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Liver cancer took nearly four times longer to progress after yttrium-90 (Y90) radioembolization than after conventional transarterial chemoembolization (cTACE), according to a single-center, randomized, phase II trial of 45 patients reported in the December issue of Gastroenterology (2016 Aug 26. doi: 10.1053/j.gastro.2016.08.029).

Median time to progression remained unreached more than 26 months after patients underwent Y90 treatment, but was only 6.8 months in the cTACE group (P = .001), Riad Salem, MD, and his associates at Northwestern University,Chicago, reported. Slow accrual limited the study size, but a post-hoc analysis showed that Y90 would have a 97% chance of significantly outperforming chemoembolization if the study had reached its enrollment target, even if the difference in time to progression was less pronounced. Furthermore, Y90 significantly outperformed chemoembolization in a competing risk analysis that accounted for liver transplantation and death, the researchers said.

Conventional transarterial chemoembolization is used in intermediate-stage liver cancer when ablation is contraindicated. However, retrospective studies have favored Y90 radioembolization, a minimally invasive procedure in which a clinician implants radioactive micron-sized particles loaded with Y90 inside blood vessels supplying a tumor. To further study this approach, the investigators randomly assigned patients with unresectable, unablatable hepatocellular carcinoma without vascular invasion, who had Child-Pugh scores of A or B, serum bilirubin levels up to 2 mg/dL, and liver enzymes up to five times the normal upper limit, to undergo selective Y90 at a dose of 120 Gy, or lipiodol-based chemoembolization at a dose of 75 mg/m^2.

Source: American Gastroenterological Association

Of 179 eligible patients, 134 (75%) declined to participate in research, opted for other trials, or chose one protocol over the other. Consequently, only 21 patients were assigned to cTACE, while 24 underwent Y90. The groups resembled each other clinically and demographically at baseline, although Y90 patients tended to have more portal hypertension and higher serum bilirubin levels. No patients died within 30 days after treatment. Each group had one case of common femoral artery pseudoaneurysm. The Y90 patients tended to have more fatigue (P = .08), and had higher rates of diarrhea (P = .03) and hypoalbuminemia (P less than .001).

Despite the small group sizes, patients were about 88% less likely to progress at a given time point after Y90, compared with cTACE (hazard ratio, 0.12; 95% confidence interval, 0.03-0.56; P = .007). To explore what might have happened had the study reached target enrollment, the researchers added another 79 hypothetical patients at the 5.1-fold higher hazard ratio (0.625) that they had used in the power calculation. The results showed that Y90 had a 97% chance of statistically outperforming cTACE under these conditions.

Inverse probability of censoring weighting, which is performed to control for dependent censoring between groups, also showed that time to progression was significantly longer with Y90 than with cTACE, the investigators said. “While the relatively low sample size is acknowledged, the seminal studies establishing cTACE as the standard of care were also limited in sample size, [were] single center, and enrolled mostly Child-Pugh A patients,” they emphasized. “Our time to progression results favoring Y90 are in line with other uncontrolled retrospective reports in patients with compromised liver function, [but] our study validates such findings with prospective randomized level I evidence.”

The National Institutes of Health and the SIR Foundation provided funding. Dr. Salem and two coinvestigators reported serving as advisors to BTG. The other coinvestigators reported having no conflicts of interest.

Liver cancer took nearly four times longer to progress after yttrium-90 (Y90) radioembolization than after conventional transarterial chemoembolization (cTACE), according to a single-center, randomized, phase II trial of 45 patients reported in the December issue of Gastroenterology (2016 Aug 26. doi: 10.1053/j.gastro.2016.08.029).

Median time to progression remained unreached more than 26 months after patients underwent Y90 treatment, but was only 6.8 months in the cTACE group (P = .001), Riad Salem, MD, and his associates at Northwestern University,Chicago, reported. Slow accrual limited the study size, but a post-hoc analysis showed that Y90 would have a 97% chance of significantly outperforming chemoembolization if the study had reached its enrollment target, even if the difference in time to progression was less pronounced. Furthermore, Y90 significantly outperformed chemoembolization in a competing risk analysis that accounted for liver transplantation and death, the researchers said.

Conventional transarterial chemoembolization is used in intermediate-stage liver cancer when ablation is contraindicated. However, retrospective studies have favored Y90 radioembolization, a minimally invasive procedure in which a clinician implants radioactive micron-sized particles loaded with Y90 inside blood vessels supplying a tumor. To further study this approach, the investigators randomly assigned patients with unresectable, unablatable hepatocellular carcinoma without vascular invasion, who had Child-Pugh scores of A or B, serum bilirubin levels up to 2 mg/dL, and liver enzymes up to five times the normal upper limit, to undergo selective Y90 at a dose of 120 Gy, or lipiodol-based chemoembolization at a dose of 75 mg/m^2.

Source: American Gastroenterological Association

Of 179 eligible patients, 134 (75%) declined to participate in research, opted for other trials, or chose one protocol over the other. Consequently, only 21 patients were assigned to cTACE, while 24 underwent Y90. The groups resembled each other clinically and demographically at baseline, although Y90 patients tended to have more portal hypertension and higher serum bilirubin levels. No patients died within 30 days after treatment. Each group had one case of common femoral artery pseudoaneurysm. The Y90 patients tended to have more fatigue (P = .08), and had higher rates of diarrhea (P = .03) and hypoalbuminemia (P less than .001).

Despite the small group sizes, patients were about 88% less likely to progress at a given time point after Y90, compared with cTACE (hazard ratio, 0.12; 95% confidence interval, 0.03-0.56; P = .007). To explore what might have happened had the study reached target enrollment, the researchers added another 79 hypothetical patients at the 5.1-fold higher hazard ratio (0.625) that they had used in the power calculation. The results showed that Y90 had a 97% chance of statistically outperforming cTACE under these conditions.

Inverse probability of censoring weighting, which is performed to control for dependent censoring between groups, also showed that time to progression was significantly longer with Y90 than with cTACE, the investigators said. “While the relatively low sample size is acknowledged, the seminal studies establishing cTACE as the standard of care were also limited in sample size, [were] single center, and enrolled mostly Child-Pugh A patients,” they emphasized. “Our time to progression results favoring Y90 are in line with other uncontrolled retrospective reports in patients with compromised liver function, [but] our study validates such findings with prospective randomized level I evidence.”

