Thymectomy may continue to benefit patients with myasthenia gravis 5 years after the procedure, according to an extension study published in Lancet Neurology. Patients with generalized nonthymomatous myasthenia gravis who underwent thymectomy had better long-term clinical outcomes and required less prednisone, compared with patients who received prednisone alone.

Douglas Levere/University at Buffalo

The study evaluated the clinical status, medication requirements, and adverse events of patients with myasthenia gravis who completed a randomized controlled trial of thymectomy plus prednisone versus prednisone alone and agreed to participate in a rater-blinded 2-year extension.

“Thymectomy within the first few years of the disease course in addition to prednisone therapy confers benefits that persist for 5 years ... in patients with generalized nonthymomatous myasthenia gravis,” said lead study author Gil I. Wolfe, MD, chair of the department of neurology at the University at Buffalo in New York, and his research colleagues. “Results from the extension study provide further support for the use of thymectomy in management of myasthenia gravis and should encourage serious consideration of this treatment option in discussions between clinicians and their patients,” they wrote. “Our results should lead to revision of clinical guidelines in favor of thymectomy and could potentially reverse downward trends in the use of thymectomy in overall management of myasthenia gravis.”

The main 3-year results of the Thymectomy Trial in Nonthymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) were reported in 2016; the international trial found that thymectomy plus prednisone was superior to prednisone alone at 3 years (N Engl J Med. 2016 Aug 11;375[6]:511-22). The extension study aimed to assess the durability of the treatment response.

MGTX enrolled patients aged 18-65 years who had generalized nonthymomatous myasthenia gravis of less than 5 years’ duration and Myasthenia Gravis Foundation of America Clinical Classification Class II-IV disease. Of 111 patients who completed MGTX, 68 entered the extension study, and 50 completed the 60-month assessment (24 patients in the prednisone alone group and 26 patients in the prednisone plus thymectomy group).

At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted average Quantitative Myasthenia Gravis (QMG) scores (5.47 vs. 9.34) and mean alternate-day prednisone doses (24 mg vs. 48 mg), compared with patients who received prednisone alone. Twelve of 35 patients in the thymectomy group and 14 of 33 patients in the prednisone group had at least one adverse event by month 60. No treatment-related deaths occurred in the extension phase.

At 5 years, significantly more patients who underwent thymectomy had minimal manifestation status (i.e., no functional limitations from the disease other than some muscle weakness) – 88% versus 58%. The corresponding figures at 3 years were 67% and 47%.

In addition, 3-year and 5-year data indicate that the need for hospitalization is reduced after surgery, compared with medical therapy alone, Dr. Wolfe said.

Two patients in each treatment arm had an increase of 2 points or more in the QMG score, indicating clinical worsening.

“Our current findings reinforce the benefit of thymectomy seen in [MGTX], dispelling doubts about the procedure’s benefits and how long those benefits last,” said Dr. Wolfe. “We do hope that the new findings help reverse the apparent reluctance to do thymectomy and that the proportion of patients with myasthenia gravis who undergo thymectomy will increase.”

The authors noted that the small sample size of the extension study may limit its generalizability.

The study received funding from the National Institutes of Health. Dr. Wolfe reported grants from the NIH, the Muscular Dystrophy Association, the Myasthenia Gravis Foundation of America, CSL-Behring, and ArgenX, as well as personal fees from Grifols, Shire, and Alexion Pharmaceuticals. Coauthors reported working with and receiving funds from agencies, foundations, and pharmaceutical companies.

[email protected]

SOURCE: Wolfe GI et al. Lancet Neurol. 2019 Jan 25. doi: 10.1016/S1474-4422(18)30392-2.

Thymectomy may continue to benefit patients with myasthenia gravis 5 years after the procedure, according to an extension study published in Lancet Neurology. Patients with generalized nonthymomatous myasthenia gravis who underwent thymectomy had better long-term clinical outcomes and required less prednisone, compared with patients who received prednisone alone.

Douglas Levere/University at Buffalo

The study evaluated the clinical status, medication requirements, and adverse events of patients with myasthenia gravis who completed a randomized controlled trial of thymectomy plus prednisone versus prednisone alone and agreed to participate in a rater-blinded 2-year extension.

“Thymectomy within the first few years of the disease course in addition to prednisone therapy confers benefits that persist for 5 years ... in patients with generalized nonthymomatous myasthenia gravis,” said lead study author Gil I. Wolfe, MD, chair of the department of neurology at the University at Buffalo in New York, and his research colleagues. “Results from the extension study provide further support for the use of thymectomy in management of myasthenia gravis and should encourage serious consideration of this treatment option in discussions between clinicians and their patients,” they wrote. “Our results should lead to revision of clinical guidelines in favor of thymectomy and could potentially reverse downward trends in the use of thymectomy in overall management of myasthenia gravis.”

The main 3-year results of the Thymectomy Trial in Nonthymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) were reported in 2016; the international trial found that thymectomy plus prednisone was superior to prednisone alone at 3 years (N Engl J Med. 2016 Aug 11;375[6]:511-22). The extension study aimed to assess the durability of the treatment response.

MGTX enrolled patients aged 18-65 years who had generalized nonthymomatous myasthenia gravis of less than 5 years’ duration and Myasthenia Gravis Foundation of America Clinical Classification Class II-IV disease. Of 111 patients who completed MGTX, 68 entered the extension study, and 50 completed the 60-month assessment (24 patients in the prednisone alone group and 26 patients in the prednisone plus thymectomy group).

At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted average Quantitative Myasthenia Gravis (QMG) scores (5.47 vs. 9.34) and mean alternate-day prednisone doses (24 mg vs. 48 mg), compared with patients who received prednisone alone. Twelve of 35 patients in the thymectomy group and 14 of 33 patients in the prednisone group had at least one adverse event by month 60. No treatment-related deaths occurred in the extension phase.

At 5 years, significantly more patients who underwent thymectomy had minimal manifestation status (i.e., no functional limitations from the disease other than some muscle weakness) – 88% versus 58%. The corresponding figures at 3 years were 67% and 47%.

In addition, 3-year and 5-year data indicate that the need for hospitalization is reduced after surgery, compared with medical therapy alone, Dr. Wolfe said.

Two patients in each treatment arm had an increase of 2 points or more in the QMG score, indicating clinical worsening.

“Our current findings reinforce the benefit of thymectomy seen in [MGTX], dispelling doubts about the procedure’s benefits and how long those benefits last,” said Dr. Wolfe. “We do hope that the new findings help reverse the apparent reluctance to do thymectomy and that the proportion of patients with myasthenia gravis who undergo thymectomy will increase.”

The authors noted that the small sample size of the extension study may limit its generalizability.

The study received funding from the National Institutes of Health. Dr. Wolfe reported grants from the NIH, the Muscular Dystrophy Association, the Myasthenia Gravis Foundation of America, CSL-Behring, and ArgenX, as well as personal fees from Grifols, Shire, and Alexion Pharmaceuticals. Coauthors reported working with and receiving funds from agencies, foundations, and pharmaceutical companies.

[email protected]

SOURCE: Wolfe GI et al. Lancet Neurol. 2019 Jan 25. doi: 10.1016/S1474-4422(18)30392-2.

Thymectomy may continue to benefit patients with myasthenia gravis 5 years after the procedure, according to an extension study published in Lancet Neurology. Patients with generalized nonthymomatous myasthenia gravis who underwent thymectomy had better long-term clinical outcomes and required less prednisone, compared with patients who received prednisone alone.

Douglas Levere/University at Buffalo

The study evaluated the clinical status, medication requirements, and adverse events of patients with myasthenia gravis who completed a randomized controlled trial of thymectomy plus prednisone versus prednisone alone and agreed to participate in a rater-blinded 2-year extension.

“Thymectomy within the first few years of the disease course in addition to prednisone therapy confers benefits that persist for 5 years ... in patients with generalized nonthymomatous myasthenia gravis,” said lead study author Gil I. Wolfe, MD, chair of the department of neurology at the University at Buffalo in New York, and his research colleagues. “Results from the extension study provide further support for the use of thymectomy in management of myasthenia gravis and should encourage serious consideration of this treatment option in discussions between clinicians and their patients,” they wrote. “Our results should lead to revision of clinical guidelines in favor of thymectomy and could potentially reverse downward trends in the use of thymectomy in overall management of myasthenia gravis.”

The main 3-year results of the Thymectomy Trial in Nonthymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) were reported in 2016; the international trial found that thymectomy plus prednisone was superior to prednisone alone at 3 years (N Engl J Med. 2016 Aug 11;375[6]:511-22). The extension study aimed to assess the durability of the treatment response.

MGTX enrolled patients aged 18-65 years who had generalized nonthymomatous myasthenia gravis of less than 5 years’ duration and Myasthenia Gravis Foundation of America Clinical Classification Class II-IV disease. Of 111 patients who completed MGTX, 68 entered the extension study, and 50 completed the 60-month assessment (24 patients in the prednisone alone group and 26 patients in the prednisone plus thymectomy group).

At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted average Quantitative Myasthenia Gravis (QMG) scores (5.47 vs. 9.34) and mean alternate-day prednisone doses (24 mg vs. 48 mg), compared with patients who received prednisone alone. Twelve of 35 patients in the thymectomy group and 14 of 33 patients in the prednisone group had at least one adverse event by month 60. No treatment-related deaths occurred in the extension phase.

At 5 years, significantly more patients who underwent thymectomy had minimal manifestation status (i.e., no functional limitations from the disease other than some muscle weakness) – 88% versus 58%. The corresponding figures at 3 years were 67% and 47%.

In addition, 3-year and 5-year data indicate that the need for hospitalization is reduced after surgery, compared with medical therapy alone, Dr. Wolfe said.

Two patients in each treatment arm had an increase of 2 points or more in the QMG score, indicating clinical worsening.

“Our current findings reinforce the benefit of thymectomy seen in [MGTX], dispelling doubts about the procedure’s benefits and how long those benefits last,” said Dr. Wolfe. “We do hope that the new findings help reverse the apparent reluctance to do thymectomy and that the proportion of patients with myasthenia gravis who undergo thymectomy will increase.”

The authors noted that the small sample size of the extension study may limit its generalizability.

The study received funding from the National Institutes of Health. Dr. Wolfe reported grants from the NIH, the Muscular Dystrophy Association, the Myasthenia Gravis Foundation of America, CSL-Behring, and ArgenX, as well as personal fees from Grifols, Shire, and Alexion Pharmaceuticals. Coauthors reported working with and receiving funds from agencies, foundations, and pharmaceutical companies.

[email protected]

SOURCE: Wolfe GI et al. Lancet Neurol. 2019 Jan 25. doi: 10.1016/S1474-4422(18)30392-2.

TRANSforming Gynecology is a column about the ways in which ob.gyns. can become leaders in addressing the needs of the transgender/gender-nonconforming population. We hope to provide readers with some basic tools to help open the door to this marginalized population. We will lay the groundwork with an article on terminology and the importance of language before moving onto more focused discussions of topics that intersect with medical care of gender-nonconforming individuals. Transgender individuals experience among the worst health care outcomes of any demographic, and we hope that this column can be a starting point for providers to continue affirming the needs of marginalized populations in their everyday practice.

Josve05a/Getty Images

We live in a society in which most people’s gender identities are congruent with the sex they were assigned at birth based on physical characteristics. Transgender and gender-nonconforming people – often referred to as trans people, broadly – feel that their gender identity does not match their sex assigned at birth. This gender nonconformity, or the extent to which someone’s gender identity or expression differs from the cultural norm assigned to people with certain sexual organs, is in fact a matter of diversity, not pathology.

To truly provide sensitive care to trans patients, medical providers must first gain familiarity with the terminology used when discussing gender diversity. Gender identity, for starters, refers to an individual’s own personal and internal experience of themselves as a man, woman, some of both, or neither gender.¹ It is only possible to learn a person’s gender identity through direct communication because gender identity is not always signaled by a certain gender expression. Gender expression is an external display usually through clothing, attitudes, or body language, that may or may not fit into socially recognized masculine or feminine categories.¹ A separate aspect of the human experience is sexuality, such as gay, straight, bisexual, lesbian, etc. Sexuality should not be confused with sexual practices, which can sometimes deviate from a person’s sexuality. Gender identity is distinct from sexuality and sexual practices because people of any gender identity can hold any sexuality and engage in any sexual practices. Tied up in all of these categories is sex assigned at birth, which is a process by which health care providers categorize babies into two buckets based on the appearance of the external genitalia at the time of birth. It bears mentioning that the assignment of sex based on the appearance of external genitalia at the time of birth is a biologically inconsistent method that can lead to the exclusion of and nonconsensual mutilation of intersex people, who are individuals born with ambiguous genitalia and/or discrepancies between sex chromosome genotype and phenotype (stay tuned for more on people who are intersex in a future article).

