Physicians should aim for hemoglobin A_1c levels between 7% and 8% in patients with type 2 diabetes, according to recommendations by the American College of Physicians.

But the guidance drew strong condemnation from diabetes and endocrinology organizations, which warned the higher target range could do more harm than good.

Evidence presented in the ACP statement shows the intensive therapy commonly used to reach the previous target of 6.5%-7% is likely either to increase risk of adverse cardiovascular and hypoglycemic events or have the same risk as less intensive therapy.

“Treatment with drugs targeted to 7%, in contrast to 8%, does not prevent heart attacks or strokes,” said Jack Ende, MD, president of the ACP. “But it does result in substantial harm, including low blood sugar, increased medication burden, and increased cost.”

The ACP recommends clinicians should talk with patients about creating personalized treatment plans based on the risks and benefits of different drugs, what the patients prefers, life expectancy, and cost of care.

 

Previous guidelines on reaching HbA_1c had been developed to reduce micro- and macrovascular complications; however, evidence that lowering levels also would lower events was not substantial enough to prove correct, as results were limited to reductions in less serious complications, according to Dr. Ende.

Physicians whose patients have HbA_1c levels less than 6.5% are advised to deintensify patients’ pharmacologic therapy by reducing the dosage, or taking a medication out completely.

New guidelines were based on evaluation of four drug-therapy trials, which encompassed long- and short-term effects of intensive pharmacological therapy compared with more moderate treatment.

 

In the Veterans Affairs Diabetes Trial, patients given intensive treatment found no reduction in major cardiovascular, microvascular events, or death in a 5.6-year follow-up. The intensive group did show fewer cardiovascular events after a longer period of time – 12 years – but this difference was small (8.6 events per 1,000 patient-years), according to the investigators.

Because of these long-term improvements, which were found across almost all studies evaluated, the ACP also recommends treatment of symptoms related to hyperglycemia instead of HbA_1c for patients with lower life expectancy, including those older than 80 years, those in nursing homes, and those with chronic conditions such as cancer or dementia.

“Setting stringent targets in these populations is not an optimal approach, and clinicians should instead focus on treating to reduce symptoms from both disease and treatment,” wrote Amir Qaseem, MD, PhD, vice president, Clinical Policy and Center for Evidence Reviews, ACP, and fellow investigators. “The ACP guidance statement in persons with a life expectancy less than 10 years is based on the small death or cardiovascular benefit of lower HbA_1c targets through at least 10 years, which should be balanced with treatment harms.”

The policy implications of these recommendations address physician performance evaluations, which the ACP recommends should not have a target HbA_1c level below 8%, nor any target level for patients with limited life expectancies.

But many diabetes organizations aren't embracing the new target levels. 

The ACP's recommendations could keep many diabetes patients from achieving all the benefits from long-term intensive glucose control, warned the Endocrine Society, the American Diabetes Association, the American Association for Clinical Endocrinologists, and the American Association of Diabetes Educators in a joint statement. And the ACP's recommendations overlook the positive impact that newer diabetes drugs have shown on morbidity and mortality in high-risk type 2 diabetes patients.

 

Coauthor Michael J. Barry, MD, reported receiving grants from the nonprofit Healthwise, outside of this statement.

All other authors reported no relevant financial disclosures.

[email protected]

 

Physicians should aim for hemoglobin A_1c levels between 7% and 8% in patients with type 2 diabetes, according to recommendations by the American College of Physicians.

But the guidance drew strong condemnation from diabetes and endocrinology organizations, which warned the higher target range could do more harm than good.

Evidence presented in the ACP statement shows the intensive therapy commonly used to reach the previous target of 6.5%-7% is likely either to increase risk of adverse cardiovascular and hypoglycemic events or have the same risk as less intensive therapy.

“Treatment with drugs targeted to 7%, in contrast to 8%, does not prevent heart attacks or strokes,” said Jack Ende, MD, president of the ACP. “But it does result in substantial harm, including low blood sugar, increased medication burden, and increased cost.”

The ACP recommends clinicians should talk with patients about creating personalized treatment plans based on the risks and benefits of different drugs, what the patients prefers, life expectancy, and cost of care.

 

Previous guidelines on reaching HbA_1c had been developed to reduce micro- and macrovascular complications; however, evidence that lowering levels also would lower events was not substantial enough to prove correct, as results were limited to reductions in less serious complications, according to Dr. Ende.

Physicians whose patients have HbA_1c levels less than 6.5% are advised to deintensify patients’ pharmacologic therapy by reducing the dosage, or taking a medication out completely.

New guidelines were based on evaluation of four drug-therapy trials, which encompassed long- and short-term effects of intensive pharmacological therapy compared with more moderate treatment.

 

In the Veterans Affairs Diabetes Trial, patients given intensive treatment found no reduction in major cardiovascular, microvascular events, or death in a 5.6-year follow-up. The intensive group did show fewer cardiovascular events after a longer period of time – 12 years – but this difference was small (8.6 events per 1,000 patient-years), according to the investigators.

Because of these long-term improvements, which were found across almost all studies evaluated, the ACP also recommends treatment of symptoms related to hyperglycemia instead of HbA_1c for patients with lower life expectancy, including those older than 80 years, those in nursing homes, and those with chronic conditions such as cancer or dementia.

“Setting stringent targets in these populations is not an optimal approach, and clinicians should instead focus on treating to reduce symptoms from both disease and treatment,” wrote Amir Qaseem, MD, PhD, vice president, Clinical Policy and Center for Evidence Reviews, ACP, and fellow investigators. “The ACP guidance statement in persons with a life expectancy less than 10 years is based on the small death or cardiovascular benefit of lower HbA_1c targets through at least 10 years, which should be balanced with treatment harms.”

The policy implications of these recommendations address physician performance evaluations, which the ACP recommends should not have a target HbA_1c level below 8%, nor any target level for patients with limited life expectancies.

But many diabetes organizations aren't embracing the new target levels. 

The ACP's recommendations could keep many diabetes patients from achieving all the benefits from long-term intensive glucose control, warned the Endocrine Society, the American Diabetes Association, the American Association for Clinical Endocrinologists, and the American Association of Diabetes Educators in a joint statement. And the ACP's recommendations overlook the positive impact that newer diabetes drugs have shown on morbidity and mortality in high-risk type 2 diabetes patients.

 

Coauthor Michael J. Barry, MD, reported receiving grants from the nonprofit Healthwise, outside of this statement.

All other authors reported no relevant financial disclosures.

[email protected]

 

Physicians should aim for hemoglobin A_1c levels between 7% and 8% in patients with type 2 diabetes, according to recommendations by the American College of Physicians.

But the guidance drew strong condemnation from diabetes and endocrinology organizations, which warned the higher target range could do more harm than good.

Evidence presented in the ACP statement shows the intensive therapy commonly used to reach the previous target of 6.5%-7% is likely either to increase risk of adverse cardiovascular and hypoglycemic events or have the same risk as less intensive therapy.

“Treatment with drugs targeted to 7%, in contrast to 8%, does not prevent heart attacks or strokes,” said Jack Ende, MD, president of the ACP. “But it does result in substantial harm, including low blood sugar, increased medication burden, and increased cost.”

The ACP recommends clinicians should talk with patients about creating personalized treatment plans based on the risks and benefits of different drugs, what the patients prefers, life expectancy, and cost of care.

 

Previous guidelines on reaching HbA_1c had been developed to reduce micro- and macrovascular complications; however, evidence that lowering levels also would lower events was not substantial enough to prove correct, as results were limited to reductions in less serious complications, according to Dr. Ende.

Physicians whose patients have HbA_1c levels less than 6.5% are advised to deintensify patients’ pharmacologic therapy by reducing the dosage, or taking a medication out completely.

New guidelines were based on evaluation of four drug-therapy trials, which encompassed long- and short-term effects of intensive pharmacological therapy compared with more moderate treatment.

 

In the Veterans Affairs Diabetes Trial, patients given intensive treatment found no reduction in major cardiovascular, microvascular events, or death in a 5.6-year follow-up. The intensive group did show fewer cardiovascular events after a longer period of time – 12 years – but this difference was small (8.6 events per 1,000 patient-years), according to the investigators.

Because of these long-term improvements, which were found across almost all studies evaluated, the ACP also recommends treatment of symptoms related to hyperglycemia instead of HbA_1c for patients with lower life expectancy, including those older than 80 years, those in nursing homes, and those with chronic conditions such as cancer or dementia.

“Setting stringent targets in these populations is not an optimal approach, and clinicians should instead focus on treating to reduce symptoms from both disease and treatment,” wrote Amir Qaseem, MD, PhD, vice president, Clinical Policy and Center for Evidence Reviews, ACP, and fellow investigators. “The ACP guidance statement in persons with a life expectancy less than 10 years is based on the small death or cardiovascular benefit of lower HbA_1c targets through at least 10 years, which should be balanced with treatment harms.”

The policy implications of these recommendations address physician performance evaluations, which the ACP recommends should not have a target HbA_1c level below 8%, nor any target level for patients with limited life expectancies.

But many diabetes organizations aren't embracing the new target levels. 

The ACP's recommendations could keep many diabetes patients from achieving all the benefits from long-term intensive glucose control, warned the Endocrine Society, the American Diabetes Association, the American Association for Clinical Endocrinologists, and the American Association of Diabetes Educators in a joint statement. And the ACP's recommendations overlook the positive impact that newer diabetes drugs have shown on morbidity and mortality in high-risk type 2 diabetes patients.

 

Coauthor Michael J. Barry, MD, reported receiving grants from the nonprofit Healthwise, outside of this statement.

All other authors reported no relevant financial disclosures.

[email protected]

 

Prophylactic haloperidol did not prevent delirium or improve survival in a placebo-controlled trial of 1,789 critically ill adults at 21 ICUs in the Netherlands.

Haloperidol is used routinely in ICUs to both treat and prevent delirium, which strikes up to half of ICU patients and is associated with prolonged mechanical ventilation, longer ICU and hospital stays, and increased mortality. Results of past studies have been mixed, with some showing a benefit for haloperidol in the ICU and others not.

“These findings do not support the use of prophylactic haloperidol in critically ill adults,” said the authors of a new study, led by Mark van den Boogaard, PhD, of Radboud University Medical Center, Nijmegen, the Netherlands (JAMA. 2018 Feb 20;319[7]:680-90).

The subjects were all expected to be in the ICU for at least 2 days, and were not delirious at baseline. The patients were randomly assigned to receive one of two treatments or a placebo three times daily, with 350 receiving 1 mg of haloperidol; 732 receiving 2 mg of haloperidol; and 707 receiving a 0.9% sodium chloride placebo. The 1-mg haloperidol arm was stopped early because of futility.

XiXinXing/ThinkStock

The ICUs also used nonpharmacologic interventions to prevent delirium, including early mobilization and noise reduction.

There was no statistically significant difference in survival at the primary endpoint of 28 days following entrance into the study. At that point, 83.3% of the patients who received 2-mg does of haloperidol and 82.7% of the of the subjects who received the placebo were alive (absolute difference 0.6%, 95% confidence interval –3.4% to 4.6%).

 

Prophylactic haloperidol had no effect on reducing the incidence of delirium, which was diagnosed in 33.3% of haloperidol subjects and 33.0% of placebo patients. Likewise, there were no significant differences between the groups in the number of delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay. The number of reported adverse events with treatment also did not differ significantly between the groups: 0.3% in the 2-mg haloperidol group versus 0.1% in the placebo arm.

The duration of prophylactic therapy was a median of 2 days, but a subgroup analysis in patients treated for more than 2 days also did not show any benefits with haloperidol.

“The study population included severely ill ICU adults whose brains may have been too seriously affected for haloperidol to exert a prophylactic effect, since in non-ICU adults, prophylactic haloperidol may have beneficial effects. But the subgroup of patients with a low severity of illness score also demonstrated no beneficial effects,” the investigators said.

Subjects were a mean of 66.6 years old; 61.4% were men. Most of the ICU admissions were urgent and for medical or surgical reasons.

This study was supported by ZonMw, the Netherlands Organization for Health Research and Development. Dr. van den Boogaard had no disclosures. One author reported grants and consultant and speaker fees from Pfizer, Merck, Astellas, and Gilead, among others.

[email protected]

SOURCE: van den Boogaard M, et al. JAMA. 2018 Feb 20;319(7):680-90.

 

Prophylactic haloperidol did not prevent delirium or improve survival in a placebo-controlled trial of 1,789 critically ill adults at 21 ICUs in the Netherlands.

Haloperidol is used routinely in ICUs to both treat and prevent delirium, which strikes up to half of ICU patients and is associated with prolonged mechanical ventilation, longer ICU and hospital stays, and increased mortality. Results of past studies have been mixed, with some showing a benefit for haloperidol in the ICU and others not.

“These findings do not support the use of prophylactic haloperidol in critically ill adults,” said the authors of a new study, led by Mark van den Boogaard, PhD, of Radboud University Medical Center, Nijmegen, the Netherlands (JAMA. 2018 Feb 20;319[7]:680-90).

The subjects were all expected to be in the ICU for at least 2 days, and were not delirious at baseline. The patients were randomly assigned to receive one of two treatments or a placebo three times daily, with 350 receiving 1 mg of haloperidol; 732 receiving 2 mg of haloperidol; and 707 receiving a 0.9% sodium chloride placebo. The 1-mg haloperidol arm was stopped early because of futility.

XiXinXing/ThinkStock

The ICUs also used nonpharmacologic interventions to prevent delirium, including early mobilization and noise reduction.

There was no statistically significant difference in survival at the primary endpoint of 28 days following entrance into the study. At that point, 83.3% of the patients who received 2-mg does of haloperidol and 82.7% of the of the subjects who received the placebo were alive (absolute difference 0.6%, 95% confidence interval –3.4% to 4.6%).

 

Prophylactic haloperidol had no effect on reducing the incidence of delirium, which was diagnosed in 33.3% of haloperidol subjects and 33.0% of placebo patients. Likewise, there were no significant differences between the groups in the number of delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay. The number of reported adverse events with treatment also did not differ significantly between the groups: 0.3% in the 2-mg haloperidol group versus 0.1% in the placebo arm.

The duration of prophylactic therapy was a median of 2 days, but a subgroup analysis in patients treated for more than 2 days also did not show any benefits with haloperidol.

