Men who illicitly used anabolic-androgenic steroids to bulk up and then turned to illegal, web-based regimens for treating their steroid withdrawal complications have provided important clues for new approaches to treating a growing worldwide population of men who abuse steroids.

A retrospective, observational study at one steroid addiction center in Glasgow examined 641 men who had stopped using steroids within the prior 3 years in 2015-2022 and who had self-administered certain agents, collectively known as post-cycle therapy (PCT) – within 3 months of stopping steroids.

They had a significant 3.8-fold increased rate of normalization of their levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), compared with men who either never used PCT or began it more than 3 months after stopping steroids, Channa N. Jayasena, PhD, MRCP, FRCPath, reported at the annual meeting of the Endocrine Society.

These testosterone, LH, and FSH levels served as a “surrogate marker of biochemical recovery from hypogonadism,” he explained. Normalization also occurred “slightly sooner” in men who began using PCT early after steroid cessation, added Dr. Jayasena, a reproductive endocrinologist at Imperial College, London.

When men recovered their endogenous testosterone-producing capacity, it occurred after an average of about 13 weeks on PCT and after an average of about 19 weeks without PCT, a significant difference.

“There is a vacuum of medical advice on what to do” when men stop taking steroids, said Dr. Jayasena during a press briefing at the meeting. “We can’t recommend anything yet because [our studies] have not proven causality” between the post-cycle therapy that many men start after stopping steroids and any symptom improvement they experience.”

The next step is to test the PCT agents in a prospective, controlled study, an investigation Dr. Jayasena and colleagues are eager to launch. The goal is to determine whether PCT is truly effective, the optimal doses, and whether the treatments are safe.
 

‘Incredibly sophisticated’ online community

The agents that constitute PCT include human chorionic gonadotropin (hCG, the “pregnancy hormone”), selective estrogen receptor modulators (SERMs), and aromatase inhibitors (AIs). SERMs and AIs are licensed only for use in women, the former for osteoporosis and breast cancer and the latter for breast cancer.

All of these agents, as well as others, are advertised by various illegal websites as treatments that can restore endogenous testosterone production in men whose native testosterone shut down during their steroid self-medication.

Restored testosterone resolves many of the adverse effects of steroid withdrawal such as diminished libido and erections, and depressed mood and energy.

Men buy PCT agents illegally from various websites. “There is an enormous, incredibly sophisticated community online that influences” PCT, and an “incredibly refined worldwide distribution network,” Dr. Jayasena explained.

His study included 410 men who turned to PCT after steroid cessation and 170 who did not.
 

Largest study of hormone recovery when men stop taking steroids

In a further multivariate analysis of the observational data, men who had used four or more different steroid treatments fared worse – with a significant 75% reduced rate of testosterone normalization with PCT – compared with men who had used a single steroid agent.

And men who had been on a steroid regimen for more than 6 months also fared badly – with a significant 66% reduced rate of testosterone normalization with PCT, compared with men on a steroid regimen for 3 months or less.

“This is the largest study of hormone recovery when men stop taking steroids,” Dr. Jayasena noted.

And the data “require corroboration within an interventional study to determine causality.”

“We need further studies to help doctors and other health care professionals advise men about the risks of anabolic steroid use and support those who are motivated to stop,” Dr. Jayasena said.

He cautioned that the study has several limitations: biases were potentially introduced based on recruitment and on recall by participants; clinicians drew blood specimens used to measure hormone levels at random times; and participants may have engaged in concealed drug use and used steroid and PCT agents that did not contain the substances advertised.

Nevertheless, “Our data provide primary evidence that self-administered PCT drugs may be associated with improved biochemical recovery” from steroid-induced hypogonadism, and they “may have important therapeutic implications for the future treatment of men who are motivated to stop” steroids.

The study received no commercial funding. Dr. Jayasena has received research funding from Logixx Pharma.

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

Men who illicitly used anabolic-androgenic steroids to bulk up and then turned to illegal, web-based regimens for treating their steroid withdrawal complications have provided important clues for new approaches to treating a growing worldwide population of men who abuse steroids.

A retrospective, observational study at one steroid addiction center in Glasgow examined 641 men who had stopped using steroids within the prior 3 years in 2015-2022 and who had self-administered certain agents, collectively known as post-cycle therapy (PCT) – within 3 months of stopping steroids.

They had a significant 3.8-fold increased rate of normalization of their levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), compared with men who either never used PCT or began it more than 3 months after stopping steroids, Channa N. Jayasena, PhD, MRCP, FRCPath, reported at the annual meeting of the Endocrine Society.

These testosterone, LH, and FSH levels served as a “surrogate marker of biochemical recovery from hypogonadism,” he explained. Normalization also occurred “slightly sooner” in men who began using PCT early after steroid cessation, added Dr. Jayasena, a reproductive endocrinologist at Imperial College, London.

When men recovered their endogenous testosterone-producing capacity, it occurred after an average of about 13 weeks on PCT and after an average of about 19 weeks without PCT, a significant difference.

“There is a vacuum of medical advice on what to do” when men stop taking steroids, said Dr. Jayasena during a press briefing at the meeting. “We can’t recommend anything yet because [our studies] have not proven causality” between the post-cycle therapy that many men start after stopping steroids and any symptom improvement they experience.”

The next step is to test the PCT agents in a prospective, controlled study, an investigation Dr. Jayasena and colleagues are eager to launch. The goal is to determine whether PCT is truly effective, the optimal doses, and whether the treatments are safe.
 

‘Incredibly sophisticated’ online community

The agents that constitute PCT include human chorionic gonadotropin (hCG, the “pregnancy hormone”), selective estrogen receptor modulators (SERMs), and aromatase inhibitors (AIs). SERMs and AIs are licensed only for use in women, the former for osteoporosis and breast cancer and the latter for breast cancer.

All of these agents, as well as others, are advertised by various illegal websites as treatments that can restore endogenous testosterone production in men whose native testosterone shut down during their steroid self-medication.

Restored testosterone resolves many of the adverse effects of steroid withdrawal such as diminished libido and erections, and depressed mood and energy.

Men buy PCT agents illegally from various websites. “There is an enormous, incredibly sophisticated community online that influences” PCT, and an “incredibly refined worldwide distribution network,” Dr. Jayasena explained.

His study included 410 men who turned to PCT after steroid cessation and 170 who did not.
 

Largest study of hormone recovery when men stop taking steroids

In a further multivariate analysis of the observational data, men who had used four or more different steroid treatments fared worse – with a significant 75% reduced rate of testosterone normalization with PCT – compared with men who had used a single steroid agent.

And men who had been on a steroid regimen for more than 6 months also fared badly – with a significant 66% reduced rate of testosterone normalization with PCT, compared with men on a steroid regimen for 3 months or less.

“This is the largest study of hormone recovery when men stop taking steroids,” Dr. Jayasena noted.

And the data “require corroboration within an interventional study to determine causality.”

“We need further studies to help doctors and other health care professionals advise men about the risks of anabolic steroid use and support those who are motivated to stop,” Dr. Jayasena said.

He cautioned that the study has several limitations: biases were potentially introduced based on recruitment and on recall by participants; clinicians drew blood specimens used to measure hormone levels at random times; and participants may have engaged in concealed drug use and used steroid and PCT agents that did not contain the substances advertised.

Nevertheless, “Our data provide primary evidence that self-administered PCT drugs may be associated with improved biochemical recovery” from steroid-induced hypogonadism, and they “may have important therapeutic implications for the future treatment of men who are motivated to stop” steroids.

The study received no commercial funding. Dr. Jayasena has received research funding from Logixx Pharma.

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

Men who illicitly used anabolic-androgenic steroids to bulk up and then turned to illegal, web-based regimens for treating their steroid withdrawal complications have provided important clues for new approaches to treating a growing worldwide population of men who abuse steroids.

A retrospective, observational study at one steroid addiction center in Glasgow examined 641 men who had stopped using steroids within the prior 3 years in 2015-2022 and who had self-administered certain agents, collectively known as post-cycle therapy (PCT) – within 3 months of stopping steroids.

They had a significant 3.8-fold increased rate of normalization of their levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), compared with men who either never used PCT or began it more than 3 months after stopping steroids, Channa N. Jayasena, PhD, MRCP, FRCPath, reported at the annual meeting of the Endocrine Society.

These testosterone, LH, and FSH levels served as a “surrogate marker of biochemical recovery from hypogonadism,” he explained. Normalization also occurred “slightly sooner” in men who began using PCT early after steroid cessation, added Dr. Jayasena, a reproductive endocrinologist at Imperial College, London.

When men recovered their endogenous testosterone-producing capacity, it occurred after an average of about 13 weeks on PCT and after an average of about 19 weeks without PCT, a significant difference.

“There is a vacuum of medical advice on what to do” when men stop taking steroids, said Dr. Jayasena during a press briefing at the meeting. “We can’t recommend anything yet because [our studies] have not proven causality” between the post-cycle therapy that many men start after stopping steroids and any symptom improvement they experience.”

The next step is to test the PCT agents in a prospective, controlled study, an investigation Dr. Jayasena and colleagues are eager to launch. The goal is to determine whether PCT is truly effective, the optimal doses, and whether the treatments are safe.
 

‘Incredibly sophisticated’ online community

The agents that constitute PCT include human chorionic gonadotropin (hCG, the “pregnancy hormone”), selective estrogen receptor modulators (SERMs), and aromatase inhibitors (AIs). SERMs and AIs are licensed only for use in women, the former for osteoporosis and breast cancer and the latter for breast cancer.

All of these agents, as well as others, are advertised by various illegal websites as treatments that can restore endogenous testosterone production in men whose native testosterone shut down during their steroid self-medication.

Restored testosterone resolves many of the adverse effects of steroid withdrawal such as diminished libido and erections, and depressed mood and energy.

Men buy PCT agents illegally from various websites. “There is an enormous, incredibly sophisticated community online that influences” PCT, and an “incredibly refined worldwide distribution network,” Dr. Jayasena explained.

His study included 410 men who turned to PCT after steroid cessation and 170 who did not.
 

Largest study of hormone recovery when men stop taking steroids

In a further multivariate analysis of the observational data, men who had used four or more different steroid treatments fared worse – with a significant 75% reduced rate of testosterone normalization with PCT – compared with men who had used a single steroid agent.

And men who had been on a steroid regimen for more than 6 months also fared badly – with a significant 66% reduced rate of testosterone normalization with PCT, compared with men on a steroid regimen for 3 months or less.

“This is the largest study of hormone recovery when men stop taking steroids,” Dr. Jayasena noted.

And the data “require corroboration within an interventional study to determine causality.”

“We need further studies to help doctors and other health care professionals advise men about the risks of anabolic steroid use and support those who are motivated to stop,” Dr. Jayasena said.

He cautioned that the study has several limitations: biases were potentially introduced based on recruitment and on recall by participants; clinicians drew blood specimens used to measure hormone levels at random times; and participants may have engaged in concealed drug use and used steroid and PCT agents that did not contain the substances advertised.

Nevertheless, “Our data provide primary evidence that self-administered PCT drugs may be associated with improved biochemical recovery” from steroid-induced hypogonadism, and they “may have important therapeutic implications for the future treatment of men who are motivated to stop” steroids.

The study received no commercial funding. Dr. Jayasena has received research funding from Logixx Pharma.

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

Rusfertide, a first-in-class mimetic of hepcidin, shows high efficacy in the treatment of erythrocytosis polycythemia vera (PV), with substantial improvements in hematocrit levels that can potentially eliminate the need for phlebotomies that are typically required – but usually ineffective.

“The results are surprisingly positive,” said senior author Ronald Hoffman, MD, of the Icahn School of Medicine at Mount Sinai, New York, in discussing the late-breaking research at a press briefing during the European Hematology Association Hybrid Congress 2023.

“Importantly, the study met all of its efficacy endpoints, including the proportion of responders, absence of phlebotomy eligibility, and hematocrit control,” Dr. Hoffman said.

PV, a relatively common clonal myeloproliferative neoplasm, is characterized by uncontrolled erythrocytosis, or excessive production of red blood cells, increasing the risk for serious complications such as thromboembolic and cardiovascular events – the most common causes of morbidity and mortality in this blood cancer.

To treat PV, the maintenance of hematocrit levels at below 45% is critical. However, the current standard of care, therapeutic phlebotomy, with or without cytoreductive agents, falls short in maintaining those lower levels in the majority of patients, Dr. Hoffman explained.

To improve responses, rusfertide was developed as a novel, synthetic form of hepcidin, a peptide hormone that is produced by the liver and functions to maintain iron homeostasis and control the formation of red blood cells.

“This is somewhat of a paradigm shift,” said Dr. Hoffman in the press briefing. “We’re trying to use a hormone made by the liver to control excessive red blood cell production from polycythemia vera.”

For the phase 2 REVIVE study evaluating rusfertide in PV, the authors enrolled 53 patients with PV who had a high phlebotomy burden while receiving the current standard of care. The study’s criteria called for patients to have received at least three therapeutic phlebotomies in the 28 weeks prior to enrollment, with or without concurrent cytoreductive agents.

During a first part of the study, patients received subcutaneous rusfertide once weekly over 28 weeks, during which period the dose was adjusted individually to achieve control of HCT levels below 45%.

The second part was a withdrawal phase extending from weeks 29 to 41, in which patients were randomized in a blinded fashion to either continue on rusfertide (n = 26) or receive a placebo (n = 27).

The patients had a median age of 58; they were 71.7% male, and 54.7% had previously been treated with therapeutic phlebotomy alone while 45.3% received therapeutic phlebotomy plus cytoreductive agents.

Patients were considered to be responders if they met three criteria, including having HCT control without phlebotomy eligibility, no therapeutic phlebotomy, and having completed 12 weeks of treatment.

At the end of the second phase, 69.2% of patients receiving rusfertide were responders versus just 18.5% in the placebo group (P = .0003).

Notably, the improvement with rusfertide was observed among those receiving therapeutic phlebotomy alone, as well as with cytoreductive agents (both P = .02).

Compared with placebo, rusfertide provided significant improvement in measures including the maintenance of response, the absence of the need for therapeutic phlebotomy, and persistent HCT control (P < .0001 for all).

Whereas the phlebotomy-free rate with rusfertide during the dose-finding weeks of 1-17 was 76.9% and in weeks 17-29, 87.3%, the rate increased in part 2 of the study to 92.3%.

Additional symptom benefits reported with rusfertide at week 29 versus baseline in part 1 of the study included significant improvements in concentration (P = .0018), itching (P = .0054), fatigue (P = .0074), and inactivity (P = .0005).

In terms of safety, rusfertide was generally well tolerated, with 83% of treatment-emergent adverse events (TEAEs) being grade 1-2, while 17% were grade 3, and none were grade 4 or 5.

The most common TEAEs consisted of injection-site reactions, which were localized, and grade 1-2 in severity. The incidence of reactions decreased with ongoing treatment. There were only two discontinuations resulting from TEAEs.

Among a total of 70 patients who were enrolled, 52 (74.3%) have continued to receive rusfertide for at least 1 year, 32 (45.7%) for at least 1.5 years, and 10 (14.3%) for at least 2 years, indicating the long-term tolerability of rusfertide.

Further commenting, first author Marina Kremyanskaya, MD, PhD, an assistant professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai, added that a key benefit is rusfertide’s tolerability with combination therapies, which is important in enabling the avoidance of phlebotomies.

“Many patients on cytoreductive therapies still require phlebotomies, and they can’t tolerate a dose increase, either due to cytopenias or other adverse reactions,” she said in an interview. “So adding rusfertide allows for better control of their hematocrits on a lower dose of their respective cytoreductive drug.”

“The combination treatment thus allows for elimination of phlebotomy requirements and potentially improves their symptoms,” Dr. Kremyanskaya said, adding that “using a lower dose of cytoreductive drug such as interferon or hydroxyurea could offer a symptomatic relief to patients as well.”

Overall, she agreed that the responses are remarkably positive.

“I think this is what is so impressive about this agent – basically everybody responds,” Dr. Kremyanskaya said. “When we first started treating patients, we were so impressed, as none of the other drugs we use to treat PV, or any other hematologic malignancy, come anywhere close to this response rate.”

In commenting on the study, Claire Harrison, MD, a professor of myeloproliferative neoplasms and deputy medical director of research at Guy’s and St Thomas’ NHS Foundation Trust in London, agreed that “these data show a strong signal for effectiveness of this therapy in controlling red cell proliferation in PV without inducing iron deficiency and adding to the symptom burden of patients.”

