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Topical calcineurin inhibitors are an effective treatment option for pediatric periorificial dermatitis
AUSTIN, TEX. – , results from a retrospective cohort study showed.
The mainstays of treatment for POD include topical and oral antibiotics. In an interview prior to the annual meeting of the Society for Pediatric Dermatology, Ayelet Ollech, MD, said that the most common systemic agents used include erythromycin, azithromycin, and, in patients older than 8-10 years of age, minocycline or doxycycline. Topical agents, which are often used as monotherapy in mild disease, include metronidazole, clindamycin, erythromycin, sodium sulfacetamide, and, less often, azelaic acid, topical retinoids, and ivermectin. “TCIs (pimecrolimus 1% cream and tacrolimus 0.03% or 0.1% ointment) are a good steroid sparing option for POD,” said Dr. Ollech, a pediatric dermatology fellow at Ann & Robert H. Lurie Children’s Hospital of Chicago. “In the adult population, two randomized controlled studies of pimecrolimus 1% cream showed good results. In the pediatric population, there are only a few case series and case reports of TCIs for the treatment of POD.”
In what is believed to be the largest study of its kind, Dr. Ollech, Anthony J. Mancini, MD, and colleagues assessed the clinical utility of TCI in 132 pediatric patients with POD who were treated in the division of dermatology at Children’s Hospital of Chicago between 2008 and 2018. The researchers made note of epidemiologic variables, personal and family medical histories, possible triggers, duration of illness, previous treatments, distribution (periocular, perinasal, perioral, extra facial regions), severity of POD, treatment(s) prescribed, duration of therapy, clinical response, recurrences, and side effects. In an effort to capture missing data, the researchers performed follow-up via telephone for all patients who lacked appropriate follow-up documentation in the medical record.
Of the 132 patients, the female: male ratio was 1.2:1 and the median age at diagnosis was 4.2 years. About one-third of patients (33%) had involvement of one region, 38% had involvement of two regions, 26% had involvement of three regions, and 3% patients had involvement of all regions. The most common disorders on medical history were atopic dermatitis and asthma (in 29% and 17% of patients, respectively).
Dr. Ollech reported that 72 of the 132 patients (55%) had evaluable follow up data via either medical record documentation or the phone questionnaire. Of these, 67% were treated with TCI alone, 19% were treated with a combination of TCI and topical metronidazole, and 10% were treated with a combination of TCI and a systemic antibiotic. The median duration of treatment was 60 days. The researchers observed complete response in 65% of patients treated with TCI alone, in 64% of those treated with TCI and metronidazole, and in 70% of those treated with TCI and a systemic antibiotic. Adverse events attributed to TCI were rare and mild in severity.
“We were surprised that there were almost no reported side effects from the usage of TCIs as it is known that these agents can cause a burning or stinging sensation,” Dr. Ollech said. “Only one case described this side effect. We found 30% of the patients to have associated atopic dermatitis (AD) as well as a few patients with irritant dermatitis. We were also surprised how convenient the TCI treatment was for a patient who had POD and concomitant facial AD or even irritant dermatitis as an agent that can treat both. This can be very helpful for the parents that apply the medication to have a single solution to more than one rash.”
The researchers noted recurrence of POD in 14% of patients overall, including 6% of patients treated with TCI alone, 29% of patients treated with TCI and metronidazole, and 30% of patients treated with TCI and a systemic antibiotic.
Dr. Ollech acknowledged certain limitations of the study, including its retrospective design and lack of a control group. She and her colleagues reported having no financial disclosures.
SOURCE: Ollech A et al. SPD 2019, poster 23.
AUSTIN, TEX. – , results from a retrospective cohort study showed.
The mainstays of treatment for POD include topical and oral antibiotics. In an interview prior to the annual meeting of the Society for Pediatric Dermatology, Ayelet Ollech, MD, said that the most common systemic agents used include erythromycin, azithromycin, and, in patients older than 8-10 years of age, minocycline or doxycycline. Topical agents, which are often used as monotherapy in mild disease, include metronidazole, clindamycin, erythromycin, sodium sulfacetamide, and, less often, azelaic acid, topical retinoids, and ivermectin. “TCIs (pimecrolimus 1% cream and tacrolimus 0.03% or 0.1% ointment) are a good steroid sparing option for POD,” said Dr. Ollech, a pediatric dermatology fellow at Ann & Robert H. Lurie Children’s Hospital of Chicago. “In the adult population, two randomized controlled studies of pimecrolimus 1% cream showed good results. In the pediatric population, there are only a few case series and case reports of TCIs for the treatment of POD.”