“The study population included severely ill ICU adults whose brains may have been too seriously affected for haloperidol to exert a prophylactic effect, since in non-ICU adults, prophylactic haloperidol may have beneficial effects. But the subgroup of patients with a low severity of illness score also demonstrated no beneficial effects,” the investigators said.

Subjects were a mean of 66.6 years old; 61.4% were men. Most of the ICU admissions were urgent and for medical or surgical reasons.

This study was supported by ZonMw, the Netherlands Organization for Health Research and Development. Dr. van den Boogaard had no disclosures. One author reported grants and consultant and speaker fees from Pfizer, Merck, Astellas, and Gilead, among others.

[email protected]

SOURCE: van den Boogaard M, et al. JAMA. 2018 Feb 20;319(7):680-90.

 

Prophylactic haloperidol did not prevent delirium or improve survival in a placebo-controlled trial of 1,789 critically ill adults at 21 ICUs in the Netherlands.

Haloperidol is used routinely in ICUs to both treat and prevent delirium, which strikes up to half of ICU patients and is associated with prolonged mechanical ventilation, longer ICU and hospital stays, and increased mortality. Results of past studies have been mixed, with some showing a benefit for haloperidol in the ICU and others not.

“These findings do not support the use of prophylactic haloperidol in critically ill adults,” said the authors of a new study, led by Mark van den Boogaard, PhD, of Radboud University Medical Center, Nijmegen, the Netherlands (JAMA. 2018 Feb 20;319[7]:680-90).

The subjects were all expected to be in the ICU for at least 2 days, and were not delirious at baseline. The patients were randomly assigned to receive one of two treatments or a placebo three times daily, with 350 receiving 1 mg of haloperidol; 732 receiving 2 mg of haloperidol; and 707 receiving a 0.9% sodium chloride placebo. The 1-mg haloperidol arm was stopped early because of futility.

XiXinXing/ThinkStock

The ICUs also used nonpharmacologic interventions to prevent delirium, including early mobilization and noise reduction.

There was no statistically significant difference in survival at the primary endpoint of 28 days following entrance into the study. At that point, 83.3% of the patients who received 2-mg does of haloperidol and 82.7% of the of the subjects who received the placebo were alive (absolute difference 0.6%, 95% confidence interval –3.4% to 4.6%).

 

Prophylactic haloperidol had no effect on reducing the incidence of delirium, which was diagnosed in 33.3% of haloperidol subjects and 33.0% of placebo patients. Likewise, there were no significant differences between the groups in the number of delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay. The number of reported adverse events with treatment also did not differ significantly between the groups: 0.3% in the 2-mg haloperidol group versus 0.1% in the placebo arm.

The duration of prophylactic therapy was a median of 2 days, but a subgroup analysis in patients treated for more than 2 days also did not show any benefits with haloperidol.

“The study population included severely ill ICU adults whose brains may have been too seriously affected for haloperidol to exert a prophylactic effect, since in non-ICU adults, prophylactic haloperidol may have beneficial effects. But the subgroup of patients with a low severity of illness score also demonstrated no beneficial effects,” the investigators said.

Subjects were a mean of 66.6 years old; 61.4% were men. Most of the ICU admissions were urgent and for medical or surgical reasons.

This study was supported by ZonMw, the Netherlands Organization for Health Research and Development. Dr. van den Boogaard had no disclosures. One author reported grants and consultant and speaker fees from Pfizer, Merck, Astellas, and Gilead, among others.

[email protected]

SOURCE: van den Boogaard M, et al. JAMA. 2018 Feb 20;319(7):680-90.

 

Alterations in DNA damage response and repair genes may be useful biomarkers for response to immune checkpoint inhibitors in patients with urothelial carcinoma, investigators contend.

Among 60 patients with urothelial carcinoma in prospective trials of antibodies directed against the immune checkpoint inhibitor programmed cell death protein-1 and its ligand (PD-1/PD-L1), 28 (47%) had a damage response and repair (DDR) gene of any kind, and 15 (25%) had DDR mutations that are thought to be deleterious. Patients with any DDR mutations were more likely to have a clinical response to anti–PD-1/PD-L1 therapy, especially patients with likely deleterious mutations, reported Jonathan E. Rosenberg, MD and colleagues from Memorial Sloan Kettering Cancer Center, New York.

In addition to higher objective response rates, patients with DDR gene alterations had longer progression-free survival (PFS) and better overall survival (OS) than did patients with wild-type DDR genes, they noted in a study published in the Journal of Clinical Oncology.

“This study shows that patients with DDR gene alterations are more likely to experience objective responses, longer PFS, and improved OS than patients with wild-type DDR genes. Whether the association is predictive or prognostic should be investigated further in larger data sets from randomized studies that have led to the FDA [Food and Drug Administration] approval of several anti–PD-1/PD-L1 agents,” they wrote.

 

Previous studies have shown that in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy, alterations in DDR genes are associated with elevations in mutational load, increases in tumor-infiltrating lymphocytes, and improved survival, the investigators noted.

To see whether DDR gene alterations were also associated with better outcomes with PD-1/PD-L1 inhibitors, the investigators examined tumor genomes and survival data from patients with metastatic urothelial carcinoma who were enrolled in prospective clinical trials of anti–PD-1/PD-L1 monotherapy. The agents used in the trials were atezolizumab(Tecentriq) and nivolumab(Opdivo).

The investigators correlated the presence of DDR gene alterations with best objective responses according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1.

They found that the presence of any DDR gene alteration was associated with higher response rates, compared with wild-type DDR (67.9% vs. 18.8%; P less than .001).

 

Additionally, patients whose tumors contained known or likely deleterious DDR mutations were significantly more likely to respond than were patients with either mutations of uncertain significance or wild-type DDR (overall response rate 80%, 54%, and 19%, respectively; P less than .001).

Patients with deleterious DDR alterations had significantly better PFS than patients without detectable alterations (hazard ratio, 0.20; P less than .001); DDR mutations of unknown significance trended toward better PFS (HR, 0.44), but was not statistically significant.

Median OS was not reached for patients with deleterious DDR gene mutations, with 71.5% alive at 12 months, compared with a median of 23 months for patients with alterations of unknown significance, and 9.3 months for patients with wild-type DDR.

In multivariable analysis, independent predictors for worse OS included hemoglobin levels below 10 g/dL and visceral metastases. In contrast, any versus no detectable DDR gene alterations was associated with better OS (HR, 0.27; P = .001).

 

The investigators are planning a prospective evaluation of the potential association between DDR alterations and outcomes in a phase 2 study of atezolizumab with or without bevacizumab(Avastin) in patients with metastatic urothelial carcinoma.

“Additional investigation is warranted to evaluate the mechanisms that link DDR alterations beyond MMR [DNA mismatch repair], [mutational] and neoantigen load, and immunotherapy response. If validated in other studies, DDR alterations may represent a useful predictive biomarker of response to anti–PD-1/PD-L1 in urothelial carcinoma,” they concluded.

The study was funded by Roche, Genentech, Bristol-Myers Squibb, and a National Cancer Institute Cancer Center support grant. Dr. Rosenberg disclosed stock or other ownership with Merck and Illumina, and consulting/advisory roles and travel support from Roche, Genentech, Bayer, and others. Multiple coauthors reported similar relationships.

[email protected]

SOURCE: Rosenberg JE et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.7740.

 

Alterations in DNA damage response and repair genes may be useful biomarkers for response to immune checkpoint inhibitors in patients with urothelial carcinoma, investigators contend.

Among 60 patients with urothelial carcinoma in prospective trials of antibodies directed against the immune checkpoint inhibitor programmed cell death protein-1 and its ligand (PD-1/PD-L1), 28 (47%) had a damage response and repair (DDR) gene of any kind, and 15 (25%) had DDR mutations that are thought to be deleterious. Patients with any DDR mutations were more likely to have a clinical response to anti–PD-1/PD-L1 therapy, especially patients with likely deleterious mutations, reported Jonathan E. Rosenberg, MD and colleagues from Memorial Sloan Kettering Cancer Center, New York.

In addition to higher objective response rates, patients with DDR gene alterations had longer progression-free survival (PFS) and better overall survival (OS) than did patients with wild-type DDR genes, they noted in a study published in the Journal of Clinical Oncology.

“This study shows that patients with DDR gene alterations are more likely to experience objective responses, longer PFS, and improved OS than patients with wild-type DDR genes. Whether the association is predictive or prognostic should be investigated further in larger data sets from randomized studies that have led to the FDA [Food and Drug Administration] approval of several anti–PD-1/PD-L1 agents,” they wrote.

 

Previous studies have shown that in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy, alterations in DDR genes are associated with elevations in mutational load, increases in tumor-infiltrating lymphocytes, and improved survival, the investigators noted.

To see whether DDR gene alterations were also associated with better outcomes with PD-1/PD-L1 inhibitors, the investigators examined tumor genomes and survival data from patients with metastatic urothelial carcinoma who were enrolled in prospective clinical trials of anti–PD-1/PD-L1 monotherapy. The agents used in the trials were atezolizumab(Tecentriq) and nivolumab(Opdivo).

The investigators correlated the presence of DDR gene alterations with best objective responses according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1.

They found that the presence of any DDR gene alteration was associated with higher response rates, compared with wild-type DDR (67.9% vs. 18.8%; P less than .001).

 

Additionally, patients whose tumors contained known or likely deleterious DDR mutations were significantly more likely to respond than were patients with either mutations of uncertain significance or wild-type DDR (overall response rate 80%, 54%, and 19%, respectively; P less than .001).

Patients with deleterious DDR alterations had significantly better PFS than patients without detectable alterations (hazard ratio, 0.20; P less than .001); DDR mutations of unknown significance trended toward better PFS (HR, 0.44), but was not statistically significant.

Median OS was not reached for patients with deleterious DDR gene mutations, with 71.5% alive at 12 months, compared with a median of 23 months for patients with alterations of unknown significance, and 9.3 months for patients with wild-type DDR.

In multivariable analysis, independent predictors for worse OS included hemoglobin levels below 10 g/dL and visceral metastases. In contrast, any versus no detectable DDR gene alterations was associated with better OS (HR, 0.27; P = .001).

 

The investigators are planning a prospective evaluation of the potential association between DDR alterations and outcomes in a phase 2 study of atezolizumab with or without bevacizumab(Avastin) in patients with metastatic urothelial carcinoma.

“Additional investigation is warranted to evaluate the mechanisms that link DDR alterations beyond MMR [DNA mismatch repair], [mutational] and neoantigen load, and immunotherapy response. If validated in other studies, DDR alterations may represent a useful predictive biomarker of response to anti–PD-1/PD-L1 in urothelial carcinoma,” they concluded.

The study was funded by Roche, Genentech, Bristol-Myers Squibb, and a National Cancer Institute Cancer Center support grant. Dr. Rosenberg disclosed stock or other ownership with Merck and Illumina, and consulting/advisory roles and travel support from Roche, Genentech, Bayer, and others. Multiple coauthors reported similar relationships.

[email protected]

SOURCE: Rosenberg JE et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.7740.

 

Alterations in DNA damage response and repair genes may be useful biomarkers for response to immune checkpoint inhibitors in patients with urothelial carcinoma, investigators contend.

Among 60 patients with urothelial carcinoma in prospective trials of antibodies directed against the immune checkpoint inhibitor programmed cell death protein-1 and its ligand (PD-1/PD-L1), 28 (47%) had a damage response and repair (DDR) gene of any kind, and 15 (25%) had DDR mutations that are thought to be deleterious. Patients with any DDR mutations were more likely to have a clinical response to anti–PD-1/PD-L1 therapy, especially patients with likely deleterious mutations, reported Jonathan E. Rosenberg, MD and colleagues from Memorial Sloan Kettering Cancer Center, New York.

In addition to higher objective response rates, patients with DDR gene alterations had longer progression-free survival (PFS) and better overall survival (OS) than did patients with wild-type DDR genes, they noted in a study published in the Journal of Clinical Oncology.

“This study shows that patients with DDR gene alterations are more likely to experience objective responses, longer PFS, and improved OS than patients with wild-type DDR genes. Whether the association is predictive or prognostic should be investigated further in larger data sets from randomized studies that have led to the FDA [Food and Drug Administration] approval of several anti–PD-1/PD-L1 agents,” they wrote.

 

Previous studies have shown that in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy, alterations in DDR genes are associated with elevations in mutational load, increases in tumor-infiltrating lymphocytes, and improved survival, the investigators noted.

To see whether DDR gene alterations were also associated with better outcomes with PD-1/PD-L1 inhibitors, the investigators examined tumor genomes and survival data from patients with metastatic urothelial carcinoma who were enrolled in prospective clinical trials of anti–PD-1/PD-L1 monotherapy. The agents used in the trials were atezolizumab(Tecentriq) and nivolumab(Opdivo).

The investigators correlated the presence of DDR gene alterations with best objective responses according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1.

They found that the presence of any DDR gene alteration was associated with higher response rates, compared with wild-type DDR (67.9% vs. 18.8%; P less than .001).

 

Additionally, patients whose tumors contained known or likely deleterious DDR mutations were significantly more likely to respond than were patients with either mutations of uncertain significance or wild-type DDR (overall response rate 80%, 54%, and 19%, respectively; P less than .001).

Patients with deleterious DDR alterations had significantly better PFS than patients without detectable alterations (hazard ratio, 0.20; P less than .001); DDR mutations of unknown significance trended toward better PFS (HR, 0.44), but was not statistically significant.

Median OS was not reached for patients with deleterious DDR gene mutations, with 71.5% alive at 12 months, compared with a median of 23 months for patients with alterations of unknown significance, and 9.3 months for patients with wild-type DDR.

In multivariable analysis, independent predictors for worse OS included hemoglobin levels below 10 g/dL and visceral metastases. In contrast, any versus no detectable DDR gene alterations was associated with better OS (HR, 0.27; P = .001).

 

The investigators are planning a prospective evaluation of the potential association between DDR alterations and outcomes in a phase 2 study of atezolizumab with or without bevacizumab(Avastin) in patients with metastatic urothelial carcinoma.