The National Institutes of Health and the SIR Foundation provided funding. Dr. Salem and two coinvestigators reported serving as advisors to BTG. The other coinvestigators reported having no conflicts of interest.

Liver cancer took nearly four times longer to progress after yttrium-90 (Y90) radioembolization than after conventional transarterial chemoembolization (cTACE), according to a single-center, randomized, phase II trial of 45 patients reported in the December issue of Gastroenterology (2016 Aug 26. doi: 10.1053/j.gastro.2016.08.029).

Median time to progression remained unreached more than 26 months after patients underwent Y90 treatment, but was only 6.8 months in the cTACE group (P = .001), Riad Salem, MD, and his associates at Northwestern University,Chicago, reported. Slow accrual limited the study size, but a post-hoc analysis showed that Y90 would have a 97% chance of significantly outperforming chemoembolization if the study had reached its enrollment target, even if the difference in time to progression was less pronounced. Furthermore, Y90 significantly outperformed chemoembolization in a competing risk analysis that accounted for liver transplantation and death, the researchers said.

Conventional transarterial chemoembolization is used in intermediate-stage liver cancer when ablation is contraindicated. However, retrospective studies have favored Y90 radioembolization, a minimally invasive procedure in which a clinician implants radioactive micron-sized particles loaded with Y90 inside blood vessels supplying a tumor. To further study this approach, the investigators randomly assigned patients with unresectable, unablatable hepatocellular carcinoma without vascular invasion, who had Child-Pugh scores of A or B, serum bilirubin levels up to 2 mg/dL, and liver enzymes up to five times the normal upper limit, to undergo selective Y90 at a dose of 120 Gy, or lipiodol-based chemoembolization at a dose of 75 mg/m^2.

Source: American Gastroenterological Association

Of 179 eligible patients, 134 (75%) declined to participate in research, opted for other trials, or chose one protocol over the other. Consequently, only 21 patients were assigned to cTACE, while 24 underwent Y90. The groups resembled each other clinically and demographically at baseline, although Y90 patients tended to have more portal hypertension and higher serum bilirubin levels. No patients died within 30 days after treatment. Each group had one case of common femoral artery pseudoaneurysm. The Y90 patients tended to have more fatigue (P = .08), and had higher rates of diarrhea (P = .03) and hypoalbuminemia (P less than .001).

Despite the small group sizes, patients were about 88% less likely to progress at a given time point after Y90, compared with cTACE (hazard ratio, 0.12; 95% confidence interval, 0.03-0.56; P = .007). To explore what might have happened had the study reached target enrollment, the researchers added another 79 hypothetical patients at the 5.1-fold higher hazard ratio (0.625) that they had used in the power calculation. The results showed that Y90 had a 97% chance of statistically outperforming cTACE under these conditions.

Inverse probability of censoring weighting, which is performed to control for dependent censoring between groups, also showed that time to progression was significantly longer with Y90 than with cTACE, the investigators said. “While the relatively low sample size is acknowledged, the seminal studies establishing cTACE as the standard of care were also limited in sample size, [were] single center, and enrolled mostly Child-Pugh A patients,” they emphasized. “Our time to progression results favoring Y90 are in line with other uncontrolled retrospective reports in patients with compromised liver function, [but] our study validates such findings with prospective randomized level I evidence.”

The National Institutes of Health and the SIR Foundation provided funding. Dr. Salem and two coinvestigators reported serving as advisors to BTG. The other coinvestigators reported having no conflicts of interest.

BOSTON – Patients with serious liver disease who also had hepato-adrenal syndrome had significantly longer hospital stays; these patients had significantly longer ICU courses as well.

According to a recent study of this under-recognized syndrome, patients with cirrhosis, acute liver failure, or acute liver injury who also had clinically significant adrenocortical dysfunction had longer hospital stays when compared to patients without hepato-adrenal syndrome (HAS).
 

Presenting the study findings at a poster session at the annual meeting of the American Association for the Study of Liver Disease, Christina Lindenmeyer, MD, and her associates noted that the longer stays for HAS patients with serious liver disease held true even after adjustment for gender, blood glucose levels, and Child-Pugh score (median 29 days, HAS; 17 days, non-HAS; P = .001).

Further, the patients with HAS were more likely to have a prolonged ICU stay, after multivariable analysis adjusted for a variety of factors including the need for mechanical ventilation, age, bilirubin level, Model for End-stage Liver Disease (MELD) score, and severity of encephalopathy (13.5 vs. 4.9 days; P = .002).

“Patients with cirrhosis commonly have hypotension, and I think it’s underrecognized that the elevated levels of endotoxin and the low levels of lipoprotein circulating in patients with cirrhosis can lead to adrenocortical dysfunction,” Dr. Lindenmeyer said in a video interview.

The single-center study enrolled ICU patients with cirrhosis, acute liver injury, and/or acute liver failure who had random cortisol or adrenocorticotropin-releasing hormone (ACTH) stimulation test results. From 2008 to 2014, the tertiary care center saw 69 patients meeting these criteria; 32 patients (46%) had HAS. The mean age was 57.4 years, and 63.8% of enrolled patients were male. There were no significant differences in these demographics between the groups. Serum bicarbonate was higher in patients with HAS (21.4 vs. 17.5 mEq/L; P = .020); other blood chemistries, mean arterial pressures, and the MELD and Child-Pugh scores did not differ significantly between groups.

Dr. Lindenmeyer, a fellow in the Cleveland Clinic’s department of gastroenterology and hepatology, said that the accepted definition of HAS is a random cortisol level of less than 15 mcg/dL in “patients who were highly stressed in the ICU, typically with respiratory failure or hypotension,” she said. For non-ICU patients, the random cortisol level should be less than 20 mcg/dL. An alternative criterion is a post-ACTH stimulation test cortisol level of less than 20 mcg/dL.

