a second glucose-lowering agent (J Am Coll Cardiol. 2018 Dec 18;72[24]:3200-23). The DECLARE-TIMI 58 subanalysis bolsters that guidance and shows, more specifically, that the cardioprotective benefits of dapagliflozin are significantly greater in T2D with prior MI than in those with known ASCVD but no history of MI, the cardiologist explained.
The main results of DECLARE-TIMI 58 have been published. The trial included 17,160 patients with T2D, 6,974 of whom had established ASCVD, while the remainder had multiple ASCVD risk factors. Participants were randomized to oral dapagliflozin at 10 mg/day or placebo on top of background guideline-directed medical therapy and followed for a median of 4.2 years. The dapagliflozin group had a 27% reduction in heart failure hospitalizations, compared with controls, but there were no significant between-group differences in the composite MACE (major adverse cardiovascular events) endpoint of cardiovascular death, MI, or ischemic stroke (N Engl J Med. 2019 Jan 24;380[4]:347-57).
Dr. Furtado presented a prespecified subgroup analysis focused on the 3,584 study participants with prior MI. Their rate of the composite endpoint of cardiovascular death, MI, or ischemic stroke was 15.2%, compared with 17.8% in controls, for a statistically significant and clinically meaningful 16% relative risk reduction and an absolute 2.6% risk reduction. Of note, the risk of recurrent MI was reduced by 22%. In contrast, there was no difference in MACE risk between the dapagliflozin and placebo groups in patients with no prior MI, even if they had established ASCVD.
A noteworthy finding was that the benefit in MACE reduction in patients with prior MI was greater in those who were closer in time to their most recent MI at enrollment in the study. Those who started on dapagliflozin within 12 months of their last MI had a 34% relative risk reduction in MACE, compared with placebo, while those who enrolled 12-24 months after their last MI enjoyed an even more robust 58% relative risk reduction on dapagliflozin. In contrast, patients who enrolled 24-36 months post MI had only a 17% relative risk reduction, and the 2,400 patients who enrolled more than 36 months after their last MI had a subsequent MACE rate no different from controls.
Session cochair Nadia R. Sutton, MD, a cardiologist at the University of Michigan, Ann Arbor, commented that she found this time-dependent benefit fascinating.
“Do you think this has anything to do with the escalation of other therapies, such as Plavix [clopidogrel]?” she asked.
Dr. Furtado replied, “This is a finding that we should interpret with a little bit of caution.” For one thing, patients in the acute phase of an MI were excluded from participation in the trial, so nothing is known about how they would fare on dapagliflozin. For another, only 844 of the 3,584 patients with T2D and prior MI had their most recent MI within 24 months of enrollment, so even though the differences were statistically significant, the confidence intervals are fairly wide.
That being said, the finding does underscore a truism about cardiovascular prevention: The higher the risk, the greater the benefit of effective therapy – and, of course, the initial months following an MI are a particularly high-risk period.
“Also, this finding is a caution to the clinicians to avoid clinical inertia in prescribing an SGLT-2i, because maybe you can get an early benefit if you prescribe the drug closer to the acute phase and not wait until some months after the patient has tried diet and exercise and so on,” he added.
With regard to the second coprimary endpoint comprising cardiovascular death or heart failure hospitalization in T2D patients with prior MI, the rate in the dapagliflozin group was 8.6%, a 19% relative risk reduction and absolute risk reduction of 1.9%, compared with the 10.5% rate with placebo.
Dr. Furtado noted that the main results of DECLARE TIMI-58 are consistent with a recent systematic review and meta-analysis of three randomized cardiovascular outcome trials of SGLT-2is for primary and secondary prevention of cardiovascular and renal outcomes in T2D. The meta-analysis included more than 34,000 patients, roughly half drawn from DECLARE-TIMI 58. SGLT-2i therapy reduced MACE by 14% in patients with established ASCVD but not significantly in those without. And the agents reduced the risk of cardiovascular death/heart failure hospitalization by 23%, regardless of whether or not patients had known ASCVD or a history of heart failure (Lancet. 2019 Jan 5;393[10166]:31-9).
Dr. Furtado reported serving as a consultant to AstraZeneca, which funded DECLARE-TIMI 58, as well as receiving direct institutional research grants from half a dozen other pharmaceutical companies.