“Additional investigation is warranted to evaluate the mechanisms that link DDR alterations beyond MMR [DNA mismatch repair], [mutational] and neoantigen load, and immunotherapy response. If validated in other studies, DDR alterations may represent a useful predictive biomarker of response to anti–PD-1/PD-L1 in urothelial carcinoma,” they concluded.

The study was funded by Roche, Genentech, Bristol-Myers Squibb, and a National Cancer Institute Cancer Center support grant. Dr. Rosenberg disclosed stock or other ownership with Merck and Illumina, and consulting/advisory roles and travel support from Roche, Genentech, Bayer, and others. Multiple coauthors reported similar relationships.

[email protected]

SOURCE: Rosenberg JE et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.7740.

 

MAUI, HAWAII – Two recent Scandinavian studies highlight the considerable room for improvement that exists in psoriatic arthritis outcomes, according to speakers at the 2018 Rheumatology Winter Clinical Symposium.

“We’re not doing so well. I think that in general, if you think of the treatments that we have and the treat-to-target approach, psoriatic arthritis lags behind rheumatoid arthritis, maybe by a decade,” declared Arthur Kavanaugh, MD, program director for the symposium and professor of medicine at the University of California, San Diego.

Bruce Jancin/Frontline Medical News

He was a coauthor of a Norwegian cross-sectional study of 141 psoriatic arthritis patients assessed during 2013-2014 by investigators who used an array of disease activity measures. Among the findings: The group’s median Disease Activity index for PSoriatic Arthritis (DAPSA) score was 14.5, the Disease Activity Score for 28 joints using erythrocyte sedimentation rate was 3.2, and – most tellingly – only 22.9% of them fulfilled the criteria for minimal disease activity (MDA), which requires very low or no activity in five of seven domains of psoriatic arthritis. Moreover, 42 patients weren’t on any disease-modifying antirheumatic drugs whatsoever (J Rheumatol. 2017 Apr;44[4]:431-6).

“If you say that MDA is remission, a 23% remission rate is not good enough. And there are some people who are not on treatment. So I think we’re still seeing a lag in psoriatic arthritis. We’re not treating it as aggressively as we are rheumatoid arthritis,” said Dr. Kavanaugh, director of the Center for Innovative Therapy in the university’s division of rheumatology, allergy, and immunology.

 

“This study was a surprise,” he continued. “I think it’s like rheumatoid arthritis was years ago. If you asked docs how they were doing, they would say, ‘My patients are doing great!’ But then you go to the office and measure the patients and it’s like, ‘Well, not so much.’ ”

Another speaker, Eric M. Ruderman, MD, concurred.

“If you say 23% of your rheumatoid arthritis patients are in remission, you’d have to say, ‘I’m not doing a very good job,’ because we’re getting 50%-60% rates of remission these days if you really push medications. And we have good drugs for psoriatic arthritis, too, but I don’t think we’re pushing as hard,” said Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University in Chicago.

That being said, it’s also clear that rheumatologists aren’t doing as well in managing psoriatic arthritis as dermatologists are with psoriasis, where skin clearance or almost-clear rates unimaginable just a few years ago are now routinely attainable, he added.

“In dermatology they’re getting better and better and better and better with each successive new cytokine target. We’re not. The ACR responses with risankizumab [an investigational anti-interleukin-23 p19 inhibitor] are very much like we saw with the tumor necrosis factor inhibitors. The interleukin-12/23 inhibitor responses are very much like we’ve seen with the interleukin-17 inhibitors. So each successive improvement in getting skin disease under control hasn’t really gotten us very much further with joint disease. I don’t know that we’ve cracked that yet,” Dr. Ruderman said.

 

Another recent Scandinavian psoriatic arthritis study that particularly impressed Dr. Kavanaugh was a Danish nationwide cohort registry study that shed new light upon the burdens imposed by the disease in terms of societal costs, comorbid conditions, and disability. The subjects were 10,525 Danes with psoriatic arthritis and nearly 21,000 matched general population controls evaluated during the period from 5 years prior to diagnosis of psoriatic arthritis through 10 years after.

The costs were impressive: an average of 10,641 euros more per year per psoriatic arthritis patient, compared with controls, during the 10-year period following diagnosis, with most of the difference attributed to higher health care costs and forgone earnings due to unemployment, early retirement, or receipt of a disability pension.

At the time of their diagnosis, psoriatic arthritis patients had a significantly higher burden of comorbid conditions than did controls, including a 1.7-fold higher likelihood of cardiovascular disease, a 1.73-fold increase in risk for pulmonary disease, a 2.03-fold greater likelihood of infectious diseases, and a 1.94-fold increased risk of hematologic disorders.

Five years prior to diagnosis of psoriatic arthritis, affected individuals were 1.36-fold more likely than were controls to be on a disability pension. At diagnosis, they were 1.6-fold more likely. Ten years after diagnosis of psoriatic arthritis, they were 2.69-fold more likely to be on a disability pension. Indeed, by that point, 21.8% of Danish psoriatic arthritis patients were on disability (Ann Rheum Dis. 2017 Sep;76([9]:1495-1501).

 

Health care costs began rising steeply at least 3 years prior to diagnosis of psoriatic arthritis, as well.

“We need to do better with our psoriatic arthritis patients. I think this beautiful study is a call to attention for us to make sure that we’re identifying people with psoriatic arthritis as early as we can,” Dr. Kavanaugh said.

As for the treat-to-target approach that has become so widespread in the management of rheumatoid arthritis, it has gained a toehold in the treatment of psoriatic arthritis. Dr. Kavanaugh was a member of an international task force that recently published treat-to-target recommendations for psoriatic arthritis and axial spondyloarthritis (Ann Rheum Dis. 2018 Jan;77[1]:3-17).

The recommendation for defining the target in psoriatic arthritis was to use the DAPSA or MDA. However, this was a controversial recommendation because of the dearth of evidence. It passed with 51.6% of the task force votes and a level of agreement of 7.9 on a 0-10 scale.

Despite the demonstrable room for improvement in psoriatic arthritis treatment outcomes, better times are likely to be coming for affected patients. A record-breaking number of publications on psoriatic arthritis was published in 2017, and three additional drugs received marketing approval for the disease.

Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.

 

[email protected]

 

MAUI, HAWAII – Two recent Scandinavian studies highlight the considerable room for improvement that exists in psoriatic arthritis outcomes, according to speakers at the 2018 Rheumatology Winter Clinical Symposium.

“We’re not doing so well. I think that in general, if you think of the treatments that we have and the treat-to-target approach, psoriatic arthritis lags behind rheumatoid arthritis, maybe by a decade,” declared Arthur Kavanaugh, MD, program director for the symposium and professor of medicine at the University of California, San Diego.

Bruce Jancin/Frontline Medical News

He was a coauthor of a Norwegian cross-sectional study of 141 psoriatic arthritis patients assessed during 2013-2014 by investigators who used an array of disease activity measures. Among the findings: The group’s median Disease Activity index for PSoriatic Arthritis (DAPSA) score was 14.5, the Disease Activity Score for 28 joints using erythrocyte sedimentation rate was 3.2, and – most tellingly – only 22.9% of them fulfilled the criteria for minimal disease activity (MDA), which requires very low or no activity in five of seven domains of psoriatic arthritis. Moreover, 42 patients weren’t on any disease-modifying antirheumatic drugs whatsoever (J Rheumatol. 2017 Apr;44[4]:431-6).

“If you say that MDA is remission, a 23% remission rate is not good enough. And there are some people who are not on treatment. So I think we’re still seeing a lag in psoriatic arthritis. We’re not treating it as aggressively as we are rheumatoid arthritis,” said Dr. Kavanaugh, director of the Center for Innovative Therapy in the university’s division of rheumatology, allergy, and immunology.

 

“This study was a surprise,” he continued. “I think it’s like rheumatoid arthritis was years ago. If you asked docs how they were doing, they would say, ‘My patients are doing great!’ But then you go to the office and measure the patients and it’s like, ‘Well, not so much.’ ”

Another speaker, Eric M. Ruderman, MD, concurred.

“If you say 23% of your rheumatoid arthritis patients are in remission, you’d have to say, ‘I’m not doing a very good job,’ because we’re getting 50%-60% rates of remission these days if you really push medications. And we have good drugs for psoriatic arthritis, too, but I don’t think we’re pushing as hard,” said Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University in Chicago.

That being said, it’s also clear that rheumatologists aren’t doing as well in managing psoriatic arthritis as dermatologists are with psoriasis, where skin clearance or almost-clear rates unimaginable just a few years ago are now routinely attainable, he added.

“In dermatology they’re getting better and better and better and better with each successive new cytokine target. We’re not. The ACR responses with risankizumab [an investigational anti-interleukin-23 p19 inhibitor] are very much like we saw with the tumor necrosis factor inhibitors. The interleukin-12/23 inhibitor responses are very much like we’ve seen with the interleukin-17 inhibitors. So each successive improvement in getting skin disease under control hasn’t really gotten us very much further with joint disease. I don’t know that we’ve cracked that yet,” Dr. Ruderman said.

 

Another recent Scandinavian psoriatic arthritis study that particularly impressed Dr. Kavanaugh was a Danish nationwide cohort registry study that shed new light upon the burdens imposed by the disease in terms of societal costs, comorbid conditions, and disability. The subjects were 10,525 Danes with psoriatic arthritis and nearly 21,000 matched general population controls evaluated during the period from 5 years prior to diagnosis of psoriatic arthritis through 10 years after.

The costs were impressive: an average of 10,641 euros more per year per psoriatic arthritis patient, compared with controls, during the 10-year period following diagnosis, with most of the difference attributed to higher health care costs and forgone earnings due to unemployment, early retirement, or receipt of a disability pension.

At the time of their diagnosis, psoriatic arthritis patients had a significantly higher burden of comorbid conditions than did controls, including a 1.7-fold higher likelihood of cardiovascular disease, a 1.73-fold increase in risk for pulmonary disease, a 2.03-fold greater likelihood of infectious diseases, and a 1.94-fold increased risk of hematologic disorders.

Five years prior to diagnosis of psoriatic arthritis, affected individuals were 1.36-fold more likely than were controls to be on a disability pension. At diagnosis, they were 1.6-fold more likely. Ten years after diagnosis of psoriatic arthritis, they were 2.69-fold more likely to be on a disability pension. Indeed, by that point, 21.8% of Danish psoriatic arthritis patients were on disability (Ann Rheum Dis. 2017 Sep;76([9]:1495-1501).

 

Health care costs began rising steeply at least 3 years prior to diagnosis of psoriatic arthritis, as well.

“We need to do better with our psoriatic arthritis patients. I think this beautiful study is a call to attention for us to make sure that we’re identifying people with psoriatic arthritis as early as we can,” Dr. Kavanaugh said.

As for the treat-to-target approach that has become so widespread in the management of rheumatoid arthritis, it has gained a toehold in the treatment of psoriatic arthritis. Dr. Kavanaugh was a member of an international task force that recently published treat-to-target recommendations for psoriatic arthritis and axial spondyloarthritis (Ann Rheum Dis. 2018 Jan;77[1]:3-17).

The recommendation for defining the target in psoriatic arthritis was to use the DAPSA or MDA. However, this was a controversial recommendation because of the dearth of evidence. It passed with 51.6% of the task force votes and a level of agreement of 7.9 on a 0-10 scale.

Despite the demonstrable room for improvement in psoriatic arthritis treatment outcomes, better times are likely to be coming for affected patients. A record-breaking number of publications on psoriatic arthritis was published in 2017, and three additional drugs received marketing approval for the disease.

Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.

 

[email protected]

 

MAUI, HAWAII – Two recent Scandinavian studies highlight the considerable room for improvement that exists in psoriatic arthritis outcomes, according to speakers at the 2018 Rheumatology Winter Clinical Symposium.

“We’re not doing so well. I think that in general, if you think of the treatments that we have and the treat-to-target approach, psoriatic arthritis lags behind rheumatoid arthritis, maybe by a decade,” declared Arthur Kavanaugh, MD, program director for the symposium and professor of medicine at the University of California, San Diego.

Bruce Jancin/Frontline Medical News

He was a coauthor of a Norwegian cross-sectional study of 141 psoriatic arthritis patients assessed during 2013-2014 by investigators who used an array of disease activity measures. Among the findings: The group’s median Disease Activity index for PSoriatic Arthritis (DAPSA) score was 14.5, the Disease Activity Score for 28 joints using erythrocyte sedimentation rate was 3.2, and – most tellingly – only 22.9% of them fulfilled the criteria for minimal disease activity (MDA), which requires very low or no activity in five of seven domains of psoriatic arthritis. Moreover, 42 patients weren’t on any disease-modifying antirheumatic drugs whatsoever (J Rheumatol. 2017 Apr;44[4]:431-6).

“If you say that MDA is remission, a 23% remission rate is not good enough. And there are some people who are not on treatment. So I think we’re still seeing a lag in psoriatic arthritis. We’re not treating it as aggressively as we are rheumatoid arthritis,” said Dr. Kavanaugh, director of the Center for Innovative Therapy in the university’s division of rheumatology, allergy, and immunology.

 

“This study was a surprise,” he continued. “I think it’s like rheumatoid arthritis was years ago. If you asked docs how they were doing, they would say, ‘My patients are doing great!’ But then you go to the office and measure the patients and it’s like, ‘Well, not so much.’ ”

Another speaker, Eric M. Ruderman, MD, concurred.

“If you say 23% of your rheumatoid arthritis patients are in remission, you’d have to say, ‘I’m not doing a very good job,’ because we’re getting 50%-60% rates of remission these days if you really push medications. And we have good drugs for psoriatic arthritis, too, but I don’t think we’re pushing as hard,” said Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University in Chicago.

That being said, it’s also clear that rheumatologists aren’t doing as well in managing psoriatic arthritis as dermatologists are with psoriasis, where skin clearance or almost-clear rates unimaginable just a few years ago are now routinely attainable, he added.

“In dermatology they’re getting better and better and better and better with each successive new cytokine target. We’re not. The ACR responses with risankizumab [an investigational anti-interleukin-23 p19 inhibitor] are very much like we saw with the tumor necrosis factor inhibitors. The interleukin-12/23 inhibitor responses are very much like we’ve seen with the interleukin-17 inhibitors. So each successive improvement in getting skin disease under control hasn’t really gotten us very much further with joint disease. I don’t know that we’ve cracked that yet,” Dr. Ruderman said.