A simplified way of remembering the distinctions between these concepts is that gender identity is who you go to bed as; gender expression is what you were wearing before you went to bed; sexuality is whom you tell others/yourself you go to bed with; sexual practice is whom you actually go to bed with; and sex assigned at birth is what you have between your legs when you are born (generally in a bed).

It is pivotal that medical providers understand that a person’s sex assigned at birth, gender identity, gender expression, sexuality, sexual practice, and romantic attraction can vary widely along a spectrum in each distinct category.² For example, the current social norm dictates that someone born with a penis and assigned male at birth (AMAB) will feel that he is male, dress in a masculine fashion, and be both sexually and romantically attracted to someone born with a vagina who was assigned female at birth (AFAB), feels that she is female, dresses femininely, and likewise is sexually and romantically attracted to him. One possible alternative reality is a person who was born with a vagina that was therefore AFAB that experiences a masculine gender identity while engaging in a feminine gender expression in order to conform to social norms. In addition, they may be sexually attracted to people whom they perceive to be feminine while engaging in sexual activity with people who were AMAB. Informed medical care for trans persons starts with the basic understanding that an individual’s gender identity may not necessarily align with their gender expression, sex assigned at birth, sexual attraction, or romantic attraction.

As obstetrician-gynecologists, we are tasked by the American College of Obstetricians and Gynecologists to provide nondiscriminatory care to all patients, regardless of gender identity.³ We must be careful not to assume that all of our patients are cisgender women who use “she/hers/her” pronouns. By simply asking patients what names or pronouns they would like us to use before initiating care, we become more sensitive to variations in gender identity. Many providers may feel uncertain about how to initiate or respond to this line of questioning. One way that health care practices can begin to respectfully access information around gender identity is to create intake forms that include more than two options for gender or to alter their office visit note templates to include a section that prompts the provider to include a discussion surrounding gender identity. By offering these opportunities for inclusion, we become more welcoming of gender minorities like transgender men seeking cervical cancer screening.

There are a number of reasons that trans persons have limited access to the health care system, but the greatest barrier reported by transgender patients is the paucity of knowledgeable providers.⁴Learning the common terminology used by the trans population is a logical first step for physicians seeking to provide more affirming care to an already marginalized patient population. Familiarity with this terminology normalizes the idea of gender diversity and subsequently reduces the risk of providers making assumptions about patients that contributes to suboptimal care.

Dr. Joyner is an assistant professor at Emory University, Atlanta, and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Joey Bahng is a PGY-1 resident physician in Emory University’s gynecology & obstetrics residency program. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Joyner and Dr. Bahng reported no financial disclosures.

1. Lancet. 2016 Jul 23;388(10042):390-400.

2. www.genderbread.org/resource/genderbread-person-v4-0.

3. Obstet Gynecol. 2011 Dec;118(6):1454-8.

4. Curr Opin Endocrinol Diabetes Obes. 2016 Apr 1;23(2):168-71.

TRANSforming Gynecology is a column about the ways in which ob.gyns. can become leaders in addressing the needs of the transgender/gender-nonconforming population. We hope to provide readers with some basic tools to help open the door to this marginalized population. We will lay the groundwork with an article on terminology and the importance of language before moving onto more focused discussions of topics that intersect with medical care of gender-nonconforming individuals. Transgender individuals experience among the worst health care outcomes of any demographic, and we hope that this column can be a starting point for providers to continue affirming the needs of marginalized populations in their everyday practice.

Josve05a/Getty Images

We live in a society in which most people’s gender identities are congruent with the sex they were assigned at birth based on physical characteristics. Transgender and gender-nonconforming people – often referred to as trans people, broadly – feel that their gender identity does not match their sex assigned at birth. This gender nonconformity, or the extent to which someone’s gender identity or expression differs from the cultural norm assigned to people with certain sexual organs, is in fact a matter of diversity, not pathology.

To truly provide sensitive care to trans patients, medical providers must first gain familiarity with the terminology used when discussing gender diversity. Gender identity, for starters, refers to an individual’s own personal and internal experience of themselves as a man, woman, some of both, or neither gender.¹ It is only possible to learn a person’s gender identity through direct communication because gender identity is not always signaled by a certain gender expression. Gender expression is an external display usually through clothing, attitudes, or body language, that may or may not fit into socially recognized masculine or feminine categories.¹ A separate aspect of the human experience is sexuality, such as gay, straight, bisexual, lesbian, etc. Sexuality should not be confused with sexual practices, which can sometimes deviate from a person’s sexuality. Gender identity is distinct from sexuality and sexual practices because people of any gender identity can hold any sexuality and engage in any sexual practices. Tied up in all of these categories is sex assigned at birth, which is a process by which health care providers categorize babies into two buckets based on the appearance of the external genitalia at the time of birth. It bears mentioning that the assignment of sex based on the appearance of external genitalia at the time of birth is a biologically inconsistent method that can lead to the exclusion of and nonconsensual mutilation of intersex people, who are individuals born with ambiguous genitalia and/or discrepancies between sex chromosome genotype and phenotype (stay tuned for more on people who are intersex in a future article).

A simplified way of remembering the distinctions between these concepts is that gender identity is who you go to bed as; gender expression is what you were wearing before you went to bed; sexuality is whom you tell others/yourself you go to bed with; sexual practice is whom you actually go to bed with; and sex assigned at birth is what you have between your legs when you are born (generally in a bed).

It is pivotal that medical providers understand that a person’s sex assigned at birth, gender identity, gender expression, sexuality, sexual practice, and romantic attraction can vary widely along a spectrum in each distinct category.² For example, the current social norm dictates that someone born with a penis and assigned male at birth (AMAB) will feel that he is male, dress in a masculine fashion, and be both sexually and romantically attracted to someone born with a vagina who was assigned female at birth (AFAB), feels that she is female, dresses femininely, and likewise is sexually and romantically attracted to him. One possible alternative reality is a person who was born with a vagina that was therefore AFAB that experiences a masculine gender identity while engaging in a feminine gender expression in order to conform to social norms. In addition, they may be sexually attracted to people whom they perceive to be feminine while engaging in sexual activity with people who were AMAB. Informed medical care for trans persons starts with the basic understanding that an individual’s gender identity may not necessarily align with their gender expression, sex assigned at birth, sexual attraction, or romantic attraction.

As obstetrician-gynecologists, we are tasked by the American College of Obstetricians and Gynecologists to provide nondiscriminatory care to all patients, regardless of gender identity.³ We must be careful not to assume that all of our patients are cisgender women who use “she/hers/her” pronouns. By simply asking patients what names or pronouns they would like us to use before initiating care, we become more sensitive to variations in gender identity. Many providers may feel uncertain about how to initiate or respond to this line of questioning. One way that health care practices can begin to respectfully access information around gender identity is to create intake forms that include more than two options for gender or to alter their office visit note templates to include a section that prompts the provider to include a discussion surrounding gender identity. By offering these opportunities for inclusion, we become more welcoming of gender minorities like transgender men seeking cervical cancer screening.

There are a number of reasons that trans persons have limited access to the health care system, but the greatest barrier reported by transgender patients is the paucity of knowledgeable providers.⁴Learning the common terminology used by the trans population is a logical first step for physicians seeking to provide more affirming care to an already marginalized patient population. Familiarity with this terminology normalizes the idea of gender diversity and subsequently reduces the risk of providers making assumptions about patients that contributes to suboptimal care.

Dr. Joyner is an assistant professor at Emory University, Atlanta, and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Joey Bahng is a PGY-1 resident physician in Emory University’s gynecology & obstetrics residency program. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Joyner and Dr. Bahng reported no financial disclosures.

1. Lancet. 2016 Jul 23;388(10042):390-400.

2. www.genderbread.org/resource/genderbread-person-v4-0.

3. Obstet Gynecol. 2011 Dec;118(6):1454-8.

4. Curr Opin Endocrinol Diabetes Obes. 2016 Apr 1;23(2):168-71.

TRANSforming Gynecology is a column about the ways in which ob.gyns. can become leaders in addressing the needs of the transgender/gender-nonconforming population. We hope to provide readers with some basic tools to help open the door to this marginalized population. We will lay the groundwork with an article on terminology and the importance of language before moving onto more focused discussions of topics that intersect with medical care of gender-nonconforming individuals. Transgender individuals experience among the worst health care outcomes of any demographic, and we hope that this column can be a starting point for providers to continue affirming the needs of marginalized populations in their everyday practice.

Josve05a/Getty Images

We live in a society in which most people’s gender identities are congruent with the sex they were assigned at birth based on physical characteristics. Transgender and gender-nonconforming people – often referred to as trans people, broadly – feel that their gender identity does not match their sex assigned at birth. This gender nonconformity, or the extent to which someone’s gender identity or expression differs from the cultural norm assigned to people with certain sexual organs, is in fact a matter of diversity, not pathology.

To truly provide sensitive care to trans patients, medical providers must first gain familiarity with the terminology used when discussing gender diversity. Gender identity, for starters, refers to an individual’s own personal and internal experience of themselves as a man, woman, some of both, or neither gender.¹ It is only possible to learn a person’s gender identity through direct communication because gender identity is not always signaled by a certain gender expression. Gender expression is an external display usually through clothing, attitudes, or body language, that may or may not fit into socially recognized masculine or feminine categories.¹ A separate aspect of the human experience is sexuality, such as gay, straight, bisexual, lesbian, etc. Sexuality should not be confused with sexual practices, which can sometimes deviate from a person’s sexuality. Gender identity is distinct from sexuality and sexual practices because people of any gender identity can hold any sexuality and engage in any sexual practices. Tied up in all of these categories is sex assigned at birth, which is a process by which health care providers categorize babies into two buckets based on the appearance of the external genitalia at the time of birth. It bears mentioning that the assignment of sex based on the appearance of external genitalia at the time of birth is a biologically inconsistent method that can lead to the exclusion of and nonconsensual mutilation of intersex people, who are individuals born with ambiguous genitalia and/or discrepancies between sex chromosome genotype and phenotype (stay tuned for more on people who are intersex in a future article).

A simplified way of remembering the distinctions between these concepts is that gender identity is who you go to bed as; gender expression is what you were wearing before you went to bed; sexuality is whom you tell others/yourself you go to bed with; sexual practice is whom you actually go to bed with; and sex assigned at birth is what you have between your legs when you are born (generally in a bed).

It is pivotal that medical providers understand that a person’s sex assigned at birth, gender identity, gender expression, sexuality, sexual practice, and romantic attraction can vary widely along a spectrum in each distinct category.² For example, the current social norm dictates that someone born with a penis and assigned male at birth (AMAB) will feel that he is male, dress in a masculine fashion, and be both sexually and romantically attracted to someone born with a vagina who was assigned female at birth (AFAB), feels that she is female, dresses femininely, and likewise is sexually and romantically attracted to him. One possible alternative reality is a person who was born with a vagina that was therefore AFAB that experiences a masculine gender identity while engaging in a feminine gender expression in order to conform to social norms. In addition, they may be sexually attracted to people whom they perceive to be feminine while engaging in sexual activity with people who were AMAB. Informed medical care for trans persons starts with the basic understanding that an individual’s gender identity may not necessarily align with their gender expression, sex assigned at birth, sexual attraction, or romantic attraction.

As obstetrician-gynecologists, we are tasked by the American College of Obstetricians and Gynecologists to provide nondiscriminatory care to all patients, regardless of gender identity.³ We must be careful not to assume that all of our patients are cisgender women who use “she/hers/her” pronouns. By simply asking patients what names or pronouns they would like us to use before initiating care, we become more sensitive to variations in gender identity. Many providers may feel uncertain about how to initiate or respond to this line of questioning. One way that health care practices can begin to respectfully access information around gender identity is to create intake forms that include more than two options for gender or to alter their office visit note templates to include a section that prompts the provider to include a discussion surrounding gender identity. By offering these opportunities for inclusion, we become more welcoming of gender minorities like transgender men seeking cervical cancer screening.

