Individualizing risk prediction for positive COVID-19 testing: results from 11,672 patients. By Dr. Lara Jehi, et al.



Airway clearance techniques in bronchiectasis: Analysis from the United States Bronchiectasis and NTM research registry. By Dr. Ashwin Basavaraj, et al.



Emotional experiences and coping strategies of family members of critically ill patients. By Dr. Emily Harlan, et al.



Coronavirus disease and smoking: How and why we implemented a tobacco treatment campaign. By Dr. Adam Lang, et al.

Individualizing risk prediction for positive COVID-19 testing: results from 11,672 patients. By Dr. Lara Jehi, et al.



Airway clearance techniques in bronchiectasis: Analysis from the United States Bronchiectasis and NTM research registry. By Dr. Ashwin Basavaraj, et al.



Emotional experiences and coping strategies of family members of critically ill patients. By Dr. Emily Harlan, et al.



Coronavirus disease and smoking: How and why we implemented a tobacco treatment campaign. By Dr. Adam Lang, et al.

Individualizing risk prediction for positive COVID-19 testing: results from 11,672 patients. By Dr. Lara Jehi, et al.



Airway clearance techniques in bronchiectasis: Analysis from the United States Bronchiectasis and NTM research registry. By Dr. Ashwin Basavaraj, et al.



Emotional experiences and coping strategies of family members of critically ill patients. By Dr. Emily Harlan, et al.



Coronavirus disease and smoking: How and why we implemented a tobacco treatment campaign. By Dr. Adam Lang, et al.

Join the CHEST Foundation at one of its many virtual events designed around the three pillars of the organization—access, empowerment, and research—during CHEST 2020. Please check CHESTMeeting.chestnet.org for more details on each event.
 

Virtual Champion’s Circle Donor Lounge

The virtual donor lounge will act as the hub of a wheel – linking the spokes of Foundation programming and events to a central location for easy accessibility. Foundation staff and Board of Trustee members will staff the donor lounge throughout the meeting.
 

Women & Pulmonary Event – Sunday, October 18 at 11:00 AM – 12:30 PM CT

Connect with key thought leaders and participants to support the advancement of women in the fields of pulmonary, critical care, sleep medicine, and in leadership. The event includes a panel discussion on How to remain in control during a pandemic: family, career and mental wellness, followed by an intimate roundtable discussion moderated by the Women & Pulmonary council. RSVPs are necessary to attend this event.
 

CHEST Foundation Donor Reception– Sunday, October 18 7:30 PM CT

Join your colleagues and CHEST leadership for a night of fun and networking. Learn to play Texas Hold’em in a complimentary, casual poker tournament and join the high stakes tournament later this month!

Wine Night with CEO Bob Musacchio – Invite Only – Sunday, October 18 7:30 CST

Join CHEST’s CEO, Bob Musacchio for an interactive, exclusive wine night. The evening will include wine chosen from Bob’s personal favorites and kick off the CHEST 2020 annual meeting as we have never done before!
 

Young Professionals Reception – Monday, October 19, 2020 at 8:00 PM CT – Invite Only

Join your colleagues for a fun evening of trivia, prizes, and celebration! Let the Foundation show some appreciation for your commitment to chest medicine and come learn more about our work!

 

Join the CHEST Foundation at one of its many virtual events designed around the three pillars of the organization—access, empowerment, and research—during CHEST 2020. Please check CHESTMeeting.chestnet.org for more details on each event.
 

Virtual Champion’s Circle Donor Lounge

The virtual donor lounge will act as the hub of a wheel – linking the spokes of Foundation programming and events to a central location for easy accessibility. Foundation staff and Board of Trustee members will staff the donor lounge throughout the meeting.
 

Women & Pulmonary Event – Sunday, October 18 at 11:00 AM – 12:30 PM CT

Connect with key thought leaders and participants to support the advancement of women in the fields of pulmonary, critical care, sleep medicine, and in leadership. The event includes a panel discussion on How to remain in control during a pandemic: family, career and mental wellness, followed by an intimate roundtable discussion moderated by the Women & Pulmonary council. RSVPs are necessary to attend this event.
 

CHEST Foundation Donor Reception– Sunday, October 18 7:30 PM CT

Join your colleagues and CHEST leadership for a night of fun and networking. Learn to play Texas Hold’em in a complimentary, casual poker tournament and join the high stakes tournament later this month!

Wine Night with CEO Bob Musacchio – Invite Only – Sunday, October 18 7:30 CST

Join CHEST’s CEO, Bob Musacchio for an interactive, exclusive wine night. The evening will include wine chosen from Bob’s personal favorites and kick off the CHEST 2020 annual meeting as we have never done before!
 

Young Professionals Reception – Monday, October 19, 2020 at 8:00 PM CT – Invite Only

Join your colleagues for a fun evening of trivia, prizes, and celebration! Let the Foundation show some appreciation for your commitment to chest medicine and come learn more about our work!

 

Join the CHEST Foundation at one of its many virtual events designed around the three pillars of the organization—access, empowerment, and research—during CHEST 2020. Please check CHESTMeeting.chestnet.org for more details on each event.
 

Virtual Champion’s Circle Donor Lounge

The virtual donor lounge will act as the hub of a wheel – linking the spokes of Foundation programming and events to a central location for easy accessibility. Foundation staff and Board of Trustee members will staff the donor lounge throughout the meeting.
 

Women & Pulmonary Event – Sunday, October 18 at 11:00 AM – 12:30 PM CT

Connect with key thought leaders and participants to support the advancement of women in the fields of pulmonary, critical care, sleep medicine, and in leadership. The event includes a panel discussion on How to remain in control during a pandemic: family, career and mental wellness, followed by an intimate roundtable discussion moderated by the Women & Pulmonary council. RSVPs are necessary to attend this event.
 

CHEST Foundation Donor Reception– Sunday, October 18 7:30 PM CT

Join your colleagues and CHEST leadership for a night of fun and networking. Learn to play Texas Hold’em in a complimentary, casual poker tournament and join the high stakes tournament later this month!

Wine Night with CEO Bob Musacchio – Invite Only – Sunday, October 18 7:30 CST

Join CHEST’s CEO, Bob Musacchio for an interactive, exclusive wine night. The evening will include wine chosen from Bob’s personal favorites and kick off the CHEST 2020 annual meeting as we have never done before!
 

Young Professionals Reception – Monday, October 19, 2020 at 8:00 PM CT – Invite Only

Join your colleagues for a fun evening of trivia, prizes, and celebration! Let the Foundation show some appreciation for your commitment to chest medicine and come learn more about our work!

 

A final report from the multinational placebo-controlled ACTT-1 trial confirms that remdesivir is effective and well tolerated for shortening the time to recovery from COVID-19 infection.

In May 2020, remdesivir received Food and Drug Administration approval for emergency treatment of severe COVID-19 on the basis of a preliminary report on this trial. In August 2020, the FDA expanded the indication to include all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19 infection irrespective of severity.

“Our findings were consistent with the findings of the preliminary report: a 10-day course of remdesivir was superior to placebo in the treatment of hospitalized patients with COVID-19,” reported a team of investigators led by John H. Beigel, MD, of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, in the New England Journal of Medicine.

The drug’s broadened indication was not based on the ACTT-1 trial, according to Dr. Beigel. “Other data have demonstrated that remdesivir shortens recovery in patients with lower acuity. In our study, evidence of pneumonia was an enrollment requirement,” he explained in an interview.

In the newly published final ACTT-1 data, the median time to recovery was 10 days for those on active therapy versus 15 days for those randomized to placebo. With a rate ratio of 1.29 (P less than .001), this translated to a recovery that was about one third faster.