Though there was no statistically significant difference between in-hospital mortality for those patients meeting HAS criteria, the trend was actually for those patients to have lower in-hospital mortality (44% vs. 51%; P = .53). This was true even after correction for MELD scores and serum potassium levels. Dr. Lindenmeyer said these results were “a little surprising,” and noted that the study didn’t examine 90-day or 1-year mortality. “That would be something interesting to look at,” she said.

“Early recognition and treatment of HAS may improve judicious allocation of critical care and hospital resources,” wrote Dr. Lindenmeyer and her colleagues.

Dr. Lindenmeyer reported no conflicts of interest, and there were no outside sources of funding reported.

[email protected]

On Twitter @karioakes

BOSTON – Patients with serious liver disease who also had hepato-adrenal syndrome had significantly longer hospital stays; these patients had significantly longer ICU courses as well.

According to a recent study of this under-recognized syndrome, patients with cirrhosis, acute liver failure, or acute liver injury who also had clinically significant adrenocortical dysfunction had longer hospital stays when compared to patients without hepato-adrenal syndrome (HAS).
 

Presenting the study findings at a poster session at the annual meeting of the American Association for the Study of Liver Disease, Christina Lindenmeyer, MD, and her associates noted that the longer stays for HAS patients with serious liver disease held true even after adjustment for gender, blood glucose levels, and Child-Pugh score (median 29 days, HAS; 17 days, non-HAS; P = .001).

Further, the patients with HAS were more likely to have a prolonged ICU stay, after multivariable analysis adjusted for a variety of factors including the need for mechanical ventilation, age, bilirubin level, Model for End-stage Liver Disease (MELD) score, and severity of encephalopathy (13.5 vs. 4.9 days; P = .002).

“Patients with cirrhosis commonly have hypotension, and I think it’s underrecognized that the elevated levels of endotoxin and the low levels of lipoprotein circulating in patients with cirrhosis can lead to adrenocortical dysfunction,” Dr. Lindenmeyer said in a video interview.

The single-center study enrolled ICU patients with cirrhosis, acute liver injury, and/or acute liver failure who had random cortisol or adrenocorticotropin-releasing hormone (ACTH) stimulation test results. From 2008 to 2014, the tertiary care center saw 69 patients meeting these criteria; 32 patients (46%) had HAS. The mean age was 57.4 years, and 63.8% of enrolled patients were male. There were no significant differences in these demographics between the groups. Serum bicarbonate was higher in patients with HAS (21.4 vs. 17.5 mEq/L; P = .020); other blood chemistries, mean arterial pressures, and the MELD and Child-Pugh scores did not differ significantly between groups.

Dr. Lindenmeyer, a fellow in the Cleveland Clinic’s department of gastroenterology and hepatology, said that the accepted definition of HAS is a random cortisol level of less than 15 mcg/dL in “patients who were highly stressed in the ICU, typically with respiratory failure or hypotension,” she said. For non-ICU patients, the random cortisol level should be less than 20 mcg/dL. An alternative criterion is a post-ACTH stimulation test cortisol level of less than 20 mcg/dL.

Though there was no statistically significant difference between in-hospital mortality for those patients meeting HAS criteria, the trend was actually for those patients to have lower in-hospital mortality (44% vs. 51%; P = .53). This was true even after correction for MELD scores and serum potassium levels. Dr. Lindenmeyer said these results were “a little surprising,” and noted that the study didn’t examine 90-day or 1-year mortality. “That would be something interesting to look at,” she said.

“Early recognition and treatment of HAS may improve judicious allocation of critical care and hospital resources,” wrote Dr. Lindenmeyer and her colleagues.

Dr. Lindenmeyer reported no conflicts of interest, and there were no outside sources of funding reported.

[email protected]

On Twitter @karioakes

BOSTON – Patients with serious liver disease who also had hepato-adrenal syndrome had significantly longer hospital stays; these patients had significantly longer ICU courses as well.

According to a recent study of this under-recognized syndrome, patients with cirrhosis, acute liver failure, or acute liver injury who also had clinically significant adrenocortical dysfunction had longer hospital stays when compared to patients without hepato-adrenal syndrome (HAS).
 

Presenting the study findings at a poster session at the annual meeting of the American Association for the Study of Liver Disease, Christina Lindenmeyer, MD, and her associates noted that the longer stays for HAS patients with serious liver disease held true even after adjustment for gender, blood glucose levels, and Child-Pugh score (median 29 days, HAS; 17 days, non-HAS; P = .001).

Further, the patients with HAS were more likely to have a prolonged ICU stay, after multivariable analysis adjusted for a variety of factors including the need for mechanical ventilation, age, bilirubin level, Model for End-stage Liver Disease (MELD) score, and severity of encephalopathy (13.5 vs. 4.9 days; P = .002).

“Patients with cirrhosis commonly have hypotension, and I think it’s underrecognized that the elevated levels of endotoxin and the low levels of lipoprotein circulating in patients with cirrhosis can lead to adrenocortical dysfunction,” Dr. Lindenmeyer said in a video interview.

The single-center study enrolled ICU patients with cirrhosis, acute liver injury, and/or acute liver failure who had random cortisol or adrenocorticotropin-releasing hormone (ACTH) stimulation test results. From 2008 to 2014, the tertiary care center saw 69 patients meeting these criteria; 32 patients (46%) had HAS. The mean age was 57.4 years, and 63.8% of enrolled patients were male. There were no significant differences in these demographics between the groups. Serum bicarbonate was higher in patients with HAS (21.4 vs. 17.5 mEq/L; P = .020); other blood chemistries, mean arterial pressures, and the MELD and Child-Pugh scores did not differ significantly between groups.

Dr. Lindenmeyer, a fellow in the Cleveland Clinic’s department of gastroenterology and hepatology, said that the accepted definition of HAS is a random cortisol level of less than 15 mcg/dL in “patients who were highly stressed in the ICU, typically with respiratory failure or hypotension,” she said. For non-ICU patients, the random cortisol level should be less than 20 mcg/dL. An alternative criterion is a post-ACTH stimulation test cortisol level of less than 20 mcg/dL.

Though there was no statistically significant difference between in-hospital mortality for those patients meeting HAS criteria, the trend was actually for those patients to have lower in-hospital mortality (44% vs. 51%; P = .53). This was true even after correction for MELD scores and serum potassium levels. Dr. Lindenmeyer said these results were “a little surprising,” and noted that the study didn’t examine 90-day or 1-year mortality. “That would be something interesting to look at,” she said.