Simultaneous with his presentation at ACC 2019 in New Orleans, the subanalysis results were published online (Circulation. 2019 Mar 18. doi: 10.1161/CIRCULATIONAHA.119.039996. [Epub ahead of print]).
NEW ORLEANS – Dapagliflozin markedly reduces the risks of both major adverse cardiovascular events and heart failure hospitalization in the subset of patients with type 2 diabetes (T2D) and prior MI, according to a new subanalysis of the landmark DECLARE-TIMI 58 trial.
The effectiveness of dapagliflozin (Farxiga), an oral sodium glucose transporter-2 inhibitor (SGLT-2i), was particularly striking with regard to prevention of recurrent MI, Remo H.M. Furtado, MD, reported at the annual meeting of the American College of Cardiology.
“The 22% relative risk reduction in recurrent MI with dapagliflozin is comparable to other established therapies used in secondary prevention after MI, like DAPT [dual-antiplatelet therapy] and intensive lipid lowering,” observed Dr. Furtado of Brigham and Women’s Hospital, Boston.
Not bad for a drug developed as a glucose-lowering agent.
The new DECLARE-TIMI 58 subanalysis provides information that’s relevant to ACC guidelines issued in late 2018. The guidelines, in the form of an “expert consensus decision pathway,” emphatically recommend that all patients with T2D and known atherosclerotic cardiovascular disease (ASCVD) should have metformin as their first-line glucose-lowering agent, while at the same time giving serious consideration to the addition of either an oral SGLT-2i or a subcutaneously injected glucagonlike peptide–1 receptor agonist (GLP-1RA) with demonstrated cardiovascular benefit as a second glucose-lowering agent (J Am Coll Cardiol. 2018 Dec 18;72[24]:3200-23). The DECLARE-TIMI 58 subanalysis bolsters that guidance and shows, more specifically, that the cardioprotective benefits of dapagliflozin are significantly greater in T2D with prior MI than in those with known ASCVD but no history of MI, the cardiologist explained.
The main results of DECLARE-TIMI 58 have been published. The trial included 17,160 patients with T2D, 6,974 of whom had established ASCVD, while the remainder had multiple ASCVD risk factors. Participants were randomized to oral dapagliflozin at 10 mg/day or placebo on top of background guideline-directed medical therapy and followed for a median of 4.2 years. The dapagliflozin group had a 27% reduction in heart failure hospitalizations, compared with controls, but there were no significant between-group differences in the composite MACE (major adverse cardiovascular events) endpoint of cardiovascular death, MI, or ischemic stroke (N Engl J Med. 2019 Jan 24;380[4]:347-57).
Dr. Furtado presented a prespecified subgroup analysis focused on the 3,584 study participants with prior MI. Their rate of the composite endpoint of cardiovascular death, MI, or ischemic stroke was 15.2%, compared with 17.8% in controls, for a statistically significant and clinically meaningful 16% relative risk reduction and an absolute 2.6% risk reduction. Of note, the risk of recurrent MI was reduced by 22%. In contrast, there was no difference in MACE risk between the dapagliflozin and placebo groups in patients with no prior MI, even if they had established ASCVD.
A noteworthy finding was that the benefit in MACE reduction in patients with prior MI was greater in those who were closer in time to their most recent MI at enrollment in the study. Those who started on dapagliflozin within 12 months of their last MI had a 34% relative risk reduction in MACE, compared with placebo, while those who enrolled 12-24 months after their last MI enjoyed an even more robust 58% relative risk reduction on dapagliflozin. In contrast, patients who enrolled 24-36 months post MI had only a 17% relative risk reduction, and the 2,400 patients who enrolled more than 36 months after their last MI had a subsequent MACE rate no different from controls.
Session cochair Nadia R. Sutton, MD, a cardiologist at the University of Michigan, Ann Arbor, commented that she found this time-dependent benefit fascinating.
“Do you think this has anything to do with the escalation of other therapies, such as Plavix [clopidogrel]?” she asked.
Dr. Furtado replied, “This is a finding that we should interpret with a little bit of caution.” For one thing, patients in the acute phase of an MI were excluded from participation in the trial, so nothing is known about how they would fare on dapagliflozin. For another, only 844 of the 3,584 patients with T2D and prior MI had their most recent MI within 24 months of enrollment, so even though the differences were statistically significant, the confidence intervals are fairly wide.
