REVIEW

FEMCERV^®: Well-designed technology that can minimize patient discomfort

The FemCerv^® Endocervical Sampler, developed by Femasys, Inc (Suwanee, Georgia) expands options for colposcopy biopsy.


Background. In the United States, approximately 3 million women per year undergo colposcopic evaluation to work-up abnormal screening cytology. While some controversy exists regarding the exact role of endocervical curettage (ECC) within each age group and clinical situation, it is nonetheless an important component of the colposcopy-biopsy examination in many cases. For over a century, the 3 mm metal endocervical curette has been the primary tool employed to obtain the tissue sample from the endocervical canal. Unfortunately, sharp curettage with a metal curette can have inadequate sampling rates as high as 14%,¹ it runs the risk of ectocervical contamination, and it is painful, with almost half the participants in one study rating the procedural pain 3 ̶ 5 out of 8 on a VAS scale.² So, maybe there is a better way.


Design/Functionality. According to Femasys, the FemCerv^® Endocervical Sampler was designed to be the better way of performing an endocervical curettage. FemCerv is a single-use sterile device that comes in a standard 13 F size as well as an 11 F size for the narrower/stenotic os. In truth, at first glance it looks pretty complicated compared with a Kevorkian curette or an endocervical brush. The user end has a handle with a rotatable knob that transitions to a shaft with a flange at the end right before the sampling mechanism. To use the device, the sampling end is inserted into the endocervical canal up to the flange. The knob on the handle is then turned clockwise to open the sheath, thereby exposing sharp rigid plastic edges. The device is then rotated 360° clockwise and then 360° counterclockwise to “curette” the endocervical canal. Finally, the knob on the handle is turned counterclockwise to close the sheath and the device is removed. The specimen is then transferred to a standard vial for processing.

In my experience with its use, it actually exceeded my expectations. The device was easy to use, and the specimens were more than adequate. Truth be told, I came into the trial with a negative mindset having already convinced myself that this device was a waste of money given that doing an ECC with traditional methods is so straightforward. What I had not anticipated was the complete lack of patient discomfort when I used the FemCerv compared with a Kevorkian device.

Innovation. From an innovation standpoint, FemCerv is not super-disruptive technology, but it is well designed and pretty clever in that the opening and closing sheath prevents ectocervical cellular contamination, and the rotational sampling, rather than in-and-out sampling, does dramatically reduce the patient discomfort.


Summary. As I previously noted, before trying it, I did not anticipate liking FemCerv as much as I did. Does it add some non-reimbursable cost to a relatively low-reimbursing procedure? Absolutely. But it is not too expensive and, for me, making a painful procedure relatively painless is good value every time. I think all our patients would agree.

For more information, visit https://femasys.com/.

UPDATE

Hologic, Inc. announces that they received the following 2022 IMV ServiceTrak^TM Awards for Mammography: Best Service, Best Customer Satisfaction, and Best System Performance. In addition, Hologic announces that their Affirm Contrast Biopsy software is commercially available in the United States. Tissue samples may be targeted and acquired using the Affirm Contrast Biopsy software from lesions identified using Hologic’s I-View Contrast Enhanced Mammography software. The latter software allows health care facilities an alternative to breast magnetic resonance imaging, which is used as supplemental imaging to mammography and/or ultrasonography.

For more information, visit https://www.hologic.com/

REVIEW

FEMCERV^®: Well-designed technology that can minimize patient discomfort

The FemCerv^® Endocervical Sampler, developed by Femasys, Inc (Suwanee, Georgia) expands options for colposcopy biopsy.


Background. In the United States, approximately 3 million women per year undergo colposcopic evaluation to work-up abnormal screening cytology. While some controversy exists regarding the exact role of endocervical curettage (ECC) within each age group and clinical situation, it is nonetheless an important component of the colposcopy-biopsy examination in many cases. For over a century, the 3 mm metal endocervical curette has been the primary tool employed to obtain the tissue sample from the endocervical canal. Unfortunately, sharp curettage with a metal curette can have inadequate sampling rates as high as 14%,¹ it runs the risk of ectocervical contamination, and it is painful, with almost half the participants in one study rating the procedural pain 3 ̶ 5 out of 8 on a VAS scale.² So, maybe there is a better way.


Design/Functionality. According to Femasys, the FemCerv^® Endocervical Sampler was designed to be the better way of performing an endocervical curettage. FemCerv is a single-use sterile device that comes in a standard 13 F size as well as an 11 F size for the narrower/stenotic os. In truth, at first glance it looks pretty complicated compared with a Kevorkian curette or an endocervical brush. The user end has a handle with a rotatable knob that transitions to a shaft with a flange at the end right before the sampling mechanism. To use the device, the sampling end is inserted into the endocervical canal up to the flange. The knob on the handle is then turned clockwise to open the sheath, thereby exposing sharp rigid plastic edges. The device is then rotated 360° clockwise and then 360° counterclockwise to “curette” the endocervical canal. Finally, the knob on the handle is turned counterclockwise to close the sheath and the device is removed. The specimen is then transferred to a standard vial for processing.

In my experience with its use, it actually exceeded my expectations. The device was easy to use, and the specimens were more than adequate. Truth be told, I came into the trial with a negative mindset having already convinced myself that this device was a waste of money given that doing an ECC with traditional methods is so straightforward. What I had not anticipated was the complete lack of patient discomfort when I used the FemCerv compared with a Kevorkian device.

Innovation. From an innovation standpoint, FemCerv is not super-disruptive technology, but it is well designed and pretty clever in that the opening and closing sheath prevents ectocervical cellular contamination, and the rotational sampling, rather than in-and-out sampling, does dramatically reduce the patient discomfort.