There are a number of reasons that trans persons have limited access to the health care system, but the greatest barrier reported by transgender patients is the paucity of knowledgeable providers.⁴Learning the common terminology used by the trans population is a logical first step for physicians seeking to provide more affirming care to an already marginalized patient population. Familiarity with this terminology normalizes the idea of gender diversity and subsequently reduces the risk of providers making assumptions about patients that contributes to suboptimal care.

Dr. Joyner is an assistant professor at Emory University, Atlanta, and is the director of gynecologic services in the Gender Center at Grady Memorial Hospital in Atlanta. Dr. Joyner identifies as a cisgender female and uses she/hers/her as her personal pronouns. Dr. Joey Bahng is a PGY-1 resident physician in Emory University’s gynecology & obstetrics residency program. Dr. Bahng identifies as nonbinary and uses they/them/their as their personal pronouns. Dr. Joyner and Dr. Bahng reported no financial disclosures.

1. Lancet. 2016 Jul 23;388(10042):390-400.

2. www.genderbread.org/resource/genderbread-person-v4-0.

3. Obstet Gynecol. 2011 Dec;118(6):1454-8.

4. Curr Opin Endocrinol Diabetes Obes. 2016 Apr 1;23(2):168-71.

Integrating comprehensive and collaborative hepatitis C virus (HCV) care within a Veterans Affairs residential treatment program can substantially increase diagnosis and treatment of HCV-infected veterans with substance use disorder (SUD), according to the results of an evaluation study for the period from December 2014 to April 2018.

s-c-s/Thinkstock

A total of 97.5% (582/597) of patient admissions to the program were screened for HCV infection, and 12.7% (74/582) of the cases were confirmed to be HCV positive. All of the positive cases were sent to an infectious disease (ID) clinic for further evaluation and, if appropriate, to begin HCV pharmacotherapy, according to the report, published in the Journal of Substance Abuse Treatment.

Of the HCV-positive cases, 78.4% (58/74) received pharmacotherapy, with a sustained virologic response rate of 82.8% (48/58), wrote Mary Jane Burton, MD, of the G.V. (Sonny) Montgomery VA Medical Center, Jackson, Miss., and her colleagues.

As part of the program, all veterans admitted to the SUD residential program were offered screening for HCV. Veterans with negative screening results received education about how to remain HCV negative via handouts and veterans who screened positive received brief supportive counseling and were referred to the ID clinic via a consult. Veterans confirmed to have chronic HCV infection receive education and evaluation in the HCV clinic while they attend the residential SUD program. Treatment for HCV is instituted as early as feasible and prescribing is in accordance with VA guidelines (Department of Veterans Affairs, 2018), with the goal of initiating pharmacotherapy treatment for HCV while the veteran is still in the residential program, according to the researchers.

Following discharge from the program, veterans on HCV treatment are scheduled for follow-up every 2 weeks in the HCV treatment clinic for the remainder of their pharmacotherapy, the researchers added.

Patient-level barriers to HCV treatment among the SUD population include reduced health literacy, low health care utilization, comorbid mental health conditions, and poor social support, according to the literature. Because multidisciplinary approaches to HCV treatment that mitigate these barriers have been shown to increase treatment uptake among these patients, the VA program was initiated, the researchers stated. Dr. Burton and her colleagues reported that 18.9% (14/74) of the HCV-positive cases were newly diagnosed and would have likely gone undetected without this program (J Substance Abuse Treatment. 2019;98:9-14).

“We have demonstrated that integrating a comprehensive HCV screening, education, referral, and treatment program within residential SUD treatment is feasible and effective in diagnosing previously unrecognized HCV infections, transitioning veterans into HCV care, and promoting treatment initiation,” the researchers concluded.

The Department of Veterans Affairs and the VA Center for Innovation supported the study. Dr. Burton reported research support from Merck Sharpe & Dohme.

[email protected]

Integrating comprehensive and collaborative hepatitis C virus (HCV) care within a Veterans Affairs residential treatment program can substantially increase diagnosis and treatment of HCV-infected veterans with substance use disorder (SUD), according to the results of an evaluation study for the period from December 2014 to April 2018.

s-c-s/Thinkstock

A total of 97.5% (582/597) of patient admissions to the program were screened for HCV infection, and 12.7% (74/582) of the cases were confirmed to be HCV positive. All of the positive cases were sent to an infectious disease (ID) clinic for further evaluation and, if appropriate, to begin HCV pharmacotherapy, according to the report, published in the Journal of Substance Abuse Treatment.

Of the HCV-positive cases, 78.4% (58/74) received pharmacotherapy, with a sustained virologic response rate of 82.8% (48/58), wrote Mary Jane Burton, MD, of the G.V. (Sonny) Montgomery VA Medical Center, Jackson, Miss., and her colleagues.

As part of the program, all veterans admitted to the SUD residential program were offered screening for HCV. Veterans with negative screening results received education about how to remain HCV negative via handouts and veterans who screened positive received brief supportive counseling and were referred to the ID clinic via a consult. Veterans confirmed to have chronic HCV infection receive education and evaluation in the HCV clinic while they attend the residential SUD program. Treatment for HCV is instituted as early as feasible and prescribing is in accordance with VA guidelines (Department of Veterans Affairs, 2018), with the goal of initiating pharmacotherapy treatment for HCV while the veteran is still in the residential program, according to the researchers.

Following discharge from the program, veterans on HCV treatment are scheduled for follow-up every 2 weeks in the HCV treatment clinic for the remainder of their pharmacotherapy, the researchers added.

Patient-level barriers to HCV treatment among the SUD population include reduced health literacy, low health care utilization, comorbid mental health conditions, and poor social support, according to the literature. Because multidisciplinary approaches to HCV treatment that mitigate these barriers have been shown to increase treatment uptake among these patients, the VA program was initiated, the researchers stated. Dr. Burton and her colleagues reported that 18.9% (14/74) of the HCV-positive cases were newly diagnosed and would have likely gone undetected without this program (J Substance Abuse Treatment. 2019;98:9-14).

“We have demonstrated that integrating a comprehensive HCV screening, education, referral, and treatment program within residential SUD treatment is feasible and effective in diagnosing previously unrecognized HCV infections, transitioning veterans into HCV care, and promoting treatment initiation,” the researchers concluded.

The Department of Veterans Affairs and the VA Center for Innovation supported the study. Dr. Burton reported research support from Merck Sharpe & Dohme.

[email protected]

Integrating comprehensive and collaborative hepatitis C virus (HCV) care within a Veterans Affairs residential treatment program can substantially increase diagnosis and treatment of HCV-infected veterans with substance use disorder (SUD), according to the results of an evaluation study for the period from December 2014 to April 2018.

s-c-s/Thinkstock

A total of 97.5% (582/597) of patient admissions to the program were screened for HCV infection, and 12.7% (74/582) of the cases were confirmed to be HCV positive. All of the positive cases were sent to an infectious disease (ID) clinic for further evaluation and, if appropriate, to begin HCV pharmacotherapy, according to the report, published in the Journal of Substance Abuse Treatment.

Of the HCV-positive cases, 78.4% (58/74) received pharmacotherapy, with a sustained virologic response rate of 82.8% (48/58), wrote Mary Jane Burton, MD, of the G.V. (Sonny) Montgomery VA Medical Center, Jackson, Miss., and her colleagues.

As part of the program, all veterans admitted to the SUD residential program were offered screening for HCV. Veterans with negative screening results received education about how to remain HCV negative via handouts and veterans who screened positive received brief supportive counseling and were referred to the ID clinic via a consult. Veterans confirmed to have chronic HCV infection receive education and evaluation in the HCV clinic while they attend the residential SUD program. Treatment for HCV is instituted as early as feasible and prescribing is in accordance with VA guidelines (Department of Veterans Affairs, 2018), with the goal of initiating pharmacotherapy treatment for HCV while the veteran is still in the residential program, according to the researchers.

Following discharge from the program, veterans on HCV treatment are scheduled for follow-up every 2 weeks in the HCV treatment clinic for the remainder of their pharmacotherapy, the researchers added.

Patient-level barriers to HCV treatment among the SUD population include reduced health literacy, low health care utilization, comorbid mental health conditions, and poor social support, according to the literature. Because multidisciplinary approaches to HCV treatment that mitigate these barriers have been shown to increase treatment uptake among these patients, the VA program was initiated, the researchers stated. Dr. Burton and her colleagues reported that 18.9% (14/74) of the HCV-positive cases were newly diagnosed and would have likely gone undetected without this program (J Substance Abuse Treatment. 2019;98:9-14).

“We have demonstrated that integrating a comprehensive HCV screening, education, referral, and treatment program within residential SUD treatment is feasible and effective in diagnosing previously unrecognized HCV infections, transitioning veterans into HCV care, and promoting treatment initiation,” the researchers concluded.

The Department of Veterans Affairs and the VA Center for Innovation supported the study. Dr. Burton reported research support from Merck Sharpe & Dohme.

[email protected]

No significant difference in rate of death was found in patients who underwent either bilateral or single internal thoracic artery grafting during coronary artery bypass grafting (CABG) surgery, according to a randomized trial of patients who were scheduled to undergo CABG.

“At 10 years, in intention-to-treat analyses, there were no significant between-group differences in all-cause mortality,” wrote lead author David P. Taggart, MD, PhD, of the University of Oxford (England), and his coauthors, adding that “the results of this trial are not consistent with data from previous, nonrandomized studies.” The study was published in the New England Journal of Medicine.

In the multicenter, unblinded Arterial Revascularization Trial (ART), 3,102 patients with multivessel coronary artery disease were divided into two groups: the bilateral-graft group (1,548 patients) and the single-graft group (1,554). They were assigned to receive bilateral internal thoracic artery grafts or a standard single left internal thoracic artery graft during CABG, respectively. However, 13.9% of the patients in the bilateral-graft group received only a single internal thoracic artery graft, while 21.8% of those in the single-graft group also received a radial artery graft.


At 10-year follow-up, 644 patients (20.8%) had died; 315 deaths (20.3%) occurred in the bilateral-graft group and 329 (21.2%) occurred in the single-graft group. A total of 385 patients (24.9%) suffered MI, stroke, or death in the bilateral-graft group, compared with 425 (27.3%) in the single-graft group (hazard ratio, 0.90; 95% confidence interval, 0.79-1.03).

The coauthors noted several reasons that the results of their trial may not have matched previous data, including conflicting evidence about vein graft failure’s clinical effect on survival and the aforementioned patients who were assigned to a specific group but received alternate grafting. In addition, they acknowledged that ART was an unblinded trial and “biases may be introduced in the treatment of patients, depending on their randomization assignment.”

The study was supported by grants from the British Heart Foundation, the U.K. Medical Research Council, and the National Institute of Health Research Efficacy and Mechanistic Evaluation Program. No relevant conflicts of interest were reported.

SOURCE: Taggart DP et al. N Engl J Med. 2019 Jan 31. doi: 10.1056/NEJMoa1808783.

No significant difference in rate of death was found in patients who underwent either bilateral or single internal thoracic artery grafting during coronary artery bypass grafting (CABG) surgery, according to a randomized trial of patients who were scheduled to undergo CABG.

“At 10 years, in intention-to-treat analyses, there were no significant between-group differences in all-cause mortality,” wrote lead author David P. Taggart, MD, PhD, of the University of Oxford (England), and his coauthors, adding that “the results of this trial are not consistent with data from previous, nonrandomized studies.” The study was published in the New England Journal of Medicine.

In the multicenter, unblinded Arterial Revascularization Trial (ART), 3,102 patients with multivessel coronary artery disease were divided into two groups: the bilateral-graft group (1,548 patients) and the single-graft group (1,554). They were assigned to receive bilateral internal thoracic artery grafts or a standard single left internal thoracic artery graft during CABG, respectively. However, 13.9% of the patients in the bilateral-graft group received only a single internal thoracic artery graft, while 21.8% of those in the single-graft group also received a radial artery graft.


At 10-year follow-up, 644 patients (20.8%) had died; 315 deaths (20.3%) occurred in the bilateral-graft group and 329 (21.2%) occurred in the single-graft group. A total of 385 patients (24.9%) suffered MI, stroke, or death in the bilateral-graft group, compared with 425 (27.3%) in the single-graft group (hazard ratio, 0.90; 95% confidence interval, 0.79-1.03).