“Early recognition and treatment of HAS may improve judicious allocation of critical care and hospital resources,” wrote Dr. Lindenmeyer and her colleagues.

Dr. Lindenmeyer reported no conflicts of interest, and there were no outside sources of funding reported.

[email protected]

On Twitter @karioakes

WASHINGTON – Denosumab built significantly more bone at the hip and lumbar spine than did risedronate when given for 1 year to patients with glucocorticoid-induced osteoporosis in an ongoing 2-year, head-to-head, randomized trial.

Denosumab (Prolia) is currently approved for the treatment of postmenopausal osteoporosis, and it performed so well in the trial that it could be put forward for the indication of glucocorticoid-induced osteoporosis as well, Kenneth Saag, MD, said at the annual meeting of the American College of Rheumatology.

“I would say there is definitely potential for this as a new therapeutic option for these patients,” he said in a video interview about the trial’s primary outcome of denosumab’s noninferiority to risedronate in percentage change in bone mineral density (BMD) at the lumbar spine after 1 year and secondary outcomes of the superiority of denosumab over risedronate in total hip and lumbar spine BMD at 1 year.

Denosumab is a particularly intriguing treatment option for patients with glucocorticoid-induced osteoporosis. They experience a double hit on bone health: increased RANKL, a protein that stimulates osteoclast development, and decreased osteoprotegerin, a protein that inhibits osteoclasts. Denosumab is a RANKL-inhibitor and, as such, tamps down on osteoclastic bone remodeling, said Dr. Saag, vice chair of the department of medicine and director of the Center for Education and Research on Therapeutics at the University of Alabama at Birmingham.

The phase III trial comprised 795 patients who were taking corticosteroids for a variety of rheumatic diseases, including rheumatoid arthritis, polymyalgia rheumatica, and systemic lupus erythematosus, and randomized them to denosumab or risedronate, which is already FDA approved for glucocorticoid-induced bone loss. Patients were randomized to 24 months of subcutaneous denosumab 60 mg given every 6 months or oral risedronate 5-mg daily. The study is still ongoing to test secondary outcomes at 24 months.

The patients were split into those who were continuing glucocorticoid therapy (505) and those who were just initiating it (290). Patients’ mean age ranged from 61 to 67 years, with the glucocorticoid-initiating group (GC-I) being somewhat older. The mean daily prednisone-equivalent dose was 16 mg in that group and 12 mg in the glucocorticoid-continuing group (GC-C). The mean BMD T-scores in the GC-C group were –1.96 at the lumbar spine and –1.56 at the total hip. In the GC-I group, BMD T-scores were –1.06 at the lumbar spine and –0.98 at the total hip.

In the GC-C group, denosumab increased BMD significantly more than risedronate at both spine and hip. At the lumbar spine, denosumab was associated with a mean increase of 4.4% over baseline, compared with a 2.3% increase with risedronate. Total hip BMD increased 2.1% with denosumab and 0.6% with risedronate.

The results were similar in the GC-I group. Denosumab increased lumbar spine BMD by 3.8% over baseline, compared with an increase of 0.8% with risedronate. Total hip BMD increased 1.7% with denosumab and 0.2% with risedronate.

Denosumab was also associated with significantly greater increases in femoral neck BMD in both groups, Dr. Saag noted. There were no significant differences in markers of bone turnover between the treatment groups. Adverse events, including pneumonia, diverticulitis, and bronchitis, were similar.

Amgen, manufacturer of denosumab, is sponsoring the 24-month study. Dr. Saag has been a consultant for Amgen. One coauthor is an employee of Amgen, and others disclosed financial relationships with Amgen and other pharmaceutical companies.

[email protected]

On Twitter @alz_gal

WASHINGTON – Denosumab built significantly more bone at the hip and lumbar spine than did risedronate when given for 1 year to patients with glucocorticoid-induced osteoporosis in an ongoing 2-year, head-to-head, randomized trial.

Denosumab (Prolia) is currently approved for the treatment of postmenopausal osteoporosis, and it performed so well in the trial that it could be put forward for the indication of glucocorticoid-induced osteoporosis as well, Kenneth Saag, MD, said at the annual meeting of the American College of Rheumatology.

“I would say there is definitely potential for this as a new therapeutic option for these patients,” he said in a video interview about the trial’s primary outcome of denosumab’s noninferiority to risedronate in percentage change in bone mineral density (BMD) at the lumbar spine after 1 year and secondary outcomes of the superiority of denosumab over risedronate in total hip and lumbar spine BMD at 1 year.

Denosumab is a particularly intriguing treatment option for patients with glucocorticoid-induced osteoporosis. They experience a double hit on bone health: increased RANKL, a protein that stimulates osteoclast development, and decreased osteoprotegerin, a protein that inhibits osteoclasts. Denosumab is a RANKL-inhibitor and, as such, tamps down on osteoclastic bone remodeling, said Dr. Saag, vice chair of the department of medicine and director of the Center for Education and Research on Therapeutics at the University of Alabama at Birmingham.

The phase III trial comprised 795 patients who were taking corticosteroids for a variety of rheumatic diseases, including rheumatoid arthritis, polymyalgia rheumatica, and systemic lupus erythematosus, and randomized them to denosumab or risedronate, which is already FDA approved for glucocorticoid-induced bone loss. Patients were randomized to 24 months of subcutaneous denosumab 60 mg given every 6 months or oral risedronate 5-mg daily. The study is still ongoing to test secondary outcomes at 24 months.

The patients were split into those who were continuing glucocorticoid therapy (505) and those who were just initiating it (290). Patients’ mean age ranged from 61 to 67 years, with the glucocorticoid-initiating group (GC-I) being somewhat older. The mean daily prednisone-equivalent dose was 16 mg in that group and 12 mg in the glucocorticoid-continuing group (GC-C). The mean BMD T-scores in the GC-C group were –1.96 at the lumbar spine and –1.56 at the total hip. In the GC-I group, BMD T-scores were –1.06 at the lumbar spine and –0.98 at the total hip.