Summary. As I previously noted, before trying it, I did not anticipate liking FemCerv as much as I did. Does it add some non-reimbursable cost to a relatively low-reimbursing procedure? Absolutely. But it is not too expensive and, for me, making a painful procedure relatively painless is good value every time. I think all our patients would agree.

For more information, visit https://femasys.com/.

UPDATE

Hologic, Inc. announces that they received the following 2022 IMV ServiceTrak^TM Awards for Mammography: Best Service, Best Customer Satisfaction, and Best System Performance. In addition, Hologic announces that their Affirm Contrast Biopsy software is commercially available in the United States. Tissue samples may be targeted and acquired using the Affirm Contrast Biopsy software from lesions identified using Hologic’s I-View Contrast Enhanced Mammography software. The latter software allows health care facilities an alternative to breast magnetic resonance imaging, which is used as supplemental imaging to mammography and/or ultrasonography.

For more information, visit https://www.hologic.com/

REVIEW

FEMCERV^®: Well-designed technology that can minimize patient discomfort

The FemCerv^® Endocervical Sampler, developed by Femasys, Inc (Suwanee, Georgia) expands options for colposcopy biopsy.


Background. In the United States, approximately 3 million women per year undergo colposcopic evaluation to work-up abnormal screening cytology. While some controversy exists regarding the exact role of endocervical curettage (ECC) within each age group and clinical situation, it is nonetheless an important component of the colposcopy-biopsy examination in many cases. For over a century, the 3 mm metal endocervical curette has been the primary tool employed to obtain the tissue sample from the endocervical canal. Unfortunately, sharp curettage with a metal curette can have inadequate sampling rates as high as 14%,¹ it runs the risk of ectocervical contamination, and it is painful, with almost half the participants in one study rating the procedural pain 3 ̶ 5 out of 8 on a VAS scale.² So, maybe there is a better way.


Design/Functionality. According to Femasys, the FemCerv^® Endocervical Sampler was designed to be the better way of performing an endocervical curettage. FemCerv is a single-use sterile device that comes in a standard 13 F size as well as an 11 F size for the narrower/stenotic os. In truth, at first glance it looks pretty complicated compared with a Kevorkian curette or an endocervical brush. The user end has a handle with a rotatable knob that transitions to a shaft with a flange at the end right before the sampling mechanism. To use the device, the sampling end is inserted into the endocervical canal up to the flange. The knob on the handle is then turned clockwise to open the sheath, thereby exposing sharp rigid plastic edges. The device is then rotated 360° clockwise and then 360° counterclockwise to “curette” the endocervical canal. Finally, the knob on the handle is turned counterclockwise to close the sheath and the device is removed. The specimen is then transferred to a standard vial for processing.

In my experience with its use, it actually exceeded my expectations. The device was easy to use, and the specimens were more than adequate. Truth be told, I came into the trial with a negative mindset having already convinced myself that this device was a waste of money given that doing an ECC with traditional methods is so straightforward. What I had not anticipated was the complete lack of patient discomfort when I used the FemCerv compared with a Kevorkian device.

Innovation. From an innovation standpoint, FemCerv is not super-disruptive technology, but it is well designed and pretty clever in that the opening and closing sheath prevents ectocervical cellular contamination, and the rotational sampling, rather than in-and-out sampling, does dramatically reduce the patient discomfort.


Summary. As I previously noted, before trying it, I did not anticipate liking FemCerv as much as I did. Does it add some non-reimbursable cost to a relatively low-reimbursing procedure? Absolutely. But it is not too expensive and, for me, making a painful procedure relatively painless is good value every time. I think all our patients would agree.

For more information, visit https://femasys.com/.

UPDATE

Hologic, Inc. announces that they received the following 2022 IMV ServiceTrak^TM Awards for Mammography: Best Service, Best Customer Satisfaction, and Best System Performance. In addition, Hologic announces that their Affirm Contrast Biopsy software is commercially available in the United States. Tissue samples may be targeted and acquired using the Affirm Contrast Biopsy software from lesions identified using Hologic’s I-View Contrast Enhanced Mammography software. The latter software allows health care facilities an alternative to breast magnetic resonance imaging, which is used as supplemental imaging to mammography and/or ultrasonography.

For more information, visit https://www.hologic.com/

In June 2022, the US Supreme Court’s decision in Dobbs v Jackson Women’s Health Organization removed federal protections for abortion that previously had been codified in Roe v Wade. Since this removal, most abortions have been banned in at least 13 states, and about half of states are expected to attempt to ban or heavily restrict abortion.^1,2 These laws banning abortion are having effects on patient care far beyond abortion, leading to uncertainty and fear among providers and denied or delayed care for patients.^3,4 It is critical that research documents the harmful effects of this policy change.

Patients that are pregnant with fetuses with severe malformations have had to travel long distances to other states to obtain care.⁵ Others have faced delays in obtaining treatment for ectopic pregnancy, miscarriage, and even for other conditions that use medications that could potentially cause an abortion.^6,7 These cases have the potential to result in serious harm or death of the patient with altered care. There is a published report from Texas showing how the change in practice due to the 6-week abortion ban imposed in 2021 was associated with a doubling of severe morbidity for patients presenting with preterm premature rupture of membranes and other complications before 22 weeks’ gestation.⁸

While these cases have been highlighted in the media, there has not been a resource that comprehensively documents the changes in care that clinicians have been forced to make because of abortion bans as well as the consequences for their patients’ health. The media also may not be the most desirable platform for sharing cases of substandard care if providers feel their confidentiality may be breached as they are told by their employers to avoid speaking with reporters.⁹ Bearing this in mind, our team of researchers at Advancing New Standards in Reproductive Health at the University of California San Francisco and the Texas Policy Evaluation Project at the University of Texas at Austin has launched a project aiming to collect stories of poor quality care post-Roe from health care professionals across the United States. The aim of the study is to document examples of the challenges in patient care that have arisen since the Dobbs decision.