The coauthors noted several reasons that the results of their trial may not have matched previous data, including conflicting evidence about vein graft failure’s clinical effect on survival and the aforementioned patients who were assigned to a specific group but received alternate grafting. In addition, they acknowledged that ART was an unblinded trial and “biases may be introduced in the treatment of patients, depending on their randomization assignment.”

The study was supported by grants from the British Heart Foundation, the U.K. Medical Research Council, and the National Institute of Health Research Efficacy and Mechanistic Evaluation Program. No relevant conflicts of interest were reported.

SOURCE: Taggart DP et al. N Engl J Med. 2019 Jan 31. doi: 10.1056/NEJMoa1808783.

No significant difference in rate of death was found in patients who underwent either bilateral or single internal thoracic artery grafting during coronary artery bypass grafting (CABG) surgery, according to a randomized trial of patients who were scheduled to undergo CABG.

“At 10 years, in intention-to-treat analyses, there were no significant between-group differences in all-cause mortality,” wrote lead author David P. Taggart, MD, PhD, of the University of Oxford (England), and his coauthors, adding that “the results of this trial are not consistent with data from previous, nonrandomized studies.” The study was published in the New England Journal of Medicine.

In the multicenter, unblinded Arterial Revascularization Trial (ART), 3,102 patients with multivessel coronary artery disease were divided into two groups: the bilateral-graft group (1,548 patients) and the single-graft group (1,554). They were assigned to receive bilateral internal thoracic artery grafts or a standard single left internal thoracic artery graft during CABG, respectively. However, 13.9% of the patients in the bilateral-graft group received only a single internal thoracic artery graft, while 21.8% of those in the single-graft group also received a radial artery graft.


At 10-year follow-up, 644 patients (20.8%) had died; 315 deaths (20.3%) occurred in the bilateral-graft group and 329 (21.2%) occurred in the single-graft group. A total of 385 patients (24.9%) suffered MI, stroke, or death in the bilateral-graft group, compared with 425 (27.3%) in the single-graft group (hazard ratio, 0.90; 95% confidence interval, 0.79-1.03).

The coauthors noted several reasons that the results of their trial may not have matched previous data, including conflicting evidence about vein graft failure’s clinical effect on survival and the aforementioned patients who were assigned to a specific group but received alternate grafting. In addition, they acknowledged that ART was an unblinded trial and “biases may be introduced in the treatment of patients, depending on their randomization assignment.”

The study was supported by grants from the British Heart Foundation, the U.K. Medical Research Council, and the National Institute of Health Research Efficacy and Mechanistic Evaluation Program. No relevant conflicts of interest were reported.

SOURCE: Taggart DP et al. N Engl J Med. 2019 Jan 31. doi: 10.1056/NEJMoa1808783.

If you live in Spokane, Wash., 99213 and 99214 are important numbers. Interchanging the last two digits can send your mail into the Twilight Zone. Otherwise those five digit sequences have little significance to most Americans ... unless of course you are a physician. You have been told multiple times by practice administrators and business consultants that the failure to attach the proper sequence to your bill for services can threaten the sustainability of your practice’s bottom line or put you at risk for a costly fine.

utah778/Thinkstock

Numerical codes for office visits were not handed down on stone tablets. There was a time when a physician simply charged for something he called an “office visit” and about half that for a “short” office visit that took less time and probably nothing for a “quick recheck.” He chose the fees based on what he felt was reasonable. I remember reading of one physician who pegged his charges at a dollar per penny of the cost of a regular postage stamp. For a variety of obvious and some unfortunate reasons, these loosely structured fee structures have disappeared.

Now a physician is asked to justify his or her charges by documenting what transpired during the office visit. The patient always has been the best witness, and at least has some sense of how much work the physician has had to do to arrive at diagnosis and suggest a treatment plan. Because the patient usually was paying the bill and had a personal stake in the value of the services provided, this system seemed to make sense.

However, now some large corporate entity or government agency probably is paying the bill and would like some idea of what it is being billed for. Justifying the service provided now falls on the physician. When the billing codes were first introduced and before the payers became more curious, it was easy. I simply applied 99213 to all my office visits and once or twice a day I would code out a visit that seemed more complex as a 99214. I wasn’t keeping track of how many minutes I spent in each visit, how many questions I asked, or how many body parts I examined. Except for patients with injured extremities, everyone was pretty much getting the same exam. My coding was based on my perception of value and effort. If it took more time than usual to remove a bit of cerumen or reassure an unusually concerned parent I chalked that up as my misfortune, not a reason to code the visit as a 99214. If I felt I needed more money, I assumed that my best option was to see more patients. Neither the patients nor the payers seemed to be complaining.

But obviously somewhere someone felt that there were too many providers gaming the system and there needed to be a better way to assign value to what a physician was doing in his or her examining room. Not surprisingly, the current coding system is flawed. I don’t have a workable alternative. However, I always have felt that if the folks who were paying the bills would come visit my office (unannounced if they wish) and spend a morning watching me see patients, they could more accurately assign a value to my work. I’m not sure how many of you would be comfortable with that degree of transparency. But for me it would be worth it if it freed me from the burden of coding to justify my effort.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

If you live in Spokane, Wash., 99213 and 99214 are important numbers. Interchanging the last two digits can send your mail into the Twilight Zone. Otherwise those five digit sequences have little significance to most Americans ... unless of course you are a physician. You have been told multiple times by practice administrators and business consultants that the failure to attach the proper sequence to your bill for services can threaten the sustainability of your practice’s bottom line or put you at risk for a costly fine.

utah778/Thinkstock

Numerical codes for office visits were not handed down on stone tablets. There was a time when a physician simply charged for something he called an “office visit” and about half that for a “short” office visit that took less time and probably nothing for a “quick recheck.” He chose the fees based on what he felt was reasonable. I remember reading of one physician who pegged his charges at a dollar per penny of the cost of a regular postage stamp. For a variety of obvious and some unfortunate reasons, these loosely structured fee structures have disappeared.

Now a physician is asked to justify his or her charges by documenting what transpired during the office visit. The patient always has been the best witness, and at least has some sense of how much work the physician has had to do to arrive at diagnosis and suggest a treatment plan. Because the patient usually was paying the bill and had a personal stake in the value of the services provided, this system seemed to make sense.

However, now some large corporate entity or government agency probably is paying the bill and would like some idea of what it is being billed for. Justifying the service provided now falls on the physician. When the billing codes were first introduced and before the payers became more curious, it was easy. I simply applied 99213 to all my office visits and once or twice a day I would code out a visit that seemed more complex as a 99214. I wasn’t keeping track of how many minutes I spent in each visit, how many questions I asked, or how many body parts I examined. Except for patients with injured extremities, everyone was pretty much getting the same exam. My coding was based on my perception of value and effort. If it took more time than usual to remove a bit of cerumen or reassure an unusually concerned parent I chalked that up as my misfortune, not a reason to code the visit as a 99214. If I felt I needed more money, I assumed that my best option was to see more patients. Neither the patients nor the payers seemed to be complaining.

But obviously somewhere someone felt that there were too many providers gaming the system and there needed to be a better way to assign value to what a physician was doing in his or her examining room. Not surprisingly, the current coding system is flawed. I don’t have a workable alternative. However, I always have felt that if the folks who were paying the bills would come visit my office (unannounced if they wish) and spend a morning watching me see patients, they could more accurately assign a value to my work. I’m not sure how many of you would be comfortable with that degree of transparency. But for me it would be worth it if it freed me from the burden of coding to justify my effort.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

If you live in Spokane, Wash., 99213 and 99214 are important numbers. Interchanging the last two digits can send your mail into the Twilight Zone. Otherwise those five digit sequences have little significance to most Americans ... unless of course you are a physician. You have been told multiple times by practice administrators and business consultants that the failure to attach the proper sequence to your bill for services can threaten the sustainability of your practice’s bottom line or put you at risk for a costly fine.

utah778/Thinkstock

Numerical codes for office visits were not handed down on stone tablets. There was a time when a physician simply charged for something he called an “office visit” and about half that for a “short” office visit that took less time and probably nothing for a “quick recheck.” He chose the fees based on what he felt was reasonable. I remember reading of one physician who pegged his charges at a dollar per penny of the cost of a regular postage stamp. For a variety of obvious and some unfortunate reasons, these loosely structured fee structures have disappeared.

Now a physician is asked to justify his or her charges by documenting what transpired during the office visit. The patient always has been the best witness, and at least has some sense of how much work the physician has had to do to arrive at diagnosis and suggest a treatment plan. Because the patient usually was paying the bill and had a personal stake in the value of the services provided, this system seemed to make sense.

However, now some large corporate entity or government agency probably is paying the bill and would like some idea of what it is being billed for. Justifying the service provided now falls on the physician. When the billing codes were first introduced and before the payers became more curious, it was easy. I simply applied 99213 to all my office visits and once or twice a day I would code out a visit that seemed more complex as a 99214. I wasn’t keeping track of how many minutes I spent in each visit, how many questions I asked, or how many body parts I examined. Except for patients with injured extremities, everyone was pretty much getting the same exam. My coding was based on my perception of value and effort. If it took more time than usual to remove a bit of cerumen or reassure an unusually concerned parent I chalked that up as my misfortune, not a reason to code the visit as a 99214. If I felt I needed more money, I assumed that my best option was to see more patients. Neither the patients nor the payers seemed to be complaining.

But obviously somewhere someone felt that there were too many providers gaming the system and there needed to be a better way to assign value to what a physician was doing in his or her examining room. Not surprisingly, the current coding system is flawed. I don’t have a workable alternative. However, I always have felt that if the folks who were paying the bills would come visit my office (unannounced if they wish) and spend a morning watching me see patients, they could more accurately assign a value to my work. I’m not sure how many of you would be comfortable with that degree of transparency. But for me it would be worth it if it freed me from the burden of coding to justify my effort.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

CORONADO, CALIF. – Mild obstructive sleep apnea (OSA) resolves in about one-third of children younger than age 3 years after an observation period of 3-12 months, results from a single-center study showed.

“OSA affects up to 6% of the pediatric population, and diagnosis of young children can be particularly challenging due to the heterogeneity of presenting symptoms,” Douglas C. von Allmen, MD, said at the Triological Society’s Combined Sections Meeting. “While school-age children may present with snoring, that’s less common in the younger population. Up to one-quarter of infants may have noisy breathing, which may mimic obstructive events throughout the first 3 years of life. Additionally, long-term clinical implications of mild sleep apnea in very young children is unclear.”

According to Dr. von Allmen, a fifth-year otolaryngology resident at the University of Cincinnati, management strategies of children with OSA can include a period of observation, particularly when there’s an absence of concerning findings on polysomnography (PSG), such as hypoventilation or significant hypoxia, or when the primary etiology of the OSA is unknown. “Additionally, few studies at this point have attempted to characterize the natural history of mild OSA in pediatric patients under 3 years of age,” he said.

In an effort to assess the effects of observation on the PSG outcomes of children under 3 years with mild OSA, Dr. Von Allmen and his colleagues performed a retrospective review of 26 children who had an overnight PSG with a follow-up PSG performed 3-12 months later. They excluded patients with neuromuscular disease, tracheostomy, or interstitial lung disease. All PSGs were performed at the Cincinnati Children’s Hospital Medical Center between 2012 and 2017 and were scored by a board-certified sleep physician. The researchers defined mild OSA as at least one, but fewer than five, events per hour. The mean age of the 26 patients was 7 months, 65% were male, 92% were white, and their median body mass index was in the 39th percentile. Comorbidities include laryngomalacia (40%), cardiac disease (40%), allergies (34%), asthma (23%), and Down syndrome (11%).

Between baseline and follow-up, the apnea-hypoapnea index (AHI) trended downward from 4.3 to 3.4 events per hour (P = .19), the obstructive AHI decreased significantly from 2.7 to 1.3 events per hour (P = .013), while the central apnea index also trended downward from 1.4 to 1.2 events per hour (P = .60). The oxyhemoglobin nadir and sleep efficiency did not change significantly, but there was a decrease in the arousal index (from 14.7 to 13 events per hour; P = .027) and in the percentage of REM sleep (from 33% to 30%; P = .008).

As for postobservation OSA severity outcomes, eight patients (31%) resolved spontaneously, one patient progressed from mild to moderate OSA, and the rest remained in their mild OSA state. Subanalysis revealed that OSA resolution rate was 36% in patients with laryngomalacia, compared with 27% in those with no laryngomalacia, a difference that did not reach statistical significance (P = .98).