In this final report, remdesivir’s significant advantage over placebo regarding the trial’s primary endpoint was reinforced by efficacy on multiple secondary endpoints.

This benefits on multiple secondary endpoints included a 50% greater odds ratio (OR, 1.5; 95% CI, 1.2-1.9) of significant clinical improvement by day 15 after adjustment for baseline severity, a shorter initial length of hospital stay (12 vs. 17 days) and fewer days on oxygen supplementation (13 vs. 21 days) for the subgroup of patients on oxygen at enrollment.

Although the numerically lower mortality in the remdesivir arm (6.75 vs. 11.9%) did not reach statistical significance, Dr. Beigel said, “mortality was moving in the same direction as the other key endpoints.”

According to the study investigators, the types of rates of adverse events on remdesivir, which inhibits viral replication, “were generally similar in the remdesivir and placebo groups.”

In ACTT-1, 1,062 patients were randomized to remdesivir (200 mg loading dose followed by 100 mg daily for up to 9 days) or placebo. Patients were enrolled at study sites in North America, Europe, and Asia.

The data of ACTT-1 confirm a benefit from remdesivir in hospitalized COVID-19 patients with severe disease, but Dr. Beigel said he agrees with the current FDA indication that supports treatment in any hospitalized COVID-19 patient.

“We saw bigger benefits in patients with more severe infections. The benefits are not as large in patients with mild disease, but I think remdesivir should be considered in any hospitalized patient,” Dr. Beigel said.

This point of view is shared.

“I would give this drug to anyone in the hospital infected with COVID-19 assuming there was an ample supply and no need for rationing,” said Donna E. Sweet, MD, professor of internal medicine, University of Kansas, Wichita. She noted that this study has implications for hospital and hospital staff, as well as for patients.

“This type of reduction in recovery time means a reduction in potential exposures to hospital staff, a reduced need for PPE [personal protective equipment], and it will free up beds in the ICU [intensive care unit],” said Dr. Sweet, who also serves as an editorial advisory board member for Internal Medicine News.

An infectious disease specialist at the University of Minnesota also considers remdesivir to have an important role for conserving resources that deserves emphasis.

The reduction in time to recovery “is of benefit to the health system by maintaining hospital bed capacity,” said David R. Boulware, MD, professor of medicine at the University of Minnesota, Minneapolis.

According to his reading of the available data, including those from ACTT-1, the benefit appears to be greatest in those with a moderate degree of illness, which he defined as “sick enough to be hospitalized and require oxygen, yet not severely sick [and] requiring a ventilator or [extracorporeal membrane oxygenation].”

This does not preclude a benefit in those with more severe or milder disease, but patients with mild disease “are likely to recover regardless – or despite – whatever therapy they receive,” he said.

Dr. Beigel, the principal investigator of this trial, reports no potential conflicts of interest.

SOURCE: Beigel JH et al. N Engl J Med. 2020 Oct 8. doi: 10.1056/NEJMoa2007764.

A final report from the multinational placebo-controlled ACTT-1 trial confirms that remdesivir is effective and well tolerated for shortening the time to recovery from COVID-19 infection.

In May 2020, remdesivir received Food and Drug Administration approval for emergency treatment of severe COVID-19 on the basis of a preliminary report on this trial. In August 2020, the FDA expanded the indication to include all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19 infection irrespective of severity.

“Our findings were consistent with the findings of the preliminary report: a 10-day course of remdesivir was superior to placebo in the treatment of hospitalized patients with COVID-19,” reported a team of investigators led by John H. Beigel, MD, of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, in the New England Journal of Medicine.

The drug’s broadened indication was not based on the ACTT-1 trial, according to Dr. Beigel. “Other data have demonstrated that remdesivir shortens recovery in patients with lower acuity. In our study, evidence of pneumonia was an enrollment requirement,” he explained in an interview.

In the newly published final ACTT-1 data, the median time to recovery was 10 days for those on active therapy versus 15 days for those randomized to placebo. With a rate ratio of 1.29 (P less than .001), this translated to a recovery that was about one third faster.

In this final report, remdesivir’s significant advantage over placebo regarding the trial’s primary endpoint was reinforced by efficacy on multiple secondary endpoints.

This benefits on multiple secondary endpoints included a 50% greater odds ratio (OR, 1.5; 95% CI, 1.2-1.9) of significant clinical improvement by day 15 after adjustment for baseline severity, a shorter initial length of hospital stay (12 vs. 17 days) and fewer days on oxygen supplementation (13 vs. 21 days) for the subgroup of patients on oxygen at enrollment.

Although the numerically lower mortality in the remdesivir arm (6.75 vs. 11.9%) did not reach statistical significance, Dr. Beigel said, “mortality was moving in the same direction as the other key endpoints.”

According to the study investigators, the types of rates of adverse events on remdesivir, which inhibits viral replication, “were generally similar in the remdesivir and placebo groups.”

In ACTT-1, 1,062 patients were randomized to remdesivir (200 mg loading dose followed by 100 mg daily for up to 9 days) or placebo. Patients were enrolled at study sites in North America, Europe, and Asia.

The data of ACTT-1 confirm a benefit from remdesivir in hospitalized COVID-19 patients with severe disease, but Dr. Beigel said he agrees with the current FDA indication that supports treatment in any hospitalized COVID-19 patient.

“We saw bigger benefits in patients with more severe infections. The benefits are not as large in patients with mild disease, but I think remdesivir should be considered in any hospitalized patient,” Dr. Beigel said.

This point of view is shared.

“I would give this drug to anyone in the hospital infected with COVID-19 assuming there was an ample supply and no need for rationing,” said Donna E. Sweet, MD, professor of internal medicine, University of Kansas, Wichita. She noted that this study has implications for hospital and hospital staff, as well as for patients.

“This type of reduction in recovery time means a reduction in potential exposures to hospital staff, a reduced need for PPE [personal protective equipment], and it will free up beds in the ICU [intensive care unit],” said Dr. Sweet, who also serves as an editorial advisory board member for Internal Medicine News.

An infectious disease specialist at the University of Minnesota also considers remdesivir to have an important role for conserving resources that deserves emphasis.

The reduction in time to recovery “is of benefit to the health system by maintaining hospital bed capacity,” said David R. Boulware, MD, professor of medicine at the University of Minnesota, Minneapolis.

According to his reading of the available data, including those from ACTT-1, the benefit appears to be greatest in those with a moderate degree of illness, which he defined as “sick enough to be hospitalized and require oxygen, yet not severely sick [and] requiring a ventilator or [extracorporeal membrane oxygenation].”

This does not preclude a benefit in those with more severe or milder disease, but patients with mild disease “are likely to recover regardless – or despite – whatever therapy they receive,” he said.

Dr. Beigel, the principal investigator of this trial, reports no potential conflicts of interest.

SOURCE: Beigel JH et al. N Engl J Med. 2020 Oct 8. doi: 10.1056/NEJMoa2007764.

A final report from the multinational placebo-controlled ACTT-1 trial confirms that remdesivir is effective and well tolerated for shortening the time to recovery from COVID-19 infection.

In May 2020, remdesivir received Food and Drug Administration approval for emergency treatment of severe COVID-19 on the basis of a preliminary report on this trial. In August 2020, the FDA expanded the indication to include all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19 infection irrespective of severity.

“Our findings were consistent with the findings of the preliminary report: a 10-day course of remdesivir was superior to placebo in the treatment of hospitalized patients with COVID-19,” reported a team of investigators led by John H. Beigel, MD, of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, in the New England Journal of Medicine.

The drug’s broadened indication was not based on the ACTT-1 trial, according to Dr. Beigel. “Other data have demonstrated that remdesivir shortens recovery in patients with lower acuity. In our study, evidence of pneumonia was an enrollment requirement,” he explained in an interview.