That being said, the finding does underscore a truism about cardiovascular prevention: The higher the risk, the greater the benefit of effective therapy – and, of course, the initial months following an MI are a particularly high-risk period.
“Also, this finding is a caution to the clinicians to avoid clinical inertia in prescribing an SGLT-2i, because maybe you can get an early benefit if you prescribe the drug closer to the acute phase and not wait until some months after the patient has tried diet and exercise and so on,” he added.
With regard to the second coprimary endpoint comprising cardiovascular death or heart failure hospitalization in T2D patients with prior MI, the rate in the dapagliflozin group was 8.6%, a 19% relative risk reduction and absolute risk reduction of 1.9%, compared with the 10.5% rate with placebo.
Dr. Furtado noted that the main results of DECLARE TIMI-58 are consistent with a recent systematic review and meta-analysis of three randomized cardiovascular outcome trials of SGLT-2is for primary and secondary prevention of cardiovascular and renal outcomes in T2D. The meta-analysis included more than 34,000 patients, roughly half drawn from DECLARE-TIMI 58. SGLT-2i therapy reduced MACE by 14% in patients with established ASCVD but not significantly in those without. And the agents reduced the risk of cardiovascular death/heart failure hospitalization by 23%, regardless of whether or not patients had known ASCVD or a history of heart failure (Lancet. 2019 Jan 5;393[10166]:31-9).
Dr. Furtado reported serving as a consultant to AstraZeneca, which funded DECLARE-TIMI 58, as well as receiving direct institutional research grants from half a dozen other pharmaceutical companies.
Simultaneous with his presentation at ACC 2019 in New Orleans, the subanalysis results were published online (Circulation. 2019 Mar 18. doi: 10.1161/CIRCULATIONAHA.119.039996. [Epub ahead of print]).
NEW ORLEANS – Dapagliflozin markedly reduces the risks of both major adverse cardiovascular events and heart failure hospitalization in the subset of patients with type 2 diabetes (T2D) and prior MI, according to a new subanalysis of the landmark DECLARE-TIMI 58 trial.
The effectiveness of dapagliflozin (Farxiga), an oral sodium glucose transporter-2 inhibitor (SGLT-2i), was particularly striking with regard to prevention of recurrent MI, Remo H.M. Furtado, MD, reported at the annual meeting of the American College of Cardiology.
“The 22% relative risk reduction in recurrent MI with dapagliflozin is comparable to other established therapies used in secondary prevention after MI, like DAPT [dual-antiplatelet therapy] and intensive lipid lowering,” observed Dr. Furtado of Brigham and Women’s Hospital, Boston.
Not bad for a drug developed as a glucose-lowering agent.
The new DECLARE-TIMI 58 subanalysis provides information that’s relevant to ACC guidelines issued in late 2018. The guidelines, in the form of an “expert consensus decision pathway,” emphatically recommend that all patients with T2D and known atherosclerotic cardiovascular disease (ASCVD) should have metformin as their first-line glucose-lowering agent, while at the same time giving serious consideration to the addition of either an oral SGLT-2i or a subcutaneously injected glucagonlike peptide–1 receptor agonist (GLP-1RA) with demonstrated cardiovascular benefit as a second glucose-lowering agent (J Am Coll Cardiol. 2018 Dec 18;72[24]:3200-23). The DECLARE-TIMI 58 subanalysis bolsters that guidance and shows, more specifically, that the cardioprotective benefits of dapagliflozin are significantly greater in T2D with prior MI than in those with known ASCVD but no history of MI, the cardiologist explained.
The main results of DECLARE-TIMI 58 have been published. The trial included 17,160 patients with T2D, 6,974 of whom had established ASCVD, while the remainder had multiple ASCVD risk factors. Participants were randomized to oral dapagliflozin at 10 mg/day or placebo on top of background guideline-directed medical therapy and followed for a median of 4.2 years. The dapagliflozin group had a 27% reduction in heart failure hospitalizations, compared with controls, but there were no significant between-group differences in the composite MACE (major adverse cardiovascular events) endpoint of cardiovascular death, MI, or ischemic stroke (N Engl J Med. 2019 Jan 24;380[4]:347-57).