The alternative of phlebotomy “is painful and consumes patient time and hospital resources,” she said in an interview.

Dr. Harrison noted that an earlier signal suggested squamous cell cancer might be of potential concern, but the signal “has not re-emerged [suggesting] this does indeed seem to be a safe and extremely effective therapy.”

Further commenting on the study during the press briefing, Konstanze Döhner, MD, of the University of Ulm (Germany) added that “this is exciting data.”

“For a long time, we had no therapeutic options for PV, and now the field is rapidly developing,” she said.

In ongoing research, rusfertide is currently being studied in the phase 3, placebo-controlled VERIFY randomized trial.

The study was sponsored by Protagonist Therapeutics. Dr. Hoffman reports being on the advisory board for Protagonist Therapeutics, and Dr. Kremyanskaya is a consultant for Protagonist Therapeutics. Dr. Harrison had no disclosures to report.

Rusfertide, a first-in-class mimetic of hepcidin, shows high efficacy in the treatment of erythrocytosis polycythemia vera (PV), with substantial improvements in hematocrit levels that can potentially eliminate the need for phlebotomies that are typically required – but usually ineffective.

“The results are surprisingly positive,” said senior author Ronald Hoffman, MD, of the Icahn School of Medicine at Mount Sinai, New York, in discussing the late-breaking research at a press briefing during the European Hematology Association Hybrid Congress 2023.

“Importantly, the study met all of its efficacy endpoints, including the proportion of responders, absence of phlebotomy eligibility, and hematocrit control,” Dr. Hoffman said.

PV, a relatively common clonal myeloproliferative neoplasm, is characterized by uncontrolled erythrocytosis, or excessive production of red blood cells, increasing the risk for serious complications such as thromboembolic and cardiovascular events – the most common causes of morbidity and mortality in this blood cancer.

To treat PV, the maintenance of hematocrit levels at below 45% is critical. However, the current standard of care, therapeutic phlebotomy, with or without cytoreductive agents, falls short in maintaining those lower levels in the majority of patients, Dr. Hoffman explained.

To improve responses, rusfertide was developed as a novel, synthetic form of hepcidin, a peptide hormone that is produced by the liver and functions to maintain iron homeostasis and control the formation of red blood cells.

“This is somewhat of a paradigm shift,” said Dr. Hoffman in the press briefing. “We’re trying to use a hormone made by the liver to control excessive red blood cell production from polycythemia vera.”

For the phase 2 REVIVE study evaluating rusfertide in PV, the authors enrolled 53 patients with PV who had a high phlebotomy burden while receiving the current standard of care. The study’s criteria called for patients to have received at least three therapeutic phlebotomies in the 28 weeks prior to enrollment, with or without concurrent cytoreductive agents.

During a first part of the study, patients received subcutaneous rusfertide once weekly over 28 weeks, during which period the dose was adjusted individually to achieve control of HCT levels below 45%.

The second part was a withdrawal phase extending from weeks 29 to 41, in which patients were randomized in a blinded fashion to either continue on rusfertide (n = 26) or receive a placebo (n = 27).

The patients had a median age of 58; they were 71.7% male, and 54.7% had previously been treated with therapeutic phlebotomy alone while 45.3% received therapeutic phlebotomy plus cytoreductive agents.

Patients were considered to be responders if they met three criteria, including having HCT control without phlebotomy eligibility, no therapeutic phlebotomy, and having completed 12 weeks of treatment.

At the end of the second phase, 69.2% of patients receiving rusfertide were responders versus just 18.5% in the placebo group (P = .0003).

Notably, the improvement with rusfertide was observed among those receiving therapeutic phlebotomy alone, as well as with cytoreductive agents (both P = .02).

Compared with placebo, rusfertide provided significant improvement in measures including the maintenance of response, the absence of the need for therapeutic phlebotomy, and persistent HCT control (P < .0001 for all).

Whereas the phlebotomy-free rate with rusfertide during the dose-finding weeks of 1-17 was 76.9% and in weeks 17-29, 87.3%, the rate increased in part 2 of the study to 92.3%.

Additional symptom benefits reported with rusfertide at week 29 versus baseline in part 1 of the study included significant improvements in concentration (P = .0018), itching (P = .0054), fatigue (P = .0074), and inactivity (P = .0005).

In terms of safety, rusfertide was generally well tolerated, with 83% of treatment-emergent adverse events (TEAEs) being grade 1-2, while 17% were grade 3, and none were grade 4 or 5.

The most common TEAEs consisted of injection-site reactions, which were localized, and grade 1-2 in severity. The incidence of reactions decreased with ongoing treatment. There were only two discontinuations resulting from TEAEs.

Among a total of 70 patients who were enrolled, 52 (74.3%) have continued to receive rusfertide for at least 1 year, 32 (45.7%) for at least 1.5 years, and 10 (14.3%) for at least 2 years, indicating the long-term tolerability of rusfertide.

Further commenting, first author Marina Kremyanskaya, MD, PhD, an assistant professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai, added that a key benefit is rusfertide’s tolerability with combination therapies, which is important in enabling the avoidance of phlebotomies.

“Many patients on cytoreductive therapies still require phlebotomies, and they can’t tolerate a dose increase, either due to cytopenias or other adverse reactions,” she said in an interview. “So adding rusfertide allows for better control of their hematocrits on a lower dose of their respective cytoreductive drug.”

“The combination treatment thus allows for elimination of phlebotomy requirements and potentially improves their symptoms,” Dr. Kremyanskaya said, adding that “using a lower dose of cytoreductive drug such as interferon or hydroxyurea could offer a symptomatic relief to patients as well.”

Overall, she agreed that the responses are remarkably positive.

“I think this is what is so impressive about this agent – basically everybody responds,” Dr. Kremyanskaya said. “When we first started treating patients, we were so impressed, as none of the other drugs we use to treat PV, or any other hematologic malignancy, come anywhere close to this response rate.”

In commenting on the study, Claire Harrison, MD, a professor of myeloproliferative neoplasms and deputy medical director of research at Guy’s and St Thomas’ NHS Foundation Trust in London, agreed that “these data show a strong signal for effectiveness of this therapy in controlling red cell proliferation in PV without inducing iron deficiency and adding to the symptom burden of patients.”

The alternative of phlebotomy “is painful and consumes patient time and hospital resources,” she said in an interview.

Dr. Harrison noted that an earlier signal suggested squamous cell cancer might be of potential concern, but the signal “has not re-emerged [suggesting] this does indeed seem to be a safe and extremely effective therapy.”

Further commenting on the study during the press briefing, Konstanze Döhner, MD, of the University of Ulm (Germany) added that “this is exciting data.”

“For a long time, we had no therapeutic options for PV, and now the field is rapidly developing,” she said.

In ongoing research, rusfertide is currently being studied in the phase 3, placebo-controlled VERIFY randomized trial.

The study was sponsored by Protagonist Therapeutics. Dr. Hoffman reports being on the advisory board for Protagonist Therapeutics, and Dr. Kremyanskaya is a consultant for Protagonist Therapeutics. Dr. Harrison had no disclosures to report.

Rusfertide, a first-in-class mimetic of hepcidin, shows high efficacy in the treatment of erythrocytosis polycythemia vera (PV), with substantial improvements in hematocrit levels that can potentially eliminate the need for phlebotomies that are typically required – but usually ineffective.

“The results are surprisingly positive,” said senior author Ronald Hoffman, MD, of the Icahn School of Medicine at Mount Sinai, New York, in discussing the late-breaking research at a press briefing during the European Hematology Association Hybrid Congress 2023.

“Importantly, the study met all of its efficacy endpoints, including the proportion of responders, absence of phlebotomy eligibility, and hematocrit control,” Dr. Hoffman said.

PV, a relatively common clonal myeloproliferative neoplasm, is characterized by uncontrolled erythrocytosis, or excessive production of red blood cells, increasing the risk for serious complications such as thromboembolic and cardiovascular events – the most common causes of morbidity and mortality in this blood cancer.

To treat PV, the maintenance of hematocrit levels at below 45% is critical. However, the current standard of care, therapeutic phlebotomy, with or without cytoreductive agents, falls short in maintaining those lower levels in the majority of patients, Dr. Hoffman explained.

To improve responses, rusfertide was developed as a novel, synthetic form of hepcidin, a peptide hormone that is produced by the liver and functions to maintain iron homeostasis and control the formation of red blood cells.

“This is somewhat of a paradigm shift,” said Dr. Hoffman in the press briefing. “We’re trying to use a hormone made by the liver to control excessive red blood cell production from polycythemia vera.”

For the phase 2 REVIVE study evaluating rusfertide in PV, the authors enrolled 53 patients with PV who had a high phlebotomy burden while receiving the current standard of care. The study’s criteria called for patients to have received at least three therapeutic phlebotomies in the 28 weeks prior to enrollment, with or without concurrent cytoreductive agents.

During a first part of the study, patients received subcutaneous rusfertide once weekly over 28 weeks, during which period the dose was adjusted individually to achieve control of HCT levels below 45%.

The second part was a withdrawal phase extending from weeks 29 to 41, in which patients were randomized in a blinded fashion to either continue on rusfertide (n = 26) or receive a placebo (n = 27).

The patients had a median age of 58; they were 71.7% male, and 54.7% had previously been treated with therapeutic phlebotomy alone while 45.3% received therapeutic phlebotomy plus cytoreductive agents.

Patients were considered to be responders if they met three criteria, including having HCT control without phlebotomy eligibility, no therapeutic phlebotomy, and having completed 12 weeks of treatment.

At the end of the second phase, 69.2% of patients receiving rusfertide were responders versus just 18.5% in the placebo group (P = .0003).

Notably, the improvement with rusfertide was observed among those receiving therapeutic phlebotomy alone, as well as with cytoreductive agents (both P = .02).

Compared with placebo, rusfertide provided significant improvement in measures including the maintenance of response, the absence of the need for therapeutic phlebotomy, and persistent HCT control (P < .0001 for all).

Whereas the phlebotomy-free rate with rusfertide during the dose-finding weeks of 1-17 was 76.9% and in weeks 17-29, 87.3%, the rate increased in part 2 of the study to 92.3%.

Additional symptom benefits reported with rusfertide at week 29 versus baseline in part 1 of the study included significant improvements in concentration (P = .0018), itching (P = .0054), fatigue (P = .0074), and inactivity (P = .0005).

In terms of safety, rusfertide was generally well tolerated, with 83% of treatment-emergent adverse events (TEAEs) being grade 1-2, while 17% were grade 3, and none were grade 4 or 5.

The most common TEAEs consisted of injection-site reactions, which were localized, and grade 1-2 in severity. The incidence of reactions decreased with ongoing treatment. There were only two discontinuations resulting from TEAEs.

Among a total of 70 patients who were enrolled, 52 (74.3%) have continued to receive rusfertide for at least 1 year, 32 (45.7%) for at least 1.5 years, and 10 (14.3%) for at least 2 years, indicating the long-term tolerability of rusfertide.

Further commenting, first author Marina Kremyanskaya, MD, PhD, an assistant professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai, added that a key benefit is rusfertide’s tolerability with combination therapies, which is important in enabling the avoidance of phlebotomies.

“Many patients on cytoreductive therapies still require phlebotomies, and they can’t tolerate a dose increase, either due to cytopenias or other adverse reactions,” she said in an interview. “So adding rusfertide allows for better control of their hematocrits on a lower dose of their respective cytoreductive drug.”

“The combination treatment thus allows for elimination of phlebotomy requirements and potentially improves their symptoms,” Dr. Kremyanskaya said, adding that “using a lower dose of cytoreductive drug such as interferon or hydroxyurea could offer a symptomatic relief to patients as well.”

Overall, she agreed that the responses are remarkably positive.

“I think this is what is so impressive about this agent – basically everybody responds,” Dr. Kremyanskaya said. “When we first started treating patients, we were so impressed, as none of the other drugs we use to treat PV, or any other hematologic malignancy, come anywhere close to this response rate.”

In commenting on the study, Claire Harrison, MD, a professor of myeloproliferative neoplasms and deputy medical director of research at Guy’s and St Thomas’ NHS Foundation Trust in London, agreed that “these data show a strong signal for effectiveness of this therapy in controlling red cell proliferation in PV without inducing iron deficiency and adding to the symptom burden of patients.”

The alternative of phlebotomy “is painful and consumes patient time and hospital resources,” she said in an interview.

Dr. Harrison noted that an earlier signal suggested squamous cell cancer might be of potential concern, but the signal “has not re-emerged [suggesting] this does indeed seem to be a safe and extremely effective therapy.”

Further commenting on the study during the press briefing, Konstanze Döhner, MD, of the University of Ulm (Germany) added that “this is exciting data.”

“For a long time, we had no therapeutic options for PV, and now the field is rapidly developing,” she said.

In ongoing research, rusfertide is currently being studied in the phase 3, placebo-controlled VERIFY randomized trial.

The study was sponsored by Protagonist Therapeutics. Dr. Hoffman reports being on the advisory board for Protagonist Therapeutics, and Dr. Kremyanskaya is a consultant for Protagonist Therapeutics. Dr. Harrison had no disclosures to report.

The Food and Drug Administration draft guidance released recently on possible contamination of tattoo ink was not concerning Whitney Donohue, 34, owner of Forget Me Not Tattoo in Billings, Mont. 

“I get our ink directly through the manufacturer – not at a store or through Amazon or eBay,” she said. “You never know if it’s going to be repackaged.”

Tattoo artists themselves, she said, regulate the quality of ink they use. 

Still, the threat is real, said Bruce Brod, MD, a clinical professor of dermatology at the University of Pennsylvania Health System. “I’ve seen several different infections from tattooing, and they are from organisms that tend to contaminate things in damp, liquid-type environments.”

The FDA released the new draft guidance aiming to reduce the use of pathogen-contaminated tattoo ink, which can cause stubborn infections that are especially hard to treat, dermatologists said.

“Tattooing involves puncturing the epidermis about 100 times per second with needles and depositing ink 1.5 to 2 millimeters below the surface of the skin, deep into the dermis,” the guidance states. “Contaminated tattoo ink can cause infections and serious injuries. Because these inks are injected, pathogens or other harmful substances in these inks can travel from the injection site through the blood and lymphatic systems to other parts of the body.”

The guidance comes as body art continues to get more popular. According to a 2019 poll, 30% of Americans had at least one tattoo – up from 21% in 2012. Forty percent of people 18-34 and 36% of those ages 35-54 had at least one tattoo. And though they are commonplace, tattoos come with medical risks that should be known beforehand, doctors said. 

Commonly reported symptoms of tattoo ink–associated infections include rashes, blisters, painful nodules, and severe abscesses. One of the most common bacteria found in contaminated tattoo ink is nontuberculous mycobacteria, which is related to the bacteria that causes tuberculosis and can be found in soil and water.

The guidance lists several unsanitary manufacturing conditions that may lead to ink contamination, including: 

• Preparing or packing of tattoo inks in facilities that are hard to sanitize, such as carpeted areas
• Ink or ink components left uncovered, especially near open air ducts
• Unsanitary mixing of tattoo inks, including with unclean utensils or containers
• Lack of appropriate attire by staff, failure to use hairnets, lab coats, aprons, gowns, masks, or gloves

“Infections will often spread along the drainage channels in the skin and create squiggly, uneven lines of big red, lumpy nodules,” Dr. Brod said. 

Between 2003 and 2023, there were 18 recalls of tattoo inks that were contaminated with various microorganisms, according to the FDA. In May 2019, the FDA issued a safety alert advising consumers, tattoo artists, and retailers to avoid using or selling certain tattoo inks contaminated with microorganisms.

Reputable ink manufacturers use a process called gamma radiation, which refers to electromagnetic radiation of high frequencies to kill microorganisms in the ink and its packaging.

Most of the trustworthy, high-quality ink manufacturers are well-known among tattoo artists, Ms. Donohue said. 

While she has seen customers with sensitive skin have allergic reactions, she has not seen someone come back with an infection in her 9 years working in the tattoo industry.

Because tattoo ink is considered a cosmetic product, there is not much regulatory oversight involved, which means the sterility and quality of ingredients vary, said Teo Soleymani, MD, an assistant clinical professor of dermatology and dermatological surgery at the UCLA David Geffen School of Medicine.

“Cosmeceuticals aren’t regulated by the FDA like prescription medication,” he said. “What we’ve seen many times is inadvertent contamination during the application process or contamination while the inks are being made.”

In years past, unclean needles spreading hepatitis and HIV were more of a concern, but those rates have dropped significantly, Dr. Soleymani said. 