Dr. von Allmen pointed out that the study cohort had comorbidities which may have contributed to the persistence of OSA. He also acknowledged certain limitations of the study, including its retrospective nature, the potential for selection bias, the small sample size, and the fact that it did not include a control sample of normal children. “The presence of laryngomalacia did not affect the resolution rate in our cohort, but we’ll need larger studies to better elucidate the factors that do affect persistent disease and to identify the optimal timing of intervention in children with mild OSA,” he said.

Dr. von Allmen reported having no financial disclosures. The study received a resident research award at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons.

SOURCE: von Allmen DC et al. Triological CSM, Abstracts.

CORONADO, CALIF. – Mild obstructive sleep apnea (OSA) resolves in about one-third of children younger than age 3 years after an observation period of 3-12 months, results from a single-center study showed.

“OSA affects up to 6% of the pediatric population, and diagnosis of young children can be particularly challenging due to the heterogeneity of presenting symptoms,” Douglas C. von Allmen, MD, said at the Triological Society’s Combined Sections Meeting. “While school-age children may present with snoring, that’s less common in the younger population. Up to one-quarter of infants may have noisy breathing, which may mimic obstructive events throughout the first 3 years of life. Additionally, long-term clinical implications of mild sleep apnea in very young children is unclear.”

According to Dr. von Allmen, a fifth-year otolaryngology resident at the University of Cincinnati, management strategies of children with OSA can include a period of observation, particularly when there’s an absence of concerning findings on polysomnography (PSG), such as hypoventilation or significant hypoxia, or when the primary etiology of the OSA is unknown. “Additionally, few studies at this point have attempted to characterize the natural history of mild OSA in pediatric patients under 3 years of age,” he said.

In an effort to assess the effects of observation on the PSG outcomes of children under 3 years with mild OSA, Dr. Von Allmen and his colleagues performed a retrospective review of 26 children who had an overnight PSG with a follow-up PSG performed 3-12 months later. They excluded patients with neuromuscular disease, tracheostomy, or interstitial lung disease. All PSGs were performed at the Cincinnati Children’s Hospital Medical Center between 2012 and 2017 and were scored by a board-certified sleep physician. The researchers defined mild OSA as at least one, but fewer than five, events per hour. The mean age of the 26 patients was 7 months, 65% were male, 92% were white, and their median body mass index was in the 39th percentile. Comorbidities include laryngomalacia (40%), cardiac disease (40%), allergies (34%), asthma (23%), and Down syndrome (11%).

Between baseline and follow-up, the apnea-hypoapnea index (AHI) trended downward from 4.3 to 3.4 events per hour (P = .19), the obstructive AHI decreased significantly from 2.7 to 1.3 events per hour (P = .013), while the central apnea index also trended downward from 1.4 to 1.2 events per hour (P = .60). The oxyhemoglobin nadir and sleep efficiency did not change significantly, but there was a decrease in the arousal index (from 14.7 to 13 events per hour; P = .027) and in the percentage of REM sleep (from 33% to 30%; P = .008).

As for postobservation OSA severity outcomes, eight patients (31%) resolved spontaneously, one patient progressed from mild to moderate OSA, and the rest remained in their mild OSA state. Subanalysis revealed that OSA resolution rate was 36% in patients with laryngomalacia, compared with 27% in those with no laryngomalacia, a difference that did not reach statistical significance (P = .98).

Dr. von Allmen pointed out that the study cohort had comorbidities which may have contributed to the persistence of OSA. He also acknowledged certain limitations of the study, including its retrospective nature, the potential for selection bias, the small sample size, and the fact that it did not include a control sample of normal children. “The presence of laryngomalacia did not affect the resolution rate in our cohort, but we’ll need larger studies to better elucidate the factors that do affect persistent disease and to identify the optimal timing of intervention in children with mild OSA,” he said.

Dr. von Allmen reported having no financial disclosures. The study received a resident research award at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons.

SOURCE: von Allmen DC et al. Triological CSM, Abstracts.

CORONADO, CALIF. – Mild obstructive sleep apnea (OSA) resolves in about one-third of children younger than age 3 years after an observation period of 3-12 months, results from a single-center study showed.

“OSA affects up to 6% of the pediatric population, and diagnosis of young children can be particularly challenging due to the heterogeneity of presenting symptoms,” Douglas C. von Allmen, MD, said at the Triological Society’s Combined Sections Meeting. “While school-age children may present with snoring, that’s less common in the younger population. Up to one-quarter of infants may have noisy breathing, which may mimic obstructive events throughout the first 3 years of life. Additionally, long-term clinical implications of mild sleep apnea in very young children is unclear.”

According to Dr. von Allmen, a fifth-year otolaryngology resident at the University of Cincinnati, management strategies of children with OSA can include a period of observation, particularly when there’s an absence of concerning findings on polysomnography (PSG), such as hypoventilation or significant hypoxia, or when the primary etiology of the OSA is unknown. “Additionally, few studies at this point have attempted to characterize the natural history of mild OSA in pediatric patients under 3 years of age,” he said.

In an effort to assess the effects of observation on the PSG outcomes of children under 3 years with mild OSA, Dr. Von Allmen and his colleagues performed a retrospective review of 26 children who had an overnight PSG with a follow-up PSG performed 3-12 months later. They excluded patients with neuromuscular disease, tracheostomy, or interstitial lung disease. All PSGs were performed at the Cincinnati Children’s Hospital Medical Center between 2012 and 2017 and were scored by a board-certified sleep physician. The researchers defined mild OSA as at least one, but fewer than five, events per hour. The mean age of the 26 patients was 7 months, 65% were male, 92% were white, and their median body mass index was in the 39th percentile. Comorbidities include laryngomalacia (40%), cardiac disease (40%), allergies (34%), asthma (23%), and Down syndrome (11%).

Between baseline and follow-up, the apnea-hypoapnea index (AHI) trended downward from 4.3 to 3.4 events per hour (P = .19), the obstructive AHI decreased significantly from 2.7 to 1.3 events per hour (P = .013), while the central apnea index also trended downward from 1.4 to 1.2 events per hour (P = .60). The oxyhemoglobin nadir and sleep efficiency did not change significantly, but there was a decrease in the arousal index (from 14.7 to 13 events per hour; P = .027) and in the percentage of REM sleep (from 33% to 30%; P = .008).

As for postobservation OSA severity outcomes, eight patients (31%) resolved spontaneously, one patient progressed from mild to moderate OSA, and the rest remained in their mild OSA state. Subanalysis revealed that OSA resolution rate was 36% in patients with laryngomalacia, compared with 27% in those with no laryngomalacia, a difference that did not reach statistical significance (P = .98).

Dr. von Allmen pointed out that the study cohort had comorbidities which may have contributed to the persistence of OSA. He also acknowledged certain limitations of the study, including its retrospective nature, the potential for selection bias, the small sample size, and the fact that it did not include a control sample of normal children. “The presence of laryngomalacia did not affect the resolution rate in our cohort, but we’ll need larger studies to better elucidate the factors that do affect persistent disease and to identify the optimal timing of intervention in children with mild OSA,” he said.

Dr. von Allmen reported having no financial disclosures. The study received a resident research award at the meeting, which was jointly sponsored by the Triological Society and the American College of Surgeons.

SOURCE: von Allmen DC et al. Triological CSM, Abstracts.

A new instrument for measuring disease activity in systemic lupus erythematosus had better performance than that of the current most widely-used measure, according to investigators.

enot-poloskun/iStock/Getty Images Plus

In terms of identifying clinically significant changes, the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) was superior to the SLE Disease Activity Index 2000 (SLEDAI-2K), said the authors of a longitudinal cohort study comparing the two instruments.

The SLE-DAS maintained high specificity compared with the SLEDAI-2K and had a similar clinical workup time requirement, according to Diogo Jesus, MD, of the rheumatology department at Centro Hospitalar e Universitário de Coimbra, Portugal, and his colleagues.

“Such a performance can have major implications in the interpretation of clinical trials applying the disease activity as the primary endpoint, and in daily clinical practice, where SLE-DAS could provide robust guidance for treatment in the individual patient,” Dr. Jesus and his coauthors wrote in Annals of the Rheumatic Diseases.

The longitudinal cohort study by Dr. Jesus and his colleagues included 520 patients with SLE from tertiary care centers in Coimbra, Portugal, and Padova, Italy. These included a derivation cohort of 324 patients and an external validation cohort of 196 patients (the Padova Lupus Cohort).

A cutoff value of 1.72 for change in the 17-item SLE-DAS had significantly higher sensitivities to detect a clinical meaningful improvement in both the derivation (82.1%) and external validation (89.5%) cohorts, compared with a cutoff value of 4 or higher in the SLEDAI-2K at 44.8% and 47.4%, respectively, the investigators reported. Likewise, ability to detect clinically meaningful worsening was significantly higher with SLE-DAS, with sensitivities of 93.1% in the derivation cohort and 95.5% in the external validation group versus a respective 46.6% and 59.1% for SLEDAI-2K. Both clinical improvement and worsening were defined by a change in the Physician Global Assessment score of 0.3 or more.

Specificity was high for both instruments, with values around 98%-99% in both cohorts for clinically meaningful worsening and about 97%-100% for clinically meaningful improvement, the report shows.

Further analyses showed that disease activity tracked over time with SLE-DAS had a higher predictive value for damage accrual versus the SLEDAI-2K, according to the investigators.

The SLE-DAS formula, published in the journal by Dr. Jesus and his colleagues, includes a total of 17 weighted and mostly binary variables: presence or absence of alopecia, arthritis, cardiac/pulmonary involvement, generalized cutaneous rash, hemolytic anemia, hypocomplementemia, increased anti-dsDNA levels, leukopenia, localized cutaneous rash, mucocutaneous vasculitis, mucosal ulcers, myositis, neuropsychiatric involvement, proteinuria, serositis, systemic vasculitis, and thrombocytopenia.

Next, the researchers plan to define SLE-DAS cutoff values for remission, low disease activity, and moderate or high disease activity. An online calculator is also in the works, they said.

Dr. Jesus and his coauthors did not report any outside funding for the study and said they had no competing interests related to their research.

SOURCE: Jesus D et al. Ann Rheum Dis. 2019 Jan 9. doi: 10.1136/annrheumdis-2018-214502.

A new instrument for measuring disease activity in systemic lupus erythematosus had better performance than that of the current most widely-used measure, according to investigators.

enot-poloskun/iStock/Getty Images Plus

In terms of identifying clinically significant changes, the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) was superior to the SLE Disease Activity Index 2000 (SLEDAI-2K), said the authors of a longitudinal cohort study comparing the two instruments.

The SLE-DAS maintained high specificity compared with the SLEDAI-2K and had a similar clinical workup time requirement, according to Diogo Jesus, MD, of the rheumatology department at Centro Hospitalar e Universitário de Coimbra, Portugal, and his colleagues.

“Such a performance can have major implications in the interpretation of clinical trials applying the disease activity as the primary endpoint, and in daily clinical practice, where SLE-DAS could provide robust guidance for treatment in the individual patient,” Dr. Jesus and his coauthors wrote in Annals of the Rheumatic Diseases.

The longitudinal cohort study by Dr. Jesus and his colleagues included 520 patients with SLE from tertiary care centers in Coimbra, Portugal, and Padova, Italy. These included a derivation cohort of 324 patients and an external validation cohort of 196 patients (the Padova Lupus Cohort).

A cutoff value of 1.72 for change in the 17-item SLE-DAS had significantly higher sensitivities to detect a clinical meaningful improvement in both the derivation (82.1%) and external validation (89.5%) cohorts, compared with a cutoff value of 4 or higher in the SLEDAI-2K at 44.8% and 47.4%, respectively, the investigators reported. Likewise, ability to detect clinically meaningful worsening was significantly higher with SLE-DAS, with sensitivities of 93.1% in the derivation cohort and 95.5% in the external validation group versus a respective 46.6% and 59.1% for SLEDAI-2K. Both clinical improvement and worsening were defined by a change in the Physician Global Assessment score of 0.3 or more.

Specificity was high for both instruments, with values around 98%-99% in both cohorts for clinically meaningful worsening and about 97%-100% for clinically meaningful improvement, the report shows.