Dr. Furtado presented a prespecified subgroup analysis focused on the 3,584 study participants with prior MI. Their rate of the composite endpoint of cardiovascular death, MI, or ischemic stroke was 15.2%, compared with 17.8% in controls, for a statistically significant and clinically meaningful 16% relative risk reduction and an absolute 2.6% risk reduction. Of note, the risk of recurrent MI was reduced by 22%. In contrast, there was no difference in MACE risk between the dapagliflozin and placebo groups in patients with no prior MI, even if they had established ASCVD.
A noteworthy finding was that the benefit in MACE reduction in patients with prior MI was greater in those who were closer in time to their most recent MI at enrollment in the study. Those who started on dapagliflozin within 12 months of their last MI had a 34% relative risk reduction in MACE, compared with placebo, while those who enrolled 12-24 months after their last MI enjoyed an even more robust 58% relative risk reduction on dapagliflozin. In contrast, patients who enrolled 24-36 months post MI had only a 17% relative risk reduction, and the 2,400 patients who enrolled more than 36 months after their last MI had a subsequent MACE rate no different from controls.
Session cochair Nadia R. Sutton, MD, a cardiologist at the University of Michigan, Ann Arbor, commented that she found this time-dependent benefit fascinating.
“Do you think this has anything to do with the escalation of other therapies, such as Plavix [clopidogrel]?” she asked.
Dr. Furtado replied, “This is a finding that we should interpret with a little bit of caution.” For one thing, patients in the acute phase of an MI were excluded from participation in the trial, so nothing is known about how they would fare on dapagliflozin. For another, only 844 of the 3,584 patients with T2D and prior MI had their most recent MI within 24 months of enrollment, so even though the differences were statistically significant, the confidence intervals are fairly wide.
That being said, the finding does underscore a truism about cardiovascular prevention: The higher the risk, the greater the benefit of effective therapy – and, of course, the initial months following an MI are a particularly high-risk period.
“Also, this finding is a caution to the clinicians to avoid clinical inertia in prescribing an SGLT-2i, because maybe you can get an early benefit if you prescribe the drug closer to the acute phase and not wait until some months after the patient has tried diet and exercise and so on,” he added.
With regard to the second coprimary endpoint comprising cardiovascular death or heart failure hospitalization in T2D patients with prior MI, the rate in the dapagliflozin group was 8.6%, a 19% relative risk reduction and absolute risk reduction of 1.9%, compared with the 10.5% rate with placebo.
Dr. Furtado noted that the main results of DECLARE TIMI-58 are consistent with a recent systematic review and meta-analysis of three randomized cardiovascular outcome trials of SGLT-2is for primary and secondary prevention of cardiovascular and renal outcomes in T2D. The meta-analysis included more than 34,000 patients, roughly half drawn from DECLARE-TIMI 58. SGLT-2i therapy reduced MACE by 14% in patients with established ASCVD but not significantly in those without. And the agents reduced the risk of cardiovascular death/heart failure hospitalization by 23%, regardless of whether or not patients had known ASCVD or a history of heart failure (Lancet. 2019 Jan 5;393[10166]:31-9).
Dr. Furtado reported serving as a consultant to AstraZeneca, which funded DECLARE-TIMI 58, as well as receiving direct institutional research grants from half a dozen other pharmaceutical companies.
Simultaneous with his presentation at ACC 2019 in New Orleans, the subanalysis results were published online (Circulation. 2019 Mar 18. doi: 10.1161/CIRCULATIONAHA.119.039996. [Epub ahead of print]).
REPORTING FROM ACC 19
Pembrolizumab benefits some patients with advanced cervical cancer
The checkpoint inhibitor pembrolizumab conferred a durable tumor response in patients with advanced cervical cancer, who were positive for programmed death ligand 1 (PD-L1).
Among 98 patients, all of whom had progressed despite prior treatment, overall response rate was 12.2% (95% confidence interval, 6.5%-20.4%), with three complete and nine partial responses. All 12 responses were in patients with PD-L1-positive tumors, wrote Hyun Cheol Chung, MD, and his colleagues. The report is in the Journal of Clinical Oncology.
The response curve had not peaked by the end of follow-up, suggesting further benefit of the antibody, said Dr. Chung of Yonsei Cancer Center, Seoul, South Korea. On the basis of these data, first reported at the 2018 meeting of the American Society of Clinical Oncology, the Food and Drug Administration approved the antibody for advanced cervical cancer last year.