The infections that have increased are from rare bacteria that exist in stagnant water. And they are injected into a part of the body that allows them to evade the immune system, he said: shallow enough that there aren’t many associated blood vessels, but not still below the layer of skin that gets sloughed off every 28 days. 

Sometimes, antibiotics alone won’t cut it, and the tattoo will require surgical removal. 

“The aesthetic you were going for has to be not only removed, but you’re left with a surgical scar,” Dr. Soleymani said. “Tattoos can be beautiful, but they can come with unwanted visitors that can cause months of misery.”

A version of this article first appeared on WebMD.com.

The Food and Drug Administration draft guidance released recently on possible contamination of tattoo ink was not concerning Whitney Donohue, 34, owner of Forget Me Not Tattoo in Billings, Mont. 

“I get our ink directly through the manufacturer – not at a store or through Amazon or eBay,” she said. “You never know if it’s going to be repackaged.”

Tattoo artists themselves, she said, regulate the quality of ink they use. 

Still, the threat is real, said Bruce Brod, MD, a clinical professor of dermatology at the University of Pennsylvania Health System. “I’ve seen several different infections from tattooing, and they are from organisms that tend to contaminate things in damp, liquid-type environments.”

The FDA released the new draft guidance aiming to reduce the use of pathogen-contaminated tattoo ink, which can cause stubborn infections that are especially hard to treat, dermatologists said.

“Tattooing involves puncturing the epidermis about 100 times per second with needles and depositing ink 1.5 to 2 millimeters below the surface of the skin, deep into the dermis,” the guidance states. “Contaminated tattoo ink can cause infections and serious injuries. Because these inks are injected, pathogens or other harmful substances in these inks can travel from the injection site through the blood and lymphatic systems to other parts of the body.”

The guidance comes as body art continues to get more popular. According to a 2019 poll, 30% of Americans had at least one tattoo – up from 21% in 2012. Forty percent of people 18-34 and 36% of those ages 35-54 had at least one tattoo. And though they are commonplace, tattoos come with medical risks that should be known beforehand, doctors said. 

Commonly reported symptoms of tattoo ink–associated infections include rashes, blisters, painful nodules, and severe abscesses. One of the most common bacteria found in contaminated tattoo ink is nontuberculous mycobacteria, which is related to the bacteria that causes tuberculosis and can be found in soil and water.

The guidance lists several unsanitary manufacturing conditions that may lead to ink contamination, including: 

• Preparing or packing of tattoo inks in facilities that are hard to sanitize, such as carpeted areas
• Ink or ink components left uncovered, especially near open air ducts
• Unsanitary mixing of tattoo inks, including with unclean utensils or containers
• Lack of appropriate attire by staff, failure to use hairnets, lab coats, aprons, gowns, masks, or gloves

“Infections will often spread along the drainage channels in the skin and create squiggly, uneven lines of big red, lumpy nodules,” Dr. Brod said. 

Between 2003 and 2023, there were 18 recalls of tattoo inks that were contaminated with various microorganisms, according to the FDA. In May 2019, the FDA issued a safety alert advising consumers, tattoo artists, and retailers to avoid using or selling certain tattoo inks contaminated with microorganisms.

Reputable ink manufacturers use a process called gamma radiation, which refers to electromagnetic radiation of high frequencies to kill microorganisms in the ink and its packaging.

Most of the trustworthy, high-quality ink manufacturers are well-known among tattoo artists, Ms. Donohue said. 

While she has seen customers with sensitive skin have allergic reactions, she has not seen someone come back with an infection in her 9 years working in the tattoo industry.

Because tattoo ink is considered a cosmetic product, there is not much regulatory oversight involved, which means the sterility and quality of ingredients vary, said Teo Soleymani, MD, an assistant clinical professor of dermatology and dermatological surgery at the UCLA David Geffen School of Medicine.

“Cosmeceuticals aren’t regulated by the FDA like prescription medication,” he said. “What we’ve seen many times is inadvertent contamination during the application process or contamination while the inks are being made.”

In years past, unclean needles spreading hepatitis and HIV were more of a concern, but those rates have dropped significantly, Dr. Soleymani said. 

The infections that have increased are from rare bacteria that exist in stagnant water. And they are injected into a part of the body that allows them to evade the immune system, he said: shallow enough that there aren’t many associated blood vessels, but not still below the layer of skin that gets sloughed off every 28 days. 

Sometimes, antibiotics alone won’t cut it, and the tattoo will require surgical removal. 

“The aesthetic you were going for has to be not only removed, but you’re left with a surgical scar,” Dr. Soleymani said. “Tattoos can be beautiful, but they can come with unwanted visitors that can cause months of misery.”

A version of this article first appeared on WebMD.com.

The Food and Drug Administration draft guidance released recently on possible contamination of tattoo ink was not concerning Whitney Donohue, 34, owner of Forget Me Not Tattoo in Billings, Mont. 

“I get our ink directly through the manufacturer – not at a store or through Amazon or eBay,” she said. “You never know if it’s going to be repackaged.”

Tattoo artists themselves, she said, regulate the quality of ink they use. 

Still, the threat is real, said Bruce Brod, MD, a clinical professor of dermatology at the University of Pennsylvania Health System. “I’ve seen several different infections from tattooing, and they are from organisms that tend to contaminate things in damp, liquid-type environments.”

The FDA released the new draft guidance aiming to reduce the use of pathogen-contaminated tattoo ink, which can cause stubborn infections that are especially hard to treat, dermatologists said.

“Tattooing involves puncturing the epidermis about 100 times per second with needles and depositing ink 1.5 to 2 millimeters below the surface of the skin, deep into the dermis,” the guidance states. “Contaminated tattoo ink can cause infections and serious injuries. Because these inks are injected, pathogens or other harmful substances in these inks can travel from the injection site through the blood and lymphatic systems to other parts of the body.”

The guidance comes as body art continues to get more popular. According to a 2019 poll, 30% of Americans had at least one tattoo – up from 21% in 2012. Forty percent of people 18-34 and 36% of those ages 35-54 had at least one tattoo. And though they are commonplace, tattoos come with medical risks that should be known beforehand, doctors said. 

Commonly reported symptoms of tattoo ink–associated infections include rashes, blisters, painful nodules, and severe abscesses. One of the most common bacteria found in contaminated tattoo ink is nontuberculous mycobacteria, which is related to the bacteria that causes tuberculosis and can be found in soil and water.

The guidance lists several unsanitary manufacturing conditions that may lead to ink contamination, including: 

• Preparing or packing of tattoo inks in facilities that are hard to sanitize, such as carpeted areas
• Ink or ink components left uncovered, especially near open air ducts
• Unsanitary mixing of tattoo inks, including with unclean utensils or containers
• Lack of appropriate attire by staff, failure to use hairnets, lab coats, aprons, gowns, masks, or gloves

“Infections will often spread along the drainage channels in the skin and create squiggly, uneven lines of big red, lumpy nodules,” Dr. Brod said. 

Between 2003 and 2023, there were 18 recalls of tattoo inks that were contaminated with various microorganisms, according to the FDA. In May 2019, the FDA issued a safety alert advising consumers, tattoo artists, and retailers to avoid using or selling certain tattoo inks contaminated with microorganisms.

Reputable ink manufacturers use a process called gamma radiation, which refers to electromagnetic radiation of high frequencies to kill microorganisms in the ink and its packaging.

Most of the trustworthy, high-quality ink manufacturers are well-known among tattoo artists, Ms. Donohue said. 

While she has seen customers with sensitive skin have allergic reactions, she has not seen someone come back with an infection in her 9 years working in the tattoo industry.

Because tattoo ink is considered a cosmetic product, there is not much regulatory oversight involved, which means the sterility and quality of ingredients vary, said Teo Soleymani, MD, an assistant clinical professor of dermatology and dermatological surgery at the UCLA David Geffen School of Medicine.

“Cosmeceuticals aren’t regulated by the FDA like prescription medication,” he said. “What we’ve seen many times is inadvertent contamination during the application process or contamination while the inks are being made.”

In years past, unclean needles spreading hepatitis and HIV were more of a concern, but those rates have dropped significantly, Dr. Soleymani said. 

The infections that have increased are from rare bacteria that exist in stagnant water. And they are injected into a part of the body that allows them to evade the immune system, he said: shallow enough that there aren’t many associated blood vessels, but not still below the layer of skin that gets sloughed off every 28 days. 

Sometimes, antibiotics alone won’t cut it, and the tattoo will require surgical removal. 

“The aesthetic you were going for has to be not only removed, but you’re left with a surgical scar,” Dr. Soleymani said. “Tattoos can be beautiful, but they can come with unwanted visitors that can cause months of misery.”

A version of this article first appeared on WebMD.com.

Patients with chronic lymphocytic leukemia (CLL) – even those who have multiple comorbidities – experience long-term progression-free survival (PFS) benefits with 1 year of venetoclax plus obinutuzumab versus a chemotherapy-based regimen, a 6-year follow-up analysis from CLL14 showed. The research was presented June 9 at the annual meeting of the European Hematology Association.

Initial results from the trial were shown at the EHA 2019 annual meeting and reported at the time by this news organization.

They revealed that, among more than 430 CLL patients with a median age of over 70 years and multiple comorbidities, the combination of venetoclax, a B-cell lymphoma 2 protein blocker, plus obinutuzumab, an anti-CD20 monoclonal antibody, was associated with a 65% improvement in PFS, compared with chlorambucil, a chemotherapy agent, plus obinutuzumab.

On the strength of these findings, the venetoclax-obinutuzumab combination received Food and Drug Administration approval for previously untreated CLL and small lymphocytic lymphoma in March 2019.

The latest analysis, presented by Othman Al-Sawaf, MD, University Hospital of Cologne (Germany), showed that despite having just 12 cycles of treatment, patients treated with venetoclax-obinutuzumab continued to experience a significant PFS benefit over those given the chemotherapy-based regimen, including in high-risk patients, after more than 6 years of follow-up.

Dr. Al-Sawaf noted that more than 50% of patients given the experimental combination remained without a PFS event at the latest follow-up, and that over 60% had not required a second treatment, equating to a 66% reduction in the likelihood of needing a second treatment versus chlorambucil-obinutuzumab.

Dr. Al-Sawaf said at a press conference that, “clinically, the standard of care for any CLL if it is asymptomatic” is watch and wait, which is “true in the frontline setting, but also in the relapse setting.”

Therefore, these patients “do not need to initiate the next line of treatment, and that’s why time to next treatment is so interesting.”

He added that there also were no new safety signals, with adverse event rates dropping markedly once treatment was over, although there was a suggestion of an increase in second malignancies with venetoclax-obinutuzumab.

“We’ve seen, in many studies now that use fixed-duration approaches, that there is virtually no posttreatment toxicity once patients are able to get off treatment,” Dr. Al-Sawaf said, adding: “This really highlights the benefit” of stopping treatment, “which is a clear advantage compared to having any kind of continuous treatment.”

Approached for comment, William G. Wierda, MD, PhD, professor, department of leukemia, division of cancer medicine, University of Texas MD Anderson Cancer Center, Houston, emphasized the value of the 6-year follow-up of the study, adding that these are “very impressive data.”

He told this news organization that, in terms of the ongoing PFS improvement, “we wouldn’t expect anything otherwise” with venetoclax-obinutuzumab when compared with the chemotherapy-based regimen, but that the trend for an improvement in overall survival is of particular interest.

This “is a notable feature of the update,” Dr. Wierda said, and “we will continue to watch the long-term overall survival curves with a longer follow-up,” especially as the separation of the curves between the two regimens is “more prominent” than in previous analyses of CLL14.

He also pointed to the low incidence of grade ≥ 3 adverse events in patients who are in remission, which “support the use of fixed-duration chemo-free” treatments, and the longer follow-up now allowing the contribution of high-risk features to outcomes to be teased out in multivariate analysis.

“The data that we’re looking for in the next update of this is some indication about improved outcomes between patients with a mutated and unmutated immunoglobulin heavy chain gene [IgHV], in regard to undetectable MRD [minimal residual disease] status,” Dr. Wierda said.

“We know that mutational status correlates with progression free survival,” he explained. “What we would like to see moving forward is how that is associated with undetectable MRD status at the end of treatment.”

Dr. Wierda said that the next hotly anticipated trial in the field is CLL17, which is comparing ibrutinib monotherapy to fixed-duration venetoclax-obinutuzumab to fixed-duration ibrutinib-venetoclax in patients with previously untreated CLL.

“That’s the next question: Is there any advantage of a BTK [Bruton’s tyrosine kinase] inhibitor with venetoclax over venetoclax plus the CD20 antibody?”

Dr. Al-Sawaf, in presenting the latest analysis, reminded the audience that CLL14 was a randomized phase 3 study focusing on patients with previously untreated CLL and coexisting conditions who were randomized to either venetoclax-obinutuzumab for six cycles, followed by six cycles of venetoclax, or chlorambucil-obinutuzumab for six cycles, followed by chlorambucil for six cycles.

The patients, who were enrolled between 2015 and 2016, were required to have a Cumulative Illness Rating Scale (CIRS) score > 6 and/or creatinine clearance < 70 mL/min, which Dr. Al-Sawaf explained serves as “indicator of the unfitness of the patients.”

A total of 432 patients took part in the study. The median age across the two treatment groups was 71-72 years, and the median total CIRS score was 8-9. The majority of patients (79%-80%) had Binet stage B or C CLL. An intermediate tumor lysis syndrome risk was identified in 64%-68%.

“We also had a fair share of patients with high-risk disease,” Dr. Al-Sawaf noted, with approximately 60% having an unmutated IGHV status, and 12% having a TP53 mutation, both of which are associated with a poorer prognosis.

He added that the “aim of these long-term observations that we try to do every year is not so much to do the comparisons to chlorambucil-obinutuzumab, which we appreciate is not necessarily a standard of care anymore,” but rather to understand the safety and effectiveness of venetoclax-obinutuzumab “in the long run, given that all patients are off treatment.”

Beginning with the safety data, Dr. Al-Sawaf showed that rates of grade ≥ 3 adverse events plummeted after the treatment period, with rates of neutropenia falling from 51.9% with venetoclax-obinutuzumab and 47.2% with chlorambucil-obinutuzumab during treatment to 3.8% and 1.9%, respectively, post treatment.

Similarly, rates of thrombocytopenia decreased from 14.2% on treatment to 0.5% off treatment in patients given venetoclax-obinutuzumab, and from 15.0% to 0.0% in the chlorambucil-obinutuzumab group.

One note of caution was sounded over the proportion of patients with at least one second primary malignancy following treatment, which was numerically higher with venetoclax-obinutuzumab, at 14.2% versus 8.4% with the chemotherapy-based regimen.

“But this is a rather a heterogeneous pattern of solid organ tumors and melanoma,” Dr. Al-Sawaf said, referring to the additional malignancies in the venetoclax-obinutuzumab arm. These included lung cancer, prostate cancer and breast cancer.

He said, however, there was no “specific pattern that we can really pinpoint ... and, importantly, the difference is not statistically significant.”

Turning to the efficacy outcomes, Dr. Al-Sawaf showed that, after median follow-up of 76.4 months, the separation in PFS between the two treatment arms continued, with the median PFS 76.2 months with venetoclax-obinutuzumab versus 36.4 months with chlorambucil-obinutuzumab, at a hazard ratio 0.40 (P < .0001).

The 6-year PFS rate in patients treated with venetoclax-obinutuzumab was 53.1% versus 21.7% with the chemotherapy-based regimen. Looking at the high-risk groups, Dr. Al-Sawaf reported that there was a similar pattern of benefit with venetoclax-obinutuzumab.

Among patients with a TP53 mutation, the median PFS was 51.9 months with the combination versus 20.8 months in those given chlorambucil-obinutuzumab, while the corresponding durations in patients with unmutated IGHV were 64.8 months and 26.9 months, respectively.

Multivariate analysis demonstrated that IGHV status was an independent predictor of PFS in patients treated with venetoclax-obinutuzumab, as was the presence of a TP53 mutation, and lymph node size ≥ 5 cm.

There was no significant difference in overall survival between the two treatment groups, although there was a numerical difference in 6-year overall survival rates, at 78.7% with the experimental combination versus 69.2% with chlorambucil-obinutuzumab.

Patients with a minimal residual disease (MRD) count ≥ 10-4 had a shorter overall survival than did those with MRD < 10-4.

“We are currently working up to understand which group of patients experiences these tremendous long term remissions,” Dr. Al-Sawaf said, “and we will keep you posted on this.”