In what is believed to be the largest study of its kind, Dr. Ollech, Anthony J. Mancini, MD, and colleagues assessed the clinical utility of TCI in 132 pediatric patients with POD who were treated in the division of dermatology at Children’s Hospital of Chicago between 2008 and 2018. The researchers made note of epidemiologic variables, personal and family medical histories, possible triggers, duration of illness, previous treatments, distribution (periocular, perinasal, perioral, extra facial regions), severity of POD, treatment(s) prescribed, duration of therapy, clinical response, recurrences, and side effects. In an effort to capture missing data, the researchers performed follow-up via telephone for all patients who lacked appropriate follow-up documentation in the medical record.
Of the 132 patients, the female: male ratio was 1.2:1 and the median age at diagnosis was 4.2 years. About one-third of patients (33%) had involvement of one region, 38% had involvement of two regions, 26% had involvement of three regions, and 3% patients had involvement of all regions. The most common disorders on medical history were atopic dermatitis and asthma (in 29% and 17% of patients, respectively).
Dr. Ollech reported that 72 of the 132 patients (55%) had evaluable follow up data via either medical record documentation or the phone questionnaire. Of these, 67% were treated with TCI alone, 19% were treated with a combination of TCI and topical metronidazole, and 10% were treated with a combination of TCI and a systemic antibiotic. The median duration of treatment was 60 days. The researchers observed complete response in 65% of patients treated with TCI alone, in 64% of those treated with TCI and metronidazole, and in 70% of those treated with TCI and a systemic antibiotic. Adverse events attributed to TCI were rare and mild in severity.
“We were surprised that there were almost no reported side effects from the usage of TCIs as it is known that these agents can cause a burning or stinging sensation,” Dr. Ollech said. “Only one case described this side effect. We found 30% of the patients to have associated atopic dermatitis (AD) as well as a few patients with irritant dermatitis. We were also surprised how convenient the TCI treatment was for a patient who had POD and concomitant facial AD or even irritant dermatitis as an agent that can treat both. This can be very helpful for the parents that apply the medication to have a single solution to more than one rash.”
The researchers noted recurrence of POD in 14% of patients overall, including 6% of patients treated with TCI alone, 29% of patients treated with TCI and metronidazole, and 30% of patients treated with TCI and a systemic antibiotic.
Dr. Ollech acknowledged certain limitations of the study, including its retrospective design and lack of a control group. She and her colleagues reported having no financial disclosures.
SOURCE: Ollech A et al. SPD 2019, poster 23.
AUSTIN, TEX. – , results from a retrospective cohort study showed.
The mainstays of treatment for POD include topical and oral antibiotics. In an interview prior to the annual meeting of the Society for Pediatric Dermatology, Ayelet Ollech, MD, said that the most common systemic agents used include erythromycin, azithromycin, and, in patients older than 8-10 years of age, minocycline or doxycycline. Topical agents, which are often used as monotherapy in mild disease, include metronidazole, clindamycin, erythromycin, sodium sulfacetamide, and, less often, azelaic acid, topical retinoids, and ivermectin. “TCIs (pimecrolimus 1% cream and tacrolimus 0.03% or 0.1% ointment) are a good steroid sparing option for POD,” said Dr. Ollech, a pediatric dermatology fellow at Ann & Robert H. Lurie Children’s Hospital of Chicago. “In the adult population, two randomized controlled studies of pimecrolimus 1% cream showed good results. In the pediatric population, there are only a few case series and case reports of TCIs for the treatment of POD.”
In what is believed to be the largest study of its kind, Dr. Ollech, Anthony J. Mancini, MD, and colleagues assessed the clinical utility of TCI in 132 pediatric patients with POD who were treated in the division of dermatology at Children’s Hospital of Chicago between 2008 and 2018. The researchers made note of epidemiologic variables, personal and family medical histories, possible triggers, duration of illness, previous treatments, distribution (periocular, perinasal, perioral, extra facial regions), severity of POD, treatment(s) prescribed, duration of therapy, clinical response, recurrences, and side effects. In an effort to capture missing data, the researchers performed follow-up via telephone for all patients who lacked appropriate follow-up documentation in the medical record.