In the newly published final ACTT-1 data, the median time to recovery was 10 days for those on active therapy versus 15 days for those randomized to placebo. With a rate ratio of 1.29 (P less than .001), this translated to a recovery that was about one third faster.

In this final report, remdesivir’s significant advantage over placebo regarding the trial’s primary endpoint was reinforced by efficacy on multiple secondary endpoints.

This benefits on multiple secondary endpoints included a 50% greater odds ratio (OR, 1.5; 95% CI, 1.2-1.9) of significant clinical improvement by day 15 after adjustment for baseline severity, a shorter initial length of hospital stay (12 vs. 17 days) and fewer days on oxygen supplementation (13 vs. 21 days) for the subgroup of patients on oxygen at enrollment.

Although the numerically lower mortality in the remdesivir arm (6.75 vs. 11.9%) did not reach statistical significance, Dr. Beigel said, “mortality was moving in the same direction as the other key endpoints.”

According to the study investigators, the types of rates of adverse events on remdesivir, which inhibits viral replication, “were generally similar in the remdesivir and placebo groups.”

In ACTT-1, 1,062 patients were randomized to remdesivir (200 mg loading dose followed by 100 mg daily for up to 9 days) or placebo. Patients were enrolled at study sites in North America, Europe, and Asia.

The data of ACTT-1 confirm a benefit from remdesivir in hospitalized COVID-19 patients with severe disease, but Dr. Beigel said he agrees with the current FDA indication that supports treatment in any hospitalized COVID-19 patient.

“We saw bigger benefits in patients with more severe infections. The benefits are not as large in patients with mild disease, but I think remdesivir should be considered in any hospitalized patient,” Dr. Beigel said.

This point of view is shared.

“I would give this drug to anyone in the hospital infected with COVID-19 assuming there was an ample supply and no need for rationing,” said Donna E. Sweet, MD, professor of internal medicine, University of Kansas, Wichita. She noted that this study has implications for hospital and hospital staff, as well as for patients.

“This type of reduction in recovery time means a reduction in potential exposures to hospital staff, a reduced need for PPE [personal protective equipment], and it will free up beds in the ICU [intensive care unit],” said Dr. Sweet, who also serves as an editorial advisory board member for Internal Medicine News.

An infectious disease specialist at the University of Minnesota also considers remdesivir to have an important role for conserving resources that deserves emphasis.

The reduction in time to recovery “is of benefit to the health system by maintaining hospital bed capacity,” said David R. Boulware, MD, professor of medicine at the University of Minnesota, Minneapolis.

According to his reading of the available data, including those from ACTT-1, the benefit appears to be greatest in those with a moderate degree of illness, which he defined as “sick enough to be hospitalized and require oxygen, yet not severely sick [and] requiring a ventilator or [extracorporeal membrane oxygenation].”

This does not preclude a benefit in those with more severe or milder disease, but patients with mild disease “are likely to recover regardless – or despite – whatever therapy they receive,” he said.

Dr. Beigel, the principal investigator of this trial, reports no potential conflicts of interest.

SOURCE: Beigel JH et al. N Engl J Med. 2020 Oct 8. doi: 10.1056/NEJMoa2007764.

Some young women can present with very low bone density and multiple fragility fractures. While multiple FDA-approved therapies exist for post-menopausal osteoporosis, pre-menopausal osteoporosis remains an “orphan disease.” Previous evidence suggests that bone anabolic agents such as teriparatide may be useful for women with idiopathic pre-menopausal osteoporosis (IOP). In a phase 2 randomized clinical trial from New York and Nebraska, 41 women with IOP and multiple fractures were randomized to receive placebo or teriparatide in a cross-over study design. The primary endpoint was bone density in the spine and hip after 6 months of treatment, which was significantly increased by teriparatide versus placebo. In addition, bone biopsies were obtained for measurement of bone formation rate using quadruple labeling with tetracycline and demeclocycline three months into treatment. As expected, biopsies showed that teriparatide treatment increased bone formation rates using this ‘gold standard’ method. This prospective randomized study adds to a growing body of evidence that teriparatide may be a safe method to boost bone density in women with IOP. Future studies are needed to assess the impact of this therapy on fracture risk in this specific patient population.

Type 2 diabetes and osteoporosis are both major problems in our aging population. While some diabetes medications such as thiazolidinediones clearly increase fracture risk, the effects of newer diabetes medications on bone biology and fracture risk remain incompletely understood. In addition to beneficial effects on glycemic control, SGLT2 inhibitors show promise with improving cardiovascular and renal outcomes, even in patients without diabetes. Some studies have suggested adverse effects of SGLT2 inhibitor monotherapy on bone density and fracture risk. However, the impact of combined therapy with SGLT2 inhibitors and metformin on fracture risk remains to be established. In this meta-analysis of 25 randomized controlled trials involving 19,500 patients, fracture risk was assessed, based on available information, for individuals who received metformin monotherapy or metformin plus SGLT2 inhibitor treatment. In general, combination therapy did not increase fracture risk compared to metformin alone. Only 6 of the 25 RCTs included in the meta-analysis investigated bone density or bone turnover markers. In these 6 studies, no obvious changes in skeletal outcomes were noted when comparing metformin alone versus metformin plus SGLT2 inhibitor therapy. Although these data are somewhat reassuring for the skeletal safety of combination metformin/SGLT2 inhibitor therapy, confidence is limited by relatively short follow-up time and lack of detailed information about fractures in these studies which focused primarily on diabetes-related outcomes. Future prospective studies are needed to specifically address the skeletal impact of this commonly-used combination of diabetes medications.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Some young women can present with very low bone density and multiple fragility fractures. While multiple FDA-approved therapies exist for post-menopausal osteoporosis, pre-menopausal osteoporosis remains an “orphan disease.” Previous evidence suggests that bone anabolic agents such as teriparatide may be useful for women with idiopathic pre-menopausal osteoporosis (IOP). In a phase 2 randomized clinical trial from New York and Nebraska, 41 women with IOP and multiple fractures were randomized to receive placebo or teriparatide in a cross-over study design. The primary endpoint was bone density in the spine and hip after 6 months of treatment, which was significantly increased by teriparatide versus placebo. In addition, bone biopsies were obtained for measurement of bone formation rate using quadruple labeling with tetracycline and demeclocycline three months into treatment. As expected, biopsies showed that teriparatide treatment increased bone formation rates using this ‘gold standard’ method. This prospective randomized study adds to a growing body of evidence that teriparatide may be a safe method to boost bone density in women with IOP. Future studies are needed to assess the impact of this therapy on fracture risk in this specific patient population.