He also showed that the time to next treatment (TTNT), defined as time to death or next anti-leukemic treatment, was significantly longer with venetoclax-obinutuzumab, with the median not reached before the current data lock versus 52.9 months with the chemotherapy-based regimen.

This equated to a hazard ratio in favor of the experimental combination of 0.44 (P < .0001), and a 6-year TTNT rate of 65.2% versus 37.1% for chlorambucil-obinutuzumab.

That second treatment was a Bruton’s tyrosine kinase inhibitor in 59.0% of cases in the venetoclax-obinutuzumab arm and 53.4% in the chlorambucil-obinutuzumab group.

Dr. Al-Sawaf noted, however, that 23.1% and 30.1%, respectively, of patients were given a chemotherapy or chemo-immunotherapy regimen, “which we nowadays would not necessarily consider a standard of care.”

“This ultimately reflects, as in many global clinical studies, the disparities that we still have across the world in terms of access to state-of-the-art therapies.”

The study was sponsored by Hoffmann–La Roche, and conducted in collaboration with AbbVie, and the German CLL Study Group. Dr. Al-Sawaf disclosed relationships with AbbVie, Adaptive, Ascentage, AstraZeneca, BeiGene, Gilead, Janssen, Lilly, and Roche.

Patients with chronic lymphocytic leukemia (CLL) – even those who have multiple comorbidities – experience long-term progression-free survival (PFS) benefits with 1 year of venetoclax plus obinutuzumab versus a chemotherapy-based regimen, a 6-year follow-up analysis from CLL14 showed. The research was presented June 9 at the annual meeting of the European Hematology Association.

Initial results from the trial were shown at the EHA 2019 annual meeting and reported at the time by this news organization.

They revealed that, among more than 430 CLL patients with a median age of over 70 years and multiple comorbidities, the combination of venetoclax, a B-cell lymphoma 2 protein blocker, plus obinutuzumab, an anti-CD20 monoclonal antibody, was associated with a 65% improvement in PFS, compared with chlorambucil, a chemotherapy agent, plus obinutuzumab.

On the strength of these findings, the venetoclax-obinutuzumab combination received Food and Drug Administration approval for previously untreated CLL and small lymphocytic lymphoma in March 2019.

The latest analysis, presented by Othman Al-Sawaf, MD, University Hospital of Cologne (Germany), showed that despite having just 12 cycles of treatment, patients treated with venetoclax-obinutuzumab continued to experience a significant PFS benefit over those given the chemotherapy-based regimen, including in high-risk patients, after more than 6 years of follow-up.

Dr. Al-Sawaf noted that more than 50% of patients given the experimental combination remained without a PFS event at the latest follow-up, and that over 60% had not required a second treatment, equating to a 66% reduction in the likelihood of needing a second treatment versus chlorambucil-obinutuzumab.

Dr. Al-Sawaf said at a press conference that, “clinically, the standard of care for any CLL if it is asymptomatic” is watch and wait, which is “true in the frontline setting, but also in the relapse setting.”

Therefore, these patients “do not need to initiate the next line of treatment, and that’s why time to next treatment is so interesting.”

He added that there also were no new safety signals, with adverse event rates dropping markedly once treatment was over, although there was a suggestion of an increase in second malignancies with venetoclax-obinutuzumab.

“We’ve seen, in many studies now that use fixed-duration approaches, that there is virtually no posttreatment toxicity once patients are able to get off treatment,” Dr. Al-Sawaf said, adding: “This really highlights the benefit” of stopping treatment, “which is a clear advantage compared to having any kind of continuous treatment.”

Approached for comment, William G. Wierda, MD, PhD, professor, department of leukemia, division of cancer medicine, University of Texas MD Anderson Cancer Center, Houston, emphasized the value of the 6-year follow-up of the study, adding that these are “very impressive data.”

He told this news organization that, in terms of the ongoing PFS improvement, “we wouldn’t expect anything otherwise” with venetoclax-obinutuzumab when compared with the chemotherapy-based regimen, but that the trend for an improvement in overall survival is of particular interest.

This “is a notable feature of the update,” Dr. Wierda said, and “we will continue to watch the long-term overall survival curves with a longer follow-up,” especially as the separation of the curves between the two regimens is “more prominent” than in previous analyses of CLL14.

He also pointed to the low incidence of grade ≥ 3 adverse events in patients who are in remission, which “support the use of fixed-duration chemo-free” treatments, and the longer follow-up now allowing the contribution of high-risk features to outcomes to be teased out in multivariate analysis.

“The data that we’re looking for in the next update of this is some indication about improved outcomes between patients with a mutated and unmutated immunoglobulin heavy chain gene [IgHV], in regard to undetectable MRD [minimal residual disease] status,” Dr. Wierda said.

“We know that mutational status correlates with progression free survival,” he explained. “What we would like to see moving forward is how that is associated with undetectable MRD status at the end of treatment.”

Dr. Wierda said that the next hotly anticipated trial in the field is CLL17, which is comparing ibrutinib monotherapy to fixed-duration venetoclax-obinutuzumab to fixed-duration ibrutinib-venetoclax in patients with previously untreated CLL.

“That’s the next question: Is there any advantage of a BTK [Bruton’s tyrosine kinase] inhibitor with venetoclax over venetoclax plus the CD20 antibody?”

Dr. Al-Sawaf, in presenting the latest analysis, reminded the audience that CLL14 was a randomized phase 3 study focusing on patients with previously untreated CLL and coexisting conditions who were randomized to either venetoclax-obinutuzumab for six cycles, followed by six cycles of venetoclax, or chlorambucil-obinutuzumab for six cycles, followed by chlorambucil for six cycles.

The patients, who were enrolled between 2015 and 2016, were required to have a Cumulative Illness Rating Scale (CIRS) score > 6 and/or creatinine clearance < 70 mL/min, which Dr. Al-Sawaf explained serves as “indicator of the unfitness of the patients.”

A total of 432 patients took part in the study. The median age across the two treatment groups was 71-72 years, and the median total CIRS score was 8-9. The majority of patients (79%-80%) had Binet stage B or C CLL. An intermediate tumor lysis syndrome risk was identified in 64%-68%.

“We also had a fair share of patients with high-risk disease,” Dr. Al-Sawaf noted, with approximately 60% having an unmutated IGHV status, and 12% having a TP53 mutation, both of which are associated with a poorer prognosis.

He added that the “aim of these long-term observations that we try to do every year is not so much to do the comparisons to chlorambucil-obinutuzumab, which we appreciate is not necessarily a standard of care anymore,” but rather to understand the safety and effectiveness of venetoclax-obinutuzumab “in the long run, given that all patients are off treatment.”

Beginning with the safety data, Dr. Al-Sawaf showed that rates of grade ≥ 3 adverse events plummeted after the treatment period, with rates of neutropenia falling from 51.9% with venetoclax-obinutuzumab and 47.2% with chlorambucil-obinutuzumab during treatment to 3.8% and 1.9%, respectively, post treatment.

Similarly, rates of thrombocytopenia decreased from 14.2% on treatment to 0.5% off treatment in patients given venetoclax-obinutuzumab, and from 15.0% to 0.0% in the chlorambucil-obinutuzumab group.

One note of caution was sounded over the proportion of patients with at least one second primary malignancy following treatment, which was numerically higher with venetoclax-obinutuzumab, at 14.2% versus 8.4% with the chemotherapy-based regimen.

“But this is a rather a heterogeneous pattern of solid organ tumors and melanoma,” Dr. Al-Sawaf said, referring to the additional malignancies in the venetoclax-obinutuzumab arm. These included lung cancer, prostate cancer and breast cancer.

He said, however, there was no “specific pattern that we can really pinpoint ... and, importantly, the difference is not statistically significant.”

Turning to the efficacy outcomes, Dr. Al-Sawaf showed that, after median follow-up of 76.4 months, the separation in PFS between the two treatment arms continued, with the median PFS 76.2 months with venetoclax-obinutuzumab versus 36.4 months with chlorambucil-obinutuzumab, at a hazard ratio 0.40 (P < .0001).

The 6-year PFS rate in patients treated with venetoclax-obinutuzumab was 53.1% versus 21.7% with the chemotherapy-based regimen. Looking at the high-risk groups, Dr. Al-Sawaf reported that there was a similar pattern of benefit with venetoclax-obinutuzumab.

Among patients with a TP53 mutation, the median PFS was 51.9 months with the combination versus 20.8 months in those given chlorambucil-obinutuzumab, while the corresponding durations in patients with unmutated IGHV were 64.8 months and 26.9 months, respectively.

Multivariate analysis demonstrated that IGHV status was an independent predictor of PFS in patients treated with venetoclax-obinutuzumab, as was the presence of a TP53 mutation, and lymph node size ≥ 5 cm.

There was no significant difference in overall survival between the two treatment groups, although there was a numerical difference in 6-year overall survival rates, at 78.7% with the experimental combination versus 69.2% with chlorambucil-obinutuzumab.

Patients with a minimal residual disease (MRD) count ≥ 10-4 had a shorter overall survival than did those with MRD < 10-4.

“We are currently working up to understand which group of patients experiences these tremendous long term remissions,” Dr. Al-Sawaf said, “and we will keep you posted on this.”

He also showed that the time to next treatment (TTNT), defined as time to death or next anti-leukemic treatment, was significantly longer with venetoclax-obinutuzumab, with the median not reached before the current data lock versus 52.9 months with the chemotherapy-based regimen.

This equated to a hazard ratio in favor of the experimental combination of 0.44 (P < .0001), and a 6-year TTNT rate of 65.2% versus 37.1% for chlorambucil-obinutuzumab.

That second treatment was a Bruton’s tyrosine kinase inhibitor in 59.0% of cases in the venetoclax-obinutuzumab arm and 53.4% in the chlorambucil-obinutuzumab group.

Dr. Al-Sawaf noted, however, that 23.1% and 30.1%, respectively, of patients were given a chemotherapy or chemo-immunotherapy regimen, “which we nowadays would not necessarily consider a standard of care.”

“This ultimately reflects, as in many global clinical studies, the disparities that we still have across the world in terms of access to state-of-the-art therapies.”

The study was sponsored by Hoffmann–La Roche, and conducted in collaboration with AbbVie, and the German CLL Study Group. Dr. Al-Sawaf disclosed relationships with AbbVie, Adaptive, Ascentage, AstraZeneca, BeiGene, Gilead, Janssen, Lilly, and Roche.

Patients with chronic lymphocytic leukemia (CLL) – even those who have multiple comorbidities – experience long-term progression-free survival (PFS) benefits with 1 year of venetoclax plus obinutuzumab versus a chemotherapy-based regimen, a 6-year follow-up analysis from CLL14 showed. The research was presented June 9 at the annual meeting of the European Hematology Association.

Initial results from the trial were shown at the EHA 2019 annual meeting and reported at the time by this news organization.

They revealed that, among more than 430 CLL patients with a median age of over 70 years and multiple comorbidities, the combination of venetoclax, a B-cell lymphoma 2 protein blocker, plus obinutuzumab, an anti-CD20 monoclonal antibody, was associated with a 65% improvement in PFS, compared with chlorambucil, a chemotherapy agent, plus obinutuzumab.

On the strength of these findings, the venetoclax-obinutuzumab combination received Food and Drug Administration approval for previously untreated CLL and small lymphocytic lymphoma in March 2019.

The latest analysis, presented by Othman Al-Sawaf, MD, University Hospital of Cologne (Germany), showed that despite having just 12 cycles of treatment, patients treated with venetoclax-obinutuzumab continued to experience a significant PFS benefit over those given the chemotherapy-based regimen, including in high-risk patients, after more than 6 years of follow-up.

Dr. Al-Sawaf noted that more than 50% of patients given the experimental combination remained without a PFS event at the latest follow-up, and that over 60% had not required a second treatment, equating to a 66% reduction in the likelihood of needing a second treatment versus chlorambucil-obinutuzumab.

Dr. Al-Sawaf said at a press conference that, “clinically, the standard of care for any CLL if it is asymptomatic” is watch and wait, which is “true in the frontline setting, but also in the relapse setting.”

Therefore, these patients “do not need to initiate the next line of treatment, and that’s why time to next treatment is so interesting.”

He added that there also were no new safety signals, with adverse event rates dropping markedly once treatment was over, although there was a suggestion of an increase in second malignancies with venetoclax-obinutuzumab.

“We’ve seen, in many studies now that use fixed-duration approaches, that there is virtually no posttreatment toxicity once patients are able to get off treatment,” Dr. Al-Sawaf said, adding: “This really highlights the benefit” of stopping treatment, “which is a clear advantage compared to having any kind of continuous treatment.”

Approached for comment, William G. Wierda, MD, PhD, professor, department of leukemia, division of cancer medicine, University of Texas MD Anderson Cancer Center, Houston, emphasized the value of the 6-year follow-up of the study, adding that these are “very impressive data.”

He told this news organization that, in terms of the ongoing PFS improvement, “we wouldn’t expect anything otherwise” with venetoclax-obinutuzumab when compared with the chemotherapy-based regimen, but that the trend for an improvement in overall survival is of particular interest.

This “is a notable feature of the update,” Dr. Wierda said, and “we will continue to watch the long-term overall survival curves with a longer follow-up,” especially as the separation of the curves between the two regimens is “more prominent” than in previous analyses of CLL14.

He also pointed to the low incidence of grade ≥ 3 adverse events in patients who are in remission, which “support the use of fixed-duration chemo-free” treatments, and the longer follow-up now allowing the contribution of high-risk features to outcomes to be teased out in multivariate analysis.

“The data that we’re looking for in the next update of this is some indication about improved outcomes between patients with a mutated and unmutated immunoglobulin heavy chain gene [IgHV], in regard to undetectable MRD [minimal residual disease] status,” Dr. Wierda said.

“We know that mutational status correlates with progression free survival,” he explained. “What we would like to see moving forward is how that is associated with undetectable MRD status at the end of treatment.”

Dr. Wierda said that the next hotly anticipated trial in the field is CLL17, which is comparing ibrutinib monotherapy to fixed-duration venetoclax-obinutuzumab to fixed-duration ibrutinib-venetoclax in patients with previously untreated CLL.

“That’s the next question: Is there any advantage of a BTK [Bruton’s tyrosine kinase] inhibitor with venetoclax over venetoclax plus the CD20 antibody?”

Dr. Al-Sawaf, in presenting the latest analysis, reminded the audience that CLL14 was a randomized phase 3 study focusing on patients with previously untreated CLL and coexisting conditions who were randomized to either venetoclax-obinutuzumab for six cycles, followed by six cycles of venetoclax, or chlorambucil-obinutuzumab for six cycles, followed by chlorambucil for six cycles.

The patients, who were enrolled between 2015 and 2016, were required to have a Cumulative Illness Rating Scale (CIRS) score > 6 and/or creatinine clearance < 70 mL/min, which Dr. Al-Sawaf explained serves as “indicator of the unfitness of the patients.”

A total of 432 patients took part in the study. The median age across the two treatment groups was 71-72 years, and the median total CIRS score was 8-9. The majority of patients (79%-80%) had Binet stage B or C CLL. An intermediate tumor lysis syndrome risk was identified in 64%-68%.

“We also had a fair share of patients with high-risk disease,” Dr. Al-Sawaf noted, with approximately 60% having an unmutated IGHV status, and 12% having a TP53 mutation, both of which are associated with a poorer prognosis.

He added that the “aim of these long-term observations that we try to do every year is not so much to do the comparisons to chlorambucil-obinutuzumab, which we appreciate is not necessarily a standard of care anymore,” but rather to understand the safety and effectiveness of venetoclax-obinutuzumab “in the long run, given that all patients are off treatment.”

Beginning with the safety data, Dr. Al-Sawaf showed that rates of grade ≥ 3 adverse events plummeted after the treatment period, with rates of neutropenia falling from 51.9% with venetoclax-obinutuzumab and 47.2% with chlorambucil-obinutuzumab during treatment to 3.8% and 1.9%, respectively, post treatment.

Similarly, rates of thrombocytopenia decreased from 14.2% on treatment to 0.5% off treatment in patients given venetoclax-obinutuzumab, and from 15.0% to 0.0% in the chlorambucil-obinutuzumab group.

One note of caution was sounded over the proportion of patients with at least one second primary malignancy following treatment, which was numerically higher with venetoclax-obinutuzumab, at 14.2% versus 8.4% with the chemotherapy-based regimen.