Further analyses showed that disease activity tracked over time with SLE-DAS had a higher predictive value for damage accrual versus the SLEDAI-2K, according to the investigators.

The SLE-DAS formula, published in the journal by Dr. Jesus and his colleagues, includes a total of 17 weighted and mostly binary variables: presence or absence of alopecia, arthritis, cardiac/pulmonary involvement, generalized cutaneous rash, hemolytic anemia, hypocomplementemia, increased anti-dsDNA levels, leukopenia, localized cutaneous rash, mucocutaneous vasculitis, mucosal ulcers, myositis, neuropsychiatric involvement, proteinuria, serositis, systemic vasculitis, and thrombocytopenia.

Next, the researchers plan to define SLE-DAS cutoff values for remission, low disease activity, and moderate or high disease activity. An online calculator is also in the works, they said.

Dr. Jesus and his coauthors did not report any outside funding for the study and said they had no competing interests related to their research.

SOURCE: Jesus D et al. Ann Rheum Dis. 2019 Jan 9. doi: 10.1136/annrheumdis-2018-214502.

A new instrument for measuring disease activity in systemic lupus erythematosus had better performance than that of the current most widely-used measure, according to investigators.

enot-poloskun/iStock/Getty Images Plus

In terms of identifying clinically significant changes, the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) was superior to the SLE Disease Activity Index 2000 (SLEDAI-2K), said the authors of a longitudinal cohort study comparing the two instruments.

The SLE-DAS maintained high specificity compared with the SLEDAI-2K and had a similar clinical workup time requirement, according to Diogo Jesus, MD, of the rheumatology department at Centro Hospitalar e Universitário de Coimbra, Portugal, and his colleagues.

“Such a performance can have major implications in the interpretation of clinical trials applying the disease activity as the primary endpoint, and in daily clinical practice, where SLE-DAS could provide robust guidance for treatment in the individual patient,” Dr. Jesus and his coauthors wrote in Annals of the Rheumatic Diseases.

The longitudinal cohort study by Dr. Jesus and his colleagues included 520 patients with SLE from tertiary care centers in Coimbra, Portugal, and Padova, Italy. These included a derivation cohort of 324 patients and an external validation cohort of 196 patients (the Padova Lupus Cohort).

A cutoff value of 1.72 for change in the 17-item SLE-DAS had significantly higher sensitivities to detect a clinical meaningful improvement in both the derivation (82.1%) and external validation (89.5%) cohorts, compared with a cutoff value of 4 or higher in the SLEDAI-2K at 44.8% and 47.4%, respectively, the investigators reported. Likewise, ability to detect clinically meaningful worsening was significantly higher with SLE-DAS, with sensitivities of 93.1% in the derivation cohort and 95.5% in the external validation group versus a respective 46.6% and 59.1% for SLEDAI-2K. Both clinical improvement and worsening were defined by a change in the Physician Global Assessment score of 0.3 or more.

Specificity was high for both instruments, with values around 98%-99% in both cohorts for clinically meaningful worsening and about 97%-100% for clinically meaningful improvement, the report shows.

Further analyses showed that disease activity tracked over time with SLE-DAS had a higher predictive value for damage accrual versus the SLEDAI-2K, according to the investigators.

The SLE-DAS formula, published in the journal by Dr. Jesus and his colleagues, includes a total of 17 weighted and mostly binary variables: presence or absence of alopecia, arthritis, cardiac/pulmonary involvement, generalized cutaneous rash, hemolytic anemia, hypocomplementemia, increased anti-dsDNA levels, leukopenia, localized cutaneous rash, mucocutaneous vasculitis, mucosal ulcers, myositis, neuropsychiatric involvement, proteinuria, serositis, systemic vasculitis, and thrombocytopenia.

Next, the researchers plan to define SLE-DAS cutoff values for remission, low disease activity, and moderate or high disease activity. An online calculator is also in the works, they said.

Dr. Jesus and his coauthors did not report any outside funding for the study and said they had no competing interests related to their research.

SOURCE: Jesus D et al. Ann Rheum Dis. 2019 Jan 9. doi: 10.1136/annrheumdis-2018-214502.

After a disappointing interim analysis, Roche and its collaborator AC Immune are halting two phase 3 trials of the antiamyloid antibody crenezumab.

CREAD 1 and CREAD 2 enrolled patients with prodromal-to-mild sporadic Alzheimer’s disease. The preplanned interim safety and efficacy analysis determined that neither study was likely to meet the primary endpoint of change from baseline on the Clinical Dementia Rating-sum of boxes score.

There were no unexpected safety signals associated with the drug, despite a quadrupling of the phase 3 dose from that used in phase 2. The company in its press release said that it will continue to conduct the Autosomal Dominant Alzheimer’s Disease (ADAD) trial as part of the Alzheimer’s Prevention Initiative (API). ADAD is a large South American trial of crenezumab in Colombian families with familial Alzheimer’s caused by mutations in the presenilin-1 gene (PSEN1).

Roche did not release any data but said the trial results will be discussed at an upcoming scientific meeting.

“While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer’s disease,” Sandra Horning, MD, Roche’s chief medical officer and executive vice president for global development, said in an interview. “We gratefully acknowledge the participants in the CREAD trials and the efforts of everyone involved in this important program.”

The decision was not a surprise to researchers who have followed the antibody’s development. It advanced into phase 3 with lackluster phase 2 cognitive, imaging, and biomarker data. Its selection as the therapeutic agent for the ADAD trial was a key driver in its continued development, securing Roche $100 million in federal funds to help launch ADAD, the first-ever Alzheimer’s primary prevention study.

Despite its failure in sporadic Alzheimer’s, there is still some hope that crenezumab might benefit people with the PSEN1 mutation, said Richard Caselli, MD, professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.

“The Colombian trial is aimed at dominantly-inherited AD due to a PSEN1 mutation, so it is different enough to imagine it still might make a difference in patients in whom amyloid metabolism is actually defective due to functionally altered amyloid precursor protein or gamma secretase,” he said in an interview. “Possibly some might argue that many of the patients in the crenezumab trial likely had additional pathologies so that even if the AD component responded, the overall clinical picture might not reflect it due to the other components. That would be interesting if proven and could even argue against equating young-onset with late-onset AD, at least for clinical purposes, as is currently envisioned.”

Michael Wolfe, PhD, had a different take on the matter.

“Although amyloid-beta [Abeta] production is not necessarily altered in sporadic AD, there is essentially the same pathology, presentation, and progression with familial and sporadic AD, suggesting a common molecular mechanism,” said Dr. Wolfe, who is the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “It’s hard to say Abeta is the pathogenic species in familial but not sporadic AD.

The antibodies that have been failing for 5 years now were designed in the early 2000s, Dr. Kupiec pointed out, when knowledge of the various amyloid species was still immature. Newer candidates can target specific conformations of the protein – monomers and oligomers – before they aggregate into insoluble sheets. “Solanezumab was the first of these, paving the way for this new generation of antibodies,” Dr. Kupiec said.

Because they target soluble Abeta, not amyloid plaques, these domain-specific antibodies are less likely to elicit ARIA (amyloid-related imaging abnormalities), the inflammatory reaction that’s been associated with plaque dissolution in other antibody trials. ARIA has been a dose-limiting step for antiamyloid antibodies – one that conformationally targeted antibodies could avoid, Dr. Kupiec said.

“There may be some limited success with the these, and there may be enough of a treatment effect to secure approval,” he said. “The question is: Can we generate a higher effect size with an antibody that is more selective to the toxic forms of Abeta?”

PMN310 is ProMIS’ attempt to thread this needle. In preclinical studies, the antibody did not bind to amyloid monomers, plaques, or vascular Abeta aggregates. The company expects to take this antibody into phase 1 trials later this year.

“If we have a molecule that doesn’t bind to monomers or to plaques, but only to the toxic oligomer, then that is an something well worth testing in the clinic,” he said.

Dr. Caselli and Dr. Wolfe have no financial disclosures.

[email protected]

After a disappointing interim analysis, Roche and its collaborator AC Immune are halting two phase 3 trials of the antiamyloid antibody crenezumab.

CREAD 1 and CREAD 2 enrolled patients with prodromal-to-mild sporadic Alzheimer’s disease. The preplanned interim safety and efficacy analysis determined that neither study was likely to meet the primary endpoint of change from baseline on the Clinical Dementia Rating-sum of boxes score.

There were no unexpected safety signals associated with the drug, despite a quadrupling of the phase 3 dose from that used in phase 2. The company in its press release said that it will continue to conduct the Autosomal Dominant Alzheimer’s Disease (ADAD) trial as part of the Alzheimer’s Prevention Initiative (API). ADAD is a large South American trial of crenezumab in Colombian families with familial Alzheimer’s caused by mutations in the presenilin-1 gene (PSEN1).

Roche did not release any data but said the trial results will be discussed at an upcoming scientific meeting.

“While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer’s disease,” Sandra Horning, MD, Roche’s chief medical officer and executive vice president for global development, said in an interview. “We gratefully acknowledge the participants in the CREAD trials and the efforts of everyone involved in this important program.”

The decision was not a surprise to researchers who have followed the antibody’s development. It advanced into phase 3 with lackluster phase 2 cognitive, imaging, and biomarker data. Its selection as the therapeutic agent for the ADAD trial was a key driver in its continued development, securing Roche $100 million in federal funds to help launch ADAD, the first-ever Alzheimer’s primary prevention study.

Despite its failure in sporadic Alzheimer’s, there is still some hope that crenezumab might benefit people with the PSEN1 mutation, said Richard Caselli, MD, professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.

“The Colombian trial is aimed at dominantly-inherited AD due to a PSEN1 mutation, so it is different enough to imagine it still might make a difference in patients in whom amyloid metabolism is actually defective due to functionally altered amyloid precursor protein or gamma secretase,” he said in an interview. “Possibly some might argue that many of the patients in the crenezumab trial likely had additional pathologies so that even if the AD component responded, the overall clinical picture might not reflect it due to the other components. That would be interesting if proven and could even argue against equating young-onset with late-onset AD, at least for clinical purposes, as is currently envisioned.”

Michael Wolfe, PhD, had a different take on the matter.

“Although amyloid-beta [Abeta] production is not necessarily altered in sporadic AD, there is essentially the same pathology, presentation, and progression with familial and sporadic AD, suggesting a common molecular mechanism,” said Dr. Wolfe, who is the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “It’s hard to say Abeta is the pathogenic species in familial but not sporadic AD.

The antibodies that have been failing for 5 years now were designed in the early 2000s, Dr. Kupiec pointed out, when knowledge of the various amyloid species was still immature. Newer candidates can target specific conformations of the protein – monomers and oligomers – before they aggregate into insoluble sheets. “Solanezumab was the first of these, paving the way for this new generation of antibodies,” Dr. Kupiec said.

Because they target soluble Abeta, not amyloid plaques, these domain-specific antibodies are less likely to elicit ARIA (amyloid-related imaging abnormalities), the inflammatory reaction that’s been associated with plaque dissolution in other antibody trials. ARIA has been a dose-limiting step for antiamyloid antibodies – one that conformationally targeted antibodies could avoid, Dr. Kupiec said.

“There may be some limited success with the these, and there may be enough of a treatment effect to secure approval,” he said. “The question is: Can we generate a higher effect size with an antibody that is more selective to the toxic forms of Abeta?”

PMN310 is ProMIS’ attempt to thread this needle. In preclinical studies, the antibody did not bind to amyloid monomers, plaques, or vascular Abeta aggregates. The company expects to take this antibody into phase 1 trials later this year.

“If we have a molecule that doesn’t bind to monomers or to plaques, but only to the toxic oligomer, then that is an something well worth testing in the clinic,” he said.

Dr. Caselli and Dr. Wolfe have no financial disclosures.

[email protected]

After a disappointing interim analysis, Roche and its collaborator AC Immune are halting two phase 3 trials of the antiamyloid antibody crenezumab.

CREAD 1 and CREAD 2 enrolled patients with prodromal-to-mild sporadic Alzheimer’s disease. The preplanned interim safety and efficacy analysis determined that neither study was likely to meet the primary endpoint of change from baseline on the Clinical Dementia Rating-sum of boxes score.