The study website CarePostRoe.com was launched in October 2022 to collect narratives from health care providers who participated in the care of a patient whose management was different from the usual standard due to a need to comply with new restrictions on abortion since the Dobbs decision. These providers can include physicians, nurses, nurse practitioners, midwives, physician assistants, social workers, pharmacists, psychologists, or other allied health professionals. Clinicians can share information about a case through a brief survey linked on the website that will allow them to either submit a written narrative or a voice memo. The submissions are anonymous, and providers are not asked to submit any protected health information. If the submitter would like to share more information about the case via telephone interview, they will be taken to a separate survey which is not linked to the narrative submission to give contact information to participate in an interview.

Since October, more than 40 cases have been submitted that document patient cases from over half of the states with abortion bans. Clinicians describe pregnant patients with severe fetal malformations who have had to overcome financial and logistical barriers to travel to access abortion care. Several cases of patients with cesarean scar ectopic pregnancies have been submitted, including cases that are being followed expectantly, which is inconsistent with the standard of care.¹⁰ We also have received several submissions about cases of preterm premature rupture of membranes in the second trimester where the patient was sent home and presented several days later with a severe infection requiring management in the intensive care unit. Cases of early pregnancy loss that could have been treated safely and routinely also were delayed, increasing the risk to patients who, in addition to receiving substandard medical care, had the trauma of fearing they could be prosecuted for receiving treatment.

We hope these data will be useful to document the impact of the Court’s decision and to improve patient care as health care institutions work to update their policies and protocols to reduce delays in care in the face of legal ambiguities. If you have been involved in such a case since June 2022, including caring for a patient who traveled from another state, please consider submitting it at CarePostRoe.com, and please spread the word through your networks. ●

In June 2022, the US Supreme Court’s decision in Dobbs v Jackson Women’s Health Organization removed federal protections for abortion that previously had been codified in Roe v Wade. Since this removal, most abortions have been banned in at least 13 states, and about half of states are expected to attempt to ban or heavily restrict abortion.^1,2 These laws banning abortion are having effects on patient care far beyond abortion, leading to uncertainty and fear among providers and denied or delayed care for patients.^3,4 It is critical that research documents the harmful effects of this policy change.

Patients that are pregnant with fetuses with severe malformations have had to travel long distances to other states to obtain care.⁵ Others have faced delays in obtaining treatment for ectopic pregnancy, miscarriage, and even for other conditions that use medications that could potentially cause an abortion.^6,7 These cases have the potential to result in serious harm or death of the patient with altered care. There is a published report from Texas showing how the change in practice due to the 6-week abortion ban imposed in 2021 was associated with a doubling of severe morbidity for patients presenting with preterm premature rupture of membranes and other complications before 22 weeks’ gestation.⁸

While these cases have been highlighted in the media, there has not been a resource that comprehensively documents the changes in care that clinicians have been forced to make because of abortion bans as well as the consequences for their patients’ health. The media also may not be the most desirable platform for sharing cases of substandard care if providers feel their confidentiality may be breached as they are told by their employers to avoid speaking with reporters.⁹ Bearing this in mind, our team of researchers at Advancing New Standards in Reproductive Health at the University of California San Francisco and the Texas Policy Evaluation Project at the University of Texas at Austin has launched a project aiming to collect stories of poor quality care post-Roe from health care professionals across the United States. The aim of the study is to document examples of the challenges in patient care that have arisen since the Dobbs decision.

The study website CarePostRoe.com was launched in October 2022 to collect narratives from health care providers who participated in the care of a patient whose management was different from the usual standard due to a need to comply with new restrictions on abortion since the Dobbs decision. These providers can include physicians, nurses, nurse practitioners, midwives, physician assistants, social workers, pharmacists, psychologists, or other allied health professionals. Clinicians can share information about a case through a brief survey linked on the website that will allow them to either submit a written narrative or a voice memo. The submissions are anonymous, and providers are not asked to submit any protected health information. If the submitter would like to share more information about the case via telephone interview, they will be taken to a separate survey which is not linked to the narrative submission to give contact information to participate in an interview.

Since October, more than 40 cases have been submitted that document patient cases from over half of the states with abortion bans. Clinicians describe pregnant patients with severe fetal malformations who have had to overcome financial and logistical barriers to travel to access abortion care. Several cases of patients with cesarean scar ectopic pregnancies have been submitted, including cases that are being followed expectantly, which is inconsistent with the standard of care.¹⁰ We also have received several submissions about cases of preterm premature rupture of membranes in the second trimester where the patient was sent home and presented several days later with a severe infection requiring management in the intensive care unit. Cases of early pregnancy loss that could have been treated safely and routinely also were delayed, increasing the risk to patients who, in addition to receiving substandard medical care, had the trauma of fearing they could be prosecuted for receiving treatment.

We hope these data will be useful to document the impact of the Court’s decision and to improve patient care as health care institutions work to update their policies and protocols to reduce delays in care in the face of legal ambiguities. If you have been involved in such a case since June 2022, including caring for a patient who traveled from another state, please consider submitting it at CarePostRoe.com, and please spread the word through your networks. ●

In June 2022, the US Supreme Court’s decision in Dobbs v Jackson Women’s Health Organization removed federal protections for abortion that previously had been codified in Roe v Wade. Since this removal, most abortions have been banned in at least 13 states, and about half of states are expected to attempt to ban or heavily restrict abortion.^1,2 These laws banning abortion are having effects on patient care far beyond abortion, leading to uncertainty and fear among providers and denied or delayed care for patients.^3,4 It is critical that research documents the harmful effects of this policy change.