“But this is a rather a heterogeneous pattern of solid organ tumors and melanoma,” Dr. Al-Sawaf said, referring to the additional malignancies in the venetoclax-obinutuzumab arm. These included lung cancer, prostate cancer and breast cancer.

He said, however, there was no “specific pattern that we can really pinpoint ... and, importantly, the difference is not statistically significant.”

Turning to the efficacy outcomes, Dr. Al-Sawaf showed that, after median follow-up of 76.4 months, the separation in PFS between the two treatment arms continued, with the median PFS 76.2 months with venetoclax-obinutuzumab versus 36.4 months with chlorambucil-obinutuzumab, at a hazard ratio 0.40 (P < .0001).

The 6-year PFS rate in patients treated with venetoclax-obinutuzumab was 53.1% versus 21.7% with the chemotherapy-based regimen. Looking at the high-risk groups, Dr. Al-Sawaf reported that there was a similar pattern of benefit with venetoclax-obinutuzumab.

Among patients with a TP53 mutation, the median PFS was 51.9 months with the combination versus 20.8 months in those given chlorambucil-obinutuzumab, while the corresponding durations in patients with unmutated IGHV were 64.8 months and 26.9 months, respectively.

Multivariate analysis demonstrated that IGHV status was an independent predictor of PFS in patients treated with venetoclax-obinutuzumab, as was the presence of a TP53 mutation, and lymph node size ≥ 5 cm.

There was no significant difference in overall survival between the two treatment groups, although there was a numerical difference in 6-year overall survival rates, at 78.7% with the experimental combination versus 69.2% with chlorambucil-obinutuzumab.

Patients with a minimal residual disease (MRD) count ≥ 10-4 had a shorter overall survival than did those with MRD < 10-4.

“We are currently working up to understand which group of patients experiences these tremendous long term remissions,” Dr. Al-Sawaf said, “and we will keep you posted on this.”

He also showed that the time to next treatment (TTNT), defined as time to death or next anti-leukemic treatment, was significantly longer with venetoclax-obinutuzumab, with the median not reached before the current data lock versus 52.9 months with the chemotherapy-based regimen.

This equated to a hazard ratio in favor of the experimental combination of 0.44 (P < .0001), and a 6-year TTNT rate of 65.2% versus 37.1% for chlorambucil-obinutuzumab.

That second treatment was a Bruton’s tyrosine kinase inhibitor in 59.0% of cases in the venetoclax-obinutuzumab arm and 53.4% in the chlorambucil-obinutuzumab group.

Dr. Al-Sawaf noted, however, that 23.1% and 30.1%, respectively, of patients were given a chemotherapy or chemo-immunotherapy regimen, “which we nowadays would not necessarily consider a standard of care.”

“This ultimately reflects, as in many global clinical studies, the disparities that we still have across the world in terms of access to state-of-the-art therapies.”

The study was sponsored by Hoffmann–La Roche, and conducted in collaboration with AbbVie, and the German CLL Study Group. Dr. Al-Sawaf disclosed relationships with AbbVie, Adaptive, Ascentage, AstraZeneca, BeiGene, Gilead, Janssen, Lilly, and Roche.

TOPLINE

Mean lipid levels are similar among adolescents with and without major depressive disorder (MDD), as is the proportion of adolescents with borderline-high lipid levels.

METHODOLOGY

Teen depression is associated with an increased likelihood of experiencing cardiovascular (CV) events, with dyslipidemia being a potentially modifiable risk factor.

Only a few studies have examined the association between depression and lipids during adolescence, when confounding comorbidities such as obesity and diabetes are less common.

The study included 243 adolescents (186 with MDD and 57 healthy controls [HCs]) who were mostly female and had a mean age of 15 years.

Researchers assessed CV risk factors including body mass index (BMI), blood pressure, smoking status, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride (TG), which were classified as acceptable or borderline high.

Dyslipidemia was defined as having concentration of at least one lipid outside the acceptable range.
 

TAKEAWAY

Most participants in both groups had lipid concentrations within the acceptable range.

There were no differences between study groups in mean lipid levels after adjusting for age, sex, and standardized BMI.

There were also no differences in the proportion of adolescents with borderline-high lipid concentrations.

Among youth with MDD, greater depressive symptoms were associated with higher HDL levels and a lower TG:HDL ratio after adjusting for sex, age, and standardized BMI.
 

IN PRACTICE

“Taken together, results of the current study support the need for further examination of the relationship between gender, depression, and cholesterol,” the authors write.

STUDY DETAILS

The study was conducted by Anisa F. Khalfan, Neurosciences and Mental Health research program, SickKids Research Institute, Toronto, Canada, and colleagues. It was published online in the Journal of Affective Disorders.

LIMITATIONS

The HC group was relatively small, which might have contributed to the null findings. The mean Center for Epidemiologic Studies Depression Scale for Children (CES-DC) score was 8.3 among healthy youth, compared with 37.5 among MDD youth, limiting detection of an association related to depression severity.

DISCLOSURES

The study was supported by the Lunenfeld Summer Studentship. The authors report no relevant financial relationships.

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

TOPLINE

Mean lipid levels are similar among adolescents with and without major depressive disorder (MDD), as is the proportion of adolescents with borderline-high lipid levels.

METHODOLOGY

Teen depression is associated with an increased likelihood of experiencing cardiovascular (CV) events, with dyslipidemia being a potentially modifiable risk factor.

Only a few studies have examined the association between depression and lipids during adolescence, when confounding comorbidities such as obesity and diabetes are less common.

The study included 243 adolescents (186 with MDD and 57 healthy controls [HCs]) who were mostly female and had a mean age of 15 years.

Researchers assessed CV risk factors including body mass index (BMI), blood pressure, smoking status, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride (TG), which were classified as acceptable or borderline high.

Dyslipidemia was defined as having concentration of at least one lipid outside the acceptable range.
 

TAKEAWAY

Most participants in both groups had lipid concentrations within the acceptable range.

There were no differences between study groups in mean lipid levels after adjusting for age, sex, and standardized BMI.

There were also no differences in the proportion of adolescents with borderline-high lipid concentrations.

Among youth with MDD, greater depressive symptoms were associated with higher HDL levels and a lower TG:HDL ratio after adjusting for sex, age, and standardized BMI.
 

IN PRACTICE

“Taken together, results of the current study support the need for further examination of the relationship between gender, depression, and cholesterol,” the authors write.

STUDY DETAILS

The study was conducted by Anisa F. Khalfan, Neurosciences and Mental Health research program, SickKids Research Institute, Toronto, Canada, and colleagues. It was published online in the Journal of Affective Disorders.

LIMITATIONS

The HC group was relatively small, which might have contributed to the null findings. The mean Center for Epidemiologic Studies Depression Scale for Children (CES-DC) score was 8.3 among healthy youth, compared with 37.5 among MDD youth, limiting detection of an association related to depression severity.

DISCLOSURES

The study was supported by the Lunenfeld Summer Studentship. The authors report no relevant financial relationships.

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

TOPLINE

Mean lipid levels are similar among adolescents with and without major depressive disorder (MDD), as is the proportion of adolescents with borderline-high lipid levels.

METHODOLOGY

Teen depression is associated with an increased likelihood of experiencing cardiovascular (CV) events, with dyslipidemia being a potentially modifiable risk factor.

Only a few studies have examined the association between depression and lipids during adolescence, when confounding comorbidities such as obesity and diabetes are less common.

The study included 243 adolescents (186 with MDD and 57 healthy controls [HCs]) who were mostly female and had a mean age of 15 years.

Researchers assessed CV risk factors including body mass index (BMI), blood pressure, smoking status, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride (TG), which were classified as acceptable or borderline high.

Dyslipidemia was defined as having concentration of at least one lipid outside the acceptable range.
 

TAKEAWAY

Most participants in both groups had lipid concentrations within the acceptable range.

There were no differences between study groups in mean lipid levels after adjusting for age, sex, and standardized BMI.

There were also no differences in the proportion of adolescents with borderline-high lipid concentrations.

Among youth with MDD, greater depressive symptoms were associated with higher HDL levels and a lower TG:HDL ratio after adjusting for sex, age, and standardized BMI.
 

IN PRACTICE

“Taken together, results of the current study support the need for further examination of the relationship between gender, depression, and cholesterol,” the authors write.

STUDY DETAILS

The study was conducted by Anisa F. Khalfan, Neurosciences and Mental Health research program, SickKids Research Institute, Toronto, Canada, and colleagues. It was published online in the Journal of Affective Disorders.

LIMITATIONS

The HC group was relatively small, which might have contributed to the null findings. The mean Center for Epidemiologic Studies Depression Scale for Children (CES-DC) score was 8.3 among healthy youth, compared with 37.5 among MDD youth, limiting detection of an association related to depression severity.

DISCLOSURES

The study was supported by the Lunenfeld Summer Studentship. The authors report no relevant financial relationships.

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

CHICAGO – Polycystic ovary syndrome (PCOS) appears to shorten a woman’s lifespan, new data suggest.

In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.

PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.

“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.

“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.

Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”

And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.

Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”

“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”

Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.

He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”

Women with PCOS lose a year of life

The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.

The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).

Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).

In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).

One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.

Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.

CHICAGO – Polycystic ovary syndrome (PCOS) appears to shorten a woman’s lifespan, new data suggest.

In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.

PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.

“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.

“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.

Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”

And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.

Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”

“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”

Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.

He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”

Women with PCOS lose a year of life

The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.

The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).

Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).

In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).

One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.

Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.

CHICAGO – Polycystic ovary syndrome (PCOS) appears to shorten a woman’s lifespan, new data suggest.

In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.

PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.

“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.

“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.

Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”

And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.

Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”

“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”

Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.

He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”

Women with PCOS lose a year of life

The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.

The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).

Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).

In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).

One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.

Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.

Confirming the importance of sleep health, new research shows that short and disrupted sleep increases the risk of fall-related and motor vehicle–related injury among U.S. adults.

Among the study’s key findings – adults who get 4 hours or less nightly and those who have trouble staying asleep are significantly more likely to be injured than peers who sleep the recommended 7-8 hours and those who never have trouble staying asleep.

The findings were presented at SLEEP 2023: 37th Annual Meeting of the Associated Professional Sleep Societies.
 

‘Stark differences’

In 2020, 55.4 million (roughly 1 in 6) Americans sought medical attention for nonfatal, preventable injuries.

“Poor sleep has been identified as a risk factor for preventable injuries,” study investigator Clarence Locklear, MA, who is a PhD student with the Center for Translational Sleep and Circadian Sciences, University of Miami Miller School of Medicine, told this news organization.

For the study, the researchers examined associations between different types of sleep problems and different types of injuries utilizing data on 31,568 adults who participated in the 2020 National Health Interview Survey.

They investigated three types of injuries (fall-related, sports-related, and motor vehicle–related) and four domains of past-month sleep health: (1) sleep quantity: very short (≤ 4 hours), short (5-6 hours), healthy (7-8 hours), or long (≥ 9 hours); (2) sleep quality: trouble falling asleep and trouble staying asleep; (3) feeling well rested upon waking up; and (4) sleep medications.

Overall, 9% of adults suffered an injury in the prior 3 months. Among injured adults, 47% had a fall-related injury, 29% had a sports-related injury, and 6% had a motor vehicle–related injury.

Adults with very short sleep, those with short sleep, and those with long sleep were 37%, 15%, and 22% more likely to be injured, respectively, than adults with healthy sleep (P < .05), the researchers found.

Those who had trouble staying asleep were 36% more likely to be injured than peers who never had trouble staying asleep (P < .01).

Adults who never woke up feeling rested and those who woke up feeling rested only on some days were 49% and 36% more likely to be injured (P < .01), respectively, than peers who always felt rested on waking.

Individuals who on some days took medication for sleep were 24% (P < .05) more likely to suffer an injury and those who took sleep medication every day were 36% (P < .001) more likely to get injured than those who never took sleep medication.

“These are pretty stark differences,” said Mr. Locklear.

Regarding injury type, those who had trouble staying asleep some days were 22% (P < .05) more likely to have a fall-related injury and were 3.5 times (P < .01) more likely to experience a motor vehicle–related injury than peers who didn’t have trouble staying asleep.

People who took sleep medication most days were 2.4 times more likely to suffer a fall than those who never took sleep medication. In addition, adults who reported long sleep (9+ hours nightly) were 43% less likely to have sports-related injuries (P < .05) than healthy sleepers (7-8 hours).
 

Quantity and quality matter

Michael Breus, PhD, clinical psychologist and founder of TheSleepDoctor.com, said the results are “not particularly surprising but are consistent with other data.”

Dr. Breus said, “Many people don’t realize it’s not just sleep deprivation, in terms of minutes, that’s a problem. Our quality of sleep also matters. You can get 8 hours of crappy sleep and still injure yourself playing sports or get into a car accident due to poor reaction time.”

As previously reported by this news organization, the American Heart Association recently added healthy sleep as an essential component of heart health. “It’s nice to see them recognize that sleep is a big deal, and we’ve got the data to back it up,” said Dr. Breus.

He noted that people often ask him what’s the one thing they can do to improve sleep.

“The answer is always, wake up at the same time every single day, including the weekend, because your circadian system realigns every single morning.

“I solve maybe 50%-60% of people’s problems by just telling them to just wake up at the same time 7 days a week. I personally have been doing it for a very long time,” said Dr. Breus.

The study was supported by the National Heart Lung and Blood Institute. Mr. Locklear and Dr. Breus have no relevant disclosures.

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

Confirming the importance of sleep health, new research shows that short and disrupted sleep increases the risk of fall-related and motor vehicle–related injury among U.S. adults.

Among the study’s key findings – adults who get 4 hours or less nightly and those who have trouble staying asleep are significantly more likely to be injured than peers who sleep the recommended 7-8 hours and those who never have trouble staying asleep.

The findings were presented at SLEEP 2023: 37th Annual Meeting of the Associated Professional Sleep Societies.
 

‘Stark differences’

In 2020, 55.4 million (roughly 1 in 6) Americans sought medical attention for nonfatal, preventable injuries.

“Poor sleep has been identified as a risk factor for preventable injuries,” study investigator Clarence Locklear, MA, who is a PhD student with the Center for Translational Sleep and Circadian Sciences, University of Miami Miller School of Medicine, told this news organization.

For the study, the researchers examined associations between different types of sleep problems and different types of injuries utilizing data on 31,568 adults who participated in the 2020 National Health Interview Survey.

They investigated three types of injuries (fall-related, sports-related, and motor vehicle–related) and four domains of past-month sleep health: (1) sleep quantity: very short (≤ 4 hours), short (5-6 hours), healthy (7-8 hours), or long (≥ 9 hours); (2) sleep quality: trouble falling asleep and trouble staying asleep; (3) feeling well rested upon waking up; and (4) sleep medications.

Overall, 9% of adults suffered an injury in the prior 3 months. Among injured adults, 47% had a fall-related injury, 29% had a sports-related injury, and 6% had a motor vehicle–related injury.

Adults with very short sleep, those with short sleep, and those with long sleep were 37%, 15%, and 22% more likely to be injured, respectively, than adults with healthy sleep (P < .05), the researchers found.

Those who had trouble staying asleep were 36% more likely to be injured than peers who never had trouble staying asleep (P < .01).

Adults who never woke up feeling rested and those who woke up feeling rested only on some days were 49% and 36% more likely to be injured (P < .01), respectively, than peers who always felt rested on waking.

Individuals who on some days took medication for sleep were 24% (P < .05) more likely to suffer an injury and those who took sleep medication every day were 36% (P < .001) more likely to get injured than those who never took sleep medication.

“These are pretty stark differences,” said Mr. Locklear.

Regarding injury type, those who had trouble staying asleep some days were 22% (P < .05) more likely to have a fall-related injury and were 3.5 times (P < .01) more likely to experience a motor vehicle–related injury than peers who didn’t have trouble staying asleep.

People who took sleep medication most days were 2.4 times more likely to suffer a fall than those who never took sleep medication. In addition, adults who reported long sleep (9+ hours nightly) were 43% less likely to have sports-related injuries (P < .05) than healthy sleepers (7-8 hours).
 

Quantity and quality matter

Michael Breus, PhD, clinical psychologist and founder of TheSleepDoctor.com, said the results are “not particularly surprising but are consistent with other data.”

Dr. Breus said, “Many people don’t realize it’s not just sleep deprivation, in terms of minutes, that’s a problem. Our quality of sleep also matters. You can get 8 hours of crappy sleep and still injure yourself playing sports or get into a car accident due to poor reaction time.”