Of the 132 patients, the female: male ratio was 1.2:1 and the median age at diagnosis was 4.2 years. About one-third of patients (33%) had involvement of one region, 38% had involvement of two regions, 26% had involvement of three regions, and 3% patients had involvement of all regions. The most common disorders on medical history were atopic dermatitis and asthma (in 29% and 17% of patients, respectively).
Dr. Ollech reported that 72 of the 132 patients (55%) had evaluable follow up data via either medical record documentation or the phone questionnaire. Of these, 67% were treated with TCI alone, 19% were treated with a combination of TCI and topical metronidazole, and 10% were treated with a combination of TCI and a systemic antibiotic. The median duration of treatment was 60 days. The researchers observed complete response in 65% of patients treated with TCI alone, in 64% of those treated with TCI and metronidazole, and in 70% of those treated with TCI and a systemic antibiotic. Adverse events attributed to TCI were rare and mild in severity.
“We were surprised that there were almost no reported side effects from the usage of TCIs as it is known that these agents can cause a burning or stinging sensation,” Dr. Ollech said. “Only one case described this side effect. We found 30% of the patients to have associated atopic dermatitis (AD) as well as a few patients with irritant dermatitis. We were also surprised how convenient the TCI treatment was for a patient who had POD and concomitant facial AD or even irritant dermatitis as an agent that can treat both. This can be very helpful for the parents that apply the medication to have a single solution to more than one rash.”
The researchers noted recurrence of POD in 14% of patients overall, including 6% of patients treated with TCI alone, 29% of patients treated with TCI and metronidazole, and 30% of patients treated with TCI and a systemic antibiotic.
Dr. Ollech acknowledged certain limitations of the study, including its retrospective design and lack of a control group. She and her colleagues reported having no financial disclosures.
SOURCE: Ollech A et al. SPD 2019, poster 23.
REPORTING FROM SPD 2019
First take on radiation oncology APM mixed
Radiation oncologists are applauding the Centers for Medicare & Medicaid Services’ introduction of a test radiation oncology alternative payment model (APM) to help encourage the move to value-based care, but concerns, particularly about its mandatory participation, have been raised.
The proposed radiation oncology APM, posted online as part of a larger notice of proposed rulemaking on July 10 and scheduled for publication in the Federal Register on July 18, will be tested over a 5-year period to determine if a prospective, site-neutral, episode-based payment for radiation therapy will improve the quality of care and lower costs for Medicare. Comments on the proposal are due 60 days from Federal Register publication.
According to the CMS website, the agency would make “prospective, episode-based (i.e. bundled) payments, based on a patient’s cancer diagnosis, that would cover radiotherapy services furnished in a 90-day episode for the 17 cancer types meeting the included cancer type criteria.”
The site-neutral payments would be based on a “common, adjusted national base payment amount” and would contain two components (professional and technical) “to allow for use of current claims systems for PFS [physician fee schedule] and OPPS [outpatient prospective payment system] to be used to adjudicate RO (radiation oncology) Model claims and be consistent with existing business relationships.”
Payments would be linked to quality “using reporting and performance on quality measures, clinical data reporting, and patient experience as factors when determining payment to participants.” The radiation oncology model qualifies as an advanced alternative payment model under the Quality Payment Program.
In addition to measuring whether the model improves quality and lowers costs, CMS will be studying whether it results in shorter courses of radiation therapy, more efficient care delivery, and higher-value care for Medicare beneficiaries.
The biggest detail about this proposed alternative payment model that is raising some red flags within the community is that it has a mandatory participation requirement, with participation determined by a random selection of providers in selected geographic areas.
The Community Oncology Alliance said in a statement that it has “deep reservations and fundamental opposition to a proposed mandatory or ‘required’ Center for Medicare & Medicaid Innovation model. Radiation therapy is a powerful, complex part of cancer care for patients. While the proposed CMMI model does include a much-needed policy proposal to implement site-neutral payments, COA absolutely does not support mandatory CMMI models,” adding that if models are “reasonable and would advance value-based care, then voluntary provider participation would be robust.”
Dave Adler, vice president of advocacy at the American Society for Radiation Oncology, also expressed concern regarding the requirement for participation.
“At least at the outset, having a voluntary model is the right way to start,” he said in an interview. “This is something that has not been tested before. I think it’s really important to its long-term success that we understand its impact on providers and patients before it’s required for anybody.”