Patients that are pregnant with fetuses with severe malformations have had to travel long distances to other states to obtain care.⁵ Others have faced delays in obtaining treatment for ectopic pregnancy, miscarriage, and even for other conditions that use medications that could potentially cause an abortion.^6,7 These cases have the potential to result in serious harm or death of the patient with altered care. There is a published report from Texas showing how the change in practice due to the 6-week abortion ban imposed in 2021 was associated with a doubling of severe morbidity for patients presenting with preterm premature rupture of membranes and other complications before 22 weeks’ gestation.⁸

While these cases have been highlighted in the media, there has not been a resource that comprehensively documents the changes in care that clinicians have been forced to make because of abortion bans as well as the consequences for their patients’ health. The media also may not be the most desirable platform for sharing cases of substandard care if providers feel their confidentiality may be breached as they are told by their employers to avoid speaking with reporters.⁹ Bearing this in mind, our team of researchers at Advancing New Standards in Reproductive Health at the University of California San Francisco and the Texas Policy Evaluation Project at the University of Texas at Austin has launched a project aiming to collect stories of poor quality care post-Roe from health care professionals across the United States. The aim of the study is to document examples of the challenges in patient care that have arisen since the Dobbs decision.

The study website CarePostRoe.com was launched in October 2022 to collect narratives from health care providers who participated in the care of a patient whose management was different from the usual standard due to a need to comply with new restrictions on abortion since the Dobbs decision. These providers can include physicians, nurses, nurse practitioners, midwives, physician assistants, social workers, pharmacists, psychologists, or other allied health professionals. Clinicians can share information about a case through a brief survey linked on the website that will allow them to either submit a written narrative or a voice memo. The submissions are anonymous, and providers are not asked to submit any protected health information. If the submitter would like to share more information about the case via telephone interview, they will be taken to a separate survey which is not linked to the narrative submission to give contact information to participate in an interview.

Since October, more than 40 cases have been submitted that document patient cases from over half of the states with abortion bans. Clinicians describe pregnant patients with severe fetal malformations who have had to overcome financial and logistical barriers to travel to access abortion care. Several cases of patients with cesarean scar ectopic pregnancies have been submitted, including cases that are being followed expectantly, which is inconsistent with the standard of care.¹⁰ We also have received several submissions about cases of preterm premature rupture of membranes in the second trimester where the patient was sent home and presented several days later with a severe infection requiring management in the intensive care unit. Cases of early pregnancy loss that could have been treated safely and routinely also were delayed, increasing the risk to patients who, in addition to receiving substandard medical care, had the trauma of fearing they could be prosecuted for receiving treatment.

We hope these data will be useful to document the impact of the Court’s decision and to improve patient care as health care institutions work to update their policies and protocols to reduce delays in care in the face of legal ambiguities. If you have been involved in such a case since June 2022, including caring for a patient who traveled from another state, please consider submitting it at CarePostRoe.com, and please spread the word through your networks. ●

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Scientists have identified two new genes linked to schizophrenia and discovered that a third gene previously known to be involved in the disorder may also play a role in autism.

The genes were identified through a meta-analysis comparing gene sequences of 35,828 people with schizophrenia to 107,877 people without the condition.

The study builds on a report published last year that identified 10 genes with rare variants that are directly tied to schizophrenia risk. But that study, like most prior genetic analyses on psychiatric illnesses, was done on the DNA from people of European ancestry.

About 40% of the genetic samples included in this new work came from people of non-European ancestry, which researchers say makes it the most ethnically diverse schizophrenia genetics study to date.

Based on the findings, researchers concluded that the schizophrenia risk conferred by the rare genetic variants found on the new genes they discovered and on those previously identified is conserved across ethnicities.

The new genes, SRRM2 and AKAP11, contain rare protein-truncating variants (PTVs) that investigators say could be the cause of schizophrenia in some patients. The results could have significant implications for drug development.

Icahn School of Medicine at Mount Sinai

“It’s not curing the illness, but it is taking us a step closer so that we’re able to say that this may be the cause of the illness in a particular patient,” senior investigator Alexander Charney, MD, PhD, associate professor of psychiatry, genetics and genomic sciences, neuroscience, and neurosurgery, at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The findings were published online in Nature Genetics.

 

Schizophrenia’s genetic architecture

Prior studies suggest the genetic architecture of schizophrenia may be influenced by common single-nucleotide polymorphisms, copy number variants and rare PTVs.

Investigators note that rare PTVs are important because they can link disease risk directly to individual genes. But identifying the PTVs and the genes that harbor them requires large patient cohorts, far bigger than any single institution can provide.

Dr. Charney and other researchers are part of the Psychiatric Genomics Consortium, a collaboration of researchers from hundreds of institutions around the world established in 2007 to create large cohorts for genetic studies of psychiatric disease.

For this study, investigators sequenced a new cohort of 11,580 schizophrenia cases and 10,555 controls of diverse ancestries. The analysis showed that the findings previously established in predominantly European cohorts extended to non-European populations.

They then conducted a meta-analysis of the new cohort combined with datasets from earlier studies, creating a pooled sample of 35,828 cases and 107,877 controls.

This meta-analysis revealed two new genes linked to schizophrenia, SRRM2 and AKAP11. The third gene flagged in the study, PCLO, was previously implicated in schizophrenia but is now identified as having a shared risk for schizophrenia and autism.