In the GC-C group, denosumab increased BMD significantly more than risedronate at both spine and hip. At the lumbar spine, denosumab was associated with a mean increase of 4.4% over baseline, compared with a 2.3% increase with risedronate. Total hip BMD increased 2.1% with denosumab and 0.6% with risedronate.

The results were similar in the GC-I group. Denosumab increased lumbar spine BMD by 3.8% over baseline, compared with an increase of 0.8% with risedronate. Total hip BMD increased 1.7% with denosumab and 0.2% with risedronate.

Denosumab was also associated with significantly greater increases in femoral neck BMD in both groups, Dr. Saag noted. There were no significant differences in markers of bone turnover between the treatment groups. Adverse events, including pneumonia, diverticulitis, and bronchitis, were similar.

Amgen, manufacturer of denosumab, is sponsoring the 24-month study. Dr. Saag has been a consultant for Amgen. One coauthor is an employee of Amgen, and others disclosed financial relationships with Amgen and other pharmaceutical companies.

[email protected]

On Twitter @alz_gal

WASHINGTON – Denosumab built significantly more bone at the hip and lumbar spine than did risedronate when given for 1 year to patients with glucocorticoid-induced osteoporosis in an ongoing 2-year, head-to-head, randomized trial.

Denosumab (Prolia) is currently approved for the treatment of postmenopausal osteoporosis, and it performed so well in the trial that it could be put forward for the indication of glucocorticoid-induced osteoporosis as well, Kenneth Saag, MD, said at the annual meeting of the American College of Rheumatology.

“I would say there is definitely potential for this as a new therapeutic option for these patients,” he said in a video interview about the trial’s primary outcome of denosumab’s noninferiority to risedronate in percentage change in bone mineral density (BMD) at the lumbar spine after 1 year and secondary outcomes of the superiority of denosumab over risedronate in total hip and lumbar spine BMD at 1 year.

Denosumab is a particularly intriguing treatment option for patients with glucocorticoid-induced osteoporosis. They experience a double hit on bone health: increased RANKL, a protein that stimulates osteoclast development, and decreased osteoprotegerin, a protein that inhibits osteoclasts. Denosumab is a RANKL-inhibitor and, as such, tamps down on osteoclastic bone remodeling, said Dr. Saag, vice chair of the department of medicine and director of the Center for Education and Research on Therapeutics at the University of Alabama at Birmingham.

The phase III trial comprised 795 patients who were taking corticosteroids for a variety of rheumatic diseases, including rheumatoid arthritis, polymyalgia rheumatica, and systemic lupus erythematosus, and randomized them to denosumab or risedronate, which is already FDA approved for glucocorticoid-induced bone loss. Patients were randomized to 24 months of subcutaneous denosumab 60 mg given every 6 months or oral risedronate 5-mg daily. The study is still ongoing to test secondary outcomes at 24 months.

The patients were split into those who were continuing glucocorticoid therapy (505) and those who were just initiating it (290). Patients’ mean age ranged from 61 to 67 years, with the glucocorticoid-initiating group (GC-I) being somewhat older. The mean daily prednisone-equivalent dose was 16 mg in that group and 12 mg in the glucocorticoid-continuing group (GC-C). The mean BMD T-scores in the GC-C group were –1.96 at the lumbar spine and –1.56 at the total hip. In the GC-I group, BMD T-scores were –1.06 at the lumbar spine and –0.98 at the total hip.

In the GC-C group, denosumab increased BMD significantly more than risedronate at both spine and hip. At the lumbar spine, denosumab was associated with a mean increase of 4.4% over baseline, compared with a 2.3% increase with risedronate. Total hip BMD increased 2.1% with denosumab and 0.6% with risedronate.

The results were similar in the GC-I group. Denosumab increased lumbar spine BMD by 3.8% over baseline, compared with an increase of 0.8% with risedronate. Total hip BMD increased 1.7% with denosumab and 0.2% with risedronate.

Denosumab was also associated with significantly greater increases in femoral neck BMD in both groups, Dr. Saag noted. There were no significant differences in markers of bone turnover between the treatment groups. Adverse events, including pneumonia, diverticulitis, and bronchitis, were similar.

Amgen, manufacturer of denosumab, is sponsoring the 24-month study. Dr. Saag has been a consultant for Amgen. One coauthor is an employee of Amgen, and others disclosed financial relationships with Amgen and other pharmaceutical companies.

[email protected]

On Twitter @alz_gal

NEW ORLEANS – HeartMate 3, the latest left ventricular assist device in the HeartMate line, appears to have solved the problem of pump thrombosis, a complication that has dogged ventricular pumps since the issue leapt into medical awareness about 3 years ago (New Engl J Med. 2014 Jan 2;370:33-40).

During 6 months of follow-up, none of 152 heart failure patients assigned to receive a HeartMate 3 left ventricular assist device (LVAD) developed suspected or confirmed pump thrombosis, compared with 14 patients (10%) having pump thrombosis out of 138 recipients of the prior-generation HeartMate II LVAD who served as the control group for the study.

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

NEW ORLEANS – HeartMate 3, the latest left ventricular assist device in the HeartMate line, appears to have solved the problem of pump thrombosis, a complication that has dogged ventricular pumps since the issue leapt into medical awareness about 3 years ago (New Engl J Med. 2014 Jan 2;370:33-40).

During 6 months of follow-up, none of 152 heart failure patients assigned to receive a HeartMate 3 left ventricular assist device (LVAD) developed suspected or confirmed pump thrombosis, compared with 14 patients (10%) having pump thrombosis out of 138 recipients of the prior-generation HeartMate II LVAD who served as the control group for the study.

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

NEW ORLEANS – HeartMate 3, the latest left ventricular assist device in the HeartMate line, appears to have solved the problem of pump thrombosis, a complication that has dogged ventricular pumps since the issue leapt into medical awareness about 3 years ago (New Engl J Med. 2014 Jan 2;370:33-40).

During 6 months of follow-up, none of 152 heart failure patients assigned to receive a HeartMate 3 left ventricular assist device (LVAD) developed suspected or confirmed pump thrombosis, compared with 14 patients (10%) having pump thrombosis out of 138 recipients of the prior-generation HeartMate II LVAD who served as the control group for the study.