He offered a little flexibility on that stance, noting that if CMS would not budge on the mandatory aspect, he suggested that it lower the amount of participation that will be required from the proposed 40% of radiation oncologists to something smaller, coupled with a mechanism for voluntary participation, which does not exist in the current proposal.
Outside of that immediate concern, Mr. Adler said it was really too early to tell whether the proposal is in fact adequate to meet the needs of practicing radiation oncologists, including the payment rates, and the patients they treat. He said ASTRO will be doing a deeper analysis in the coming weeks and will provide the necessary feedback to CMS on the proposal.
Another thing that stood out as concerning was the start date, which CMS suggested could be as early as January 2020, but it also suggested that could be pushed back to April 2020. Practices won’t know if they are selected as required to participate until the final rule is issued, likely in November.
“We are pleased that CMS seems to be open to considering an April 1 start date,” he said. “That’s probably the earliest that it could start,” adding that ASTRO might look to see if there is an opportunity to encourage CMS to implement a rolling start date.
He also noted that CMS did not include any sort of hardship exemption for practices that have a rationale for not wanting to or being able to participate.
That, and including a voluntary participation option, “can be done without compromising the evaluation of the model.”
That being said, Mr. Adler spoke positively in general.
“We are moving in the right direction here with the model,” he said. “We are very much committed to working with CMS and our champions in Congress constructively to improve upon what has been proposed here.”
One thing he liked was the prospective payment aspect of the model.
“Radiation oncology practices, given the expense of the equipment, the staff, and the delivery of the sophisticated treatment requires a huge up-front expense,” he noted. “The ability to have this up-front payment prospectively is something we recommended, and it is very good to see that in there.”
He also spoke positively of the quality measures that are part of the proposed model.
“They really seemed to have zeroed in on meaningful measures for radiation oncology practices ... things that are really connected to guidelines that are known to support patients,” he said. “We didn’t see anything in the list of quality measures that are off base. That was a real positive [and] consistent with things that we have recommended that CMS should consider on the quality front.”
He also said the structure of the model will drive more guideline-concordant care, and incentives are there that will make treatments more convenient for patients.
“There are some positive aspects here that we can really build on,” Mr. Adler said.
Radiation oncologists are applauding the Centers for Medicare & Medicaid Services’ introduction of a test radiation oncology alternative payment model (APM) to help encourage the move to value-based care, but concerns, particularly about its mandatory participation, have been raised.
The proposed radiation oncology APM, posted online as part of a larger notice of proposed rulemaking on July 10 and scheduled for publication in the Federal Register on July 18, will be tested over a 5-year period to determine if a prospective, site-neutral, episode-based payment for radiation therapy will improve the quality of care and lower costs for Medicare. Comments on the proposal are due 60 days from Federal Register publication.
According to the CMS website, the agency would make “prospective, episode-based (i.e. bundled) payments, based on a patient’s cancer diagnosis, that would cover radiotherapy services furnished in a 90-day episode for the 17 cancer types meeting the included cancer type criteria.”
The site-neutral payments would be based on a “common, adjusted national base payment amount” and would contain two components (professional and technical) “to allow for use of current claims systems for PFS [physician fee schedule] and OPPS [outpatient prospective payment system] to be used to adjudicate RO (radiation oncology) Model claims and be consistent with existing business relationships.”
Payments would be linked to quality “using reporting and performance on quality measures, clinical data reporting, and patient experience as factors when determining payment to participants.” The radiation oncology model qualifies as an advanced alternative payment model under the Quality Payment Program.
In addition to measuring whether the model improves quality and lowers costs, CMS will be studying whether it results in shorter courses of radiation therapy, more efficient care delivery, and higher-value care for Medicare beneficiaries.
The biggest detail about this proposed alternative payment model that is raising some red flags within the community is that it has a mandatory participation requirement, with participation determined by a random selection of providers in selected geographic areas.
The Community Oncology Alliance said in a statement that it has “deep reservations and fundamental opposition to a proposed mandatory or ‘required’ Center for Medicare & Medicaid Innovation model. Radiation therapy is a powerful, complex part of cancer care for patients. While the proposed CMMI model does include a much-needed policy proposal to implement site-neutral payments, COA absolutely does not support mandatory CMMI models,” adding that if models are “reasonable and would advance value-based care, then voluntary provider participation would be robust.”
Dave Adler, vice president of advocacy at the American Society for Radiation Oncology, also expressed concern regarding the requirement for participation.