The rare PVTs on the 12 genes identified so far through this type of study are probably only involved in a small fraction of schizophrenia cases, Dr. Charney acknowledged. However, the discovery could lead to new treatments that could benefit all patients with the disease, he added.

“There are multiple pathways to psychosis and there’s also multiple pathways to treat psychosis,” Dr. Charney said. “There’s reason to believe if you can find a mechanism by which a human being could develop a psychosis, then reversing that mechanism could help a lot of people who have psychosis for another reason.”
 

Importance of diverse cohorts

Commenting on the findings, Jennifer Gladys Mulle, MHS, PhD, associate professor of psychiatry at the Robert Wood Johnson Medical School at Rutgers University, Piscataway, N.J., noted that while genetic discoveries have led to new therapies in other medical conditions, that has not been the case with schizophrenia.

“In other disorders, having genetic findings have really opened a window into the molecular mechanisms, which has allowed us to develop pharmaceuticals and understand the disease process better,” said Dr. Mulle, who was not part of this study. “But because we haven’t had that in schizophrenia, it’s really held us back. Having genetic variants associated with schizophrenia may really help us understand the mechanism.”

The inclusion of diverse populations is also a key contribution of this study, Dr. Mulle added.

“So far a lot of the work we’ve done in genetics has been on people of European ancestry,” Dr. Mulle said. “The fact that they have found results that are generalizable across multiple ethnicities really suggests that if we develop pharmaceutical agents based on these findings, it will help many people.”

More attention has been paid recently to a growing problem in the study of genetics of psychiatric disorders: More than 95% of participants in genome-wide association studies that seek to identify gene variants linked to disease are of European ancestry.

Dr. Charney and his colleagues had that in mind when they designed the study.

“We can’t get to a place where genetics is clinically useful if we don’t know the extent to which a particular observation that’s found in one population is also true for other populations,” Dr. Charney said.

The study was funded by the National Institutes of Health. Dr. Charney and Dr. Mulle report no relevant financial relationships.

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

Scientists have identified two new genes linked to schizophrenia and discovered that a third gene previously known to be involved in the disorder may also play a role in autism.

The genes were identified through a meta-analysis comparing gene sequences of 35,828 people with schizophrenia to 107,877 people without the condition.

The study builds on a report published last year that identified 10 genes with rare variants that are directly tied to schizophrenia risk. But that study, like most prior genetic analyses on psychiatric illnesses, was done on the DNA from people of European ancestry.

About 40% of the genetic samples included in this new work came from people of non-European ancestry, which researchers say makes it the most ethnically diverse schizophrenia genetics study to date.

Based on the findings, researchers concluded that the schizophrenia risk conferred by the rare genetic variants found on the new genes they discovered and on those previously identified is conserved across ethnicities.

The new genes, SRRM2 and AKAP11, contain rare protein-truncating variants (PTVs) that investigators say could be the cause of schizophrenia in some patients. The results could have significant implications for drug development.

Icahn School of Medicine at Mount Sinai

“It’s not curing the illness, but it is taking us a step closer so that we’re able to say that this may be the cause of the illness in a particular patient,” senior investigator Alexander Charney, MD, PhD, associate professor of psychiatry, genetics and genomic sciences, neuroscience, and neurosurgery, at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The findings were published online in Nature Genetics.

 

Schizophrenia’s genetic architecture

Prior studies suggest the genetic architecture of schizophrenia may be influenced by common single-nucleotide polymorphisms, copy number variants and rare PTVs.

Investigators note that rare PTVs are important because they can link disease risk directly to individual genes. But identifying the PTVs and the genes that harbor them requires large patient cohorts, far bigger than any single institution can provide.

Dr. Charney and other researchers are part of the Psychiatric Genomics Consortium, a collaboration of researchers from hundreds of institutions around the world established in 2007 to create large cohorts for genetic studies of psychiatric disease.

For this study, investigators sequenced a new cohort of 11,580 schizophrenia cases and 10,555 controls of diverse ancestries. The analysis showed that the findings previously established in predominantly European cohorts extended to non-European populations.

They then conducted a meta-analysis of the new cohort combined with datasets from earlier studies, creating a pooled sample of 35,828 cases and 107,877 controls.

This meta-analysis revealed two new genes linked to schizophrenia, SRRM2 and AKAP11. The third gene flagged in the study, PCLO, was previously implicated in schizophrenia but is now identified as having a shared risk for schizophrenia and autism.

The rare PVTs on the 12 genes identified so far through this type of study are probably only involved in a small fraction of schizophrenia cases, Dr. Charney acknowledged. However, the discovery could lead to new treatments that could benefit all patients with the disease, he added.

“There are multiple pathways to psychosis and there’s also multiple pathways to treat psychosis,” Dr. Charney said. “There’s reason to believe if you can find a mechanism by which a human being could develop a psychosis, then reversing that mechanism could help a lot of people who have psychosis for another reason.”
 

Importance of diverse cohorts

Commenting on the findings, Jennifer Gladys Mulle, MHS, PhD, associate professor of psychiatry at the Robert Wood Johnson Medical School at Rutgers University, Piscataway, N.J., noted that while genetic discoveries have led to new therapies in other medical conditions, that has not been the case with schizophrenia.

“In other disorders, having genetic findings have really opened a window into the molecular mechanisms, which has allowed us to develop pharmaceuticals and understand the disease process better,” said Dr. Mulle, who was not part of this study. “But because we haven’t had that in schizophrenia, it’s really held us back. Having genetic variants associated with schizophrenia may really help us understand the mechanism.”

The inclusion of diverse populations is also a key contribution of this study, Dr. Mulle added.