 

Another recent Scandinavian psoriatic arthritis study that particularly impressed Dr. Kavanaugh was a Danish nationwide cohort registry study that shed new light upon the burdens imposed by the disease in terms of societal costs, comorbid conditions, and disability. The subjects were 10,525 Danes with psoriatic arthritis and nearly 21,000 matched general population controls evaluated during the period from 5 years prior to diagnosis of psoriatic arthritis through 10 years after.

The costs were impressive: an average of 10,641 euros more per year per psoriatic arthritis patient, compared with controls, during the 10-year period following diagnosis, with most of the difference attributed to higher health care costs and forgone earnings due to unemployment, early retirement, or receipt of a disability pension.

At the time of their diagnosis, psoriatic arthritis patients had a significantly higher burden of comorbid conditions than did controls, including a 1.7-fold higher likelihood of cardiovascular disease, a 1.73-fold increase in risk for pulmonary disease, a 2.03-fold greater likelihood of infectious diseases, and a 1.94-fold increased risk of hematologic disorders.

Five years prior to diagnosis of psoriatic arthritis, affected individuals were 1.36-fold more likely than were controls to be on a disability pension. At diagnosis, they were 1.6-fold more likely. Ten years after diagnosis of psoriatic arthritis, they were 2.69-fold more likely to be on a disability pension. Indeed, by that point, 21.8% of Danish psoriatic arthritis patients were on disability (Ann Rheum Dis. 2017 Sep;76([9]:1495-1501).

 

Health care costs began rising steeply at least 3 years prior to diagnosis of psoriatic arthritis, as well.

“We need to do better with our psoriatic arthritis patients. I think this beautiful study is a call to attention for us to make sure that we’re identifying people with psoriatic arthritis as early as we can,” Dr. Kavanaugh said.

As for the treat-to-target approach that has become so widespread in the management of rheumatoid arthritis, it has gained a toehold in the treatment of psoriatic arthritis. Dr. Kavanaugh was a member of an international task force that recently published treat-to-target recommendations for psoriatic arthritis and axial spondyloarthritis (Ann Rheum Dis. 2018 Jan;77[1]:3-17).

The recommendation for defining the target in psoriatic arthritis was to use the DAPSA or MDA. However, this was a controversial recommendation because of the dearth of evidence. It passed with 51.6% of the task force votes and a level of agreement of 7.9 on a 0-10 scale.

Despite the demonstrable room for improvement in psoriatic arthritis treatment outcomes, better times are likely to be coming for affected patients. A record-breaking number of publications on psoriatic arthritis was published in 2017, and three additional drugs received marketing approval for the disease.

Dr. Kavanaugh and Dr. Ruderman reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.

 

[email protected]

 

The child is well-known in the halls in which state bureaucrats oversee health care for millions of Californians – not by name, but by a number: $21 million.

His medications alone cost state taxpayers that much in a single year, not including other health care. The boy, whose identity has not been released, was California’s most expensive Medicaid patient in recent years. His case was singled out in a tweet last year by the state’s top health care official to highlight the public insurance program’s extraordinary obligations as a backstop for low-income patients.

How on earth can a single child’s treatment cost that much? The answer: He has hemophilia and needs large quantities of a pricey drug – known as clotting factor – that makes blood coagulate.

Hemophilia drugs are among the most costly drugs in the nation, and taxpayers are footing the bill for many patients on Medicaid who could never afford them on their own. Officials in California and other states are doing what they can to manage the costs, but it’s a daunting task that highlights the complexity and secrecy of prescription drug pricing.

 

Kaiser Health News is examining how America has become a “Medicaid Nation” – where tens of millions of poor and disabled people now rely on the support of the federal and state insurance program. Hemophilia is one those diseases that helps explain its burgeoning cost.

Medications for hemophilia are crucial to patients – overwhelmingly male – with the rare genetic condition that prevents clotting and puts them at great risk of bleeding to death, even from a minor injury. There is no question the drugs prolong and save lives, and state officials are not arguing that they should be withheld.

“It’s a highly vulnerable population,” said Ken Kizer, a veteran federal and state health administrator who formerly oversaw Medi-Cal, California’s version of Medicaid. “If anyone has seen a hemophiliac in crisis, you’re not going to say no.”

But drugmakers profit handsomely, competing vigorously for the limited number of patients.

The U.S. hemophilia market, which serves about 20,000 patients, is worth $4.6 billion a year, according to AllianceBernstein, a research and investment firm.

 

“There are millions being made out there on these kids – it’s a huge business,” said Doris Quon, MD, medical director of the Orthopaedic Hemophilia Treatment Center at the University of California, Los Angeles.

Contributing to the costs is the fact that there is no cure for hemophilia and no cheaper substitute for blood factor. Factor may be prescribed at high doses for a lifetime, even more so when a patient has an injury or complications.

Nationwide, a third of adults and children living with hemophilia are covered by Medicaid. And the Medicaid program’s three most expensive drugs per prescription are for hemophilia, according to an analysis by the Kaiser Family Foundation. (California Healthline is produced by Kaiser Health News, an editorially independent publication of the foundation.)

In 2015 alone, Medicaid paid about $353 million for prescriptions of Advate, the most commonly prescribed blood-clotting medication for hemophilia – a 273% increase from 2011.

Generally speaking, the price of hemophilia drugs rise as rival drugs hit the market. But, in addition, doctors are prescribing ever more clotting factor for prevention of joint-damaging bleeds and for improved long-term health. The increase in the cost of Advate, for example, was nearly all attributed to increased use.

Tab for 145 kids: $195 million

The California boy whose drugs cost $21 million in a single year was an extreme case, and the circumstances of his care have not been disclosed because of confidentiality protections. Still, medications to treat hemophilia on average annual cost more than $270,000 per patient, according to a 2015 Express Scripts report, and they can easily soar past $1 million annually.

In contrast to more common diseases like hepatitis C, hemophilia treatment is not a state “budget buster” per se: about 4,000 patients live in California. About 1,100 of them are covered by Medi-Cal or two other government-funded programs for chronically ill children in California, according to Jennifer Kent, director of the state Department of Health Care Services and author of last year’s tweet. But the amount of money spent per person dwarfs that spent on people with other serious diseases.

One Stanford University study of 34,000 California kids with severe chronic diseases found that the tiny portion of children who needed blood factor accounted for 41% of the state’s outpatient drug spending on this entire patient population. About $195 million was spent on just 145 kids over a 3-year period, although some of that money came back to the state in rebates from drug companies – a portion of the cost that Medicaid can recoup after purchase.

Caitlin Carroll, director of public affairs for PhRMA, the pharmaceutical industry lobbying group, said high development costs and the complicated and lengthy manufacturing process play a role in how hemophilia drugs are priced. She added that federally mandated rebates significantly reduce the cost of blood factor. They amount to 17% of the average manufacturer price per unit.

Manufacturers also note that some newer and more expensive hemophilia drugs last longer and do not need to be administered as frequently, so they can prove less costly to payers overall.

Even so, some patients require a monumental investment to survive.
 

 

‘Extremely fortunate’

Colleen Tuite’s son Kevin, a 7-year-old, has severe hemophilia with a complication known as an inhibitor – an antibody that makes his regular blood-factor infusions less effective. Inhibitors can dramatically increase the cost of care, because massive doses of blood factor or expensive, specialized blood products known as bypassing agents may be needed.

Ms. Tuite and her husband initially were Kevin’s foster parents, then adopted the boy as a toddler. Because he has been a foster child, Kevin qualifies for Medi-Cal until he is 26.

The Monrovia, Calif., family also has private health insurance, which pays for about half of Kevin’s medical bills. These can run upward of $200,000 per month, Ms. Tuite said.

“We definitely would not have been able to adopt him without the help of Medi-Cal,” Ms. Tuite said. “We’ve been extremely fortunate.”

With the support of drug manufacturers and hemophilia advocacy groups, patients and their families have significant political clout. Some experts say they also have a moral claim on public resources: In the early days of the AIDS epidemic, thousands of the nation’s hemophilia patients died after they contracted HIV through transfusions before the virus was eliminated from the blood supply.

State health officials say the costs of hemophilia are hard to anticipate and control, even with rebates.

“We do a really aggressive job of collecting rebates on our pharmacy costs,” said Ms. Kent, California’s top Medicaid official. “But there’s just not any way around blood factor. It is just a very, very expensive product. It’s nonnegotiable for people that require it.”

In 2016, California’s Medicaid program paid at least $205 million for medications used to treat hemophilia, according to a Kaiser Health News analysis of federal Medicaid data. That figure doesn’t account for the federal rebates.

States can negotiate “supplemental” rebates with drugmakers for individual medications – but those must be kept secret under federal and some state laws. Such secrecy is becoming increasingly controversial as states continue to confront spiraling drug prices.

 

Limited options for states

In 2016, Pfizer sued Texas’ state health agency for giving data on the drug company’s supplemental Medicaid rebates to state lawmakers who requested it. The drugmaker alleged that releasing the confidential information would undermine the company’s competitiveness and give away trade secrets, and warned that the discounts it gave Texas could disappear.

In early October, a judge ruled that lawmakers should be able to obtain some of that data, noting dryly that “in Pfizer’s view, legislators are not necessary to carry out the state’s Medicaid program.”

Instead of seeking additional rebates from manufacturers for blood factor, some states, including Washington and Oregon, have chosen to require patients to get their blood factor from federally designated Hemophilia Treatment Centers only. That allows state Medicaid programs to take advantage of a federal drug-discount program known as “340B.”

However, officials in California said they studied that option and determined it wouldn’t save them any more money than the rebates they negotiate with drugmakers.

Whatever their approach, state health officials say they are struggling against forces they are nearly powerless to change.

“There aren’t a lot of options available to Medicaid programs in terms of controlling costs, because we don’t set the initial costs,” said Deborah Weston, pharmacy program manager for Oregon’s Medicaid program.
 

Kaiser Health News data correspondent Sydney Lupkin contributed to this report. KHN’s coverage of these topics is supported by Laura and John Arnold Foundation and Heising-Simons Foundation. This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

 

The child is well-known in the halls in which state bureaucrats oversee health care for millions of Californians – not by name, but by a number: $21 million.

His medications alone cost state taxpayers that much in a single year, not including other health care. The boy, whose identity has not been released, was California’s most expensive Medicaid patient in recent years. His case was singled out in a tweet last year by the state’s top health care official to highlight the public insurance program’s extraordinary obligations as a backstop for low-income patients.

How on earth can a single child’s treatment cost that much? The answer: He has hemophilia and needs large quantities of a pricey drug – known as clotting factor – that makes blood coagulate.

Hemophilia drugs are among the most costly drugs in the nation, and taxpayers are footing the bill for many patients on Medicaid who could never afford them on their own. Officials in California and other states are doing what they can to manage the costs, but it’s a daunting task that highlights the complexity and secrecy of prescription drug pricing.

 

Kaiser Health News is examining how America has become a “Medicaid Nation” – where tens of millions of poor and disabled people now rely on the support of the federal and state insurance program. Hemophilia is one those diseases that helps explain its burgeoning cost.

Medications for hemophilia are crucial to patients – overwhelmingly male – with the rare genetic condition that prevents clotting and puts them at great risk of bleeding to death, even from a minor injury. There is no question the drugs prolong and save lives, and state officials are not arguing that they should be withheld.

“It’s a highly vulnerable population,” said Ken Kizer, a veteran federal and state health administrator who formerly oversaw Medi-Cal, California’s version of Medicaid. “If anyone has seen a hemophiliac in crisis, you’re not going to say no.”

But drugmakers profit handsomely, competing vigorously for the limited number of patients.

The U.S. hemophilia market, which serves about 20,000 patients, is worth $4.6 billion a year, according to AllianceBernstein, a research and investment firm.

 

“There are millions being made out there on these kids – it’s a huge business,” said Doris Quon, MD, medical director of the Orthopaedic Hemophilia Treatment Center at the University of California, Los Angeles.

Contributing to the costs is the fact that there is no cure for hemophilia and no cheaper substitute for blood factor. Factor may be prescribed at high doses for a lifetime, even more so when a patient has an injury or complications.

Nationwide, a third of adults and children living with hemophilia are covered by Medicaid. And the Medicaid program’s three most expensive drugs per prescription are for hemophilia, according to an analysis by the Kaiser Family Foundation. (California Healthline is produced by Kaiser Health News, an editorially independent publication of the foundation.)

In 2015 alone, Medicaid paid about $353 million for prescriptions of Advate, the most commonly prescribed blood-clotting medication for hemophilia – a 273% increase from 2011.

Generally speaking, the price of hemophilia drugs rise as rival drugs hit the market. But, in addition, doctors are prescribing ever more clotting factor for prevention of joint-damaging bleeds and for improved long-term health. The increase in the cost of Advate, for example, was nearly all attributed to increased use.

Tab for 145 kids: $195 million

The California boy whose drugs cost $21 million in a single year was an extreme case, and the circumstances of his care have not been disclosed because of confidentiality protections. Still, medications to treat hemophilia on average annual cost more than $270,000 per patient, according to a 2015 Express Scripts report, and they can easily soar past $1 million annually.

In contrast to more common diseases like hepatitis C, hemophilia treatment is not a state “budget buster” per se: about 4,000 patients live in California. About 1,100 of them are covered by Medi-Cal or two other government-funded programs for chronically ill children in California, according to Jennifer Kent, director of the state Department of Health Care Services and author of last year’s tweet. But the amount of money spent per person dwarfs that spent on people with other serious diseases.

One Stanford University study of 34,000 California kids with severe chronic diseases found that the tiny portion of children who needed blood factor accounted for 41% of the state’s outpatient drug spending on this entire patient population. About $195 million was spent on just 145 kids over a 3-year period, although some of that money came back to the state in rebates from drug companies – a portion of the cost that Medicaid can recoup after purchase.

Caitlin Carroll, director of public affairs for PhRMA, the pharmaceutical industry lobbying group, said high development costs and the complicated and lengthy manufacturing process play a role in how hemophilia drugs are priced. She added that federally mandated rebates significantly reduce the cost of blood factor. They amount to 17% of the average manufacturer price per unit.

Manufacturers also note that some newer and more expensive hemophilia drugs last longer and do not need to be administered as frequently, so they can prove less costly to payers overall.