“At least at the outset, having a voluntary model is the right way to start,” he said in an interview. “This is something that has not been tested before. I think it’s really important to its long-term success that we understand its impact on providers and patients before it’s required for anybody.”
He offered a little flexibility on that stance, noting that if CMS would not budge on the mandatory aspect, he suggested that it lower the amount of participation that will be required from the proposed 40% of radiation oncologists to something smaller, coupled with a mechanism for voluntary participation, which does not exist in the current proposal.
Outside of that immediate concern, Mr. Adler said it was really too early to tell whether the proposal is in fact adequate to meet the needs of practicing radiation oncologists, including the payment rates, and the patients they treat. He said ASTRO will be doing a deeper analysis in the coming weeks and will provide the necessary feedback to CMS on the proposal.
Another thing that stood out as concerning was the start date, which CMS suggested could be as early as January 2020, but it also suggested that could be pushed back to April 2020. Practices won’t know if they are selected as required to participate until the final rule is issued, likely in November.
“We are pleased that CMS seems to be open to considering an April 1 start date,” he said. “That’s probably the earliest that it could start,” adding that ASTRO might look to see if there is an opportunity to encourage CMS to implement a rolling start date.
He also noted that CMS did not include any sort of hardship exemption for practices that have a rationale for not wanting to or being able to participate.
That, and including a voluntary participation option, “can be done without compromising the evaluation of the model.”
That being said, Mr. Adler spoke positively in general.
“We are moving in the right direction here with the model,” he said. “We are very much committed to working with CMS and our champions in Congress constructively to improve upon what has been proposed here.”
One thing he liked was the prospective payment aspect of the model.
“Radiation oncology practices, given the expense of the equipment, the staff, and the delivery of the sophisticated treatment requires a huge up-front expense,” he noted. “The ability to have this up-front payment prospectively is something we recommended, and it is very good to see that in there.”
He also spoke positively of the quality measures that are part of the proposed model.
“They really seemed to have zeroed in on meaningful measures for radiation oncology practices ... things that are really connected to guidelines that are known to support patients,” he said. “We didn’t see anything in the list of quality measures that are off base. That was a real positive [and] consistent with things that we have recommended that CMS should consider on the quality front.”
He also said the structure of the model will drive more guideline-concordant care, and incentives are there that will make treatments more convenient for patients.
“There are some positive aspects here that we can really build on,” Mr. Adler said.
Radiation oncologists are applauding the Centers for Medicare & Medicaid Services’ introduction of a test radiation oncology alternative payment model (APM) to help encourage the move to value-based care, but concerns, particularly about its mandatory participation, have been raised.
The proposed radiation oncology APM, posted online as part of a larger notice of proposed rulemaking on July 10 and scheduled for publication in the Federal Register on July 18, will be tested over a 5-year period to determine if a prospective, site-neutral, episode-based payment for radiation therapy will improve the quality of care and lower costs for Medicare. Comments on the proposal are due 60 days from Federal Register publication.
According to the CMS website, the agency would make “prospective, episode-based (i.e. bundled) payments, based on a patient’s cancer diagnosis, that would cover radiotherapy services furnished in a 90-day episode for the 17 cancer types meeting the included cancer type criteria.”
The site-neutral payments would be based on a “common, adjusted national base payment amount” and would contain two components (professional and technical) “to allow for use of current claims systems for PFS [physician fee schedule] and OPPS [outpatient prospective payment system] to be used to adjudicate RO (radiation oncology) Model claims and be consistent with existing business relationships.”
Payments would be linked to quality “using reporting and performance on quality measures, clinical data reporting, and patient experience as factors when determining payment to participants.” The radiation oncology model qualifies as an advanced alternative payment model under the Quality Payment Program.
In addition to measuring whether the model improves quality and lowers costs, CMS will be studying whether it results in shorter courses of radiation therapy, more efficient care delivery, and higher-value care for Medicare beneficiaries.
The biggest detail about this proposed alternative payment model that is raising some red flags within the community is that it has a mandatory participation requirement, with participation determined by a random selection of providers in selected geographic areas.
The Community Oncology Alliance said in a statement that it has “deep reservations and fundamental opposition to a proposed mandatory or ‘required’ Center for Medicare & Medicaid Innovation model. Radiation therapy is a powerful, complex part of cancer care for patients. While the proposed CMMI model does include a much-needed policy proposal to implement site-neutral payments, COA absolutely does not support mandatory CMMI models,” adding that if models are “reasonable and would advance value-based care, then voluntary provider participation would be robust.”