“So far a lot of the work we’ve done in genetics has been on people of European ancestry,” Dr. Mulle said. “The fact that they have found results that are generalizable across multiple ethnicities really suggests that if we develop pharmaceutical agents based on these findings, it will help many people.”

More attention has been paid recently to a growing problem in the study of genetics of psychiatric disorders: More than 95% of participants in genome-wide association studies that seek to identify gene variants linked to disease are of European ancestry.

Dr. Charney and his colleagues had that in mind when they designed the study.

“We can’t get to a place where genetics is clinically useful if we don’t know the extent to which a particular observation that’s found in one population is also true for other populations,” Dr. Charney said.

The study was funded by the National Institutes of Health. Dr. Charney and Dr. Mulle report no relevant financial relationships.

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

Scientists have identified two new genes linked to schizophrenia and discovered that a third gene previously known to be involved in the disorder may also play a role in autism.

The genes were identified through a meta-analysis comparing gene sequences of 35,828 people with schizophrenia to 107,877 people without the condition.

The study builds on a report published last year that identified 10 genes with rare variants that are directly tied to schizophrenia risk. But that study, like most prior genetic analyses on psychiatric illnesses, was done on the DNA from people of European ancestry.

About 40% of the genetic samples included in this new work came from people of non-European ancestry, which researchers say makes it the most ethnically diverse schizophrenia genetics study to date.

Based on the findings, researchers concluded that the schizophrenia risk conferred by the rare genetic variants found on the new genes they discovered and on those previously identified is conserved across ethnicities.

The new genes, SRRM2 and AKAP11, contain rare protein-truncating variants (PTVs) that investigators say could be the cause of schizophrenia in some patients. The results could have significant implications for drug development.

Icahn School of Medicine at Mount Sinai

“It’s not curing the illness, but it is taking us a step closer so that we’re able to say that this may be the cause of the illness in a particular patient,” senior investigator Alexander Charney, MD, PhD, associate professor of psychiatry, genetics and genomic sciences, neuroscience, and neurosurgery, at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

The findings were published online in Nature Genetics.

 

Schizophrenia’s genetic architecture

Prior studies suggest the genetic architecture of schizophrenia may be influenced by common single-nucleotide polymorphisms, copy number variants and rare PTVs.

Investigators note that rare PTVs are important because they can link disease risk directly to individual genes. But identifying the PTVs and the genes that harbor them requires large patient cohorts, far bigger than any single institution can provide.

Dr. Charney and other researchers are part of the Psychiatric Genomics Consortium, a collaboration of researchers from hundreds of institutions around the world established in 2007 to create large cohorts for genetic studies of psychiatric disease.

For this study, investigators sequenced a new cohort of 11,580 schizophrenia cases and 10,555 controls of diverse ancestries. The analysis showed that the findings previously established in predominantly European cohorts extended to non-European populations.

They then conducted a meta-analysis of the new cohort combined with datasets from earlier studies, creating a pooled sample of 35,828 cases and 107,877 controls.

This meta-analysis revealed two new genes linked to schizophrenia, SRRM2 and AKAP11. The third gene flagged in the study, PCLO, was previously implicated in schizophrenia but is now identified as having a shared risk for schizophrenia and autism.

The rare PVTs on the 12 genes identified so far through this type of study are probably only involved in a small fraction of schizophrenia cases, Dr. Charney acknowledged. However, the discovery could lead to new treatments that could benefit all patients with the disease, he added.

“There are multiple pathways to psychosis and there’s also multiple pathways to treat psychosis,” Dr. Charney said. “There’s reason to believe if you can find a mechanism by which a human being could develop a psychosis, then reversing that mechanism could help a lot of people who have psychosis for another reason.”
 

Importance of diverse cohorts

Commenting on the findings, Jennifer Gladys Mulle, MHS, PhD, associate professor of psychiatry at the Robert Wood Johnson Medical School at Rutgers University, Piscataway, N.J., noted that while genetic discoveries have led to new therapies in other medical conditions, that has not been the case with schizophrenia.

“In other disorders, having genetic findings have really opened a window into the molecular mechanisms, which has allowed us to develop pharmaceuticals and understand the disease process better,” said Dr. Mulle, who was not part of this study. “But because we haven’t had that in schizophrenia, it’s really held us back. Having genetic variants associated with schizophrenia may really help us understand the mechanism.”

The inclusion of diverse populations is also a key contribution of this study, Dr. Mulle added.

“So far a lot of the work we’ve done in genetics has been on people of European ancestry,” Dr. Mulle said. “The fact that they have found results that are generalizable across multiple ethnicities really suggests that if we develop pharmaceutical agents based on these findings, it will help many people.”

More attention has been paid recently to a growing problem in the study of genetics of psychiatric disorders: More than 95% of participants in genome-wide association studies that seek to identify gene variants linked to disease are of European ancestry.

Dr. Charney and his colleagues had that in mind when they designed the study.

“We can’t get to a place where genetics is clinically useful if we don’t know the extent to which a particular observation that’s found in one population is also true for other populations,” Dr. Charney said.

The study was funded by the National Institutes of Health. Dr. Charney and Dr. Mulle report no relevant financial relationships.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

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

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

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

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

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

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

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

Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.

The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.

“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.

The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.

Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”

“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.

“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.

“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.

Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.

He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.

“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.

But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
 

‘Denosumab is a more potent antiresorptive than bisphosphonates’

Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.

Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.

Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.

After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.

Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.

Similar results were found for hip and vertebral fractures analyzed individually.  

Women had a lower mortality risk than men.

Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.

Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”

The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.

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

Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.

The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.

“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.

The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.

Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”

“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.

“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.

“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.

Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.

He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.

“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.

But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
 

‘Denosumab is a more potent antiresorptive than bisphosphonates’

Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.

Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.

Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.

After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.

Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.

Similar results were found for hip and vertebral fractures analyzed individually.  

Women had a lower mortality risk than men.

Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.

Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”

The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.

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

Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.

The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.

“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.

The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.

Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”

“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.

“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.

“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.

Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.

He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.

“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.

But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
 

‘Denosumab is a more potent antiresorptive than bisphosphonates’

Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.

Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.

Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.

After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.

Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.

Similar results were found for hip and vertebral fractures analyzed individually.  

Women had a lower mortality risk than men.

Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.

Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”

The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.

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

Ascend Laboratories is recalling 10 lots of the oral anticoagulant dabigatran etexilate capsules (75 mg and 150 mg) because of unacceptable levels of a potential carcinogen.

The nationwide recall, to the consumer level, is because of the detection of the nitrosamine impurity, N-nitroso-dabigatran, which may increase the risk of cancer with prolonged exposure to levels higher than acceptable.

To date, Ascend Laboratories has not received any reports of adverse events related to this recall.

The recalled product was distributed nationwide to wholesalers, distributors, and retailers in the United States from June 2022 to October 2022.

Complete details of the recalled product, including national drug code, lot numbers, expiration dates, and configuration/counts, are provided in a company announcement that was posted on the Food and Drug Administration website.

The company is advising patients who have any dabigatran that has been recalled to continue taking their medication and to contact their physician for advice regarding an alternative treatment.

Wholesalers/distributors and pharmacies with an existing inventory of the affected lots should stop use and distribution and quarantine the product immediately. Wholesalers and distributors should also recall the distributed product.

Questions regarding this recall can call Ascend Laboratories at 877.272.7901 (24 hours, 7 days a week).

Problems with this product should be reported to the FDA through MedWatch, its adverse event reporting program.

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

Ascend Laboratories is recalling 10 lots of the oral anticoagulant dabigatran etexilate capsules (75 mg and 150 mg) because of unacceptable levels of a potential carcinogen.

The nationwide recall, to the consumer level, is because of the detection of the nitrosamine impurity, N-nitroso-dabigatran, which may increase the risk of cancer with prolonged exposure to levels higher than acceptable.

To date, Ascend Laboratories has not received any reports of adverse events related to this recall.

The recalled product was distributed nationwide to wholesalers, distributors, and retailers in the United States from June 2022 to October 2022.

Complete details of the recalled product, including national drug code, lot numbers, expiration dates, and configuration/counts, are provided in a company announcement that was posted on the Food and Drug Administration website.

The company is advising patients who have any dabigatran that has been recalled to continue taking their medication and to contact their physician for advice regarding an alternative treatment.

Wholesalers/distributors and pharmacies with an existing inventory of the affected lots should stop use and distribution and quarantine the product immediately. Wholesalers and distributors should also recall the distributed product.

Questions regarding this recall can call Ascend Laboratories at 877.272.7901 (24 hours, 7 days a week).

Problems with this product should be reported to the FDA through MedWatch, its adverse event reporting program.

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

Ascend Laboratories is recalling 10 lots of the oral anticoagulant dabigatran etexilate capsules (75 mg and 150 mg) because of unacceptable levels of a potential carcinogen.

The nationwide recall, to the consumer level, is because of the detection of the nitrosamine impurity, N-nitroso-dabigatran, which may increase the risk of cancer with prolonged exposure to levels higher than acceptable.

To date, Ascend Laboratories has not received any reports of adverse events related to this recall.

The recalled product was distributed nationwide to wholesalers, distributors, and retailers in the United States from June 2022 to October 2022.

Complete details of the recalled product, including national drug code, lot numbers, expiration dates, and configuration/counts, are provided in a company announcement that was posted on the Food and Drug Administration website.

The company is advising patients who have any dabigatran that has been recalled to continue taking their medication and to contact their physician for advice regarding an alternative treatment.

Wholesalers/distributors and pharmacies with an existing inventory of the affected lots should stop use and distribution and quarantine the product immediately. Wholesalers and distributors should also recall the distributed product.

Questions regarding this recall can call Ascend Laboratories at 877.272.7901 (24 hours, 7 days a week).

Problems with this product should be reported to the FDA through MedWatch, its adverse event reporting program.

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

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

An electronic nose effectively detected Staphylococcus aureus in children with cystic fibrosis, based on data from 100 individuals.

Staphylococcus aureus is the most common pathogen found in children with cystic fibrosis (CF), but current detection strategies are based on microbiology cultures, wrote Johann-Christoph Licht, a medical student at the University of Toronto, and colleagues.

Noninvasive tools are needed to screen children with CF early for respiratory infections, the researchers said.

The electronic Nose (eNose) is a technology that detects volatile organic compounds (VOCs). Although exhaled breath can be used to create distinct profiles, the ability of eNose to identify S. aureus (SA) in the breath of children with CF remains unclear, they wrote.

In a study published in the Journal of Cystic Fibrosis, the researchers analyzed breath profiles data from 100 children with CF. The study population included children aged 5-18 years with clinically stable CF who were recruited from CF clinics during routine visits. Patients with a CF pulmonary exacerbation were excluded.

The children’s median predicted FEV₁ was 91%. The researchers collected sputum from 67 patients and throat cultures for 33 patients. A group of 25 age-matched healthy controls served for comparison.

Eighty patients were positive for CF pathogens. Of these, 67 were positive for SA (44 with SA only and 23 with SA and at least one other pathogen).

Overall, patients with any CF pathogen on airway cultures were identified compared to airway cultures with no CF pathogens with an area under the curve accuracy of 79.0%.