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

BOSTON – Though criteria for insurance approval for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) are loosening, many patients are still denied by both public and private carriers. Providers and patients should know that it’s worthwhile to appeal these denials; 78.1% (115 of 145) of initial DAA denials were approved on appeal, according to a recent study.

Jane Giang, PharmD, a clinical pharmacist at the University of North Carolina Health System, Chapel Hill, worked with colleagues to conduct a retrospective study of patients at her facility who were prescribed a DAA for HCV between October 2014 and April 2016.

Dr. Giang, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases, said that she works alongside physicians in her clinic to craft appeals, tailoring appeal letters to individual patients’ circumstances.

[email protected]

On Twitter@karioakes

BOSTON – Though criteria for insurance approval for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) are loosening, many patients are still denied by both public and private carriers. Providers and patients should know that it’s worthwhile to appeal these denials; 78.1% (115 of 145) of initial DAA denials were approved on appeal, according to a recent study.

Jane Giang, PharmD, a clinical pharmacist at the University of North Carolina Health System, Chapel Hill, worked with colleagues to conduct a retrospective study of patients at her facility who were prescribed a DAA for HCV between October 2014 and April 2016.

Dr. Giang, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases, said that she works alongside physicians in her clinic to craft appeals, tailoring appeal letters to individual patients’ circumstances.

[email protected]

On Twitter@karioakes

BOSTON – Though criteria for insurance approval for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) are loosening, many patients are still denied by both public and private carriers. Providers and patients should know that it’s worthwhile to appeal these denials; 78.1% (115 of 145) of initial DAA denials were approved on appeal, according to a recent study.

Jane Giang, PharmD, a clinical pharmacist at the University of North Carolina Health System, Chapel Hill, worked with colleagues to conduct a retrospective study of patients at her facility who were prescribed a DAA for HCV between October 2014 and April 2016.

Dr. Giang, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases, said that she works alongside physicians in her clinic to craft appeals, tailoring appeal letters to individual patients’ circumstances.

[email protected]

On Twitter@karioakes

WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.

The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.

The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.

The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.

The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.

“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.

The authors had no relevant financial disclosures.

WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.

The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.

The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.

The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.

The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.

“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.

The authors had no relevant financial disclosures.

WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.

The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.

The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.

The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.

The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.

“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.

The authors had no relevant financial disclosures.

LAS VEGAS – In a presentation at Skin Disease Education Foundation’s annual Las Vegas dermatology seminar, Miriam S. Bettencourt, MD, shared a challenging diagnostic case of erythema multiforme associated with herpes simplex, in a patient who presented with blisters all over his body.

“We know that 90% of cases of erythema multiforme are related to herpetic infections,” but this patient had no recent history of herpes simplex outbreaks, Dr. Bettencourt, of the University of Nevada, Las Vegas, said in a video interview.

‘“Let’s remember that HSV [herpes simplex virus] ... can be associated with erythema multiforme even if a patient does not have any flares,” Dr. Bettencourt said. A consult with a rheumatologist can be helpful, as in this case, if a patient has a positive antinuclear antibody test, which could not be explained, she added, noting that the patient is doing well after 6 months of therapy.

Dr. Bettencourt disclosed relationships with AbbVie, Allergan, Aqua, Celgene, Janssen, IntraDerm, Leo, Promius, and Valeant.

SDEF and this news organization are owned by the same parent company.

LAS VEGAS – In a presentation at Skin Disease Education Foundation’s annual Las Vegas dermatology seminar, Miriam S. Bettencourt, MD, shared a challenging diagnostic case of erythema multiforme associated with herpes simplex, in a patient who presented with blisters all over his body.

“We know that 90% of cases of erythema multiforme are related to herpetic infections,” but this patient had no recent history of herpes simplex outbreaks, Dr. Bettencourt, of the University of Nevada, Las Vegas, said in a video interview.

‘“Let’s remember that HSV [herpes simplex virus] ... can be associated with erythema multiforme even if a patient does not have any flares,” Dr. Bettencourt said. A consult with a rheumatologist can be helpful, as in this case, if a patient has a positive antinuclear antibody test, which could not be explained, she added, noting that the patient is doing well after 6 months of therapy.

Dr. Bettencourt disclosed relationships with AbbVie, Allergan, Aqua, Celgene, Janssen, IntraDerm, Leo, Promius, and Valeant.

SDEF and this news organization are owned by the same parent company.

LAS VEGAS – In a presentation at Skin Disease Education Foundation’s annual Las Vegas dermatology seminar, Miriam S. Bettencourt, MD, shared a challenging diagnostic case of erythema multiforme associated with herpes simplex, in a patient who presented with blisters all over his body.

“We know that 90% of cases of erythema multiforme are related to herpetic infections,” but this patient had no recent history of herpes simplex outbreaks, Dr. Bettencourt, of the University of Nevada, Las Vegas, said in a video interview.

‘“Let’s remember that HSV [herpes simplex virus] ... can be associated with erythema multiforme even if a patient does not have any flares,” Dr. Bettencourt said. A consult with a rheumatologist can be helpful, as in this case, if a patient has a positive antinuclear antibody test, which could not be explained, she added, noting that the patient is doing well after 6 months of therapy.

Dr. Bettencourt disclosed relationships with AbbVie, Allergan, Aqua, Celgene, Janssen, IntraDerm, Leo, Promius, and Valeant.

SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Both heating and cooling techniques can provide effective results for patients seeking to improve their appearance with body sculpting, Christopher Zachary, MD, said at Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Whether the clinician chooses devices that use radiofrequency, laser, or cryolipolysis to target fat, the key is bulk treatment, Dr. Zachary, professor and chair of the department of dermatology at the University of California, Irvine, said in a video interview.

When cooling or heating the fat, “it has to been done in bulk; it has to be done for a certain length of time,” he said, noting that treatment times vary with devices, from 5 to 60 minutes. “I can’t stress enough the importance of bulk cooling or bulk heating,” which induce a chronic reaction “that results in localized fat reduction,” he added.