Type 2 diabetes and osteoporosis are both major problems in our aging population. While some diabetes medications such as thiazolidinediones clearly increase fracture risk, the effects of newer diabetes medications on bone biology and fracture risk remain incompletely understood. In addition to beneficial effects on glycemic control, SGLT2 inhibitors show promise with improving cardiovascular and renal outcomes, even in patients without diabetes. Some studies have suggested adverse effects of SGLT2 inhibitor monotherapy on bone density and fracture risk. However, the impact of combined therapy with SGLT2 inhibitors and metformin on fracture risk remains to be established. In this meta-analysis of 25 randomized controlled trials involving 19,500 patients, fracture risk was assessed, based on available information, for individuals who received metformin monotherapy or metformin plus SGLT2 inhibitor treatment. In general, combination therapy did not increase fracture risk compared to metformin alone. Only 6 of the 25 RCTs included in the meta-analysis investigated bone density or bone turnover markers. In these 6 studies, no obvious changes in skeletal outcomes were noted when comparing metformin alone versus metformin plus SGLT2 inhibitor therapy. Although these data are somewhat reassuring for the skeletal safety of combination metformin/SGLT2 inhibitor therapy, confidence is limited by relatively short follow-up time and lack of detailed information about fractures in these studies which focused primarily on diabetes-related outcomes. Future prospective studies are needed to specifically address the skeletal impact of this commonly-used combination of diabetes medications.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Some young women can present with very low bone density and multiple fragility fractures. While multiple FDA-approved therapies exist for post-menopausal osteoporosis, pre-menopausal osteoporosis remains an “orphan disease.” Previous evidence suggests that bone anabolic agents such as teriparatide may be useful for women with idiopathic pre-menopausal osteoporosis (IOP). In a phase 2 randomized clinical trial from New York and Nebraska, 41 women with IOP and multiple fractures were randomized to receive placebo or teriparatide in a cross-over study design. The primary endpoint was bone density in the spine and hip after 6 months of treatment, which was significantly increased by teriparatide versus placebo. In addition, bone biopsies were obtained for measurement of bone formation rate using quadruple labeling with tetracycline and demeclocycline three months into treatment. As expected, biopsies showed that teriparatide treatment increased bone formation rates using this ‘gold standard’ method. This prospective randomized study adds to a growing body of evidence that teriparatide may be a safe method to boost bone density in women with IOP. Future studies are needed to assess the impact of this therapy on fracture risk in this specific patient population.

Type 2 diabetes and osteoporosis are both major problems in our aging population. While some diabetes medications such as thiazolidinediones clearly increase fracture risk, the effects of newer diabetes medications on bone biology and fracture risk remain incompletely understood. In addition to beneficial effects on glycemic control, SGLT2 inhibitors show promise with improving cardiovascular and renal outcomes, even in patients without diabetes. Some studies have suggested adverse effects of SGLT2 inhibitor monotherapy on bone density and fracture risk. However, the impact of combined therapy with SGLT2 inhibitors and metformin on fracture risk remains to be established. In this meta-analysis of 25 randomized controlled trials involving 19,500 patients, fracture risk was assessed, based on available information, for individuals who received metformin monotherapy or metformin plus SGLT2 inhibitor treatment. In general, combination therapy did not increase fracture risk compared to metformin alone. Only 6 of the 25 RCTs included in the meta-analysis investigated bone density or bone turnover markers. In these 6 studies, no obvious changes in skeletal outcomes were noted when comparing metformin alone versus metformin plus SGLT2 inhibitor therapy. Although these data are somewhat reassuring for the skeletal safety of combination metformin/SGLT2 inhibitor therapy, confidence is limited by relatively short follow-up time and lack of detailed information about fractures in these studies which focused primarily on diabetes-related outcomes. Future prospective studies are needed to specifically address the skeletal impact of this commonly-used combination of diabetes medications.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Key clinical point: Sodium-glucose transporter-2 inhibitors (SGLT2is) combined with metformin therapy did not influence fracture risk in patients with type 2 diabetes mellitus (T2DM).

Major finding: SGLT2is and metformin combination therapy did not increase the risk of fracture vs. metformin monotherapy or other comparators in patients with T2DM (odds ratio, 0.97; 95% confidence interval, 0.71-1.32).

Study details: A meta-analysis of 25 randomized controlled trials including 19,500 participants with T2DM.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Qian BB et al. Osteoporos Int. 2020 Aug 11. doi: 10.1007/s00198-020-05590-y.

Key clinical point: Sodium-glucose transporter-2 inhibitors (SGLT2is) combined with metformin therapy did not influence fracture risk in patients with type 2 diabetes mellitus (T2DM).

Major finding: SGLT2is and metformin combination therapy did not increase the risk of fracture vs. metformin monotherapy or other comparators in patients with T2DM (odds ratio, 0.97; 95% confidence interval, 0.71-1.32).

Study details: A meta-analysis of 25 randomized controlled trials including 19,500 participants with T2DM.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Qian BB et al. Osteoporos Int. 2020 Aug 11. doi: 10.1007/s00198-020-05590-y.

Key clinical point: Sodium-glucose transporter-2 inhibitors (SGLT2is) combined with metformin therapy did not influence fracture risk in patients with type 2 diabetes mellitus (T2DM).

Major finding: SGLT2is and metformin combination therapy did not increase the risk of fracture vs. metformin monotherapy or other comparators in patients with T2DM (odds ratio, 0.97; 95% confidence interval, 0.71-1.32).

Study details: A meta-analysis of 25 randomized controlled trials including 19,500 participants with T2DM.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Qian BB et al. Osteoporos Int. 2020 Aug 11. doi: 10.1007/s00198-020-05590-y.

Key clinical point: Adults younger than 65 years with sepsis are at an increased risk of developing osteoporosis.

Major finding: The risk for osteoporosis was significantly higher in the sepsis vs. nonsepsis group (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.04-1.31). The risk for osteoporosis in the sepsis vs. nonsepsis group was significantly higher for young patients aged 20-49 years (aHR, 1.93; 95% CI, 1.08-3.44) and patients aged 50-64 years (aHR, 2.01; 95% CI, 1.52-2.65).

Study details: This Taiwanese population-based study included 13,178 patients diagnosed with sepsis and 13,178 propensity-score matched individuals without sepsis using data from the insurance claims database.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Lee YF et al. Osteoporos Int. 2020 Aug 22. doi: 10.1007/s00198-020-05599-3.

Key clinical point: Adults younger than 65 years with sepsis are at an increased risk of developing osteoporosis.

Major finding: The risk for osteoporosis was significantly higher in the sepsis vs. nonsepsis group (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.04-1.31). The risk for osteoporosis in the sepsis vs. nonsepsis group was significantly higher for young patients aged 20-49 years (aHR, 1.93; 95% CI, 1.08-3.44) and patients aged 50-64 years (aHR, 2.01; 95% CI, 1.52-2.65).

Study details: This Taiwanese population-based study included 13,178 patients diagnosed with sepsis and 13,178 propensity-score matched individuals without sepsis using data from the insurance claims database.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Lee YF et al. Osteoporos Int. 2020 Aug 22. doi: 10.1007/s00198-020-05599-3.

Key clinical point: Adults younger than 65 years with sepsis are at an increased risk of developing osteoporosis.

Major finding: The risk for osteoporosis was significantly higher in the sepsis vs. nonsepsis group (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.04-1.31). The risk for osteoporosis in the sepsis vs. nonsepsis group was significantly higher for young patients aged 20-49 years (aHR, 1.93; 95% CI, 1.08-3.44) and patients aged 50-64 years (aHR, 2.01; 95% CI, 1.52-2.65).

Study details: This Taiwanese population-based study included 13,178 patients diagnosed with sepsis and 13,178 propensity-score matched individuals without sepsis using data from the insurance claims database.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Lee YF et al. Osteoporos Int. 2020 Aug 22. doi: 10.1007/s00198-020-05599-3.

Key clinical point: The presence of osteoporosis correlates with a higher likelihood for revision surgery within 2 years following a long spinal fusion for adult spinal deformity (ASD).

Major finding: The rate of revision surgery was significantly higher in ASD patients with osteoporosis vs. those without osteoporosis (40.5% vs. 28.0%; P = .01). The incidence of multiple revision surgeries was similar in both groups (8.4% vs. 8.6%; P = .95). Age and sex were not statistically correlated with the incidence of revision surgery.

Study details: A retrospective comparative study of 399 patients with ASD (40 years or older) who underwent long spinal fusion surgery (osteoporotic group, n=131; nonosteoporotic group, n=268).

Disclosures: The study did not receive any funding.