Even so, some patients require a monumental investment to survive.
 

 

‘Extremely fortunate’

Colleen Tuite’s son Kevin, a 7-year-old, has severe hemophilia with a complication known as an inhibitor – an antibody that makes his regular blood-factor infusions less effective. Inhibitors can dramatically increase the cost of care, because massive doses of blood factor or expensive, specialized blood products known as bypassing agents may be needed.

Ms. Tuite and her husband initially were Kevin’s foster parents, then adopted the boy as a toddler. Because he has been a foster child, Kevin qualifies for Medi-Cal until he is 26.

The Monrovia, Calif., family also has private health insurance, which pays for about half of Kevin’s medical bills. These can run upward of $200,000 per month, Ms. Tuite said.

“We definitely would not have been able to adopt him without the help of Medi-Cal,” Ms. Tuite said. “We’ve been extremely fortunate.”

With the support of drug manufacturers and hemophilia advocacy groups, patients and their families have significant political clout. Some experts say they also have a moral claim on public resources: In the early days of the AIDS epidemic, thousands of the nation’s hemophilia patients died after they contracted HIV through transfusions before the virus was eliminated from the blood supply.

State health officials say the costs of hemophilia are hard to anticipate and control, even with rebates.

“We do a really aggressive job of collecting rebates on our pharmacy costs,” said Ms. Kent, California’s top Medicaid official. “But there’s just not any way around blood factor. It is just a very, very expensive product. It’s nonnegotiable for people that require it.”

In 2016, California’s Medicaid program paid at least $205 million for medications used to treat hemophilia, according to a Kaiser Health News analysis of federal Medicaid data. That figure doesn’t account for the federal rebates.

States can negotiate “supplemental” rebates with drugmakers for individual medications – but those must be kept secret under federal and some state laws. Such secrecy is becoming increasingly controversial as states continue to confront spiraling drug prices.

 

Limited options for states

In 2016, Pfizer sued Texas’ state health agency for giving data on the drug company’s supplemental Medicaid rebates to state lawmakers who requested it. The drugmaker alleged that releasing the confidential information would undermine the company’s competitiveness and give away trade secrets, and warned that the discounts it gave Texas could disappear.

In early October, a judge ruled that lawmakers should be able to obtain some of that data, noting dryly that “in Pfizer’s view, legislators are not necessary to carry out the state’s Medicaid program.”

Instead of seeking additional rebates from manufacturers for blood factor, some states, including Washington and Oregon, have chosen to require patients to get their blood factor from federally designated Hemophilia Treatment Centers only. That allows state Medicaid programs to take advantage of a federal drug-discount program known as “340B.”

However, officials in California said they studied that option and determined it wouldn’t save them any more money than the rebates they negotiate with drugmakers.

Whatever their approach, state health officials say they are struggling against forces they are nearly powerless to change.

“There aren’t a lot of options available to Medicaid programs in terms of controlling costs, because we don’t set the initial costs,” said Deborah Weston, pharmacy program manager for Oregon’s Medicaid program.
 

Kaiser Health News data correspondent Sydney Lupkin contributed to this report. KHN’s coverage of these topics is supported by Laura and John Arnold Foundation and Heising-Simons Foundation. This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

 

The child is well-known in the halls in which state bureaucrats oversee health care for millions of Californians – not by name, but by a number: $21 million.

His medications alone cost state taxpayers that much in a single year, not including other health care. The boy, whose identity has not been released, was California’s most expensive Medicaid patient in recent years. His case was singled out in a tweet last year by the state’s top health care official to highlight the public insurance program’s extraordinary obligations as a backstop for low-income patients.

How on earth can a single child’s treatment cost that much? The answer: He has hemophilia and needs large quantities of a pricey drug – known as clotting factor – that makes blood coagulate.

Hemophilia drugs are among the most costly drugs in the nation, and taxpayers are footing the bill for many patients on Medicaid who could never afford them on their own. Officials in California and other states are doing what they can to manage the costs, but it’s a daunting task that highlights the complexity and secrecy of prescription drug pricing.

 

Kaiser Health News is examining how America has become a “Medicaid Nation” – where tens of millions of poor and disabled people now rely on the support of the federal and state insurance program. Hemophilia is one those diseases that helps explain its burgeoning cost.

Medications for hemophilia are crucial to patients – overwhelmingly male – with the rare genetic condition that prevents clotting and puts them at great risk of bleeding to death, even from a minor injury. There is no question the drugs prolong and save lives, and state officials are not arguing that they should be withheld.

“It’s a highly vulnerable population,” said Ken Kizer, a veteran federal and state health administrator who formerly oversaw Medi-Cal, California’s version of Medicaid. “If anyone has seen a hemophiliac in crisis, you’re not going to say no.”

But drugmakers profit handsomely, competing vigorously for the limited number of patients.

The U.S. hemophilia market, which serves about 20,000 patients, is worth $4.6 billion a year, according to AllianceBernstein, a research and investment firm.

 

“There are millions being made out there on these kids – it’s a huge business,” said Doris Quon, MD, medical director of the Orthopaedic Hemophilia Treatment Center at the University of California, Los Angeles.

Contributing to the costs is the fact that there is no cure for hemophilia and no cheaper substitute for blood factor. Factor may be prescribed at high doses for a lifetime, even more so when a patient has an injury or complications.

Nationwide, a third of adults and children living with hemophilia are covered by Medicaid. And the Medicaid program’s three most expensive drugs per prescription are for hemophilia, according to an analysis by the Kaiser Family Foundation. (California Healthline is produced by Kaiser Health News, an editorially independent publication of the foundation.)

In 2015 alone, Medicaid paid about $353 million for prescriptions of Advate, the most commonly prescribed blood-clotting medication for hemophilia – a 273% increase from 2011.

Generally speaking, the price of hemophilia drugs rise as rival drugs hit the market. But, in addition, doctors are prescribing ever more clotting factor for prevention of joint-damaging bleeds and for improved long-term health. The increase in the cost of Advate, for example, was nearly all attributed to increased use.

Tab for 145 kids: $195 million

The California boy whose drugs cost $21 million in a single year was an extreme case, and the circumstances of his care have not been disclosed because of confidentiality protections. Still, medications to treat hemophilia on average annual cost more than $270,000 per patient, according to a 2015 Express Scripts report, and they can easily soar past $1 million annually.

In contrast to more common diseases like hepatitis C, hemophilia treatment is not a state “budget buster” per se: about 4,000 patients live in California. About 1,100 of them are covered by Medi-Cal or two other government-funded programs for chronically ill children in California, according to Jennifer Kent, director of the state Department of Health Care Services and author of last year’s tweet. But the amount of money spent per person dwarfs that spent on people with other serious diseases.

One Stanford University study of 34,000 California kids with severe chronic diseases found that the tiny portion of children who needed blood factor accounted for 41% of the state’s outpatient drug spending on this entire patient population. About $195 million was spent on just 145 kids over a 3-year period, although some of that money came back to the state in rebates from drug companies – a portion of the cost that Medicaid can recoup after purchase.

Caitlin Carroll, director of public affairs for PhRMA, the pharmaceutical industry lobbying group, said high development costs and the complicated and lengthy manufacturing process play a role in how hemophilia drugs are priced. She added that federally mandated rebates significantly reduce the cost of blood factor. They amount to 17% of the average manufacturer price per unit.

Manufacturers also note that some newer and more expensive hemophilia drugs last longer and do not need to be administered as frequently, so they can prove less costly to payers overall.

Even so, some patients require a monumental investment to survive.
 

 

‘Extremely fortunate’

Colleen Tuite’s son Kevin, a 7-year-old, has severe hemophilia with a complication known as an inhibitor – an antibody that makes his regular blood-factor infusions less effective. Inhibitors can dramatically increase the cost of care, because massive doses of blood factor or expensive, specialized blood products known as bypassing agents may be needed.

Ms. Tuite and her husband initially were Kevin’s foster parents, then adopted the boy as a toddler. Because he has been a foster child, Kevin qualifies for Medi-Cal until he is 26.

The Monrovia, Calif., family also has private health insurance, which pays for about half of Kevin’s medical bills. These can run upward of $200,000 per month, Ms. Tuite said.

“We definitely would not have been able to adopt him without the help of Medi-Cal,” Ms. Tuite said. “We’ve been extremely fortunate.”

With the support of drug manufacturers and hemophilia advocacy groups, patients and their families have significant political clout. Some experts say they also have a moral claim on public resources: In the early days of the AIDS epidemic, thousands of the nation’s hemophilia patients died after they contracted HIV through transfusions before the virus was eliminated from the blood supply.

State health officials say the costs of hemophilia are hard to anticipate and control, even with rebates.

“We do a really aggressive job of collecting rebates on our pharmacy costs,” said Ms. Kent, California’s top Medicaid official. “But there’s just not any way around blood factor. It is just a very, very expensive product. It’s nonnegotiable for people that require it.”

In 2016, California’s Medicaid program paid at least $205 million for medications used to treat hemophilia, according to a Kaiser Health News analysis of federal Medicaid data. That figure doesn’t account for the federal rebates.

States can negotiate “supplemental” rebates with drugmakers for individual medications – but those must be kept secret under federal and some state laws. Such secrecy is becoming increasingly controversial as states continue to confront spiraling drug prices.

 

Limited options for states

In 2016, Pfizer sued Texas’ state health agency for giving data on the drug company’s supplemental Medicaid rebates to state lawmakers who requested it. The drugmaker alleged that releasing the confidential information would undermine the company’s competitiveness and give away trade secrets, and warned that the discounts it gave Texas could disappear.

In early October, a judge ruled that lawmakers should be able to obtain some of that data, noting dryly that “in Pfizer’s view, legislators are not necessary to carry out the state’s Medicaid program.”

Instead of seeking additional rebates from manufacturers for blood factor, some states, including Washington and Oregon, have chosen to require patients to get their blood factor from federally designated Hemophilia Treatment Centers only. That allows state Medicaid programs to take advantage of a federal drug-discount program known as “340B.”

However, officials in California said they studied that option and determined it wouldn’t save them any more money than the rebates they negotiate with drugmakers.

Whatever their approach, state health officials say they are struggling against forces they are nearly powerless to change.

“There aren’t a lot of options available to Medicaid programs in terms of controlling costs, because we don’t set the initial costs,” said Deborah Weston, pharmacy program manager for Oregon’s Medicaid program.
 

Kaiser Health News data correspondent Sydney Lupkin contributed to this report. KHN’s coverage of these topics is supported by Laura and John Arnold Foundation and Heising-Simons Foundation. This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation. Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

 

SALT LAKE CITY – Scores of 3 or higher on the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) are associated with an increased risk of posttransplant mortality in certain patients undergoing allogeneic HCT for nonmalignant disease, according to findings from a review of more than 4,000 patients.

The exception was in patients undergoing HCT for hemoglobinopathies, Larisa Broglie, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The findings of the study, which is the largest to date to validate the usefulness of the HCT-CI for risk assessment in HCT patients with nonmalignant disease, have important implications for patient counseling and decision making, said Dr. Broglie of the Medical College of Wisconsin, Milwaukee.

Of 4,083 children and adults who underwent a first allogeneic HCT for a nonmalignant disease between 2007 and 2014 and who had sufficient follow-up (median, 39 months), 61% had an HCT-CI score of 0, 20% had a score of 1-2, and 19% had a score of 3 or higher.

 

After adjustment for age, disease, donor, graft source, recipient cytomegalovirus status, and performance status, scores of 3 or greater were associated with an overall increased hazard ratio for poor survival (HRs of 1.33 for scores of 3-4 and 2.31 for scores of 5 or greater, vs. 1.0 and 1.127 for scores of 0 or 1-2, respectively), she said.

Patients with an HCT-CI score of 0 had estimated 2-year overall survival of 82.7%, compared with 80.3% for scores 1-2, 74.0% for scores 3-4, and 55.8% for scores of 5 or greater.

Patients included in this study were identified from the Center for International Blood & Marrow Transplant Research database. They ranged in age from under 1 year to 77 years but most were young; the median age was 9 years and 78% of patients were under age 20.

HCT was performed for acquired aplastic anemia in 33% of patients, immune deficiencies in 19%, hemoglobinopathies in 16%, bone marrow failure in 12%, histiocytic disorders in 11%, metabolic disease in 9%, or autoimmune disease in less than 1%, she said, noting that the most frequent comorbidities seen within the entire cohort were moderate pulmonary disease, hepatic disease, and infection requiring ongoing treatment.

The effect of HCT-CI score on survival was present regardless of conditioning intensity and graft-versus-host disease prophylaxis, but scores predicted mortality risk differently based on underlying disease, and different comorbidities predominated in each disease category, she said, explaining that this was apparent when patients were stratified by the seven represented nonmalignant disease categories to account for disease heterogeneity.

 

For example, HCT-CI score predicted mortality risk in patients with aplastic anemia (HRs of 1.00, 1.19, and 2.06 for scores of 0, 1-2, and 3 or greater, respectively), and in patients with immune deficiency (HRs of 1.00, 1.37, and 1.87 for scores of 0, 1-2, and 3 or greater, respectively), and the distribution of comorbidities in patients in these two disease categories was similar to that of the overall cohort.

However, HCT-CI score did not predict mortality risk in those undergoing HCT for hemoglobinopathies (HRs of 1.00, 0.46, and 0.59 for scores of 0, 1-2, and 3 or greater, respectively), Dr. Broglie said, noting that these patients had overall high survival rates regardless of HCT-CI scores, and they had comorbidities that differed from the overall cohort.

HCT is a curative treatment strategy for many patients with nonmalignant diseases but transplant-related mortality remains a concern, she said. While HCT-CI has been shown to be useful for discriminating the risks of nonrelapse and overall survival among patients with hematologic malignancies who undergo allogeneic HCT, its usefulness in patients undergoing HCT for nonmalignant diseases has been less clear.

The distinction is important, as patients with nonmalignant diseases have different pretransplant exposures and may have comorbidities specific to their underlying disease. Furthermore, transplantation approaches – including conditioning regimens and intensities – differ, she said.

 

“And the HCT-CI was developed to predict risk of nonrelapse mortality, but relapse in nonmalignant diseases can often be difficult to define,” she added.