There were no unexpected safety signals associated with the drug, despite a quadrupling of the phase 3 dose from that used in phase 2. The company in its press release said that it will continue to conduct the Autosomal Dominant Alzheimer’s Disease (ADAD) trial as part of the Alzheimer’s Prevention Initiative (API). ADAD is a large South American trial of crenezumab in Colombian families with familial Alzheimer’s caused by mutations in the presenilin-1 gene (PSEN1).

Roche did not release any data but said the trial results will be discussed at an upcoming scientific meeting.

“While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer’s disease,” Sandra Horning, MD, Roche’s chief medical officer and executive vice president for global development, said in an interview. “We gratefully acknowledge the participants in the CREAD trials and the efforts of everyone involved in this important program.”

The decision was not a surprise to researchers who have followed the antibody’s development. It advanced into phase 3 with lackluster phase 2 cognitive, imaging, and biomarker data. Its selection as the therapeutic agent for the ADAD trial was a key driver in its continued development, securing Roche $100 million in federal funds to help launch ADAD, the first-ever Alzheimer’s primary prevention study.

Despite its failure in sporadic Alzheimer’s, there is still some hope that crenezumab might benefit people with the PSEN1 mutation, said Richard Caselli, MD, professor of neurology at the Mayo Clinic Arizona in Scottsdale and associate director and clinical core director of the Arizona Alzheimer’s Disease Center.

“The Colombian trial is aimed at dominantly-inherited AD due to a PSEN1 mutation, so it is different enough to imagine it still might make a difference in patients in whom amyloid metabolism is actually defective due to functionally altered amyloid precursor protein or gamma secretase,” he said in an interview. “Possibly some might argue that many of the patients in the crenezumab trial likely had additional pathologies so that even if the AD component responded, the overall clinical picture might not reflect it due to the other components. That would be interesting if proven and could even argue against equating young-onset with late-onset AD, at least for clinical purposes, as is currently envisioned.”

Michael Wolfe, PhD, had a different take on the matter.

“Although amyloid-beta [Abeta] production is not necessarily altered in sporadic AD, there is essentially the same pathology, presentation, and progression with familial and sporadic AD, suggesting a common molecular mechanism,” said Dr. Wolfe, who is the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “It’s hard to say Abeta is the pathogenic species in familial but not sporadic AD.

The antibodies that have been failing for 5 years now were designed in the early 2000s, Dr. Kupiec pointed out, when knowledge of the various amyloid species was still immature. Newer candidates can target specific conformations of the protein – monomers and oligomers – before they aggregate into insoluble sheets. “Solanezumab was the first of these, paving the way for this new generation of antibodies,” Dr. Kupiec said.

Because they target soluble Abeta, not amyloid plaques, these domain-specific antibodies are less likely to elicit ARIA (amyloid-related imaging abnormalities), the inflammatory reaction that’s been associated with plaque dissolution in other antibody trials. ARIA has been a dose-limiting step for antiamyloid antibodies – one that conformationally targeted antibodies could avoid, Dr. Kupiec said.

“There may be some limited success with the these, and there may be enough of a treatment effect to secure approval,” he said. “The question is: Can we generate a higher effect size with an antibody that is more selective to the toxic forms of Abeta?”

PMN310 is ProMIS’ attempt to thread this needle. In preclinical studies, the antibody did not bind to amyloid monomers, plaques, or vascular Abeta aggregates. The company expects to take this antibody into phase 1 trials later this year.

“If we have a molecule that doesn’t bind to monomers or to plaques, but only to the toxic oligomer, then that is an something well worth testing in the clinic,” he said.

Dr. Caselli and Dr. Wolfe have no financial disclosures.

[email protected]

The addition of docetaxel to androgen deprivation therapy in patients with localized, high-risk prostate cancer does not appear to impact progression-free survival rates, a study has found.

In JAMA Oncology, researchers reported the results of an open-label, phase 3, randomized superiority trial comparing androgen deprivation therapy (ADT) plus docetaxel with androgen therapy alone in 254 patients who had received primary local therapy for prostate cancer but showed significant risk factors for metastatic disease.

These risk factors included positive surgical margins, a Gleason score of 8 or above, prostate-specific antigen (PSA) velocity greater than 0.75 ng/mL per year, PSA doubling time of 6 months or less, and time to PSA recurrence of 12 months or less.

Overall, 63.2% of patients in the ADT plus docetaxel group and 64.8% of the ADT-only group experienced PSA progression, defined as a 50% or more relative increase in PSA levels above the nadir. After a median follow-up of 30 months, the median PSA progression-free survival (PFS) was 20.3 months in the combined therapy arm and 19.3 months in the monotherapy arm (hazard ratio, 0.85; P = .31).

“It follows that docetaxel may not be as suitable in a high-risk setting as in a metastatic setting,” wrote Stéphane Oudard, MD, PhD, from the department of medical oncology at Georges Pompidou Hospital in Paris, and his coauthors.

However individuals in the combined therapy arm showed a significantly higher complete PSA response rate, compared with those in the ADT-only group (72.8% vs. 64.8%).

In subgroup analysis, based on the various risk factors for progression to metastatic disease, the combined therapy approach was always better than the monotherapy in PSA PFS, but never achieved statistical significance. The authors noted a 15% improvement in time to PSA progression with combined therapy.

Researchers followed the group for a median of 10.5 years, during which time they saw a similar median time to radiologic progression in both arms (8.9 years for ADT plus docetaxel and 9 years for ADT alone; HR, 1.03; P = 0.88).

There was also no significant difference in all-cause mortality between the two groups.

The authors acknowledged that the clinical relevance of their chosen end point of PSA PFS was likely to be disputed, as some preferred to use endpoints such as prostate cancer mortality, metastasis-free survival, or time to metastasis.

“However, PSA PFS was an appropriate choice within our study setting and time frame because PFS depends on any subsequent PSA relapse management [e.g., reintroduction of intermittent or continuous ADT, administration of new drugs] and regular PSA sampling for landmark analyses would have been more difficult to obtain as main endpoint.”

The study was supported by Sanofi, Ipsen, and the Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie. Four authors reported receiving funding from private industry, including the study sponsors, either during the conduct of the study or outside it.

SOURCE: Oudard S et al. JAMA Oncol. 2019 Jan 31. doi: 10.1001/jamaoncol.2018.6607.

The addition of docetaxel to androgen deprivation therapy in patients with localized, high-risk prostate cancer does not appear to impact progression-free survival rates, a study has found.

In JAMA Oncology, researchers reported the results of an open-label, phase 3, randomized superiority trial comparing androgen deprivation therapy (ADT) plus docetaxel with androgen therapy alone in 254 patients who had received primary local therapy for prostate cancer but showed significant risk factors for metastatic disease.

These risk factors included positive surgical margins, a Gleason score of 8 or above, prostate-specific antigen (PSA) velocity greater than 0.75 ng/mL per year, PSA doubling time of 6 months or less, and time to PSA recurrence of 12 months or less.

Overall, 63.2% of patients in the ADT plus docetaxel group and 64.8% of the ADT-only group experienced PSA progression, defined as a 50% or more relative increase in PSA levels above the nadir. After a median follow-up of 30 months, the median PSA progression-free survival (PFS) was 20.3 months in the combined therapy arm and 19.3 months in the monotherapy arm (hazard ratio, 0.85; P = .31).

“It follows that docetaxel may not be as suitable in a high-risk setting as in a metastatic setting,” wrote Stéphane Oudard, MD, PhD, from the department of medical oncology at Georges Pompidou Hospital in Paris, and his coauthors.

However individuals in the combined therapy arm showed a significantly higher complete PSA response rate, compared with those in the ADT-only group (72.8% vs. 64.8%).

In subgroup analysis, based on the various risk factors for progression to metastatic disease, the combined therapy approach was always better than the monotherapy in PSA PFS, but never achieved statistical significance. The authors noted a 15% improvement in time to PSA progression with combined therapy.

Researchers followed the group for a median of 10.5 years, during which time they saw a similar median time to radiologic progression in both arms (8.9 years for ADT plus docetaxel and 9 years for ADT alone; HR, 1.03; P = 0.88).

There was also no significant difference in all-cause mortality between the two groups.

The authors acknowledged that the clinical relevance of their chosen end point of PSA PFS was likely to be disputed, as some preferred to use endpoints such as prostate cancer mortality, metastasis-free survival, or time to metastasis.

“However, PSA PFS was an appropriate choice within our study setting and time frame because PFS depends on any subsequent PSA relapse management [e.g., reintroduction of intermittent or continuous ADT, administration of new drugs] and regular PSA sampling for landmark analyses would have been more difficult to obtain as main endpoint.”

The study was supported by Sanofi, Ipsen, and the Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie. Four authors reported receiving funding from private industry, including the study sponsors, either during the conduct of the study or outside it.

SOURCE: Oudard S et al. JAMA Oncol. 2019 Jan 31. doi: 10.1001/jamaoncol.2018.6607.

The addition of docetaxel to androgen deprivation therapy in patients with localized, high-risk prostate cancer does not appear to impact progression-free survival rates, a study has found.

In JAMA Oncology, researchers reported the results of an open-label, phase 3, randomized superiority trial comparing androgen deprivation therapy (ADT) plus docetaxel with androgen therapy alone in 254 patients who had received primary local therapy for prostate cancer but showed significant risk factors for metastatic disease.

These risk factors included positive surgical margins, a Gleason score of 8 or above, prostate-specific antigen (PSA) velocity greater than 0.75 ng/mL per year, PSA doubling time of 6 months or less, and time to PSA recurrence of 12 months or less.

Overall, 63.2% of patients in the ADT plus docetaxel group and 64.8% of the ADT-only group experienced PSA progression, defined as a 50% or more relative increase in PSA levels above the nadir. After a median follow-up of 30 months, the median PSA progression-free survival (PFS) was 20.3 months in the combined therapy arm and 19.3 months in the monotherapy arm (hazard ratio, 0.85; P = .31).

“It follows that docetaxel may not be as suitable in a high-risk setting as in a metastatic setting,” wrote Stéphane Oudard, MD, PhD, from the department of medical oncology at Georges Pompidou Hospital in Paris, and his coauthors.

However individuals in the combined therapy arm showed a significantly higher complete PSA response rate, compared with those in the ADT-only group (72.8% vs. 64.8%).

In subgroup analysis, based on the various risk factors for progression to metastatic disease, the combined therapy approach was always better than the monotherapy in PSA PFS, but never achieved statistical significance. The authors noted a 15% improvement in time to PSA progression with combined therapy.

Researchers followed the group for a median of 10.5 years, during which time they saw a similar median time to radiologic progression in both arms (8.9 years for ADT plus docetaxel and 9 years for ADT alone; HR, 1.03; P = 0.88).

There was also no significant difference in all-cause mortality between the two groups.

The authors acknowledged that the clinical relevance of their chosen end point of PSA PFS was likely to be disputed, as some preferred to use endpoints such as prostate cancer mortality, metastasis-free survival, or time to metastasis.

“However, PSA PFS was an appropriate choice within our study setting and time frame because PFS depends on any subsequent PSA relapse management [e.g., reintroduction of intermittent or continuous ADT, administration of new drugs] and regular PSA sampling for landmark analyses would have been more difficult to obtain as main endpoint.”

The study was supported by Sanofi, Ipsen, and the Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie. Four authors reported receiving funding from private industry, including the study sponsors, either during the conduct of the study or outside it.

SOURCE: Oudard S et al. JAMA Oncol. 2019 Jan 31. doi: 10.1001/jamaoncol.2018.6607.

LA JOLLA, CALIF. – Results from the ECHELON-2 trial led to the U.S. approval of brentuximab vedotin (BV) in combination with cyclophosphamide, doxorubicin, and prednisone (CHP), but there are still questions about how to apply the trial results to practice.

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At the annual T-cell Lymphoma Forum, trial investigators and other physicians debated the best use of this combination.

BV-CHP is approved to treat patients with previously untreated systemic anaplastic large-cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS).

Patients who received BV-CHP in ECHELON-2 had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

These results were initially presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in The Lancet (2019 Jan 19;393[10168]:229-40).

ECHELON-2 investigator Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, also presented details on the trial at the T-cell Lymphoma Forum. His presentation was followed by a discussion with meeting attendees about applying the trial results to clinical practice.

CD30 expression

One of the issues discussed was the importance of CD30 expression in deciding which patients should receive BV.

For a patient to be eligible for ECHELON-2, the diagnostic biopsy had to show at least 10% of the neoplastic cells were CD30-positive. However, the Food and Drug Administration (FDA) has not made a similar requirement for prescribing BV. PTCL patients with any level of CD30 expression are eligible for treatment with BV-CHP, according to the FDA.