Source: Gupta A et al. Spine J. 2020 Aug 10. doi: 10.1016/j.spinee.2020.08.002.

Key clinical point: The presence of osteoporosis correlates with a higher likelihood for revision surgery within 2 years following a long spinal fusion for adult spinal deformity (ASD).

Major finding: The rate of revision surgery was significantly higher in ASD patients with osteoporosis vs. those without osteoporosis (40.5% vs. 28.0%; P = .01). The incidence of multiple revision surgeries was similar in both groups (8.4% vs. 8.6%; P = .95). Age and sex were not statistically correlated with the incidence of revision surgery.

Study details: A retrospective comparative study of 399 patients with ASD (40 years or older) who underwent long spinal fusion surgery (osteoporotic group, n=131; nonosteoporotic group, n=268).

Disclosures: The study did not receive any funding.

Source: Gupta A et al. Spine J. 2020 Aug 10. doi: 10.1016/j.spinee.2020.08.002.

Key clinical point: The presence of osteoporosis correlates with a higher likelihood for revision surgery within 2 years following a long spinal fusion for adult spinal deformity (ASD).

Major finding: The rate of revision surgery was significantly higher in ASD patients with osteoporosis vs. those without osteoporosis (40.5% vs. 28.0%; P = .01). The incidence of multiple revision surgeries was similar in both groups (8.4% vs. 8.6%; P = .95). Age and sex were not statistically correlated with the incidence of revision surgery.

Study details: A retrospective comparative study of 399 patients with ASD (40 years or older) who underwent long spinal fusion surgery (osteoporotic group, n=131; nonosteoporotic group, n=268).

Disclosures: The study did not receive any funding.

Source: Gupta A et al. Spine J. 2020 Aug 10. doi: 10.1016/j.spinee.2020.08.002.

Across the United States, an explosive growth in recreational facilities boasting trampolines coincides with alarming growth in trampoline-related injuries in children, including those to the spine, according to new research.

Among youths, the risk for trampoline park–related fractures is about three times higher than for home-based trampoline fractures, said study author Serena Freiman, MD, of Washington University, St. Louis.

Recreational sports facilities with trampolines “pose a public health hazard,” Dr. Freiman said during a presentation at the virtual American Academy of Pediatrics 2020 National Conference.

“There aren’t any set regulations for these parks, so the American Society for Testing and Materials released a set of standards, but only Michigan and Arizona enforced those,” Dr. Freiman explained.

“Hopefully, since we’re showing a significant increased risk of injuries, the federal government will enforce regulations throughout the United States,” she said in an interview.

The first trampoline park in the United States opened in 2004, Dr. Freiman said. By 2018, there were more than 800 recreational facilities with trampolines across the country. This rapid growth coincided with a 45% increase in ED visits for trampoline-related injuries, from 61,509 in 2014 to more than 89,000 in 2017.

“There’s been exponential growth since their founding,” she said, “and with that we’ve also seen an exponential growth in injuries, whereas home injuries [from trampolines] remained stable during that time period.”

To assess the rates of trampoline-related injuries, Dr. Freiman and colleague analyzed data from the National Electronic Injury Surveillance System (NEISS). They included all patients whose records include a code for trampoline injury and who presented to a hospital ED between 1998 and 2017. They compared home trampoline injuries with those sustained at recreational facilities.

During the study period, more than 1.37 million patients presented to the ED for trampoline-related injuries. Of those, 125,473 occurred at recreational facilities, and 1.22 million occurred at home. Injuries at trampoline parks increased 90-fold between 2004 and 2017 (0.04 per 10,000 ED visits in 2004 to 0.9 per 10,000 in 2017), with 69% of those injuries occurring between 2012 and 2017.

Home-based trampoline injuries dropped during the study period, from 2.8 per 10,000 ED visits in 2014 to 1.6 in 2017.

Patients injured at trampoline facilities tended to present at large hospitals, Dr. Freiman noted, likely because of these parks being located in more populated regions.

The type of injury differed between locations. Severe injuries, such as spine fractures, occurred three times as often at trampoline parks than at home (2.7% vs. 0.9%; P = .016).

Internal organ injuries occurred more frequently on home-based trampolines (20.1% vs. 2.3% ; P < .001), whereas strains and sprains were more common at trampoline parks (32% vs. 51%; P < .001).

“Since home trampolines are often off the ground, I would speculate that you’re more likely to hit the edge of the trampoline or fall from it,” she said, “whereas at recreational sports facilities, there are often multiple jumpers, and you’re not falling off ― you’re falling in general or colliding with other jumpers.”

The authors noted that lower-extremity fractures occurred more often in trampoline parks (35.6% home vs. 51.7% parks; P < .0001), and upper-extremity fractures were more prevalent from home trampolines (60.2% vs. 42.5%; P < .0001). Also, a larger proportion of trampoline park injuries occurred among adolescents and young adults aged 15-34 years in comparison with home-based injuries (28.2% vs. 13.6%). No race or gender differences were noted.

Dr. Freiman noted one possible study limitation. The NEISS data only included patients tagged as being injured on trampolines, so “it may be incomplete,” she said. “Also, anyone presenting to their personal physician or urgent care centers weren’t included, so there’s likely an underestimation of cases.

“We hope people gain a better understanding of risks associated with these facilities and dive further into research and [to] identify areas that can be improved within these facilities,” Dr. Freiman added.

To drive home the importance of caution, physicians should relay data about trampoline injuries to parents and children, said Amber Hardeman, MD, MPH, MBA, of Tulane University, New Orleans.

Because most injuries at trampoline parks occur among people aged 15-34 years, Dr. Hardeman said, babysitters or parents may also “be indulging as well” when they take their young charges there to jump.

“They need to understand how to set a good example and teach kids proper safety precautions, such as not jumping too close together or maybe not doing things like splits,” she said.

Dr. Hardeman said in an interview that “there’s a lot of truth” to the study’s conclusion that recreational sports facilities with trampolines pose a public health hazard. Additional research should focus on what types of safety measures trampoline parks may be taking. Such measures could include increased padding, hiring more staff, or placing firmer limits on how many people can jump in each area at a time.

“Some centers don’t have as much padding around as others, and some allow multiple children to jump in the same area at the same time,” she said. “What exact scenarios are kids encountering more so than being on a trampoline at home?

“Trampoline centers are exciting and fun, but they are a hazard, and the fact that such an aggregate population being impacted by increasing numbers shows it’s definitely an issue right now,” Dr. Hardeman added.

Dr. Freiman and Dr. Hardeman have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Across the United States, an explosive growth in recreational facilities boasting trampolines coincides with alarming growth in trampoline-related injuries in children, including those to the spine, according to new research.

Among youths, the risk for trampoline park–related fractures is about three times higher than for home-based trampoline fractures, said study author Serena Freiman, MD, of Washington University, St. Louis.

Recreational sports facilities with trampolines “pose a public health hazard,” Dr. Freiman said during a presentation at the virtual American Academy of Pediatrics 2020 National Conference.

“There aren’t any set regulations for these parks, so the American Society for Testing and Materials released a set of standards, but only Michigan and Arizona enforced those,” Dr. Freiman explained.

“Hopefully, since we’re showing a significant increased risk of injuries, the federal government will enforce regulations throughout the United States,” she said in an interview.

The first trampoline park in the United States opened in 2004, Dr. Freiman said. By 2018, there were more than 800 recreational facilities with trampolines across the country. This rapid growth coincided with a 45% increase in ED visits for trampoline-related injuries, from 61,509 in 2014 to more than 89,000 in 2017.

“There’s been exponential growth since their founding,” she said, “and with that we’ve also seen an exponential growth in injuries, whereas home injuries [from trampolines] remained stable during that time period.”