“These results show that treatment with pembrolizumab offers a clinically meaningful therapeutic option for a subset of patients with previously treated advanced cervical cancer,” the researchers said. The approval makes pembrolizumab the first immunotherapy approved for the treatment of an advanced gynecologic malignancy.
The phase 2 KEYNOTE-158 study comprised 98 women (median age 46 years) with advanced cervical cancer with progression after chemotherapy. All received pembrolizumab 200 mg every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision.
Most of the patients (83.7%) were positive for PD-L1. All had received at least one or more lines of chemotherapy before entering the study. The median follow-up was 10 months and the median treatment duration 2.9 months, with a range of 1 day-22 months.
By the study’s end, most patients (85.7%) had experienced disease progression or had died. Overall survival was poor even in the PD-L1-positive patients, with 82.9% experiencing progression or death. Overall mortality was 69.4% and 64.6%, respectively. However, PD-L1 patients did live longer, a median of 11 months, compared with 9.4 months in the entire cohort.
At 6 months, overall survival estimates were 75.2% in the total cohort and 80.2% in the PD-L1 patients; 12-month overall survival estimates were 41.4% and 47.3%, respectively.
However, among the 12 responders with PD-L1-postitive tumors, just one had died by the data cutoff, suggesting that longer treatment with pembrolizumab could be beneficial in this group.
“Responses typically occurred within 2.1 months and were durable, with a median duration of response that had not been reached after a median follow-up of 10.2 months and an estimated 90.9% of responses ongoing at 6 months” Dr. Chung and his colleagues wrote.
Adverse events were common (65.3%) with 12.2% graded as serious. But none were lethal, and only four patients discontinued pembrolizumab because of a treatment-related adverse event.
“Our results from an interim analysis of data from the phase II KEYNOTE-158 clinical trial show that pembrolizumab has promising antitumor activity in patients with previously treated advanced cervical cancer,” the researchers said. “These response rates are similar or superior to those observed with other treatment options in this setting.”
Pembrolizumab is now being evaluated in combination with concurrent chemoradiotherapy and with concurrent versus sequential chemoradiotherapy.
Merck & Co. sponsored the study.
SOURCE: Chung HC et al. J Clin Oncol. 2019 April 3. doi: 10.1200/JCO.18.01265.
The checkpoint inhibitor pembrolizumab conferred a durable tumor response in patients with advanced cervical cancer, who were positive for programmed death ligand 1 (PD-L1).
Among 98 patients, all of whom had progressed despite prior treatment, overall response rate was 12.2% (95% confidence interval, 6.5%-20.4%), with three complete and nine partial responses. All 12 responses were in patients with PD-L1-positive tumors, wrote Hyun Cheol Chung, MD, and his colleagues. The report is in the Journal of Clinical Oncology.
The response curve had not peaked by the end of follow-up, suggesting further benefit of the antibody, said Dr. Chung of Yonsei Cancer Center, Seoul, South Korea. On the basis of these data, first reported at the 2018 meeting of the American Society of Clinical Oncology, the Food and Drug Administration approved the antibody for advanced cervical cancer last year.
“These results show that treatment with pembrolizumab offers a clinically meaningful therapeutic option for a subset of patients with previously treated advanced cervical cancer,” the researchers said. The approval makes pembrolizumab the first immunotherapy approved for the treatment of an advanced gynecologic malignancy.
The phase 2 KEYNOTE-158 study comprised 98 women (median age 46 years) with advanced cervical cancer with progression after chemotherapy. All received pembrolizumab 200 mg every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision.
Most of the patients (83.7%) were positive for PD-L1. All had received at least one or more lines of chemotherapy before entering the study. The median follow-up was 10 months and the median treatment duration 2.9 months, with a range of 1 day-22 months.
By the study’s end, most patients (85.7%) had experienced disease progression or had died. Overall survival was poor even in the PD-L1-positive patients, with 82.9% experiencing progression or death. Overall mortality was 69.4% and 64.6%, respectively. However, PD-L1 patients did live longer, a median of 11 months, compared with 9.4 months in the entire cohort.
At 6 months, overall survival estimates were 75.2% in the total cohort and 80.2% in the PD-L1 patients; 12-month overall survival estimates were 41.4% and 47.3%, respectively.