As previously reported by this news organization, the American Heart Association recently added healthy sleep as an essential component of heart health. “It’s nice to see them recognize that sleep is a big deal, and we’ve got the data to back it up,” said Dr. Breus.

He noted that people often ask him what’s the one thing they can do to improve sleep.

“The answer is always, wake up at the same time every single day, including the weekend, because your circadian system realigns every single morning.

“I solve maybe 50%-60% of people’s problems by just telling them to just wake up at the same time 7 days a week. I personally have been doing it for a very long time,” said Dr. Breus.

The study was supported by the National Heart Lung and Blood Institute. Mr. Locklear and Dr. Breus have no relevant disclosures.

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

Confirming the importance of sleep health, new research shows that short and disrupted sleep increases the risk of fall-related and motor vehicle–related injury among U.S. adults.

Among the study’s key findings – adults who get 4 hours or less nightly and those who have trouble staying asleep are significantly more likely to be injured than peers who sleep the recommended 7-8 hours and those who never have trouble staying asleep.

The findings were presented at SLEEP 2023: 37th Annual Meeting of the Associated Professional Sleep Societies.
 

‘Stark differences’

In 2020, 55.4 million (roughly 1 in 6) Americans sought medical attention for nonfatal, preventable injuries.

“Poor sleep has been identified as a risk factor for preventable injuries,” study investigator Clarence Locklear, MA, who is a PhD student with the Center for Translational Sleep and Circadian Sciences, University of Miami Miller School of Medicine, told this news organization.

For the study, the researchers examined associations between different types of sleep problems and different types of injuries utilizing data on 31,568 adults who participated in the 2020 National Health Interview Survey.

They investigated three types of injuries (fall-related, sports-related, and motor vehicle–related) and four domains of past-month sleep health: (1) sleep quantity: very short (≤ 4 hours), short (5-6 hours), healthy (7-8 hours), or long (≥ 9 hours); (2) sleep quality: trouble falling asleep and trouble staying asleep; (3) feeling well rested upon waking up; and (4) sleep medications.

Overall, 9% of adults suffered an injury in the prior 3 months. Among injured adults, 47% had a fall-related injury, 29% had a sports-related injury, and 6% had a motor vehicle–related injury.

Adults with very short sleep, those with short sleep, and those with long sleep were 37%, 15%, and 22% more likely to be injured, respectively, than adults with healthy sleep (P < .05), the researchers found.

Those who had trouble staying asleep were 36% more likely to be injured than peers who never had trouble staying asleep (P < .01).

Adults who never woke up feeling rested and those who woke up feeling rested only on some days were 49% and 36% more likely to be injured (P < .01), respectively, than peers who always felt rested on waking.

Individuals who on some days took medication for sleep were 24% (P < .05) more likely to suffer an injury and those who took sleep medication every day were 36% (P < .001) more likely to get injured than those who never took sleep medication.

“These are pretty stark differences,” said Mr. Locklear.

Regarding injury type, those who had trouble staying asleep some days were 22% (P < .05) more likely to have a fall-related injury and were 3.5 times (P < .01) more likely to experience a motor vehicle–related injury than peers who didn’t have trouble staying asleep.

People who took sleep medication most days were 2.4 times more likely to suffer a fall than those who never took sleep medication. In addition, adults who reported long sleep (9+ hours nightly) were 43% less likely to have sports-related injuries (P < .05) than healthy sleepers (7-8 hours).
 

Quantity and quality matter

Michael Breus, PhD, clinical psychologist and founder of TheSleepDoctor.com, said the results are “not particularly surprising but are consistent with other data.”

Dr. Breus said, “Many people don’t realize it’s not just sleep deprivation, in terms of minutes, that’s a problem. Our quality of sleep also matters. You can get 8 hours of crappy sleep and still injure yourself playing sports or get into a car accident due to poor reaction time.”

As previously reported by this news organization, the American Heart Association recently added healthy sleep as an essential component of heart health. “It’s nice to see them recognize that sleep is a big deal, and we’ve got the data to back it up,” said Dr. Breus.

He noted that people often ask him what’s the one thing they can do to improve sleep.

“The answer is always, wake up at the same time every single day, including the weekend, because your circadian system realigns every single morning.

“I solve maybe 50%-60% of people’s problems by just telling them to just wake up at the same time 7 days a week. I personally have been doing it for a very long time,” said Dr. Breus.

The study was supported by the National Heart Lung and Blood Institute. Mr. Locklear and Dr. Breus have no relevant disclosures.

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

Human Rights Watch, the nonprofit that for decades has called attention to the victims of war, famine, and political repression around the world, is taking aim at U.S. hospitals for pushing millions of American patients into debt.

In a new report, the group calls for stronger government action to protect Americans from aggressive billing and debt collection by nonprofit hospitals, which Human Rights Watch said are systematically undermining patients’ human rights.

“Given the high prevalence of hospital-related medical debt in the U.S., this system is clearly not working,” concludes the report, which draws extensively on an ongoing investigation of medical debt by KFF Health News and NPR.

The report continues: “The U.S. model of subsidizing privately operated hospitals with tax exemptions in the hope that they will increase the accessibility of hospital care for un- and underinsured patients allows for abusive medical billing and debt collection practices and undermines human rights, including the right to health.”

Nationwide, about 100 million people – or 41% of adults – have some form of health care debt, a KFF survey conducted for the KFF Health News–NPR project found. And while patient debt is being driven by a range of medical and dental bills, polls and studies suggest hospitals are a major contributor.

About a third of U.S. adults with health care debt owed money for hospitalization, KFF’s polling found. Close to half of those owed at least $5,000. About a quarter owed $10,000 or more.

The scale of this crisis – which is unparalleled among wealthy nations – compelled Human Rights Watch to release the new report, said researcher Matt McConnell, its author. “Historically, Human Rights Watch has been an organization that has focused on international human rights issues,” he said. “But on medical debt, the U.S. is a real outlier. What you see is a system that privileges a few but creates large barriers to people accessing basic health rights.”

Hospital industry officials defend their work, citing hospitals’ broader work to help the communities they serve. “As a field, hospitals provide more benefit to their communities than any other sector in health care,” Melinda Hatton, general counsel at the American Hospital Association, wrote in a response to the Human Right Watch report.

Federal law requires private, tax-exempt hospitals – which make up more than half the nation’s medical centers – to provide care at no cost or at a discount to low-income patients. But reporting by KFF Health News and others has found that many hospitals make this aid difficult for patients to get.

At the same time, thousands of medical centers – including many tax-exempt ones – engage in aggressive debt collection tactics to pursue patients, including garnishing patients’ wages, placing liens on their homes, or selling their debt to third-party debt collectors.

Overall, KFF Health News found that most of the nation’s approximately 5,100 hospitals serving the general public have policies to use legal action or other aggressive tactics against patients. And one in five will deny nonemergency care to people with outstanding debt.

“Medical debt is drowning many low-income and working families while hospitals continue to benefit from nonprofit tax status as they pursue families for medical debt,” said Marceline White, executive director of Economic Action Maryland. The advocacy group has helped enact tighter rules to ensure Maryland hospitals make financial assistance more easily accessible and to restrict hospitals from some aggressive debt collection tactics, such as placing liens on patients’ homes.

Similar efforts are underway in other states, including Colorado, New Mexico, New York, Oregon, and Washington. But many patient and consumer advocates say stronger federal action is needed to expand patient protections.

The Human Rights Watch report – titled “In Sheep’s Clothing: United States’ Poorly Regulated Nonprofit Hospitals Undermine Health Care Access” – lists more than a dozen recommendations. These include:

• Congress should pass legislation to ensure that hospitals provide at least the same amount of charity care as they receive in public subsidies.
• The IRS should set uniform national standards on patients’ eligibility for financial assistance at nonprofit hospitals. Currently, hospitals are free to set their own standards, resulting in widespread variation, which can confuse patients.
• The Consumer Financial Protection Bureau, a federal watchdog agency, should crack down on debt collectors that do not ensure that patients have been screened for financial assistance before being pursued.
• The federal Centers for Medicare & Medicaid Services, which administers the two mammoth public insurance programs, should penalize hospitals that do not provide adequate financial assistance to patients.

“Nonprofit hospitals are contributing to medical debt and engaging in abusive billing and debt collection practices,” Mr. McConnell said. “The reason this keeps happening is the absence of clear guidelines and the federal government’s inadequate enforcement of existing regulations.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

Human Rights Watch, the nonprofit that for decades has called attention to the victims of war, famine, and political repression around the world, is taking aim at U.S. hospitals for pushing millions of American patients into debt.

In a new report, the group calls for stronger government action to protect Americans from aggressive billing and debt collection by nonprofit hospitals, which Human Rights Watch said are systematically undermining patients’ human rights.

“Given the high prevalence of hospital-related medical debt in the U.S., this system is clearly not working,” concludes the report, which draws extensively on an ongoing investigation of medical debt by KFF Health News and NPR.

The report continues: “The U.S. model of subsidizing privately operated hospitals with tax exemptions in the hope that they will increase the accessibility of hospital care for un- and underinsured patients allows for abusive medical billing and debt collection practices and undermines human rights, including the right to health.”

Nationwide, about 100 million people – or 41% of adults – have some form of health care debt, a KFF survey conducted for the KFF Health News–NPR project found. And while patient debt is being driven by a range of medical and dental bills, polls and studies suggest hospitals are a major contributor.

About a third of U.S. adults with health care debt owed money for hospitalization, KFF’s polling found. Close to half of those owed at least $5,000. About a quarter owed $10,000 or more.

The scale of this crisis – which is unparalleled among wealthy nations – compelled Human Rights Watch to release the new report, said researcher Matt McConnell, its author. “Historically, Human Rights Watch has been an organization that has focused on international human rights issues,” he said. “But on medical debt, the U.S. is a real outlier. What you see is a system that privileges a few but creates large barriers to people accessing basic health rights.”

Hospital industry officials defend their work, citing hospitals’ broader work to help the communities they serve. “As a field, hospitals provide more benefit to their communities than any other sector in health care,” Melinda Hatton, general counsel at the American Hospital Association, wrote in a response to the Human Right Watch report.

Federal law requires private, tax-exempt hospitals – which make up more than half the nation’s medical centers – to provide care at no cost or at a discount to low-income patients. But reporting by KFF Health News and others has found that many hospitals make this aid difficult for patients to get.

At the same time, thousands of medical centers – including many tax-exempt ones – engage in aggressive debt collection tactics to pursue patients, including garnishing patients’ wages, placing liens on their homes, or selling their debt to third-party debt collectors.

Overall, KFF Health News found that most of the nation’s approximately 5,100 hospitals serving the general public have policies to use legal action or other aggressive tactics against patients. And one in five will deny nonemergency care to people with outstanding debt.

“Medical debt is drowning many low-income and working families while hospitals continue to benefit from nonprofit tax status as they pursue families for medical debt,” said Marceline White, executive director of Economic Action Maryland. The advocacy group has helped enact tighter rules to ensure Maryland hospitals make financial assistance more easily accessible and to restrict hospitals from some aggressive debt collection tactics, such as placing liens on patients’ homes.

Similar efforts are underway in other states, including Colorado, New Mexico, New York, Oregon, and Washington. But many patient and consumer advocates say stronger federal action is needed to expand patient protections.

The Human Rights Watch report – titled “In Sheep’s Clothing: United States’ Poorly Regulated Nonprofit Hospitals Undermine Health Care Access” – lists more than a dozen recommendations. These include:

• Congress should pass legislation to ensure that hospitals provide at least the same amount of charity care as they receive in public subsidies.
• The IRS should set uniform national standards on patients’ eligibility for financial assistance at nonprofit hospitals. Currently, hospitals are free to set their own standards, resulting in widespread variation, which can confuse patients.
• The Consumer Financial Protection Bureau, a federal watchdog agency, should crack down on debt collectors that do not ensure that patients have been screened for financial assistance before being pursued.
• The federal Centers for Medicare & Medicaid Services, which administers the two mammoth public insurance programs, should penalize hospitals that do not provide adequate financial assistance to patients.

“Nonprofit hospitals are contributing to medical debt and engaging in abusive billing and debt collection practices,” Mr. McConnell said. “The reason this keeps happening is the absence of clear guidelines and the federal government’s inadequate enforcement of existing regulations.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

Human Rights Watch, the nonprofit that for decades has called attention to the victims of war, famine, and political repression around the world, is taking aim at U.S. hospitals for pushing millions of American patients into debt.

In a new report, the group calls for stronger government action to protect Americans from aggressive billing and debt collection by nonprofit hospitals, which Human Rights Watch said are systematically undermining patients’ human rights.

“Given the high prevalence of hospital-related medical debt in the U.S., this system is clearly not working,” concludes the report, which draws extensively on an ongoing investigation of medical debt by KFF Health News and NPR.

The report continues: “The U.S. model of subsidizing privately operated hospitals with tax exemptions in the hope that they will increase the accessibility of hospital care for un- and underinsured patients allows for abusive medical billing and debt collection practices and undermines human rights, including the right to health.”

Nationwide, about 100 million people – or 41% of adults – have some form of health care debt, a KFF survey conducted for the KFF Health News–NPR project found. And while patient debt is being driven by a range of medical and dental bills, polls and studies suggest hospitals are a major contributor.

About a third of U.S. adults with health care debt owed money for hospitalization, KFF’s polling found. Close to half of those owed at least $5,000. About a quarter owed $10,000 or more.

The scale of this crisis – which is unparalleled among wealthy nations – compelled Human Rights Watch to release the new report, said researcher Matt McConnell, its author. “Historically, Human Rights Watch has been an organization that has focused on international human rights issues,” he said. “But on medical debt, the U.S. is a real outlier. What you see is a system that privileges a few but creates large barriers to people accessing basic health rights.”

Hospital industry officials defend their work, citing hospitals’ broader work to help the communities they serve. “As a field, hospitals provide more benefit to their communities than any other sector in health care,” Melinda Hatton, general counsel at the American Hospital Association, wrote in a response to the Human Right Watch report.

Federal law requires private, tax-exempt hospitals – which make up more than half the nation’s medical centers – to provide care at no cost or at a discount to low-income patients. But reporting by KFF Health News and others has found that many hospitals make this aid difficult for patients to get.

At the same time, thousands of medical centers – including many tax-exempt ones – engage in aggressive debt collection tactics to pursue patients, including garnishing patients’ wages, placing liens on their homes, or selling their debt to third-party debt collectors.

Overall, KFF Health News found that most of the nation’s approximately 5,100 hospitals serving the general public have policies to use legal action or other aggressive tactics against patients. And one in five will deny nonemergency care to people with outstanding debt.

“Medical debt is drowning many low-income and working families while hospitals continue to benefit from nonprofit tax status as they pursue families for medical debt,” said Marceline White, executive director of Economic Action Maryland. The advocacy group has helped enact tighter rules to ensure Maryland hospitals make financial assistance more easily accessible and to restrict hospitals from some aggressive debt collection tactics, such as placing liens on patients’ homes.

Similar efforts are underway in other states, including Colorado, New Mexico, New York, Oregon, and Washington. But many patient and consumer advocates say stronger federal action is needed to expand patient protections.

The Human Rights Watch report – titled “In Sheep’s Clothing: United States’ Poorly Regulated Nonprofit Hospitals Undermine Health Care Access” – lists more than a dozen recommendations. These include:

• Congress should pass legislation to ensure that hospitals provide at least the same amount of charity care as they receive in public subsidies.
• The IRS should set uniform national standards on patients’ eligibility for financial assistance at nonprofit hospitals. Currently, hospitals are free to set their own standards, resulting in widespread variation, which can confuse patients.
• The Consumer Financial Protection Bureau, a federal watchdog agency, should crack down on debt collectors that do not ensure that patients have been screened for financial assistance before being pursued.
• The federal Centers for Medicare & Medicaid Services, which administers the two mammoth public insurance programs, should penalize hospitals that do not provide adequate financial assistance to patients.

“Nonprofit hospitals are contributing to medical debt and engaging in abusive billing and debt collection practices,” Mr. McConnell said. “The reason this keeps happening is the absence of clear guidelines and the federal government’s inadequate enforcement of existing regulations.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

CHICAGO – Testosterone replacement therapy does not appear to raise the risk for adverse cardiac events among middle-aged and older men with hypogonadism at high risk for heart disease, long-awaited results from a major clinical trial show.

Among over 5,000 men aged 45-80 years randomized to daily transdermal testosterone gel or matching placebo gel for an average of 22 months, no increased risk was seen for a first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.