“[I]t’s still a matter of great debate and controversy as to whether we have good enough data to suggest that there’s a threshold effect with regard to the expression of CD30 and responsiveness or sensitivity to brentuximab vedotin,” Dr. O’Connor said.

“This has been an issue from the very first day with this drug, which is, ‘Just how much CD30 do you need to get a response?’ I can’t speak on behalf of the FDA, but I think they are not absolutely convinced that there’s a threshold. They take [CD30-] positive as ‘good enough’ across the board.”

“The FDA has said, ‘The data we’ve seen says there’s a lot of heterogeneity [with biopsies].’ You may do a biopsy and find 30% [of cells are CD30-positive], and you may do another biopsy [in the same patient] and find less than 10%. I don’t think the regulatory agencies are convinced that a single biopsy looking at CD30 ... is representative of the entire tumor burden.”

Andrei Shustov, MD, an ECHELON-2 investigator from the University of Washington in Seattle, questioned whether CD30 expression should be considered when deciding on the use of BV in PTCL.

“Is CD30 staining relevant at all, or should we default back to studies, say, in colon cancer where we didn’t even care about EGFR because we might be missing it by current techniques?” Dr. Shustov asked. “Should we even worry about CD30 expression ... because we cannot reliably detect low levels of CD30?”

Some attendees echoed this sentiment, questioning the utility of assessing CD30 expression. Other attendees said they would defer to the trial data and only treat patients with BV-CHP if they had at least 10% CD30.

 

 

PTCL subtypes

Meeting attendees also discussed the value of BV in different PTCL subtypes.

At the request of European regulatory agencies, ECHELON-2 was largely focused on patients with sALCL. They made up 70% of the total trial population, while 16% of patients had PTCL-NOS, 12% had AITL, and a small number of patients had other subtypes. These numbers meant ECHELON-2 was not powered to determine differences in OS or PFS in non-sALCL subtypes.

As a result, some attendees expressed concerns about using BV-CHP to treat PTCL-NOS or AITL. They argued that it wasn’t clear whether patients with these subtypes would derive more benefit from BV-CHP, CHOP, or CHOP plus etoposide (CHOEP).

Other attendees said they would feel comfortable using BV-CHP in patients with PTCL-NOS or AITL based on ECHELON-2 results.
 

CHOP vs. CHOEP

The use of CHOP in ECHELON-2 was another point of discussion. Some attendees said CHOEP should have been used as the comparator instead.

A few individuals mentioned retrospective data suggesting CHOEP may confer a benefit over CHOP in PTCL (Blood. 2010 Nov 4;116[18]:3418-25).

Marek Trneny, MD, of Charles University General Hospital in Prague, referenced new data from the Czech National Lymphoma Registry, which showed that patients newly diagnosed with PTCL had superior PFS and OS when they received CHOEP rather than CHOP.

Based on these findings, Dr. Trneny said he would consider treating CD30-positive PTCL patients with CHOEP plus BV rather than BV-CHP.

However, most other attendees said they would not consider adding BV to CHOEP due to the absence of clinical trial data supporting this approach.

Some attendees did say they would use CHOEP instead of BV-CHP, particularly in patients with PTCL-NOS or AITL and in patients with CD30 expression below 10%.

ECHELON-2 was funded by Seattle Genetics and Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.

Dr. O’Connor and Dr. Shustov were investigators on ECHELON-2. Dr. O’Connor is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – Results from the ECHELON-2 trial led to the U.S. approval of brentuximab vedotin (BV) in combination with cyclophosphamide, doxorubicin, and prednisone (CHP), but there are still questions about how to apply the trial results to practice.

Vidyard Video

At the annual T-cell Lymphoma Forum, trial investigators and other physicians debated the best use of this combination.

BV-CHP is approved to treat patients with previously untreated systemic anaplastic large-cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS).

Patients who received BV-CHP in ECHELON-2 had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

These results were initially presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in The Lancet (2019 Jan 19;393[10168]:229-40).

ECHELON-2 investigator Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, also presented details on the trial at the T-cell Lymphoma Forum. His presentation was followed by a discussion with meeting attendees about applying the trial results to clinical practice.

CD30 expression

One of the issues discussed was the importance of CD30 expression in deciding which patients should receive BV.

For a patient to be eligible for ECHELON-2, the diagnostic biopsy had to show at least 10% of the neoplastic cells were CD30-positive. However, the Food and Drug Administration (FDA) has not made a similar requirement for prescribing BV. PTCL patients with any level of CD30 expression are eligible for treatment with BV-CHP, according to the FDA.

“[I]t’s still a matter of great debate and controversy as to whether we have good enough data to suggest that there’s a threshold effect with regard to the expression of CD30 and responsiveness or sensitivity to brentuximab vedotin,” Dr. O’Connor said.

“This has been an issue from the very first day with this drug, which is, ‘Just how much CD30 do you need to get a response?’ I can’t speak on behalf of the FDA, but I think they are not absolutely convinced that there’s a threshold. They take [CD30-] positive as ‘good enough’ across the board.”

“The FDA has said, ‘The data we’ve seen says there’s a lot of heterogeneity [with biopsies].’ You may do a biopsy and find 30% [of cells are CD30-positive], and you may do another biopsy [in the same patient] and find less than 10%. I don’t think the regulatory agencies are convinced that a single biopsy looking at CD30 ... is representative of the entire tumor burden.”

Andrei Shustov, MD, an ECHELON-2 investigator from the University of Washington in Seattle, questioned whether CD30 expression should be considered when deciding on the use of BV in PTCL.

“Is CD30 staining relevant at all, or should we default back to studies, say, in colon cancer where we didn’t even care about EGFR because we might be missing it by current techniques?” Dr. Shustov asked. “Should we even worry about CD30 expression ... because we cannot reliably detect low levels of CD30?”

Some attendees echoed this sentiment, questioning the utility of assessing CD30 expression. Other attendees said they would defer to the trial data and only treat patients with BV-CHP if they had at least 10% CD30.

 

 

PTCL subtypes

Meeting attendees also discussed the value of BV in different PTCL subtypes.

At the request of European regulatory agencies, ECHELON-2 was largely focused on patients with sALCL. They made up 70% of the total trial population, while 16% of patients had PTCL-NOS, 12% had AITL, and a small number of patients had other subtypes. These numbers meant ECHELON-2 was not powered to determine differences in OS or PFS in non-sALCL subtypes.

As a result, some attendees expressed concerns about using BV-CHP to treat PTCL-NOS or AITL. They argued that it wasn’t clear whether patients with these subtypes would derive more benefit from BV-CHP, CHOP, or CHOP plus etoposide (CHOEP).

Other attendees said they would feel comfortable using BV-CHP in patients with PTCL-NOS or AITL based on ECHELON-2 results.
 

CHOP vs. CHOEP

The use of CHOP in ECHELON-2 was another point of discussion. Some attendees said CHOEP should have been used as the comparator instead.

A few individuals mentioned retrospective data suggesting CHOEP may confer a benefit over CHOP in PTCL (Blood. 2010 Nov 4;116[18]:3418-25).

Marek Trneny, MD, of Charles University General Hospital in Prague, referenced new data from the Czech National Lymphoma Registry, which showed that patients newly diagnosed with PTCL had superior PFS and OS when they received CHOEP rather than CHOP.

Based on these findings, Dr. Trneny said he would consider treating CD30-positive PTCL patients with CHOEP plus BV rather than BV-CHP.

However, most other attendees said they would not consider adding BV to CHOEP due to the absence of clinical trial data supporting this approach.

Some attendees did say they would use CHOEP instead of BV-CHP, particularly in patients with PTCL-NOS or AITL and in patients with CD30 expression below 10%.

ECHELON-2 was funded by Seattle Genetics and Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.

Dr. O’Connor and Dr. Shustov were investigators on ECHELON-2. Dr. O’Connor is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – Results from the ECHELON-2 trial led to the U.S. approval of brentuximab vedotin (BV) in combination with cyclophosphamide, doxorubicin, and prednisone (CHP), but there are still questions about how to apply the trial results to practice.

Vidyard Video

At the annual T-cell Lymphoma Forum, trial investigators and other physicians debated the best use of this combination.

BV-CHP is approved to treat patients with previously untreated systemic anaplastic large-cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS).

Patients who received BV-CHP in ECHELON-2 had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

These results were initially presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in The Lancet (2019 Jan 19;393[10168]:229-40).

ECHELON-2 investigator Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, also presented details on the trial at the T-cell Lymphoma Forum. His presentation was followed by a discussion with meeting attendees about applying the trial results to clinical practice.

CD30 expression

One of the issues discussed was the importance of CD30 expression in deciding which patients should receive BV.

For a patient to be eligible for ECHELON-2, the diagnostic biopsy had to show at least 10% of the neoplastic cells were CD30-positive. However, the Food and Drug Administration (FDA) has not made a similar requirement for prescribing BV. PTCL patients with any level of CD30 expression are eligible for treatment with BV-CHP, according to the FDA.

“[I]t’s still a matter of great debate and controversy as to whether we have good enough data to suggest that there’s a threshold effect with regard to the expression of CD30 and responsiveness or sensitivity to brentuximab vedotin,” Dr. O’Connor said.

“This has been an issue from the very first day with this drug, which is, ‘Just how much CD30 do you need to get a response?’ I can’t speak on behalf of the FDA, but I think they are not absolutely convinced that there’s a threshold. They take [CD30-] positive as ‘good enough’ across the board.”

“The FDA has said, ‘The data we’ve seen says there’s a lot of heterogeneity [with biopsies].’ You may do a biopsy and find 30% [of cells are CD30-positive], and you may do another biopsy [in the same patient] and find less than 10%. I don’t think the regulatory agencies are convinced that a single biopsy looking at CD30 ... is representative of the entire tumor burden.”

Andrei Shustov, MD, an ECHELON-2 investigator from the University of Washington in Seattle, questioned whether CD30 expression should be considered when deciding on the use of BV in PTCL.

“Is CD30 staining relevant at all, or should we default back to studies, say, in colon cancer where we didn’t even care about EGFR because we might be missing it by current techniques?” Dr. Shustov asked. “Should we even worry about CD30 expression ... because we cannot reliably detect low levels of CD30?”

Some attendees echoed this sentiment, questioning the utility of assessing CD30 expression. Other attendees said they would defer to the trial data and only treat patients with BV-CHP if they had at least 10% CD30.

 

 

PTCL subtypes

Meeting attendees also discussed the value of BV in different PTCL subtypes.

At the request of European regulatory agencies, ECHELON-2 was largely focused on patients with sALCL. They made up 70% of the total trial population, while 16% of patients had PTCL-NOS, 12% had AITL, and a small number of patients had other subtypes. These numbers meant ECHELON-2 was not powered to determine differences in OS or PFS in non-sALCL subtypes.

As a result, some attendees expressed concerns about using BV-CHP to treat PTCL-NOS or AITL. They argued that it wasn’t clear whether patients with these subtypes would derive more benefit from BV-CHP, CHOP, or CHOP plus etoposide (CHOEP).

Other attendees said they would feel comfortable using BV-CHP in patients with PTCL-NOS or AITL based on ECHELON-2 results.
 

CHOP vs. CHOEP

The use of CHOP in ECHELON-2 was another point of discussion. Some attendees said CHOEP should have been used as the comparator instead.

A few individuals mentioned retrospective data suggesting CHOEP may confer a benefit over CHOP in PTCL (Blood. 2010 Nov 4;116[18]:3418-25).

Marek Trneny, MD, of Charles University General Hospital in Prague, referenced new data from the Czech National Lymphoma Registry, which showed that patients newly diagnosed with PTCL had superior PFS and OS when they received CHOEP rather than CHOP.

Based on these findings, Dr. Trneny said he would consider treating CD30-positive PTCL patients with CHOEP plus BV rather than BV-CHP.

However, most other attendees said they would not consider adding BV to CHOEP due to the absence of clinical trial data supporting this approach.

Some attendees did say they would use CHOEP instead of BV-CHP, particularly in patients with PTCL-NOS or AITL and in patients with CD30 expression below 10%.

ECHELON-2 was funded by Seattle Genetics and Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.

Dr. O’Connor and Dr. Shustov were investigators on ECHELON-2. Dr. O’Connor is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]