Dr. Zachary disclosed relationships with multiple companies, including Solta, Zeltiq, Scion, Amway, and Candela. SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Both heating and cooling techniques can provide effective results for patients seeking to improve their appearance with body sculpting, Christopher Zachary, MD, said at Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Whether the clinician chooses devices that use radiofrequency, laser, or cryolipolysis to target fat, the key is bulk treatment, Dr. Zachary, professor and chair of the department of dermatology at the University of California, Irvine, said in a video interview.

When cooling or heating the fat, “it has to been done in bulk; it has to be done for a certain length of time,” he said, noting that treatment times vary with devices, from 5 to 60 minutes. “I can’t stress enough the importance of bulk cooling or bulk heating,” which induce a chronic reaction “that results in localized fat reduction,” he added.

Dr. Zachary disclosed relationships with multiple companies, including Solta, Zeltiq, Scion, Amway, and Candela. SDEF and this news organization are owned by the same parent company.

LAS VEGAS – Both heating and cooling techniques can provide effective results for patients seeking to improve their appearance with body sculpting, Christopher Zachary, MD, said at Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Whether the clinician chooses devices that use radiofrequency, laser, or cryolipolysis to target fat, the key is bulk treatment, Dr. Zachary, professor and chair of the department of dermatology at the University of California, Irvine, said in a video interview.

When cooling or heating the fat, “it has to been done in bulk; it has to be done for a certain length of time,” he said, noting that treatment times vary with devices, from 5 to 60 minutes. “I can’t stress enough the importance of bulk cooling or bulk heating,” which induce a chronic reaction “that results in localized fat reduction,” he added.

Dr. Zachary disclosed relationships with multiple companies, including Solta, Zeltiq, Scion, Amway, and Candela. SDEF and this news organization are owned by the same parent company.

WASHINGTON – New American College of Rheumatology recommendations for glucocorticoid-induced osteoporosis prevention and treatment include refinements in risk assessment and treatment.

“These are draft recommendations not yet accepted by ACR,” said Lenore M. Buckley, MD, of Yale University, New Haven, Conn. “They are intended to be dynamic, because risk factors change for patients over time,” she added.

The draft recommendations build upon the 2010 ACR recommendations.

“About 1% of the United States population is on glucocorticoid treatment. Fracture is the most common adverse event, and trabecular bone in the spine is the most vulnerable,” Dr. Buckley explained in her presentation of the recommendations at the annual meeting of the American College of Rheumatology. “The risk of glucocorticoid (GC)-induced fracture is related to dose level and cumulative dose.”

Recommendations for risk assessment

Risk assessment for GC-induced osteoporosis is individualized. “You need to know the patient in front of you. Fracture risk is not just related to GC use, but also to bone mass, age, and race. Older age, female gender, Caucasian race all increase risk, and these factors need to be brought in to assessment,” Dr. Buckley explained.

For men and women over age 40, the Fracture Risk Assessment Tool (FRAX), which calculates the 10-year fracture risk in adults over age 40, should be used for risk assessment, incorporating GC use as a risk factor, she said.

“Adjust risk of FRAX according to dose of glucocorticoid. For 2.5-7.5 mg/day, the FRAX risk is fine, but if the patient is on higher doses, adjust the FRAX accordingly,” she said.

FRAX is not valid for women and men under age 40, she continued. A new recommendation is the inclusion of a moderate risk group based on very low bone mass score (Z score less than –3 below the standard deviation of the mean) and/or rapid bone loss (greater than 10% in 1 year). Patients who had prior GC-associated fracture under 40 years are considered high risk.

A thorough history and physical exam are necessary for all patients, and risk assessment should be done within 6 months of GC initiation. Physical exam should be repeated annually, and bone mineral density (BMD) should be assessed every 2-3 years for patients who continue on GC.
 

Treatment

The proposed treatment recommendations were not age dependent. Patients with moderate to high risk should be treated, in descending order, with oral bisphosphonates, intravenous bisphosphonates, teriparatide (Forteo), and denosumab (Prolia). The order of preference for these treatments was based on cost, efficacy, toxicity, and patient preference.

All patients should take calcium and vitamin D, regardless of risk level.

The proposed recommendations also addressed four special groups considered at significant risk: women of childbearing potential, organ transplant recipients, children, and people on very high doses of GC (greater than 30 mg/day, cumulative dose of 5 g/year).

“For women of childbearing potential, there are emerging data suggesting that bisphosphonates are safe. For this group, consider oral bisphosphonate and teriparatide as a second choice. Animal data suggest that IV bisphosphonates and denosumab are harmful to the fetus,” Dr. Buckley said.

For organ transplant recipients, general recommendations can be followed with two provisions: Kidney transplant recipients should have a work-up for metabolic bone disease, and denosumab should not be used in people on multiple immunosuppressants.

Optimize calcium and vitamin D for children, and treat with oral bisphosphonate, Dr. Buckley continued. If oral bisphosphonates are contraindicated, IV bisphosphonates can be used.

Patients on very high GC dose should be treated with oral bisphosphonates if they are age 30 or older.

Osteoporosis medications can be discontinued in low-risk patients who stop taking GC, but should be continued for those at moderate to high risk.

Patients who benefit from osteoporosis medications but remain at moderate to high risk at the end of 3 years should continue GC treatment.

The authors and sponsors had no relevant financial disclosures.

WASHINGTON – New American College of Rheumatology recommendations for glucocorticoid-induced osteoporosis prevention and treatment include refinements in risk assessment and treatment.

“These are draft recommendations not yet accepted by ACR,” said Lenore M. Buckley, MD, of Yale University, New Haven, Conn. “They are intended to be dynamic, because risk factors change for patients over time,” she added.

The draft recommendations build upon the 2010 ACR recommendations.

“About 1% of the United States population is on glucocorticoid treatment. Fracture is the most common adverse event, and trabecular bone in the spine is the most vulnerable,” Dr. Buckley explained in her presentation of the recommendations at the annual meeting of the American College of Rheumatology. “The risk of glucocorticoid (GC)-induced fracture is related to dose level and cumulative dose.”

Recommendations for risk assessment

Risk assessment for GC-induced osteoporosis is individualized. “You need to know the patient in front of you. Fracture risk is not just related to GC use, but also to bone mass, age, and race. Older age, female gender, Caucasian race all increase risk, and these factors need to be brought in to assessment,” Dr. Buckley explained.