Previous studies have shown a high rate of accuracy using eNose to detect Pseudomonas aeruginosa (PA). In the current study, the area under the curve accuracy for PA infection compared to no CF pathogens was 78%. Both SA-specific and PA-specific signatures were driven by different sensors in the eNose, which suggests pathogen-specific breath signatures, the researchers wrote.

The study findings were limited by several factors including the small number of patients with positive airway cultures for PA and the lack of data on variability of measures over time or treatment-induced changes, the researchers noted.

However, the results confirm the value of the eNose in real-time point-of-care detection of airway infection in children with CF, and this is the first study known to suggest the potential of an eNose to detect SA infection in particular in a routine clinical setting, the researchers wrote in their discussion.

Other points in favor of eNose compared to current practice include “low cost, ease of use and portability to the point-of-care,” they said. The eNose provides an opportunity for early detection of pathogens that challenges conventional microbiology testing, they concluded.

The study received no outside funding. Two coauthors disclosed fees and/or an interest in the company Breathomix BV.

An electronic nose effectively detected Staphylococcus aureus in children with cystic fibrosis, based on data from 100 individuals.

Staphylococcus aureus is the most common pathogen found in children with cystic fibrosis (CF), but current detection strategies are based on microbiology cultures, wrote Johann-Christoph Licht, a medical student at the University of Toronto, and colleagues.

Noninvasive tools are needed to screen children with CF early for respiratory infections, the researchers said.

The electronic Nose (eNose) is a technology that detects volatile organic compounds (VOCs). Although exhaled breath can be used to create distinct profiles, the ability of eNose to identify S. aureus (SA) in the breath of children with CF remains unclear, they wrote.

In a study published in the Journal of Cystic Fibrosis, the researchers analyzed breath profiles data from 100 children with CF. The study population included children aged 5-18 years with clinically stable CF who were recruited from CF clinics during routine visits. Patients with a CF pulmonary exacerbation were excluded.

The children’s median predicted FEV₁ was 91%. The researchers collected sputum from 67 patients and throat cultures for 33 patients. A group of 25 age-matched healthy controls served for comparison.

Eighty patients were positive for CF pathogens. Of these, 67 were positive for SA (44 with SA only and 23 with SA and at least one other pathogen).

Overall, patients with any CF pathogen on airway cultures were identified compared to airway cultures with no CF pathogens with an area under the curve accuracy of 79.0%.

Previous studies have shown a high rate of accuracy using eNose to detect Pseudomonas aeruginosa (PA). In the current study, the area under the curve accuracy for PA infection compared to no CF pathogens was 78%. Both SA-specific and PA-specific signatures were driven by different sensors in the eNose, which suggests pathogen-specific breath signatures, the researchers wrote.

The study findings were limited by several factors including the small number of patients with positive airway cultures for PA and the lack of data on variability of measures over time or treatment-induced changes, the researchers noted.

However, the results confirm the value of the eNose in real-time point-of-care detection of airway infection in children with CF, and this is the first study known to suggest the potential of an eNose to detect SA infection in particular in a routine clinical setting, the researchers wrote in their discussion.

Other points in favor of eNose compared to current practice include “low cost, ease of use and portability to the point-of-care,” they said. The eNose provides an opportunity for early detection of pathogens that challenges conventional microbiology testing, they concluded.

The study received no outside funding. Two coauthors disclosed fees and/or an interest in the company Breathomix BV.

An electronic nose effectively detected Staphylococcus aureus in children with cystic fibrosis, based on data from 100 individuals.

Staphylococcus aureus is the most common pathogen found in children with cystic fibrosis (CF), but current detection strategies are based on microbiology cultures, wrote Johann-Christoph Licht, a medical student at the University of Toronto, and colleagues.

Noninvasive tools are needed to screen children with CF early for respiratory infections, the researchers said.

The electronic Nose (eNose) is a technology that detects volatile organic compounds (VOCs). Although exhaled breath can be used to create distinct profiles, the ability of eNose to identify S. aureus (SA) in the breath of children with CF remains unclear, they wrote.

In a study published in the Journal of Cystic Fibrosis, the researchers analyzed breath profiles data from 100 children with CF. The study population included children aged 5-18 years with clinically stable CF who were recruited from CF clinics during routine visits. Patients with a CF pulmonary exacerbation were excluded.

The children’s median predicted FEV₁ was 91%. The researchers collected sputum from 67 patients and throat cultures for 33 patients. A group of 25 age-matched healthy controls served for comparison.

Eighty patients were positive for CF pathogens. Of these, 67 were positive for SA (44 with SA only and 23 with SA and at least one other pathogen).

Overall, patients with any CF pathogen on airway cultures were identified compared to airway cultures with no CF pathogens with an area under the curve accuracy of 79.0%.

Previous studies have shown a high rate of accuracy using eNose to detect Pseudomonas aeruginosa (PA). In the current study, the area under the curve accuracy for PA infection compared to no CF pathogens was 78%. Both SA-specific and PA-specific signatures were driven by different sensors in the eNose, which suggests pathogen-specific breath signatures, the researchers wrote.

The study findings were limited by several factors including the small number of patients with positive airway cultures for PA and the lack of data on variability of measures over time or treatment-induced changes, the researchers noted.

However, the results confirm the value of the eNose in real-time point-of-care detection of airway infection in children with CF, and this is the first study known to suggest the potential of an eNose to detect SA infection in particular in a routine clinical setting, the researchers wrote in their discussion.

Other points in favor of eNose compared to current practice include “low cost, ease of use and portability to the point-of-care,” they said. The eNose provides an opportunity for early detection of pathogens that challenges conventional microbiology testing, they concluded.

The study received no outside funding. Two coauthors disclosed fees and/or an interest in the company Breathomix BV.