To assess the rates of trampoline-related injuries, Dr. Freiman and colleague analyzed data from the National Electronic Injury Surveillance System (NEISS). They included all patients whose records include a code for trampoline injury and who presented to a hospital ED between 1998 and 2017. They compared home trampoline injuries with those sustained at recreational facilities.

During the study period, more than 1.37 million patients presented to the ED for trampoline-related injuries. Of those, 125,473 occurred at recreational facilities, and 1.22 million occurred at home. Injuries at trampoline parks increased 90-fold between 2004 and 2017 (0.04 per 10,000 ED visits in 2004 to 0.9 per 10,000 in 2017), with 69% of those injuries occurring between 2012 and 2017.

Home-based trampoline injuries dropped during the study period, from 2.8 per 10,000 ED visits in 2014 to 1.6 in 2017.

Patients injured at trampoline facilities tended to present at large hospitals, Dr. Freiman noted, likely because of these parks being located in more populated regions.

The type of injury differed between locations. Severe injuries, such as spine fractures, occurred three times as often at trampoline parks than at home (2.7% vs. 0.9%; P = .016).

Internal organ injuries occurred more frequently on home-based trampolines (20.1% vs. 2.3% ; P < .001), whereas strains and sprains were more common at trampoline parks (32% vs. 51%; P < .001).

“Since home trampolines are often off the ground, I would speculate that you’re more likely to hit the edge of the trampoline or fall from it,” she said, “whereas at recreational sports facilities, there are often multiple jumpers, and you’re not falling off ― you’re falling in general or colliding with other jumpers.”

The authors noted that lower-extremity fractures occurred more often in trampoline parks (35.6% home vs. 51.7% parks; P < .0001), and upper-extremity fractures were more prevalent from home trampolines (60.2% vs. 42.5%; P < .0001). Also, a larger proportion of trampoline park injuries occurred among adolescents and young adults aged 15-34 years in comparison with home-based injuries (28.2% vs. 13.6%). No race or gender differences were noted.

Dr. Freiman noted one possible study limitation. The NEISS data only included patients tagged as being injured on trampolines, so “it may be incomplete,” she said. “Also, anyone presenting to their personal physician or urgent care centers weren’t included, so there’s likely an underestimation of cases.

“We hope people gain a better understanding of risks associated with these facilities and dive further into research and [to] identify areas that can be improved within these facilities,” Dr. Freiman added.

To drive home the importance of caution, physicians should relay data about trampoline injuries to parents and children, said Amber Hardeman, MD, MPH, MBA, of Tulane University, New Orleans.

Because most injuries at trampoline parks occur among people aged 15-34 years, Dr. Hardeman said, babysitters or parents may also “be indulging as well” when they take their young charges there to jump.

“They need to understand how to set a good example and teach kids proper safety precautions, such as not jumping too close together or maybe not doing things like splits,” she said.

Dr. Hardeman said in an interview that “there’s a lot of truth” to the study’s conclusion that recreational sports facilities with trampolines pose a public health hazard. Additional research should focus on what types of safety measures trampoline parks may be taking. Such measures could include increased padding, hiring more staff, or placing firmer limits on how many people can jump in each area at a time.

“Some centers don’t have as much padding around as others, and some allow multiple children to jump in the same area at the same time,” she said. “What exact scenarios are kids encountering more so than being on a trampoline at home?

“Trampoline centers are exciting and fun, but they are a hazard, and the fact that such an aggregate population being impacted by increasing numbers shows it’s definitely an issue right now,” Dr. Hardeman added.

Dr. Freiman and Dr. Hardeman have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Across the United States, an explosive growth in recreational facilities boasting trampolines coincides with alarming growth in trampoline-related injuries in children, including those to the spine, according to new research.

Among youths, the risk for trampoline park–related fractures is about three times higher than for home-based trampoline fractures, said study author Serena Freiman, MD, of Washington University, St. Louis.

Recreational sports facilities with trampolines “pose a public health hazard,” Dr. Freiman said during a presentation at the virtual American Academy of Pediatrics 2020 National Conference.

“There aren’t any set regulations for these parks, so the American Society for Testing and Materials released a set of standards, but only Michigan and Arizona enforced those,” Dr. Freiman explained.

“Hopefully, since we’re showing a significant increased risk of injuries, the federal government will enforce regulations throughout the United States,” she said in an interview.

The first trampoline park in the United States opened in 2004, Dr. Freiman said. By 2018, there were more than 800 recreational facilities with trampolines across the country. This rapid growth coincided with a 45% increase in ED visits for trampoline-related injuries, from 61,509 in 2014 to more than 89,000 in 2017.

“There’s been exponential growth since their founding,” she said, “and with that we’ve also seen an exponential growth in injuries, whereas home injuries [from trampolines] remained stable during that time period.”

To assess the rates of trampoline-related injuries, Dr. Freiman and colleague analyzed data from the National Electronic Injury Surveillance System (NEISS). They included all patients whose records include a code for trampoline injury and who presented to a hospital ED between 1998 and 2017. They compared home trampoline injuries with those sustained at recreational facilities.

During the study period, more than 1.37 million patients presented to the ED for trampoline-related injuries. Of those, 125,473 occurred at recreational facilities, and 1.22 million occurred at home. Injuries at trampoline parks increased 90-fold between 2004 and 2017 (0.04 per 10,000 ED visits in 2004 to 0.9 per 10,000 in 2017), with 69% of those injuries occurring between 2012 and 2017.

Home-based trampoline injuries dropped during the study period, from 2.8 per 10,000 ED visits in 2014 to 1.6 in 2017.

Patients injured at trampoline facilities tended to present at large hospitals, Dr. Freiman noted, likely because of these parks being located in more populated regions.

The type of injury differed between locations. Severe injuries, such as spine fractures, occurred three times as often at trampoline parks than at home (2.7% vs. 0.9%; P = .016).

Internal organ injuries occurred more frequently on home-based trampolines (20.1% vs. 2.3% ; P < .001), whereas strains and sprains were more common at trampoline parks (32% vs. 51%; P < .001).

“Since home trampolines are often off the ground, I would speculate that you’re more likely to hit the edge of the trampoline or fall from it,” she said, “whereas at recreational sports facilities, there are often multiple jumpers, and you’re not falling off ― you’re falling in general or colliding with other jumpers.”

The authors noted that lower-extremity fractures occurred more often in trampoline parks (35.6% home vs. 51.7% parks; P < .0001), and upper-extremity fractures were more prevalent from home trampolines (60.2% vs. 42.5%; P < .0001). Also, a larger proportion of trampoline park injuries occurred among adolescents and young adults aged 15-34 years in comparison with home-based injuries (28.2% vs. 13.6%). No race or gender differences were noted.

Dr. Freiman noted one possible study limitation. The NEISS data only included patients tagged as being injured on trampolines, so “it may be incomplete,” she said. “Also, anyone presenting to their personal physician or urgent care centers weren’t included, so there’s likely an underestimation of cases.

“We hope people gain a better understanding of risks associated with these facilities and dive further into research and [to] identify areas that can be improved within these facilities,” Dr. Freiman added.

To drive home the importance of caution, physicians should relay data about trampoline injuries to parents and children, said Amber Hardeman, MD, MPH, MBA, of Tulane University, New Orleans.

Because most injuries at trampoline parks occur among people aged 15-34 years, Dr. Hardeman said, babysitters or parents may also “be indulging as well” when they take their young charges there to jump.

“They need to understand how to set a good example and teach kids proper safety precautions, such as not jumping too close together or maybe not doing things like splits,” she said.