There was also no increased risk for prostate cancer over the 33-month follow-up period. However, there were increases in rates of atrial fibrillation, acute kidney injury, and pulmonary embolism in the testosterone group.

In terms of efficacy, testosterone therapy was associated with improved sexual function over two years of treatment and correction, or prevention, of anemia, but had no effect on progression to diabetes or glycemic parameters.

And, an unexpected finding was a significant and unexplained 43% increase in fractures with testosterone therapy.

The TRAVERSE study was mandated by the Food and Drug Administration in 2015 in response to concerns and conflicting data regarding the cardiovascular safety of testosterone replacement therapy in men. It was conducted by a consortium of five manufacturers of testosterone replacement products, led by AbbVie.

The results were presented during a symposium at the annual meeting of the Endocrine Society. The mandated safety data were published online in the New England Journal of Medicine. The efficacy outcomes, undertaken opportunistically due to the trial’s large sample size and relatively long followup time, will be published later this year.

Taken together, the TRAVERSE findings are expected to transform the risk–benefit discussions with patients about the use of testosterone therapy for hypogonadism, study coauthor Shalender Bhasin, MD, told this news organization.

“Testosterone deficiency doesn’t kill people as far as we know but it is really an important symptomatic condition that affects quality of life. Many middle-aged and older men seek assistance for these symptoms, so it’s an important condition and the treatment decisions are complicated,” said Dr. Bhasin, director of the research program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital in Boston.

These new data will be incorporated into future guidelines on testosterone therapy in men with hypoandrogenism, noted Dr. Bhasin, a coauthor of The Endocrine Society’s 2018 guidelines.
 

Findings apply only to men with bona fide testosterone deficiency

Asked to comment, endocrinologist Bradley D. Anawalt, MD, told this news organization that “the community of physicians who prescribe testosterone to men was waiting with bated breath” for the TRAVERSE results.

Safety reassuring, but some concerns will require more investigation

TRAVERSE was a multicenter, randomized, double-blind, placebo-controlled noninferiority trial that enrolled 5246 men aged 45-80 years. Participants had pre-existing or were at high risk of cardiovascular disease, reported symptoms of hypogonadism, and had two fasting testosterone levels < 300 ng/dL. They were randomly assigned to receive daily transdermal 1.62% testosterone gel or placebo gel.

The primary safety endpoint event (first adjudicated major adverse cardiac event) occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; P < .001 for noninferiority). Similar results were seen in sensitivity analyses.

Pulmonary embolism occurred in 0.9% of the testosterone group versus 0.5% of the placebo group, supporting current guidelines that testosterone should be used with caution in men who have had previous thromboembolic events, the authors note.

Prostate cancer occurred in 0.5% (n = 12) of patients in the testosterone group and 0.4% (n = 11) of patients in the placebo group, not a significant difference (P = .87).

There were, however, significant differences between the testosterone and placebo groups in terms of nonfatal arrhythmias warranting intervention (5.2% vs. 3.3%; P = .001), atrial fibrillation (3.5% vs. 2.4%; P = .02), and acute kidney injury (2.3% vs. 1.5%; P = .04).

“These adverse events were not expected,” the authors wrote.

Dr. Bhasin said that the team plans to investigate those cases further to look for possible risk factors, including whether COVID-19 played a role in these outcomes because the trial took place during the pandemic and some participants in both study groups contracted the virus.

Regarding acute kidney injury, Dr. Anawalt said: “I don’t know that I believe that ... It’s probably a statistical abnormality. It barely made ... significance.”
 

Finally, ‘real data on something we’ve been prescribing for decades’

Both Dr. Bhasin and Dr. Anawalt pointed out the deficiencies in the prior literature in terms of what has been known about testosterone’s effects. According to Dr. Bhasin, “In spite of all the folklore, there isn’t very much known about the efficacy of treatment beyond sexual function, and even there, the data are really limited. Most trials have been open-label and very small.”

He added that even among the few previous randomized clinical trials, only one, the TTrials series,  had an adequate number of participants and used robust measures to assess sexual function, but that study only lasted a year.

Indeed, Dr. Anawalt noted, “[TRAVERSE] and its father study, the TTrials, were the first systematic studies to look at large groups of men getting testosterone versus placebo. We’re now starting to get real data on something that we’ve been prescribing for decades.”

At the ENDO symposium, Dr. Bhasin presented data showing significant improvements with testosterone compared to placebo in overall sexual activity (P = .011), sexual symptoms (P < .001), and sexual desire over one year, and maintained over two years in TRAVERSE. All were assessed by validated questionnaires.

“They confirmed that there’s an improvement in sexual function and that it’s sustained. That’s important because there had been doubt about that ... and it sounds like it’s clinically significant,” Dr. Anawalt said.

Testosterone therapy was also associated with lower rates of anemia among men who were not anemic at baseline, and lower incidence of anemia in those who were anemic to begin with. However, the rate of progression from prediabetes to diabetes didn’t differ significantly, nor did testosterone therapy improve glycemic control or remission in men who had diabetes at baseline, Dr. Bhasin reported.
 

‘Big surprise’ and a mystery: Testosterone increased fracture risk

The fracture data were presented by Peter J. Snyder, MD, of the University of Pennsylvania, who earlier in the session had received an Endocrine Society award for his work in the testosterone field.

“No prior trial of testosterone treatment of hypogonadal men has been large enough or long enough to assess its effect on fractures ... until the TRAVERSE trial,” he said.

The hypothesis going in was that testosterone would decrease the fracture incidence, since prior data had suggested it improves many parameters of bone quality in elderly men and in those with severe hypogonadism.

Instead, there were 91 confirmed and adjudicated clinical fractures in the testosterone group versus 64 in the placebo group, giving a hazard ratio of 1.43 (P = .03). The risk was seen across fracture types, increasing the likelihood that this finding was, in fact, real, Dr. Snyder said.

“We could speculate about a possible mechanism, but because we did not expect these results, we did not design the trial to evaluate a possible mechanism,” Dr. Snyder noted.

Dr. Anawalt told this news organization that the fracture finding “was a big surprise. None of us would have expected that there would be an increase in fractures.”

Clinically, Dr. Anawalt said it suggests consideration of expanding the use of anti-osteoporotic medication such as bisphosphonates to men with low testosterone and elevated fracture risk for whom clinicians may have assumed that just giving them testosterone replacement might also protect their bones.

“This begs the question should we reorient the way we’re thinking about these men.”

The study was funded by AbbVie, Acerus Pharmaceuticals Corporation/Aytu Biosciences, Allergan Sales, Endo Pharmaceuticals, and Upsher-Smith Laboratories. Dr. Bhasin has disclosed grants to his institution from Function Promoting Therapies and Metro International Biotech, and owns stock in XYone. Dr. Anawalt has reported no relevant financial relationships.

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

This article was updated 6/19/23.

CHICAGO – Testosterone replacement therapy does not appear to raise the risk for adverse cardiac events among middle-aged and older men with hypogonadism at high risk for heart disease, long-awaited results from a major clinical trial show.

Among over 5,000 men aged 45-80 years randomized to daily transdermal testosterone gel or matching placebo gel for an average of 22 months, no increased risk was seen for a first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.

There was also no increased risk for prostate cancer over the 33-month follow-up period. However, there were increases in rates of atrial fibrillation, acute kidney injury, and pulmonary embolism in the testosterone group.

In terms of efficacy, testosterone therapy was associated with improved sexual function over two years of treatment and correction, or prevention, of anemia, but had no effect on progression to diabetes or glycemic parameters.

And, an unexpected finding was a significant and unexplained 43% increase in fractures with testosterone therapy.

The TRAVERSE study was mandated by the Food and Drug Administration in 2015 in response to concerns and conflicting data regarding the cardiovascular safety of testosterone replacement therapy in men. It was conducted by a consortium of five manufacturers of testosterone replacement products, led by AbbVie.

The results were presented during a symposium at the annual meeting of the Endocrine Society. The mandated safety data were published online in the New England Journal of Medicine. The efficacy outcomes, undertaken opportunistically due to the trial’s large sample size and relatively long followup time, will be published later this year.

Taken together, the TRAVERSE findings are expected to transform the risk–benefit discussions with patients about the use of testosterone therapy for hypogonadism, study coauthor Shalender Bhasin, MD, told this news organization.

“Testosterone deficiency doesn’t kill people as far as we know but it is really an important symptomatic condition that affects quality of life. Many middle-aged and older men seek assistance for these symptoms, so it’s an important condition and the treatment decisions are complicated,” said Dr. Bhasin, director of the research program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital in Boston.

These new data will be incorporated into future guidelines on testosterone therapy in men with hypoandrogenism, noted Dr. Bhasin, a coauthor of The Endocrine Society’s 2018 guidelines.
 

Findings apply only to men with bona fide testosterone deficiency

Asked to comment, endocrinologist Bradley D. Anawalt, MD, told this news organization that “the community of physicians who prescribe testosterone to men was waiting with bated breath” for the TRAVERSE results.

Safety reassuring, but some concerns will require more investigation

TRAVERSE was a multicenter, randomized, double-blind, placebo-controlled noninferiority trial that enrolled 5246 men aged 45-80 years. Participants had pre-existing or were at high risk of cardiovascular disease, reported symptoms of hypogonadism, and had two fasting testosterone levels < 300 ng/dL. They were randomly assigned to receive daily transdermal 1.62% testosterone gel or placebo gel.

The primary safety endpoint event (first adjudicated major adverse cardiac event) occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; P < .001 for noninferiority). Similar results were seen in sensitivity analyses.

Pulmonary embolism occurred in 0.9% of the testosterone group versus 0.5% of the placebo group, supporting current guidelines that testosterone should be used with caution in men who have had previous thromboembolic events, the authors note.

Prostate cancer occurred in 0.5% (n = 12) of patients in the testosterone group and 0.4% (n = 11) of patients in the placebo group, not a significant difference (P = .87).

There were, however, significant differences between the testosterone and placebo groups in terms of nonfatal arrhythmias warranting intervention (5.2% vs. 3.3%; P = .001), atrial fibrillation (3.5% vs. 2.4%; P = .02), and acute kidney injury (2.3% vs. 1.5%; P = .04).

“These adverse events were not expected,” the authors wrote.

Dr. Bhasin said that the team plans to investigate those cases further to look for possible risk factors, including whether COVID-19 played a role in these outcomes because the trial took place during the pandemic and some participants in both study groups contracted the virus.

Regarding acute kidney injury, Dr. Anawalt said: “I don’t know that I believe that ... It’s probably a statistical abnormality. It barely made ... significance.”
 

Finally, ‘real data on something we’ve been prescribing for decades’

Both Dr. Bhasin and Dr. Anawalt pointed out the deficiencies in the prior literature in terms of what has been known about testosterone’s effects. According to Dr. Bhasin, “In spite of all the folklore, there isn’t very much known about the efficacy of treatment beyond sexual function, and even there, the data are really limited. Most trials have been open-label and very small.”

He added that even among the few previous randomized clinical trials, only one, the TTrials series,  had an adequate number of participants and used robust measures to assess sexual function, but that study only lasted a year.

Indeed, Dr. Anawalt noted, “[TRAVERSE] and its father study, the TTrials, were the first systematic studies to look at large groups of men getting testosterone versus placebo. We’re now starting to get real data on something that we’ve been prescribing for decades.”

At the ENDO symposium, Dr. Bhasin presented data showing significant improvements with testosterone compared to placebo in overall sexual activity (P = .011), sexual symptoms (P < .001), and sexual desire over one year, and maintained over two years in TRAVERSE. All were assessed by validated questionnaires.

“They confirmed that there’s an improvement in sexual function and that it’s sustained. That’s important because there had been doubt about that ... and it sounds like it’s clinically significant,” Dr. Anawalt said.

Testosterone therapy was also associated with lower rates of anemia among men who were not anemic at baseline, and lower incidence of anemia in those who were anemic to begin with. However, the rate of progression from prediabetes to diabetes didn’t differ significantly, nor did testosterone therapy improve glycemic control or remission in men who had diabetes at baseline, Dr. Bhasin reported.
 

‘Big surprise’ and a mystery: Testosterone increased fracture risk

The fracture data were presented by Peter J. Snyder, MD, of the University of Pennsylvania, who earlier in the session had received an Endocrine Society award for his work in the testosterone field.

“No prior trial of testosterone treatment of hypogonadal men has been large enough or long enough to assess its effect on fractures ... until the TRAVERSE trial,” he said.

The hypothesis going in was that testosterone would decrease the fracture incidence, since prior data had suggested it improves many parameters of bone quality in elderly men and in those with severe hypogonadism.

Instead, there were 91 confirmed and adjudicated clinical fractures in the testosterone group versus 64 in the placebo group, giving a hazard ratio of 1.43 (P = .03). The risk was seen across fracture types, increasing the likelihood that this finding was, in fact, real, Dr. Snyder said.

“We could speculate about a possible mechanism, but because we did not expect these results, we did not design the trial to evaluate a possible mechanism,” Dr. Snyder noted.

Dr. Anawalt told this news organization that the fracture finding “was a big surprise. None of us would have expected that there would be an increase in fractures.”

Clinically, Dr. Anawalt said it suggests consideration of expanding the use of anti-osteoporotic medication such as bisphosphonates to men with low testosterone and elevated fracture risk for whom clinicians may have assumed that just giving them testosterone replacement might also protect their bones.

“This begs the question should we reorient the way we’re thinking about these men.”

The study was funded by AbbVie, Acerus Pharmaceuticals Corporation/Aytu Biosciences, Allergan Sales, Endo Pharmaceuticals, and Upsher-Smith Laboratories. Dr. Bhasin has disclosed grants to his institution from Function Promoting Therapies and Metro International Biotech, and owns stock in XYone. Dr. Anawalt has reported no relevant financial relationships.

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

This article was updated 6/19/23.

CHICAGO – Testosterone replacement therapy does not appear to raise the risk for adverse cardiac events among middle-aged and older men with hypogonadism at high risk for heart disease, long-awaited results from a major clinical trial show.

Among over 5,000 men aged 45-80 years randomized to daily transdermal testosterone gel or matching placebo gel for an average of 22 months, no increased risk was seen for a first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.

There was also no increased risk for prostate cancer over the 33-month follow-up period. However, there were increases in rates of atrial fibrillation, acute kidney injury, and pulmonary embolism in the testosterone group.

In terms of efficacy, testosterone therapy was associated with improved sexual function over two years of treatment and correction, or prevention, of anemia, but had no effect on progression to diabetes or glycemic parameters.

And, an unexpected finding was a significant and unexplained 43% increase in fractures with testosterone therapy.

The TRAVERSE study was mandated by the Food and Drug Administration in 2015 in response to concerns and conflicting data regarding the cardiovascular safety of testosterone replacement therapy in men. It was conducted by a consortium of five manufacturers of testosterone replacement products, led by AbbVie.

The results were presented during a symposium at the annual meeting of the Endocrine Society. The mandated safety data were published online in the New England Journal of Medicine. The efficacy outcomes, undertaken opportunistically due to the trial’s large sample size and relatively long followup time, will be published later this year.

Taken together, the TRAVERSE findings are expected to transform the risk–benefit discussions with patients about the use of testosterone therapy for hypogonadism, study coauthor Shalender Bhasin, MD, told this news organization.

“Testosterone deficiency doesn’t kill people as far as we know but it is really an important symptomatic condition that affects quality of life. Many middle-aged and older men seek assistance for these symptoms, so it’s an important condition and the treatment decisions are complicated,” said Dr. Bhasin, director of the research program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital in Boston.

These new data will be incorporated into future guidelines on testosterone therapy in men with hypoandrogenism, noted Dr. Bhasin, a coauthor of The Endocrine Society’s 2018 guidelines.
 

Findings apply only to men with bona fide testosterone deficiency

Asked to comment, endocrinologist Bradley D. Anawalt, MD, told this news organization that “the community of physicians who prescribe testosterone to men was waiting with bated breath” for the TRAVERSE results.

Safety reassuring, but some concerns will require more investigation

TRAVERSE was a multicenter, randomized, double-blind, placebo-controlled noninferiority trial that enrolled 5246 men aged 45-80 years. Participants had pre-existing or were at high risk of cardiovascular disease, reported symptoms of hypogonadism, and had two fasting testosterone levels < 300 ng/dL. They were randomly assigned to receive daily transdermal 1.62% testosterone gel or placebo gel.

The primary safety endpoint event (first adjudicated major adverse cardiac event) occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; P < .001 for noninferiority). Similar results were seen in sensitivity analyses.