The current findings demonstrate the value of the HCT-CI in nonmalignant diseases, and “offer the potential to intervene with transplantation prior to the onset of comorbidities, or with efforts to prevent comorbidities prior to transplantation,” she said, concluding that “future efforts could focus on further refining pretransplant risk assessment for patients with nonmalignant diseases, especially for patients with hemoglobinopathies and HCT-CI scores of less than 3.”

Dr. Broglie reported having no financial disclosures.

[email protected]

SOURCE: Broglie L et al. Abstract 16.

 

SALT LAKE CITY – Scores of 3 or higher on the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) are associated with an increased risk of posttransplant mortality in certain patients undergoing allogeneic HCT for nonmalignant disease, according to findings from a review of more than 4,000 patients.

The exception was in patients undergoing HCT for hemoglobinopathies, Larisa Broglie, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The findings of the study, which is the largest to date to validate the usefulness of the HCT-CI for risk assessment in HCT patients with nonmalignant disease, have important implications for patient counseling and decision making, said Dr. Broglie of the Medical College of Wisconsin, Milwaukee.

Of 4,083 children and adults who underwent a first allogeneic HCT for a nonmalignant disease between 2007 and 2014 and who had sufficient follow-up (median, 39 months), 61% had an HCT-CI score of 0, 20% had a score of 1-2, and 19% had a score of 3 or higher.

 

After adjustment for age, disease, donor, graft source, recipient cytomegalovirus status, and performance status, scores of 3 or greater were associated with an overall increased hazard ratio for poor survival (HRs of 1.33 for scores of 3-4 and 2.31 for scores of 5 or greater, vs. 1.0 and 1.127 for scores of 0 or 1-2, respectively), she said.

Patients with an HCT-CI score of 0 had estimated 2-year overall survival of 82.7%, compared with 80.3% for scores 1-2, 74.0% for scores 3-4, and 55.8% for scores of 5 or greater.

Patients included in this study were identified from the Center for International Blood & Marrow Transplant Research database. They ranged in age from under 1 year to 77 years but most were young; the median age was 9 years and 78% of patients were under age 20.

HCT was performed for acquired aplastic anemia in 33% of patients, immune deficiencies in 19%, hemoglobinopathies in 16%, bone marrow failure in 12%, histiocytic disorders in 11%, metabolic disease in 9%, or autoimmune disease in less than 1%, she said, noting that the most frequent comorbidities seen within the entire cohort were moderate pulmonary disease, hepatic disease, and infection requiring ongoing treatment.

The effect of HCT-CI score on survival was present regardless of conditioning intensity and graft-versus-host disease prophylaxis, but scores predicted mortality risk differently based on underlying disease, and different comorbidities predominated in each disease category, she said, explaining that this was apparent when patients were stratified by the seven represented nonmalignant disease categories to account for disease heterogeneity.

 

For example, HCT-CI score predicted mortality risk in patients with aplastic anemia (HRs of 1.00, 1.19, and 2.06 for scores of 0, 1-2, and 3 or greater, respectively), and in patients with immune deficiency (HRs of 1.00, 1.37, and 1.87 for scores of 0, 1-2, and 3 or greater, respectively), and the distribution of comorbidities in patients in these two disease categories was similar to that of the overall cohort.

However, HCT-CI score did not predict mortality risk in those undergoing HCT for hemoglobinopathies (HRs of 1.00, 0.46, and 0.59 for scores of 0, 1-2, and 3 or greater, respectively), Dr. Broglie said, noting that these patients had overall high survival rates regardless of HCT-CI scores, and they had comorbidities that differed from the overall cohort.

HCT is a curative treatment strategy for many patients with nonmalignant diseases but transplant-related mortality remains a concern, she said. While HCT-CI has been shown to be useful for discriminating the risks of nonrelapse and overall survival among patients with hematologic malignancies who undergo allogeneic HCT, its usefulness in patients undergoing HCT for nonmalignant diseases has been less clear.

The distinction is important, as patients with nonmalignant diseases have different pretransplant exposures and may have comorbidities specific to their underlying disease. Furthermore, transplantation approaches – including conditioning regimens and intensities – differ, she said.

 

“And the HCT-CI was developed to predict risk of nonrelapse mortality, but relapse in nonmalignant diseases can often be difficult to define,” she added.

The current findings demonstrate the value of the HCT-CI in nonmalignant diseases, and “offer the potential to intervene with transplantation prior to the onset of comorbidities, or with efforts to prevent comorbidities prior to transplantation,” she said, concluding that “future efforts could focus on further refining pretransplant risk assessment for patients with nonmalignant diseases, especially for patients with hemoglobinopathies and HCT-CI scores of less than 3.”

Dr. Broglie reported having no financial disclosures.

[email protected]

SOURCE: Broglie L et al. Abstract 16.

 

SALT LAKE CITY – Scores of 3 or higher on the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) are associated with an increased risk of posttransplant mortality in certain patients undergoing allogeneic HCT for nonmalignant disease, according to findings from a review of more than 4,000 patients.

The exception was in patients undergoing HCT for hemoglobinopathies, Larisa Broglie, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The findings of the study, which is the largest to date to validate the usefulness of the HCT-CI for risk assessment in HCT patients with nonmalignant disease, have important implications for patient counseling and decision making, said Dr. Broglie of the Medical College of Wisconsin, Milwaukee.

Of 4,083 children and adults who underwent a first allogeneic HCT for a nonmalignant disease between 2007 and 2014 and who had sufficient follow-up (median, 39 months), 61% had an HCT-CI score of 0, 20% had a score of 1-2, and 19% had a score of 3 or higher.

 

After adjustment for age, disease, donor, graft source, recipient cytomegalovirus status, and performance status, scores of 3 or greater were associated with an overall increased hazard ratio for poor survival (HRs of 1.33 for scores of 3-4 and 2.31 for scores of 5 or greater, vs. 1.0 and 1.127 for scores of 0 or 1-2, respectively), she said.

Patients with an HCT-CI score of 0 had estimated 2-year overall survival of 82.7%, compared with 80.3% for scores 1-2, 74.0% for scores 3-4, and 55.8% for scores of 5 or greater.

Patients included in this study were identified from the Center for International Blood & Marrow Transplant Research database. They ranged in age from under 1 year to 77 years but most were young; the median age was 9 years and 78% of patients were under age 20.

HCT was performed for acquired aplastic anemia in 33% of patients, immune deficiencies in 19%, hemoglobinopathies in 16%, bone marrow failure in 12%, histiocytic disorders in 11%, metabolic disease in 9%, or autoimmune disease in less than 1%, she said, noting that the most frequent comorbidities seen within the entire cohort were moderate pulmonary disease, hepatic disease, and infection requiring ongoing treatment.

The effect of HCT-CI score on survival was present regardless of conditioning intensity and graft-versus-host disease prophylaxis, but scores predicted mortality risk differently based on underlying disease, and different comorbidities predominated in each disease category, she said, explaining that this was apparent when patients were stratified by the seven represented nonmalignant disease categories to account for disease heterogeneity.

 

For example, HCT-CI score predicted mortality risk in patients with aplastic anemia (HRs of 1.00, 1.19, and 2.06 for scores of 0, 1-2, and 3 or greater, respectively), and in patients with immune deficiency (HRs of 1.00, 1.37, and 1.87 for scores of 0, 1-2, and 3 or greater, respectively), and the distribution of comorbidities in patients in these two disease categories was similar to that of the overall cohort.

However, HCT-CI score did not predict mortality risk in those undergoing HCT for hemoglobinopathies (HRs of 1.00, 0.46, and 0.59 for scores of 0, 1-2, and 3 or greater, respectively), Dr. Broglie said, noting that these patients had overall high survival rates regardless of HCT-CI scores, and they had comorbidities that differed from the overall cohort.

HCT is a curative treatment strategy for many patients with nonmalignant diseases but transplant-related mortality remains a concern, she said. While HCT-CI has been shown to be useful for discriminating the risks of nonrelapse and overall survival among patients with hematologic malignancies who undergo allogeneic HCT, its usefulness in patients undergoing HCT for nonmalignant diseases has been less clear.

The distinction is important, as patients with nonmalignant diseases have different pretransplant exposures and may have comorbidities specific to their underlying disease. Furthermore, transplantation approaches – including conditioning regimens and intensities – differ, she said.

 

“And the HCT-CI was developed to predict risk of nonrelapse mortality, but relapse in nonmalignant diseases can often be difficult to define,” she added.

The current findings demonstrate the value of the HCT-CI in nonmalignant diseases, and “offer the potential to intervene with transplantation prior to the onset of comorbidities, or with efforts to prevent comorbidities prior to transplantation,” she said, concluding that “future efforts could focus on further refining pretransplant risk assessment for patients with nonmalignant diseases, especially for patients with hemoglobinopathies and HCT-CI scores of less than 3.”

Dr. Broglie reported having no financial disclosures.

[email protected]

SOURCE: Broglie L et al. Abstract 16.

 

SAN DIEGO – A simple scoring system surpassed thermal imaging for diagnosing lower extremity cellulitis in a head-to-head, single-center comparison in 67 patients.

The ALT-70 score – which tallies points for asymmetry, leukocytosis, tachycardia, and age of at least 70 years – produced a positive predictive value for lower-extremity cellulitis (LEC) of 80.4% and a negative predictive value of 90.9%, compared with values of 75.5% and 57.1%, respectively, for thermal imaging when researchers applied both methods to 67 patients, said David G. Li, a clinical research fellow in the department of dermatology at Brigham and Women’s Hospital, Boston, where the study was conducted.

Mitchel Zoler

“We recommend ALT-70 for routine practice to reduce misdiagnosis of lower-extremity cellulitis,” said Mr. Li.

The senior author of Mr. Li’s report, Arash Mostaghimi, MD, director of the inpatient consultation service, department of dermatology at Brigham and Women’s, was also lead investigator for the team of dermatology researchers – from his center and from Massachusetts General Hospital in Boston – who recently devised the ALT-70 scoring system for diagnosing LEC (J Amer Acad Dermatol. 2017 April;76[4]:618-25.e2).

 

The four-item survey can generate a score of 0-7, with a score of 0-2 suggesting need for additional monitoring, a score of 3-4 initiating a dermatology consult, and a score of 5-7 triggering immediate treatment for cellulitis, Mr. Li said. The 2017 review of ALT-70 showed that among 259 patients, those with a score of 0-2 had an 83% likelihood of having pseudocellulitis, while patients with a score of 5-7 had an 82% likelihood of having true cellulitis.

Brigham and Women's Hospital

Thermal imaging of the lower extremity, which identifies cellulitis by a higher skin temperature compared with unaffected areas on the limb, has also recently gained currency as a way to objectively diagnose cellulitis (J Invest Dermatol. 2018 March;138[3]:520-6).

The current study enrolled 67 patients who had a presumptive diagnosis of LEC while in the emergency department or inpatient wards during a 7-month period. In addition to undergoing blinded assessment by both thermal imaging and by ALT-70 scoring, all patients also underwent blinded assessment by a board-certified dermatologist, who provided the definitive diagnosis. The attending dermatologists determined that 46 of the patients had true LEC and 21 patients did not.

The calculated sensitivity of ALT-70 was 97.8%, compared with 87.0% for thermal imaging. Specificity was 47.6% for ALT-70 and 38.1% for thermal imaging, Mr. Li reported at the annual meeting of the American Academy of Dermatology.

 

He also presented an analysis of the results when he combined both methods, with a positive on both assessments required to produce a positive LEC diagnosis. This resulted in a positive predictive value of 86.7%, slightly higher than the 80.4% from ALT-70 alone, but the combination produced a negative predictive value of 68.2%, substantially less than the 90.9% rate with ALT-70 alone. This demonstrated the “marginal benefit” from combining the two methods, he said.

In a receiver operating characteristic curve analysis, in which the area under the curve (c-statistic) reflects a diagnostic test’s validity, ALT-70 produced a c-statistic of 0.85, thermal imaging had a c-statistic of 0.63, and when combined, the c-statistic was 0.88.

Mr. Li called for validation of the findings using larger and different patient populations.

He had no reported disclosures.

[email protected]

SOURCE: Li DG et al. AAD 18, Abstract 6744.

 

SAN DIEGO – A simple scoring system surpassed thermal imaging for diagnosing lower extremity cellulitis in a head-to-head, single-center comparison in 67 patients.

The ALT-70 score – which tallies points for asymmetry, leukocytosis, tachycardia, and age of at least 70 years – produced a positive predictive value for lower-extremity cellulitis (LEC) of 80.4% and a negative predictive value of 90.9%, compared with values of 75.5% and 57.1%, respectively, for thermal imaging when researchers applied both methods to 67 patients, said David G. Li, a clinical research fellow in the department of dermatology at Brigham and Women’s Hospital, Boston, where the study was conducted.

Mitchel Zoler

“We recommend ALT-70 for routine practice to reduce misdiagnosis of lower-extremity cellulitis,” said Mr. Li.

The senior author of Mr. Li’s report, Arash Mostaghimi, MD, director of the inpatient consultation service, department of dermatology at Brigham and Women’s, was also lead investigator for the team of dermatology researchers – from his center and from Massachusetts General Hospital in Boston – who recently devised the ALT-70 scoring system for diagnosing LEC (J Amer Acad Dermatol. 2017 April;76[4]:618-25.e2).

 

The four-item survey can generate a score of 0-7, with a score of 0-2 suggesting need for additional monitoring, a score of 3-4 initiating a dermatology consult, and a score of 5-7 triggering immediate treatment for cellulitis, Mr. Li said. The 2017 review of ALT-70 showed that among 259 patients, those with a score of 0-2 had an 83% likelihood of having pseudocellulitis, while patients with a score of 5-7 had an 82% likelihood of having true cellulitis.

Brigham and Women's Hospital

Thermal imaging of the lower extremity, which identifies cellulitis by a higher skin temperature compared with unaffected areas on the limb, has also recently gained currency as a way to objectively diagnose cellulitis (J Invest Dermatol. 2018 March;138[3]:520-6).

The current study enrolled 67 patients who had a presumptive diagnosis of LEC while in the emergency department or inpatient wards during a 7-month period. In addition to undergoing blinded assessment by both thermal imaging and by ALT-70 scoring, all patients also underwent blinded assessment by a board-certified dermatologist, who provided the definitive diagnosis. The attending dermatologists determined that 46 of the patients had true LEC and 21 patients did not.