However, among the 12 responders with PD-L1-postitive tumors, just one had died by the data cutoff, suggesting that longer treatment with pembrolizumab could be beneficial in this group.
“Responses typically occurred within 2.1 months and were durable, with a median duration of response that had not been reached after a median follow-up of 10.2 months and an estimated 90.9% of responses ongoing at 6 months” Dr. Chung and his colleagues wrote.
Adverse events were common (65.3%) with 12.2% graded as serious. But none were lethal, and only four patients discontinued pembrolizumab because of a treatment-related adverse event.
“Our results from an interim analysis of data from the phase II KEYNOTE-158 clinical trial show that pembrolizumab has promising antitumor activity in patients with previously treated advanced cervical cancer,” the researchers said. “These response rates are similar or superior to those observed with other treatment options in this setting.”
Pembrolizumab is now being evaluated in combination with concurrent chemoradiotherapy and with concurrent versus sequential chemoradiotherapy.
Merck & Co. sponsored the study.
SOURCE: Chung HC et al. J Clin Oncol. 2019 April 3. doi: 10.1200/JCO.18.01265.
The checkpoint inhibitor pembrolizumab conferred a durable tumor response in patients with advanced cervical cancer, who were positive for programmed death ligand 1 (PD-L1).
Among 98 patients, all of whom had progressed despite prior treatment, overall response rate was 12.2% (95% confidence interval, 6.5%-20.4%), with three complete and nine partial responses. All 12 responses were in patients with PD-L1-positive tumors, wrote Hyun Cheol Chung, MD, and his colleagues. The report is in the Journal of Clinical Oncology.
The response curve had not peaked by the end of follow-up, suggesting further benefit of the antibody, said Dr. Chung of Yonsei Cancer Center, Seoul, South Korea. On the basis of these data, first reported at the 2018 meeting of the American Society of Clinical Oncology, the Food and Drug Administration approved the antibody for advanced cervical cancer last year.
“These results show that treatment with pembrolizumab offers a clinically meaningful therapeutic option for a subset of patients with previously treated advanced cervical cancer,” the researchers said. The approval makes pembrolizumab the first immunotherapy approved for the treatment of an advanced gynecologic malignancy.
The phase 2 KEYNOTE-158 study comprised 98 women (median age 46 years) with advanced cervical cancer with progression after chemotherapy. All received pembrolizumab 200 mg every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision.
Most of the patients (83.7%) were positive for PD-L1. All had received at least one or more lines of chemotherapy before entering the study. The median follow-up was 10 months and the median treatment duration 2.9 months, with a range of 1 day-22 months.
By the study’s end, most patients (85.7%) had experienced disease progression or had died. Overall survival was poor even in the PD-L1-positive patients, with 82.9% experiencing progression or death. Overall mortality was 69.4% and 64.6%, respectively. However, PD-L1 patients did live longer, a median of 11 months, compared with 9.4 months in the entire cohort.
At 6 months, overall survival estimates were 75.2% in the total cohort and 80.2% in the PD-L1 patients; 12-month overall survival estimates were 41.4% and 47.3%, respectively.
However, among the 12 responders with PD-L1-postitive tumors, just one had died by the data cutoff, suggesting that longer treatment with pembrolizumab could be beneficial in this group.
“Responses typically occurred within 2.1 months and were durable, with a median duration of response that had not been reached after a median follow-up of 10.2 months and an estimated 90.9% of responses ongoing at 6 months” Dr. Chung and his colleagues wrote.
Adverse events were common (65.3%) with 12.2% graded as serious. But none were lethal, and only four patients discontinued pembrolizumab because of a treatment-related adverse event.
“Our results from an interim analysis of data from the phase II KEYNOTE-158 clinical trial show that pembrolizumab has promising antitumor activity in patients with previously treated advanced cervical cancer,” the researchers said. “These response rates are similar or superior to those observed with other treatment options in this setting.”
Pembrolizumab is now being evaluated in combination with concurrent chemoradiotherapy and with concurrent versus sequential chemoradiotherapy.
Merck & Co. sponsored the study.
SOURCE: Chung HC et al. J Clin Oncol. 2019 April 3. doi: 10.1200/JCO.18.01265.
FROM JOURNAL OF CLINICAL ONCOLOGY