Pulmonary embolism occurred in 0.9% of the testosterone group versus 0.5% of the placebo group, supporting current guidelines that testosterone should be used with caution in men who have had previous thromboembolic events, the authors note.

Prostate cancer occurred in 0.5% (n = 12) of patients in the testosterone group and 0.4% (n = 11) of patients in the placebo group, not a significant difference (P = .87).

There were, however, significant differences between the testosterone and placebo groups in terms of nonfatal arrhythmias warranting intervention (5.2% vs. 3.3%; P = .001), atrial fibrillation (3.5% vs. 2.4%; P = .02), and acute kidney injury (2.3% vs. 1.5%; P = .04).

“These adverse events were not expected,” the authors wrote.

Dr. Bhasin said that the team plans to investigate those cases further to look for possible risk factors, including whether COVID-19 played a role in these outcomes because the trial took place during the pandemic and some participants in both study groups contracted the virus.

Regarding acute kidney injury, Dr. Anawalt said: “I don’t know that I believe that ... It’s probably a statistical abnormality. It barely made ... significance.”
 

Finally, ‘real data on something we’ve been prescribing for decades’

Both Dr. Bhasin and Dr. Anawalt pointed out the deficiencies in the prior literature in terms of what has been known about testosterone’s effects. According to Dr. Bhasin, “In spite of all the folklore, there isn’t very much known about the efficacy of treatment beyond sexual function, and even there, the data are really limited. Most trials have been open-label and very small.”

He added that even among the few previous randomized clinical trials, only one, the TTrials series,  had an adequate number of participants and used robust measures to assess sexual function, but that study only lasted a year.

Indeed, Dr. Anawalt noted, “[TRAVERSE] and its father study, the TTrials, were the first systematic studies to look at large groups of men getting testosterone versus placebo. We’re now starting to get real data on something that we’ve been prescribing for decades.”

At the ENDO symposium, Dr. Bhasin presented data showing significant improvements with testosterone compared to placebo in overall sexual activity (P = .011), sexual symptoms (P < .001), and sexual desire over one year, and maintained over two years in TRAVERSE. All were assessed by validated questionnaires.

“They confirmed that there’s an improvement in sexual function and that it’s sustained. That’s important because there had been doubt about that ... and it sounds like it’s clinically significant,” Dr. Anawalt said.

Testosterone therapy was also associated with lower rates of anemia among men who were not anemic at baseline, and lower incidence of anemia in those who were anemic to begin with. However, the rate of progression from prediabetes to diabetes didn’t differ significantly, nor did testosterone therapy improve glycemic control or remission in men who had diabetes at baseline, Dr. Bhasin reported.
 

‘Big surprise’ and a mystery: Testosterone increased fracture risk

The fracture data were presented by Peter J. Snyder, MD, of the University of Pennsylvania, who earlier in the session had received an Endocrine Society award for his work in the testosterone field.

“No prior trial of testosterone treatment of hypogonadal men has been large enough or long enough to assess its effect on fractures ... until the TRAVERSE trial,” he said.

The hypothesis going in was that testosterone would decrease the fracture incidence, since prior data had suggested it improves many parameters of bone quality in elderly men and in those with severe hypogonadism.

Instead, there were 91 confirmed and adjudicated clinical fractures in the testosterone group versus 64 in the placebo group, giving a hazard ratio of 1.43 (P = .03). The risk was seen across fracture types, increasing the likelihood that this finding was, in fact, real, Dr. Snyder said.

“We could speculate about a possible mechanism, but because we did not expect these results, we did not design the trial to evaluate a possible mechanism,” Dr. Snyder noted.

Dr. Anawalt told this news organization that the fracture finding “was a big surprise. None of us would have expected that there would be an increase in fractures.”

Clinically, Dr. Anawalt said it suggests consideration of expanding the use of anti-osteoporotic medication such as bisphosphonates to men with low testosterone and elevated fracture risk for whom clinicians may have assumed that just giving them testosterone replacement might also protect their bones.

“This begs the question should we reorient the way we’re thinking about these men.”

The study was funded by AbbVie, Acerus Pharmaceuticals Corporation/Aytu Biosciences, Allergan Sales, Endo Pharmaceuticals, and Upsher-Smith Laboratories. Dr. Bhasin has disclosed grants to his institution from Function Promoting Therapies and Metro International Biotech, and owns stock in XYone. Dr. Anawalt has reported no relevant financial relationships.

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

This article was updated 6/19/23.

Adalimumab, sold under the brand name Humira, enjoyed a long run as one of the world’s best-selling medicines. But its 20-year, competition-free period has ended, and despite its best efforts to delay their arrival, drug manufacturer AbbVie now faces increasing competition from biosimilars entering the marketplace.
 

But one biosimilar about to be launched may be something of a game changer. Coherus BioSciences has announced plans to market its biosimilar Yusimry (adalimumab-aqvh) at a cost of $995 for two autoinjectors. This represents an approximate 85% discount over Humira’s sale list price of $6922.

This price, however, is slated to plunge even further as Coherus has also revealed that it will work with the Mark Cuban Cost Plus Drug Company (MCCPDC) to offer an even lower price. When Yusimry launches in July, it will sell for about $579 for two autoinjectors, making it the lowest-priced adalimumab biosimilar on the market.

“Coherus and Cost Plus Drug Company share a common mission, to increase access to high-quality medicine for patients at an affordable price,” said Dennis Lanfear, MBA, president, CEO and chairman of Coherus. “Mark Cuban and his team offer innovative solutions to health care problems, and Coherus is also a highly innovative company focused on unmet patient needs.”

He noted that, with adalimumab biosimilar pricing, this translates to a low list price approach. “We are pleased that Yusimry will be a part of that, as the first biologic they carry,” Mr. Lanfear said.

MCCPDC prices are based on the cost of ingredients and manufacturing plus 15% margin, a $3 pharmacy dispensing fee, and a $5 shipping fee. The company has expanded its inventory from 100 generics to more than 350 medications since it launched in January 2022. While MCCPDC is primarily directed to people who are paying cash for drugs, it does take insurance from select plans. And even for people who are covered by other insurers, the cost of drugs from Mr. Cuban’s company may be less than their out-of-pocket costs if they did go through their payer.

The low pricing of Yusimry is welcome, said Marcus Snow, MD, an assistant professor in the division of rheumatology at the University of Nebraska Medical Center, Omaha, but he pointed out that it is still a very expensive drug. “For patients who can’t afford Humira due to poor insurance coverage and high out-of-pocket costs, it is a welcome option. But it’s also unclear how many patients who lack adequate health insurance coverage can afford to pay $579 a month out of their own pockets.”
 

The biosimilars are coming

By early December 2022, the Food and Drug Administration had approved seven Humira biosimilars, and Amgen launched the first biosimilar to come on the market, Amjevita, soon afterward. By July 2023, half a dozen more are expected to enter the marketplace, said Steven Horvitz, managing director of EMC Analytics Group, a pharmaceutical research firm.

Mr. Horvitz agrees that the system is out of control, but it is unclear how much of an effect the low price tag on the Coherus product will have. “Some insurers may say, ‘we want the lowest price, and we don’t care about rebates,’ and will go with it,” he said. “PBMs [pharmacy benefit managers] are all about economics, so we have to see how many of their major clients will ask for the lowest price.”

Amgen has more or less followed the status quo on pricing for its biosimilar, but with a twist. It›s being offered at two different prices: $85,494 a year, which is only a 5% discount from Humira’s list price, or at $40,497 a year, a 55% discount. However, to date, the lower price has generally not been granted favorable formulary placement by PBMs. The plans that adopt the higher-priced biosimilar will get bigger rebates, but patients with coinsurance and deductibles will pay more out of pocket.

It is yet unknown how the pricing on Yusimry will affect the biosimilars ready to launch. “Will it give them pause for thought or not make any difference?” Mr. Horvitz said. “The companies do not reveal their pricing before the fact, so we have to wait and see.”

Large PBMs have not jumped at the opportunity to offer the Coherus biosimilar, but SmithRx, which bills itself as “next-generation pharmacy benefits management,” announced that it will offer Yusimry to its members at a discount of more than 90%.

“Unlike traditional PBMs, SmithRx prioritizes transparency and up-front cost savings. Humira is often an employer’s top drug expense so offering a low-cost alternative will have significant impact,” Jake Frenz, CEO and founder of SmithRx, said in a statement. “We’re excited to work with Cost Plus Drugs to bring this biosimilar to our members – and significantly reduce costs for them and their employers.”

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

Adalimumab, sold under the brand name Humira, enjoyed a long run as one of the world’s best-selling medicines. But its 20-year, competition-free period has ended, and despite its best efforts to delay their arrival, drug manufacturer AbbVie now faces increasing competition from biosimilars entering the marketplace.
 

But one biosimilar about to be launched may be something of a game changer. Coherus BioSciences has announced plans to market its biosimilar Yusimry (adalimumab-aqvh) at a cost of $995 for two autoinjectors. This represents an approximate 85% discount over Humira’s sale list price of $6922.

This price, however, is slated to plunge even further as Coherus has also revealed that it will work with the Mark Cuban Cost Plus Drug Company (MCCPDC) to offer an even lower price. When Yusimry launches in July, it will sell for about $579 for two autoinjectors, making it the lowest-priced adalimumab biosimilar on the market.

“Coherus and Cost Plus Drug Company share a common mission, to increase access to high-quality medicine for patients at an affordable price,” said Dennis Lanfear, MBA, president, CEO and chairman of Coherus. “Mark Cuban and his team offer innovative solutions to health care problems, and Coherus is also a highly innovative company focused on unmet patient needs.”

He noted that, with adalimumab biosimilar pricing, this translates to a low list price approach. “We are pleased that Yusimry will be a part of that, as the first biologic they carry,” Mr. Lanfear said.

MCCPDC prices are based on the cost of ingredients and manufacturing plus 15% margin, a $3 pharmacy dispensing fee, and a $5 shipping fee. The company has expanded its inventory from 100 generics to more than 350 medications since it launched in January 2022. While MCCPDC is primarily directed to people who are paying cash for drugs, it does take insurance from select plans. And even for people who are covered by other insurers, the cost of drugs from Mr. Cuban’s company may be less than their out-of-pocket costs if they did go through their payer.

The low pricing of Yusimry is welcome, said Marcus Snow, MD, an assistant professor in the division of rheumatology at the University of Nebraska Medical Center, Omaha, but he pointed out that it is still a very expensive drug. “For patients who can’t afford Humira due to poor insurance coverage and high out-of-pocket costs, it is a welcome option. But it’s also unclear how many patients who lack adequate health insurance coverage can afford to pay $579 a month out of their own pockets.”
 

The biosimilars are coming

By early December 2022, the Food and Drug Administration had approved seven Humira biosimilars, and Amgen launched the first biosimilar to come on the market, Amjevita, soon afterward. By July 2023, half a dozen more are expected to enter the marketplace, said Steven Horvitz, managing director of EMC Analytics Group, a pharmaceutical research firm.

Mr. Horvitz agrees that the system is out of control, but it is unclear how much of an effect the low price tag on the Coherus product will have. “Some insurers may say, ‘we want the lowest price, and we don’t care about rebates,’ and will go with it,” he said. “PBMs [pharmacy benefit managers] are all about economics, so we have to see how many of their major clients will ask for the lowest price.”

Amgen has more or less followed the status quo on pricing for its biosimilar, but with a twist. It›s being offered at two different prices: $85,494 a year, which is only a 5% discount from Humira’s list price, or at $40,497 a year, a 55% discount. However, to date, the lower price has generally not been granted favorable formulary placement by PBMs. The plans that adopt the higher-priced biosimilar will get bigger rebates, but patients with coinsurance and deductibles will pay more out of pocket.

It is yet unknown how the pricing on Yusimry will affect the biosimilars ready to launch. “Will it give them pause for thought or not make any difference?” Mr. Horvitz said. “The companies do not reveal their pricing before the fact, so we have to wait and see.”

Large PBMs have not jumped at the opportunity to offer the Coherus biosimilar, but SmithRx, which bills itself as “next-generation pharmacy benefits management,” announced that it will offer Yusimry to its members at a discount of more than 90%.

“Unlike traditional PBMs, SmithRx prioritizes transparency and up-front cost savings. Humira is often an employer’s top drug expense so offering a low-cost alternative will have significant impact,” Jake Frenz, CEO and founder of SmithRx, said in a statement. “We’re excited to work with Cost Plus Drugs to bring this biosimilar to our members – and significantly reduce costs for them and their employers.”

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

Adalimumab, sold under the brand name Humira, enjoyed a long run as one of the world’s best-selling medicines. But its 20-year, competition-free period has ended, and despite its best efforts to delay their arrival, drug manufacturer AbbVie now faces increasing competition from biosimilars entering the marketplace.
 

But one biosimilar about to be launched may be something of a game changer. Coherus BioSciences has announced plans to market its biosimilar Yusimry (adalimumab-aqvh) at a cost of $995 for two autoinjectors. This represents an approximate 85% discount over Humira’s sale list price of $6922.

This price, however, is slated to plunge even further as Coherus has also revealed that it will work with the Mark Cuban Cost Plus Drug Company (MCCPDC) to offer an even lower price. When Yusimry launches in July, it will sell for about $579 for two autoinjectors, making it the lowest-priced adalimumab biosimilar on the market.

“Coherus and Cost Plus Drug Company share a common mission, to increase access to high-quality medicine for patients at an affordable price,” said Dennis Lanfear, MBA, president, CEO and chairman of Coherus. “Mark Cuban and his team offer innovative solutions to health care problems, and Coherus is also a highly innovative company focused on unmet patient needs.”

He noted that, with adalimumab biosimilar pricing, this translates to a low list price approach. “We are pleased that Yusimry will be a part of that, as the first biologic they carry,” Mr. Lanfear said.

MCCPDC prices are based on the cost of ingredients and manufacturing plus 15% margin, a $3 pharmacy dispensing fee, and a $5 shipping fee. The company has expanded its inventory from 100 generics to more than 350 medications since it launched in January 2022. While MCCPDC is primarily directed to people who are paying cash for drugs, it does take insurance from select plans. And even for people who are covered by other insurers, the cost of drugs from Mr. Cuban’s company may be less than their out-of-pocket costs if they did go through their payer.

The low pricing of Yusimry is welcome, said Marcus Snow, MD, an assistant professor in the division of rheumatology at the University of Nebraska Medical Center, Omaha, but he pointed out that it is still a very expensive drug. “For patients who can’t afford Humira due to poor insurance coverage and high out-of-pocket costs, it is a welcome option. But it’s also unclear how many patients who lack adequate health insurance coverage can afford to pay $579 a month out of their own pockets.”
 

The biosimilars are coming

By early December 2022, the Food and Drug Administration had approved seven Humira biosimilars, and Amgen launched the first biosimilar to come on the market, Amjevita, soon afterward. By July 2023, half a dozen more are expected to enter the marketplace, said Steven Horvitz, managing director of EMC Analytics Group, a pharmaceutical research firm.

Mr. Horvitz agrees that the system is out of control, but it is unclear how much of an effect the low price tag on the Coherus product will have. “Some insurers may say, ‘we want the lowest price, and we don’t care about rebates,’ and will go with it,” he said. “PBMs [pharmacy benefit managers] are all about economics, so we have to see how many of their major clients will ask for the lowest price.”

Amgen has more or less followed the status quo on pricing for its biosimilar, but with a twist. It›s being offered at two different prices: $85,494 a year, which is only a 5% discount from Humira’s list price, or at $40,497 a year, a 55% discount. However, to date, the lower price has generally not been granted favorable formulary placement by PBMs. The plans that adopt the higher-priced biosimilar will get bigger rebates, but patients with coinsurance and deductibles will pay more out of pocket.

It is yet unknown how the pricing on Yusimry will affect the biosimilars ready to launch. “Will it give them pause for thought or not make any difference?” Mr. Horvitz said. “The companies do not reveal their pricing before the fact, so we have to wait and see.”

Large PBMs have not jumped at the opportunity to offer the Coherus biosimilar, but SmithRx, which bills itself as “next-generation pharmacy benefits management,” announced that it will offer Yusimry to its members at a discount of more than 90%.

“Unlike traditional PBMs, SmithRx prioritizes transparency and up-front cost savings. Humira is often an employer’s top drug expense so offering a low-cost alternative will have significant impact,” Jake Frenz, CEO and founder of SmithRx, said in a statement. “We’re excited to work with Cost Plus Drugs to bring this biosimilar to our members – and significantly reduce costs for them and their employers.”

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