The calculated sensitivity of ALT-70 was 97.8%, compared with 87.0% for thermal imaging. Specificity was 47.6% for ALT-70 and 38.1% for thermal imaging, Mr. Li reported at the annual meeting of the American Academy of Dermatology.

 

He also presented an analysis of the results when he combined both methods, with a positive on both assessments required to produce a positive LEC diagnosis. This resulted in a positive predictive value of 86.7%, slightly higher than the 80.4% from ALT-70 alone, but the combination produced a negative predictive value of 68.2%, substantially less than the 90.9% rate with ALT-70 alone. This demonstrated the “marginal benefit” from combining the two methods, he said.

In a receiver operating characteristic curve analysis, in which the area under the curve (c-statistic) reflects a diagnostic test’s validity, ALT-70 produced a c-statistic of 0.85, thermal imaging had a c-statistic of 0.63, and when combined, the c-statistic was 0.88.

Mr. Li called for validation of the findings using larger and different patient populations.

He had no reported disclosures.

[email protected]

SOURCE: Li DG et al. AAD 18, Abstract 6744.

 

SAN DIEGO – A simple scoring system surpassed thermal imaging for diagnosing lower extremity cellulitis in a head-to-head, single-center comparison in 67 patients.

The ALT-70 score – which tallies points for asymmetry, leukocytosis, tachycardia, and age of at least 70 years – produced a positive predictive value for lower-extremity cellulitis (LEC) of 80.4% and a negative predictive value of 90.9%, compared with values of 75.5% and 57.1%, respectively, for thermal imaging when researchers applied both methods to 67 patients, said David G. Li, a clinical research fellow in the department of dermatology at Brigham and Women’s Hospital, Boston, where the study was conducted.

Mitchel Zoler

“We recommend ALT-70 for routine practice to reduce misdiagnosis of lower-extremity cellulitis,” said Mr. Li.

The senior author of Mr. Li’s report, Arash Mostaghimi, MD, director of the inpatient consultation service, department of dermatology at Brigham and Women’s, was also lead investigator for the team of dermatology researchers – from his center and from Massachusetts General Hospital in Boston – who recently devised the ALT-70 scoring system for diagnosing LEC (J Amer Acad Dermatol. 2017 April;76[4]:618-25.e2).

 

The four-item survey can generate a score of 0-7, with a score of 0-2 suggesting need for additional monitoring, a score of 3-4 initiating a dermatology consult, and a score of 5-7 triggering immediate treatment for cellulitis, Mr. Li said. The 2017 review of ALT-70 showed that among 259 patients, those with a score of 0-2 had an 83% likelihood of having pseudocellulitis, while patients with a score of 5-7 had an 82% likelihood of having true cellulitis.

Brigham and Women's Hospital

Thermal imaging of the lower extremity, which identifies cellulitis by a higher skin temperature compared with unaffected areas on the limb, has also recently gained currency as a way to objectively diagnose cellulitis (J Invest Dermatol. 2018 March;138[3]:520-6).

The current study enrolled 67 patients who had a presumptive diagnosis of LEC while in the emergency department or inpatient wards during a 7-month period. In addition to undergoing blinded assessment by both thermal imaging and by ALT-70 scoring, all patients also underwent blinded assessment by a board-certified dermatologist, who provided the definitive diagnosis. The attending dermatologists determined that 46 of the patients had true LEC and 21 patients did not.

The calculated sensitivity of ALT-70 was 97.8%, compared with 87.0% for thermal imaging. Specificity was 47.6% for ALT-70 and 38.1% for thermal imaging, Mr. Li reported at the annual meeting of the American Academy of Dermatology.

 

He also presented an analysis of the results when he combined both methods, with a positive on both assessments required to produce a positive LEC diagnosis. This resulted in a positive predictive value of 86.7%, slightly higher than the 80.4% from ALT-70 alone, but the combination produced a negative predictive value of 68.2%, substantially less than the 90.9% rate with ALT-70 alone. This demonstrated the “marginal benefit” from combining the two methods, he said.

In a receiver operating characteristic curve analysis, in which the area under the curve (c-statistic) reflects a diagnostic test’s validity, ALT-70 produced a c-statistic of 0.85, thermal imaging had a c-statistic of 0.63, and when combined, the c-statistic was 0.88.

Mr. Li called for validation of the findings using larger and different patient populations.

He had no reported disclosures.

[email protected]

SOURCE: Li DG et al. AAD 18, Abstract 6744.

 

Premenopausal women with hepatitis C virus (HCV) showed increased ovarian senescence, which was associated with a lower chance of live birth. Such women also had a greater risk of infertility, as reported in the Journal of Hepatology.

Researchers examined three cohort studies, which comprised an age-matched prospectively enrolled cohort study of 100 women who were HCV positive and had chronic liver disease, 50 women who were HBV positive and had CLD, and 100 healthy women; 1,998 HCV-infected women enrolled in the Platform for the Study of Viral Hepatitis Therapies (PITER) trial from Italy; and 6,085 women infected with HCV plus 20,415 uninfected women from a United States database, according to Aimilia Karampatou, MD, of the University of Bologna, Modena, Italy, and colleagues.

s-c-s/Thinkstock

Age, reproductive status, and serum levels of anti-Müllerian hormone (AMH) – a marker of ovarian reserve – were collected from the women in the first study’s groups. There was a significant correlation between AMH levels and hepatic grade (P = .041) and stage (P = .038) in women who were HCV positive but not in those who were HBV positive. In addition, the incidence of miscarriages in women who were HCV positive was correlated with median AMH (1.0 ng/mL). No relationship was found between AMH levels in HCV-uninfected controls and risk of miscarriage.

In the second group examined, the women from the PITER trial, miscarriages occurred in 42% of the HCV-infected women with 44.6% of these women experiencing multiple miscarriages. The total fertility rate, defined as the average number of children that would be born in a lifetime, was 0.7 for the HCV-infected women, compared with 1.37 in the general Italian population.

 

Infertility data from the large U.S. study was assessed from a total of 27,525 women (20,415 HCV negative and HIV negative; 6,805 HCV positive; and 305 HCV positive/HIV positive). Women with HCV showed a significantly higher probability of infertility compared with uninfected controls (odds ratio, 2.44), and those women dually infected with HCV and HIV were affected even more (OR, 3.64).

Primarily based on the observations of AMH, which in many of the HCV-positive women fell into the menopausal range, the researchers suggested that “the reduced reproductive capacity of women who are HCV positive is related to failing ovarian function and subsequent follicular depletion in the context of a more generalized dysfunction of other fertility-related factors.”

With regard to the effect of antiviral therapy, AMH levels remained stable in women who attained a sustained virologic response but continued to fall in those for whom the therapy was a failure.

“HCV infection significantly and negatively affects many aspects of fertility. It remains to be assessed whether antiviral therapy at a very early age can positively influence the occurrence of miscarriages and can prevent ovarian senescence because the latter has broader health implications than simply preserving fertility,” the researchers concluded.

The authors reported that they had no conflicts of interest.

AGA provides resources and education for your patients about hepatitis C at www.gastro.org/HCV

[email protected]

SOURCE: Karampatou A et al. J Hepatology. 2018;68:33-41.

 

Premenopausal women with hepatitis C virus (HCV) showed increased ovarian senescence, which was associated with a lower chance of live birth. Such women also had a greater risk of infertility, as reported in the Journal of Hepatology.

Researchers examined three cohort studies, which comprised an age-matched prospectively enrolled cohort study of 100 women who were HCV positive and had chronic liver disease, 50 women who were HBV positive and had CLD, and 100 healthy women; 1,998 HCV-infected women enrolled in the Platform for the Study of Viral Hepatitis Therapies (PITER) trial from Italy; and 6,085 women infected with HCV plus 20,415 uninfected women from a United States database, according to Aimilia Karampatou, MD, of the University of Bologna, Modena, Italy, and colleagues.

s-c-s/Thinkstock

Age, reproductive status, and serum levels of anti-Müllerian hormone (AMH) – a marker of ovarian reserve – were collected from the women in the first study’s groups. There was a significant correlation between AMH levels and hepatic grade (P = .041) and stage (P = .038) in women who were HCV positive but not in those who were HBV positive. In addition, the incidence of miscarriages in women who were HCV positive was correlated with median AMH (1.0 ng/mL). No relationship was found between AMH levels in HCV-uninfected controls and risk of miscarriage.

In the second group examined, the women from the PITER trial, miscarriages occurred in 42% of the HCV-infected women with 44.6% of these women experiencing multiple miscarriages. The total fertility rate, defined as the average number of children that would be born in a lifetime, was 0.7 for the HCV-infected women, compared with 1.37 in the general Italian population.

 

Infertility data from the large U.S. study was assessed from a total of 27,525 women (20,415 HCV negative and HIV negative; 6,805 HCV positive; and 305 HCV positive/HIV positive). Women with HCV showed a significantly higher probability of infertility compared with uninfected controls (odds ratio, 2.44), and those women dually infected with HCV and HIV were affected even more (OR, 3.64).

Primarily based on the observations of AMH, which in many of the HCV-positive women fell into the menopausal range, the researchers suggested that “the reduced reproductive capacity of women who are HCV positive is related to failing ovarian function and subsequent follicular depletion in the context of a more generalized dysfunction of other fertility-related factors.”

With regard to the effect of antiviral therapy, AMH levels remained stable in women who attained a sustained virologic response but continued to fall in those for whom the therapy was a failure.

“HCV infection significantly and negatively affects many aspects of fertility. It remains to be assessed whether antiviral therapy at a very early age can positively influence the occurrence of miscarriages and can prevent ovarian senescence because the latter has broader health implications than simply preserving fertility,” the researchers concluded.

The authors reported that they had no conflicts of interest.

AGA provides resources and education for your patients about hepatitis C at www.gastro.org/HCV

[email protected]

SOURCE: Karampatou A et al. J Hepatology. 2018;68:33-41.

 

Premenopausal women with hepatitis C virus (HCV) showed increased ovarian senescence, which was associated with a lower chance of live birth. Such women also had a greater risk of infertility, as reported in the Journal of Hepatology.

Researchers examined three cohort studies, which comprised an age-matched prospectively enrolled cohort study of 100 women who were HCV positive and had chronic liver disease, 50 women who were HBV positive and had CLD, and 100 healthy women; 1,998 HCV-infected women enrolled in the Platform for the Study of Viral Hepatitis Therapies (PITER) trial from Italy; and 6,085 women infected with HCV plus 20,415 uninfected women from a United States database, according to Aimilia Karampatou, MD, of the University of Bologna, Modena, Italy, and colleagues.

s-c-s/Thinkstock

Age, reproductive status, and serum levels of anti-Müllerian hormone (AMH) – a marker of ovarian reserve – were collected from the women in the first study’s groups. There was a significant correlation between AMH levels and hepatic grade (P = .041) and stage (P = .038) in women who were HCV positive but not in those who were HBV positive. In addition, the incidence of miscarriages in women who were HCV positive was correlated with median AMH (1.0 ng/mL). No relationship was found between AMH levels in HCV-uninfected controls and risk of miscarriage.

In the second group examined, the women from the PITER trial, miscarriages occurred in 42% of the HCV-infected women with 44.6% of these women experiencing multiple miscarriages. The total fertility rate, defined as the average number of children that would be born in a lifetime, was 0.7 for the HCV-infected women, compared with 1.37 in the general Italian population.

 

Infertility data from the large U.S. study was assessed from a total of 27,525 women (20,415 HCV negative and HIV negative; 6,805 HCV positive; and 305 HCV positive/HIV positive). Women with HCV showed a significantly higher probability of infertility compared with uninfected controls (odds ratio, 2.44), and those women dually infected with HCV and HIV were affected even more (OR, 3.64).

Primarily based on the observations of AMH, which in many of the HCV-positive women fell into the menopausal range, the researchers suggested that “the reduced reproductive capacity of women who are HCV positive is related to failing ovarian function and subsequent follicular depletion in the context of a more generalized dysfunction of other fertility-related factors.”

With regard to the effect of antiviral therapy, AMH levels remained stable in women who attained a sustained virologic response but continued to fall in those for whom the therapy was a failure.

“HCV infection significantly and negatively affects many aspects of fertility. It remains to be assessed whether antiviral therapy at a very early age can positively influence the occurrence of miscarriages and can prevent ovarian senescence because the latter has broader health implications than simply preserving fertility,” the researchers concluded.

The authors reported that they had no conflicts of interest.

AGA provides resources and education for your patients about hepatitis C at www.gastro.org/HCV

[email protected]

SOURCE: Karampatou A et al. J Hepatology. 2018;68:33-41.

ANAHEIM, CALIF. – Children and young adults with type 1 or type 2 diabetes have a 7.4-fold increased risk of sudden cardiac death, compared with nondiabetic, age-matched controls, according to a first-of-its-kind Danish national study.

“Luckily the absolute risk is low, but we hope these data will make [young patients with diabetes] think more about taking their insulin and following their physicians’ recommendations about treatment,” Jesper Svane said in presenting the study findings at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

The study population consisted of all Danes aged 1-35 years in 2000-2009 and those aged 36-49 years in 2007-2009. During that 10-year period, which included 27.1 million person-years of follow-up, there were 14,294 deaths, including 669 persons with diabetes. Of the deceased diabetic patients, 70% had type 1 diabetes.

Sudden cardiac death (SCD) was the No. 1 cause of mortality in the diabetic cohort with a rate of 34.8 deaths/100,000 person-years, compared with 4.7 deaths/100,000 person-years in an age-matched nondiabetic cohort. That translates to a 7.4-fold increased risk of SCD in the diabetic cohort, noted Mr. Svane, a medical student at Copenhagen University.

When deaths caused by SCD were combined with those from other cardiac diseases, the young diabetic cohort had a rate of 68.3 deaths/100,000 person-years versus 8.2 deaths/100,000 person-years in age-matched controls, for an 8.3-fold increased risk. This observation underscores an important point: Monitoring cardiovascular risk needs to start early in young patients with diabetes.

“It’s important to pay attention when a young person with diabetes comes in complaining of chest pain or syncope,” Mr. Svane said.