Dr. Hardeman said in an interview that “there’s a lot of truth” to the study’s conclusion that recreational sports facilities with trampolines pose a public health hazard. Additional research should focus on what types of safety measures trampoline parks may be taking. Such measures could include increased padding, hiring more staff, or placing firmer limits on how many people can jump in each area at a time.

“Some centers don’t have as much padding around as others, and some allow multiple children to jump in the same area at the same time,” she said. “What exact scenarios are kids encountering more so than being on a trampoline at home?

“Trampoline centers are exciting and fun, but they are a hazard, and the fact that such an aggregate population being impacted by increasing numbers shows it’s definitely an issue right now,” Dr. Hardeman added.

Dr. Freiman and Dr. Hardeman have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Key clinical point: Both total hip bone mineral density (BMD) change and T-score can serve as surrogates for predicting vertebral fracture risk in patients with osteoporosis receiving denosumab treatment.

Major finding: Total hip BMD change and T-score were strong predictors of subsequent vertebral fracture risk, with total hip BMD change accounting for 73% and T-score accounting for 23% of the treatment effect.

Study details: Post hoc analysis of the DIRECT trial involving 1,011 Japanese postmenopausal women and men who were randomly assigned (2:2:1) to receive denosumab, placebo, or alendronate.

Disclosures: The study was funded by Daiichi Sankyo Co., Ltd., Tokyo, Japan. N Okubo, T Osakabe, K Watanabe, and H Takami were Daiichi Sankyo employees. Other authors reported relationships with various pharmaceutical companies, including Daiichi Sankyo.

Source: Okubo N et al. Calcif Tissue Int. 2020 Aug 25. doi: 10.1007/s00223-020-00750-y.

Key clinical point: Both total hip bone mineral density (BMD) change and T-score can serve as surrogates for predicting vertebral fracture risk in patients with osteoporosis receiving denosumab treatment.

Major finding: Total hip BMD change and T-score were strong predictors of subsequent vertebral fracture risk, with total hip BMD change accounting for 73% and T-score accounting for 23% of the treatment effect.

Study details: Post hoc analysis of the DIRECT trial involving 1,011 Japanese postmenopausal women and men who were randomly assigned (2:2:1) to receive denosumab, placebo, or alendronate.

Disclosures: The study was funded by Daiichi Sankyo Co., Ltd., Tokyo, Japan. N Okubo, T Osakabe, K Watanabe, and H Takami were Daiichi Sankyo employees. Other authors reported relationships with various pharmaceutical companies, including Daiichi Sankyo.

Source: Okubo N et al. Calcif Tissue Int. 2020 Aug 25. doi: 10.1007/s00223-020-00750-y.

Key clinical point: Both total hip bone mineral density (BMD) change and T-score can serve as surrogates for predicting vertebral fracture risk in patients with osteoporosis receiving denosumab treatment.

Major finding: Total hip BMD change and T-score were strong predictors of subsequent vertebral fracture risk, with total hip BMD change accounting for 73% and T-score accounting for 23% of the treatment effect.

Study details: Post hoc analysis of the DIRECT trial involving 1,011 Japanese postmenopausal women and men who were randomly assigned (2:2:1) to receive denosumab, placebo, or alendronate.

Disclosures: The study was funded by Daiichi Sankyo Co., Ltd., Tokyo, Japan. N Okubo, T Osakabe, K Watanabe, and H Takami were Daiichi Sankyo employees. Other authors reported relationships with various pharmaceutical companies, including Daiichi Sankyo.

Source: Okubo N et al. Calcif Tissue Int. 2020 Aug 25. doi: 10.1007/s00223-020-00750-y.

The Food and Drug Administration recently approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT).

In an interview, Ann S. LaCasce, MD, a lymphoma specialist, associate professor of medicine at Harvard Medical School, and director of the Dana-Farber/Massachusetts General Brigham fellowship in hematology/oncology, discussed the drug and its approval:

Question: How common is relapsed or refractory DLBCL? Have there been any changes in the rates of this disease in recent years?

Dr. LaCasce: Approximately 40% of patients with DLBCL will have relapsed or refractory disease. The rates of lymphoma have been rising over the past several decades for unclear reasons. As this is a disease predominantly of older adults, increasing life expectancy likely plays a role. Environmental factors may also be contributing.

Q: How long do patients with relapsed or refractory DLBCL who are not eligible for stem cell transplant usually survive?

Dr. LaCasce: This is highly variable, though it’s estimated to be approximately 1 year. Some patients will be cured with autologous transplantation or CAR-T cells. The pace of the disease can be highly variable, with some patients responding to multiple lines of therapy whereas others may have rapidly progressive refractory disease.

Q: What makes patients with relapsed or refractory DLBCL ineligible for ASCT?

Dr. LaCasce: To be eligible, patients need to be younger than 70-75 years or so without significant comorbidities and must have chemotherapy-responsive disease. More than half of patients will not fit these criteria.

Q: Can you briefly describe the L-MIND study that led to the approval of tafasitamab-cxix?

Dr. LaCasce: This was a single-arm, phase 2 study of tafasitamab plus lenalidomide in patients with relapsed/refractory DLBCL status after one to three prior regimens who were not candidates for ASCT. Patients received tafasitamab until progression and up to 1 year of lenalidomide. The median age was 72 years, and 50% of patients had received only one prior line of therapy.

The overall and complete response rates in 80 patients treated were 60% and 43%, respectively. The median progression-free survival was approximately 1 year. Nearly half of patients required dose reduction of lenalidomide, and about a quarter discontinued the drug. Twenty-five percent of patients discontinued therapy for adverse events.

Q: What’s the toxicity profile of tafasitamab-cxix?

Dr. LaCasce: The most common adverse events were infusion reactions and myelosuppression, which are managed with standard approaches to incident rate ratios with steroids, antihistamines, etc. Myelosuppression can occur, but in this combination is mostly driven by lenalidomide, which is dose reduced or discontinued.

Q: Where does tafasitamab-cxix fit in the treatment paradigm for relapsed or refractory DLBCL? How does it compare with other available options?

Dr. LaCasce: This is an option for patients who are not candidates for potentially curative approaches, including ASCT and CAR T-cell therapy. There are patients not eligible for ASCT who may be appropriate for CAR-T.

Tafasitamab plus lenalidomide requires frequent visits, particularly during the first 3 months, and then every other week until progression. The dose of lenalidomide will not be tolerable for many of these patients.

Other options in this population include polatuzumab plus bendamustine/rituximab or possibly selinexor. The former has similar activity and is time limited, though many patients will not tolerate the full dose of bendamustine. In the study leading to approval, selinexor had a much lower response rate of approximately 30%, and the patient population was much more favorable, given that eligibility required 60-98 days after last therapy before enrolling.

The only approval specific for nontransplant patients is tafasitamab/lenalidomide.

Q: From a cost standpoint, how does tafasitamab compare with other options in this patient population?

Dr. LaCasce: I don’t have exact figures, but all options are very expensive. CAR-T is the most expensive. Given the ongoing therapy of tafasitamab until progression, the cumulative cost could be very high. Polatuzumab plus bendamustine/rituximab and selinexor are also very costly.

Q: What other drugs are in development for relapsed or refractory DLBCL?

Dr. LaCasce: Novel CAR T-cell therapies, including lisocabtagene maraleucel that is at the FDA, are in development. Bispecific antibodies (REGN1979 and mosunetuzumab), combinations with CD47 antibodies, and loncastuximab tesirine are all in phase 2 trials.

Dr. LaCasce has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration recently approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT).