For men and women over age 40, the Fracture Risk Assessment Tool (FRAX), which calculates the 10-year fracture risk in adults over age 40, should be used for risk assessment, incorporating GC use as a risk factor, she said.

“Adjust risk of FRAX according to dose of glucocorticoid. For 2.5-7.5 mg/day, the FRAX risk is fine, but if the patient is on higher doses, adjust the FRAX accordingly,” she said.

FRAX is not valid for women and men under age 40, she continued. A new recommendation is the inclusion of a moderate risk group based on very low bone mass score (Z score less than –3 below the standard deviation of the mean) and/or rapid bone loss (greater than 10% in 1 year). Patients who had prior GC-associated fracture under 40 years are considered high risk.

A thorough history and physical exam are necessary for all patients, and risk assessment should be done within 6 months of GC initiation. Physical exam should be repeated annually, and bone mineral density (BMD) should be assessed every 2-3 years for patients who continue on GC.
 

Treatment

The proposed treatment recommendations were not age dependent. Patients with moderate to high risk should be treated, in descending order, with oral bisphosphonates, intravenous bisphosphonates, teriparatide (Forteo), and denosumab (Prolia). The order of preference for these treatments was based on cost, efficacy, toxicity, and patient preference.

All patients should take calcium and vitamin D, regardless of risk level.

The proposed recommendations also addressed four special groups considered at significant risk: women of childbearing potential, organ transplant recipients, children, and people on very high doses of GC (greater than 30 mg/day, cumulative dose of 5 g/year).

“For women of childbearing potential, there are emerging data suggesting that bisphosphonates are safe. For this group, consider oral bisphosphonate and teriparatide as a second choice. Animal data suggest that IV bisphosphonates and denosumab are harmful to the fetus,” Dr. Buckley said.

For organ transplant recipients, general recommendations can be followed with two provisions: Kidney transplant recipients should have a work-up for metabolic bone disease, and denosumab should not be used in people on multiple immunosuppressants.

Optimize calcium and vitamin D for children, and treat with oral bisphosphonate, Dr. Buckley continued. If oral bisphosphonates are contraindicated, IV bisphosphonates can be used.

Patients on very high GC dose should be treated with oral bisphosphonates if they are age 30 or older.

Osteoporosis medications can be discontinued in low-risk patients who stop taking GC, but should be continued for those at moderate to high risk.

Patients who benefit from osteoporosis medications but remain at moderate to high risk at the end of 3 years should continue GC treatment.

The authors and sponsors had no relevant financial disclosures.

WASHINGTON – New American College of Rheumatology recommendations for glucocorticoid-induced osteoporosis prevention and treatment include refinements in risk assessment and treatment.

“These are draft recommendations not yet accepted by ACR,” said Lenore M. Buckley, MD, of Yale University, New Haven, Conn. “They are intended to be dynamic, because risk factors change for patients over time,” she added.

The draft recommendations build upon the 2010 ACR recommendations.

“About 1% of the United States population is on glucocorticoid treatment. Fracture is the most common adverse event, and trabecular bone in the spine is the most vulnerable,” Dr. Buckley explained in her presentation of the recommendations at the annual meeting of the American College of Rheumatology. “The risk of glucocorticoid (GC)-induced fracture is related to dose level and cumulative dose.”

Recommendations for risk assessment

Risk assessment for GC-induced osteoporosis is individualized. “You need to know the patient in front of you. Fracture risk is not just related to GC use, but also to bone mass, age, and race. Older age, female gender, Caucasian race all increase risk, and these factors need to be brought in to assessment,” Dr. Buckley explained.

For men and women over age 40, the Fracture Risk Assessment Tool (FRAX), which calculates the 10-year fracture risk in adults over age 40, should be used for risk assessment, incorporating GC use as a risk factor, she said.

“Adjust risk of FRAX according to dose of glucocorticoid. For 2.5-7.5 mg/day, the FRAX risk is fine, but if the patient is on higher doses, adjust the FRAX accordingly,” she said.

FRAX is not valid for women and men under age 40, she continued. A new recommendation is the inclusion of a moderate risk group based on very low bone mass score (Z score less than –3 below the standard deviation of the mean) and/or rapid bone loss (greater than 10% in 1 year). Patients who had prior GC-associated fracture under 40 years are considered high risk.

A thorough history and physical exam are necessary for all patients, and risk assessment should be done within 6 months of GC initiation. Physical exam should be repeated annually, and bone mineral density (BMD) should be assessed every 2-3 years for patients who continue on GC.
 

Treatment

The proposed treatment recommendations were not age dependent. Patients with moderate to high risk should be treated, in descending order, with oral bisphosphonates, intravenous bisphosphonates, teriparatide (Forteo), and denosumab (Prolia). The order of preference for these treatments was based on cost, efficacy, toxicity, and patient preference.

All patients should take calcium and vitamin D, regardless of risk level.

The proposed recommendations also addressed four special groups considered at significant risk: women of childbearing potential, organ transplant recipients, children, and people on very high doses of GC (greater than 30 mg/day, cumulative dose of 5 g/year).

“For women of childbearing potential, there are emerging data suggesting that bisphosphonates are safe. For this group, consider oral bisphosphonate and teriparatide as a second choice. Animal data suggest that IV bisphosphonates and denosumab are harmful to the fetus,” Dr. Buckley said.

For organ transplant recipients, general recommendations can be followed with two provisions: Kidney transplant recipients should have a work-up for metabolic bone disease, and denosumab should not be used in people on multiple immunosuppressants.

Optimize calcium and vitamin D for children, and treat with oral bisphosphonate, Dr. Buckley continued. If oral bisphosphonates are contraindicated, IV bisphosphonates can be used.

Patients on very high GC dose should be treated with oral bisphosphonates if they are age 30 or older.

Osteoporosis medications can be discontinued in low-risk patients who stop taking GC, but should be continued for those at moderate to high risk.

Patients who benefit from osteoporosis medications but remain at moderate to high risk at the end of 3 years should continue GC treatment.

The authors and sponsors had no relevant financial disclosures.