 

The second and third most common causes of death in young Danish diabetic patients were pulmonary and endocrine diseases, which occurred at rates 7.2- and 79.2-fold greater in these patients, respectively, than in controls.

All-cause mortality occurred at a rate of 234.9 deaths/100,000 person-years in young patients with diabetes versus 50.9 deaths/100,000 person-years in matched controls, for a 4.6-fold increased risk.

Autopsies showed that the most common cause of death in diabetic persons aged 36-49 years was coronary artery disease, while in those up to age 35, it was sudden arrhythmic death syndrome, a label bestowed when a medical examiner can’t find an apparent cause of death.

Session moderator Robert H. Eckle, MD, a past AHA president, cautioned against routinely attributing the deaths without apparent cause at autopsy in young people with diabetes to sudden arrhythmic death syndrome. Given that the Danish registry data don’t include data on diabetic patients’ degree of metabolic control, it seems likely that an uncertain number of those deaths were really caused by hypoglycemia, observed Dr. Eckle, professor of medicine at the University of Colorado at Denver, Aurora.

Mr. Svane reported having no financial conflicts of interest.

[email protected]

SOURCE: Svane J. 2017 AHA Sessions.

ANAHEIM, CALIF. – Children and young adults with type 1 or type 2 diabetes have a 7.4-fold increased risk of sudden cardiac death, compared with nondiabetic, age-matched controls, according to a first-of-its-kind Danish national study.

“Luckily the absolute risk is low, but we hope these data will make [young patients with diabetes] think more about taking their insulin and following their physicians’ recommendations about treatment,” Jesper Svane said in presenting the study findings at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

The study population consisted of all Danes aged 1-35 years in 2000-2009 and those aged 36-49 years in 2007-2009. During that 10-year period, which included 27.1 million person-years of follow-up, there were 14,294 deaths, including 669 persons with diabetes. Of the deceased diabetic patients, 70% had type 1 diabetes.

Sudden cardiac death (SCD) was the No. 1 cause of mortality in the diabetic cohort with a rate of 34.8 deaths/100,000 person-years, compared with 4.7 deaths/100,000 person-years in an age-matched nondiabetic cohort. That translates to a 7.4-fold increased risk of SCD in the diabetic cohort, noted Mr. Svane, a medical student at Copenhagen University.

When deaths caused by SCD were combined with those from other cardiac diseases, the young diabetic cohort had a rate of 68.3 deaths/100,000 person-years versus 8.2 deaths/100,000 person-years in age-matched controls, for an 8.3-fold increased risk. This observation underscores an important point: Monitoring cardiovascular risk needs to start early in young patients with diabetes.

“It’s important to pay attention when a young person with diabetes comes in complaining of chest pain or syncope,” Mr. Svane said.

 

The second and third most common causes of death in young Danish diabetic patients were pulmonary and endocrine diseases, which occurred at rates 7.2- and 79.2-fold greater in these patients, respectively, than in controls.

All-cause mortality occurred at a rate of 234.9 deaths/100,000 person-years in young patients with diabetes versus 50.9 deaths/100,000 person-years in matched controls, for a 4.6-fold increased risk.

Autopsies showed that the most common cause of death in diabetic persons aged 36-49 years was coronary artery disease, while in those up to age 35, it was sudden arrhythmic death syndrome, a label bestowed when a medical examiner can’t find an apparent cause of death.

Session moderator Robert H. Eckle, MD, a past AHA president, cautioned against routinely attributing the deaths without apparent cause at autopsy in young people with diabetes to sudden arrhythmic death syndrome. Given that the Danish registry data don’t include data on diabetic patients’ degree of metabolic control, it seems likely that an uncertain number of those deaths were really caused by hypoglycemia, observed Dr. Eckle, professor of medicine at the University of Colorado at Denver, Aurora.

Mr. Svane reported having no financial conflicts of interest.

[email protected]

SOURCE: Svane J. 2017 AHA Sessions.

ANAHEIM, CALIF. – Children and young adults with type 1 or type 2 diabetes have a 7.4-fold increased risk of sudden cardiac death, compared with nondiabetic, age-matched controls, according to a first-of-its-kind Danish national study.

“Luckily the absolute risk is low, but we hope these data will make [young patients with diabetes] think more about taking their insulin and following their physicians’ recommendations about treatment,” Jesper Svane said in presenting the study findings at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

The study population consisted of all Danes aged 1-35 years in 2000-2009 and those aged 36-49 years in 2007-2009. During that 10-year period, which included 27.1 million person-years of follow-up, there were 14,294 deaths, including 669 persons with diabetes. Of the deceased diabetic patients, 70% had type 1 diabetes.

Sudden cardiac death (SCD) was the No. 1 cause of mortality in the diabetic cohort with a rate of 34.8 deaths/100,000 person-years, compared with 4.7 deaths/100,000 person-years in an age-matched nondiabetic cohort. That translates to a 7.4-fold increased risk of SCD in the diabetic cohort, noted Mr. Svane, a medical student at Copenhagen University.

When deaths caused by SCD were combined with those from other cardiac diseases, the young diabetic cohort had a rate of 68.3 deaths/100,000 person-years versus 8.2 deaths/100,000 person-years in age-matched controls, for an 8.3-fold increased risk. This observation underscores an important point: Monitoring cardiovascular risk needs to start early in young patients with diabetes.

“It’s important to pay attention when a young person with diabetes comes in complaining of chest pain or syncope,” Mr. Svane said.

 

The second and third most common causes of death in young Danish diabetic patients were pulmonary and endocrine diseases, which occurred at rates 7.2- and 79.2-fold greater in these patients, respectively, than in controls.

All-cause mortality occurred at a rate of 234.9 deaths/100,000 person-years in young patients with diabetes versus 50.9 deaths/100,000 person-years in matched controls, for a 4.6-fold increased risk.

Autopsies showed that the most common cause of death in diabetic persons aged 36-49 years was coronary artery disease, while in those up to age 35, it was sudden arrhythmic death syndrome, a label bestowed when a medical examiner can’t find an apparent cause of death.

Session moderator Robert H. Eckle, MD, a past AHA president, cautioned against routinely attributing the deaths without apparent cause at autopsy in young people with diabetes to sudden arrhythmic death syndrome. Given that the Danish registry data don’t include data on diabetic patients’ degree of metabolic control, it seems likely that an uncertain number of those deaths were really caused by hypoglycemia, observed Dr. Eckle, professor of medicine at the University of Colorado at Denver, Aurora.

Mr. Svane reported having no financial conflicts of interest.

[email protected]

SOURCE: Svane J. 2017 AHA Sessions.

 

High-deductible health insurance plans may be bad for women’s health, suggest results of a new study.

An analysis of data on women without evidence of breast cancer who were covered for at least 1 year in a low annual deductible plan and then switched by their employers to high annual deductible plans showed that when women were forced to shell out substantially more money before their insurance kicked in, they were significantly more likely to have delays in diagnostic breast imaging, breast biopsy, and initiation of chemotherapy.

“Such delays might lead to adverse long-term breast cancer outcomes. Policymakers, health insurers, and employers should consider designing or incentivizing health insurance benefits that facilitate transitions through key steps along the cancer care pathway,” wrote J. Frank Wharam, MB, and colleagues at Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston. The report was published in Journal of Clinical Oncology.

 

The investigators conducted a controlled pre-post study to measure the occurrence of outcomes both before and after women were switched from a low-deductible health plan, defined as a maximum annual deductible of $500 or less, to a high-deductible plan, defined as an annual deductible of $1,000 or more.

The study population comprised 273,499 women aged 25-64 years who had no evidence of breast cancer before they were included in the study. The women had all been enrolled in a low-deductible plan for at least 1 year, and were then switched by employer mandate to a high-deductible plan and followed for up to 4 additional years.

Controls included 2.4 million women matched by time of inclusion whose employers continued to offer only low-deductible health plans.

Although at baseline there were no differences between the study sample and the controls in time to first diagnostic breast imaging, breast biopsy, diagnosis of early stage breast cancer, or initiation of breast cancer chemotherapy, at follow-up the women who had been switched to the high-deductible plans had significant delays in all categories.

 

Compared with controls, the hazard ratios (HR) for each parameter were as follows:

Time to first diagnostic breast imaging: HR = 0.96 (95% confidence interval 0.94-0.96)

Time to first breast biopsy: HR = 0.92 (0.89-0.95)

Time to early stage breast cancer diagnosis: HR = 0.83 (0.78-0.90)

Time to breast cancer chemotherapy: HR = 0.79 (0.72-0.86)

“The findings imply that the high out-of-pocket obligations under HDHPs [high-deductible health plans] might be a barrier to timely receipt of essential breast cancer services. Women in HDHPs might either delay presenting for concerning symptoms or, if proceeding along the pathway from breast cancer screening to diagnostic testing to treatment, be hesitant to undergo subsequent (and generally more expensive) care,” the authors wrote.

They noted that initially modest delays in diagnostic imaging appeared to snowball into longer delays as women proceeded through stages of care.

They recommend a strategy whereby insurers carve out exemptions to high deductibles for services such as diagnostic imaging and breast biopsy.

[email protected]

SOURCE: Wharam et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.2501.

 

High-deductible health insurance plans may be bad for women’s health, suggest results of a new study.

An analysis of data on women without evidence of breast cancer who were covered for at least 1 year in a low annual deductible plan and then switched by their employers to high annual deductible plans showed that when women were forced to shell out substantially more money before their insurance kicked in, they were significantly more likely to have delays in diagnostic breast imaging, breast biopsy, and initiation of chemotherapy.

“Such delays might lead to adverse long-term breast cancer outcomes. Policymakers, health insurers, and employers should consider designing or incentivizing health insurance benefits that facilitate transitions through key steps along the cancer care pathway,” wrote J. Frank Wharam, MB, and colleagues at Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston. The report was published in Journal of Clinical Oncology.

 

The investigators conducted a controlled pre-post study to measure the occurrence of outcomes both before and after women were switched from a low-deductible health plan, defined as a maximum annual deductible of $500 or less, to a high-deductible plan, defined as an annual deductible of $1,000 or more.

The study population comprised 273,499 women aged 25-64 years who had no evidence of breast cancer before they were included in the study. The women had all been enrolled in a low-deductible plan for at least 1 year, and were then switched by employer mandate to a high-deductible plan and followed for up to 4 additional years.

Controls included 2.4 million women matched by time of inclusion whose employers continued to offer only low-deductible health plans.

Although at baseline there were no differences between the study sample and the controls in time to first diagnostic breast imaging, breast biopsy, diagnosis of early stage breast cancer, or initiation of breast cancer chemotherapy, at follow-up the women who had been switched to the high-deductible plans had significant delays in all categories.

 

Compared with controls, the hazard ratios (HR) for each parameter were as follows:

Time to first diagnostic breast imaging: HR = 0.96 (95% confidence interval 0.94-0.96)

Time to first breast biopsy: HR = 0.92 (0.89-0.95)

Time to early stage breast cancer diagnosis: HR = 0.83 (0.78-0.90)

Time to breast cancer chemotherapy: HR = 0.79 (0.72-0.86)

“The findings imply that the high out-of-pocket obligations under HDHPs [high-deductible health plans] might be a barrier to timely receipt of essential breast cancer services. Women in HDHPs might either delay presenting for concerning symptoms or, if proceeding along the pathway from breast cancer screening to diagnostic testing to treatment, be hesitant to undergo subsequent (and generally more expensive) care,” the authors wrote.

They noted that initially modest delays in diagnostic imaging appeared to snowball into longer delays as women proceeded through stages of care.

They recommend a strategy whereby insurers carve out exemptions to high deductibles for services such as diagnostic imaging and breast biopsy.

[email protected]

SOURCE: Wharam et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.2501.

 

High-deductible health insurance plans may be bad for women’s health, suggest results of a new study.

An analysis of data on women without evidence of breast cancer who were covered for at least 1 year in a low annual deductible plan and then switched by their employers to high annual deductible plans showed that when women were forced to shell out substantially more money before their insurance kicked in, they were significantly more likely to have delays in diagnostic breast imaging, breast biopsy, and initiation of chemotherapy.

“Such delays might lead to adverse long-term breast cancer outcomes. Policymakers, health insurers, and employers should consider designing or incentivizing health insurance benefits that facilitate transitions through key steps along the cancer care pathway,” wrote J. Frank Wharam, MB, and colleagues at Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston. The report was published in Journal of Clinical Oncology.

 

The investigators conducted a controlled pre-post study to measure the occurrence of outcomes both before and after women were switched from a low-deductible health plan, defined as a maximum annual deductible of $500 or less, to a high-deductible plan, defined as an annual deductible of $1,000 or more.

The study population comprised 273,499 women aged 25-64 years who had no evidence of breast cancer before they were included in the study. The women had all been enrolled in a low-deductible plan for at least 1 year, and were then switched by employer mandate to a high-deductible plan and followed for up to 4 additional years.

Controls included 2.4 million women matched by time of inclusion whose employers continued to offer only low-deductible health plans.

Although at baseline there were no differences between the study sample and the controls in time to first diagnostic breast imaging, breast biopsy, diagnosis of early stage breast cancer, or initiation of breast cancer chemotherapy, at follow-up the women who had been switched to the high-deductible plans had significant delays in all categories.

 

Compared with controls, the hazard ratios (HR) for each parameter were as follows:

Time to first diagnostic breast imaging: HR = 0.96 (95% confidence interval 0.94-0.96)

Time to first breast biopsy: HR = 0.92 (0.89-0.95)

Time to early stage breast cancer diagnosis: HR = 0.83 (0.78-0.90)

Time to breast cancer chemotherapy: HR = 0.79 (0.72-0.86)

“The findings imply that the high out-of-pocket obligations under HDHPs [high-deductible health plans] might be a barrier to timely receipt of essential breast cancer services. Women in HDHPs might either delay presenting for concerning symptoms or, if proceeding along the pathway from breast cancer screening to diagnostic testing to treatment, be hesitant to undergo subsequent (and generally more expensive) care,” the authors wrote.

They noted that initially modest delays in diagnostic imaging appeared to snowball into longer delays as women proceeded through stages of care.

They recommend a strategy whereby insurers carve out exemptions to high deductibles for services such as diagnostic imaging and breast biopsy.

[email protected]

SOURCE: Wharam et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.2501.