In an interview, Ann S. LaCasce, MD, a lymphoma specialist, associate professor of medicine at Harvard Medical School, and director of the Dana-Farber/Massachusetts General Brigham fellowship in hematology/oncology, discussed the drug and its approval:

Question: How common is relapsed or refractory DLBCL? Have there been any changes in the rates of this disease in recent years?

Dr. LaCasce: Approximately 40% of patients with DLBCL will have relapsed or refractory disease. The rates of lymphoma have been rising over the past several decades for unclear reasons. As this is a disease predominantly of older adults, increasing life expectancy likely plays a role. Environmental factors may also be contributing.

Q: How long do patients with relapsed or refractory DLBCL who are not eligible for stem cell transplant usually survive?

Dr. LaCasce: This is highly variable, though it’s estimated to be approximately 1 year. Some patients will be cured with autologous transplantation or CAR-T cells. The pace of the disease can be highly variable, with some patients responding to multiple lines of therapy whereas others may have rapidly progressive refractory disease.

Q: What makes patients with relapsed or refractory DLBCL ineligible for ASCT?

Dr. LaCasce: To be eligible, patients need to be younger than 70-75 years or so without significant comorbidities and must have chemotherapy-responsive disease. More than half of patients will not fit these criteria.

Q: Can you briefly describe the L-MIND study that led to the approval of tafasitamab-cxix?

Dr. LaCasce: This was a single-arm, phase 2 study of tafasitamab plus lenalidomide in patients with relapsed/refractory DLBCL status after one to three prior regimens who were not candidates for ASCT. Patients received tafasitamab until progression and up to 1 year of lenalidomide. The median age was 72 years, and 50% of patients had received only one prior line of therapy.

The overall and complete response rates in 80 patients treated were 60% and 43%, respectively. The median progression-free survival was approximately 1 year. Nearly half of patients required dose reduction of lenalidomide, and about a quarter discontinued the drug. Twenty-five percent of patients discontinued therapy for adverse events.

Q: What’s the toxicity profile of tafasitamab-cxix?

Dr. LaCasce: The most common adverse events were infusion reactions and myelosuppression, which are managed with standard approaches to incident rate ratios with steroids, antihistamines, etc. Myelosuppression can occur, but in this combination is mostly driven by lenalidomide, which is dose reduced or discontinued.

Q: Where does tafasitamab-cxix fit in the treatment paradigm for relapsed or refractory DLBCL? How does it compare with other available options?

Dr. LaCasce: This is an option for patients who are not candidates for potentially curative approaches, including ASCT and CAR T-cell therapy. There are patients not eligible for ASCT who may be appropriate for CAR-T.

Tafasitamab plus lenalidomide requires frequent visits, particularly during the first 3 months, and then every other week until progression. The dose of lenalidomide will not be tolerable for many of these patients.

Other options in this population include polatuzumab plus bendamustine/rituximab or possibly selinexor. The former has similar activity and is time limited, though many patients will not tolerate the full dose of bendamustine. In the study leading to approval, selinexor had a much lower response rate of approximately 30%, and the patient population was much more favorable, given that eligibility required 60-98 days after last therapy before enrolling.

The only approval specific for nontransplant patients is tafasitamab/lenalidomide.

Q: From a cost standpoint, how does tafasitamab compare with other options in this patient population?

Dr. LaCasce: I don’t have exact figures, but all options are very expensive. CAR-T is the most expensive. Given the ongoing therapy of tafasitamab until progression, the cumulative cost could be very high. Polatuzumab plus bendamustine/rituximab and selinexor are also very costly.

Q: What other drugs are in development for relapsed or refractory DLBCL?

Dr. LaCasce: Novel CAR T-cell therapies, including lisocabtagene maraleucel that is at the FDA, are in development. Bispecific antibodies (REGN1979 and mosunetuzumab), combinations with CD47 antibodies, and loncastuximab tesirine are all in phase 2 trials.

Dr. LaCasce has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration recently approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT).

In an interview, Ann S. LaCasce, MD, a lymphoma specialist, associate professor of medicine at Harvard Medical School, and director of the Dana-Farber/Massachusetts General Brigham fellowship in hematology/oncology, discussed the drug and its approval:

Question: How common is relapsed or refractory DLBCL? Have there been any changes in the rates of this disease in recent years?

Dr. LaCasce: Approximately 40% of patients with DLBCL will have relapsed or refractory disease. The rates of lymphoma have been rising over the past several decades for unclear reasons. As this is a disease predominantly of older adults, increasing life expectancy likely plays a role. Environmental factors may also be contributing.

Q: How long do patients with relapsed or refractory DLBCL who are not eligible for stem cell transplant usually survive?

Dr. LaCasce: This is highly variable, though it’s estimated to be approximately 1 year. Some patients will be cured with autologous transplantation or CAR-T cells. The pace of the disease can be highly variable, with some patients responding to multiple lines of therapy whereas others may have rapidly progressive refractory disease.

Q: What makes patients with relapsed or refractory DLBCL ineligible for ASCT?

Dr. LaCasce: To be eligible, patients need to be younger than 70-75 years or so without significant comorbidities and must have chemotherapy-responsive disease. More than half of patients will not fit these criteria.

Q: Can you briefly describe the L-MIND study that led to the approval of tafasitamab-cxix?

Dr. LaCasce: This was a single-arm, phase 2 study of tafasitamab plus lenalidomide in patients with relapsed/refractory DLBCL status after one to three prior regimens who were not candidates for ASCT. Patients received tafasitamab until progression and up to 1 year of lenalidomide. The median age was 72 years, and 50% of patients had received only one prior line of therapy.

The overall and complete response rates in 80 patients treated were 60% and 43%, respectively. The median progression-free survival was approximately 1 year. Nearly half of patients required dose reduction of lenalidomide, and about a quarter discontinued the drug. Twenty-five percent of patients discontinued therapy for adverse events.

Q: What’s the toxicity profile of tafasitamab-cxix?

Dr. LaCasce: The most common adverse events were infusion reactions and myelosuppression, which are managed with standard approaches to incident rate ratios with steroids, antihistamines, etc. Myelosuppression can occur, but in this combination is mostly driven by lenalidomide, which is dose reduced or discontinued.

Q: Where does tafasitamab-cxix fit in the treatment paradigm for relapsed or refractory DLBCL? How does it compare with other available options?

Dr. LaCasce: This is an option for patients who are not candidates for potentially curative approaches, including ASCT and CAR T-cell therapy. There are patients not eligible for ASCT who may be appropriate for CAR-T.

Tafasitamab plus lenalidomide requires frequent visits, particularly during the first 3 months, and then every other week until progression. The dose of lenalidomide will not be tolerable for many of these patients.

Other options in this population include polatuzumab plus bendamustine/rituximab or possibly selinexor. The former has similar activity and is time limited, though many patients will not tolerate the full dose of bendamustine. In the study leading to approval, selinexor had a much lower response rate of approximately 30%, and the patient population was much more favorable, given that eligibility required 60-98 days after last therapy before enrolling.

The only approval specific for nontransplant patients is tafasitamab/lenalidomide.

Q: From a cost standpoint, how does tafasitamab compare with other options in this patient population?

Dr. LaCasce: I don’t have exact figures, but all options are very expensive. CAR-T is the most expensive. Given the ongoing therapy of tafasitamab until progression, the cumulative cost could be very high. Polatuzumab plus bendamustine/rituximab and selinexor are also very costly.

Q: What other drugs are in development for relapsed or refractory DLBCL?

Dr. LaCasce: Novel CAR T-cell therapies, including lisocabtagene maraleucel that is at the FDA, are in development. Bispecific antibodies (REGN1979 and mosunetuzumab), combinations with CD47 antibodies, and loncastuximab tesirine are all in phase 2 trials.

Dr. LaCasce has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.