Dave Adler, vice president of advocacy at the American Society for Radiation Oncology, also expressed concern regarding the requirement for participation.
“At least at the outset, having a voluntary model is the right way to start,” he said in an interview. “This is something that has not been tested before. I think it’s really important to its long-term success that we understand its impact on providers and patients before it’s required for anybody.”
He offered a little flexibility on that stance, noting that if CMS would not budge on the mandatory aspect, he suggested that it lower the amount of participation that will be required from the proposed 40% of radiation oncologists to something smaller, coupled with a mechanism for voluntary participation, which does not exist in the current proposal.
Outside of that immediate concern, Mr. Adler said it was really too early to tell whether the proposal is in fact adequate to meet the needs of practicing radiation oncologists, including the payment rates, and the patients they treat. He said ASTRO will be doing a deeper analysis in the coming weeks and will provide the necessary feedback to CMS on the proposal.
Another thing that stood out as concerning was the start date, which CMS suggested could be as early as January 2020, but it also suggested that could be pushed back to April 2020. Practices won’t know if they are selected as required to participate until the final rule is issued, likely in November.
“We are pleased that CMS seems to be open to considering an April 1 start date,” he said. “That’s probably the earliest that it could start,” adding that ASTRO might look to see if there is an opportunity to encourage CMS to implement a rolling start date.
He also noted that CMS did not include any sort of hardship exemption for practices that have a rationale for not wanting to or being able to participate.
That, and including a voluntary participation option, “can be done without compromising the evaluation of the model.”
That being said, Mr. Adler spoke positively in general.
“We are moving in the right direction here with the model,” he said. “We are very much committed to working with CMS and our champions in Congress constructively to improve upon what has been proposed here.”
One thing he liked was the prospective payment aspect of the model.
“Radiation oncology practices, given the expense of the equipment, the staff, and the delivery of the sophisticated treatment requires a huge up-front expense,” he noted. “The ability to have this up-front payment prospectively is something we recommended, and it is very good to see that in there.”
He also spoke positively of the quality measures that are part of the proposed model.
“They really seemed to have zeroed in on meaningful measures for radiation oncology practices ... things that are really connected to guidelines that are known to support patients,” he said. “We didn’t see anything in the list of quality measures that are off base. That was a real positive [and] consistent with things that we have recommended that CMS should consider on the quality front.”
He also said the structure of the model will drive more guideline-concordant care, and incentives are there that will make treatments more convenient for patients.
“There are some positive aspects here that we can really build on,” Mr. Adler said.
Tocilizumab linked to refractory uveitis improvements in some JIA patients
MADRID – Tocilizumab was associated with improved vision in about half of 22 enrolled children with juvenile idiopathic arthritis (JIA) and uveitis refractory to tumor necrosis factor inhibitor (TNFi) therapy, based on results from an investigator-initiated phase 2 trial presented at the European Congress of Rheumatology.
At 12 weeks of treatment, 11 children in the study had some improvement in uveitis and 7 of them had achieved the primary study outcome, which was a two-step decrease in the level of inflammation as measured by the Standard of the Uveitis Nomenclature (SUN) criteria, Athimalaipet V. Ramanan, MBBS, of the department of paediatric rheumatology at the University Hospitals Bristol (England) NHS Foundation Trust, said. Ten of the 21 evaluable patients had no apparent response to tocilizumab. One study participant could not be included in the final analysis because of a violation in study protocol that involved use of disallowed concomitant medications.
“Although this study did not meet the prespecified criterion for efficacy (for most of those treated) ... almost half of those enrolled achieved some benefit,” reported Dr. Ramanan.
The multicenter investigator-initiated phase 2 trial conducted in the United Kingdom enrolled children with JIA and uveitis that was refractory to methotrexate and TNFi therapy. The study participants received methotrexate as well as 162 mg of tocilizumab administered subcutaneously every 2 weeks (those weighing less than 30 kg received tocilizumab treatment every 3 weeks).
Seven of 21 evaluable patients achieved the two-step reduction in inflammation that was the prespecified criterion for a response. For the study population overall, this fell short of statistical significance (P = .11).
However, Dr. Ramanan emphasized that another three patients achieved a one-step improvement, which he believes merits consideration as a sign of efficacy in a “very refractory group.” Moreover, three of four patients with macular edema at baseline had total resolution of this complication.
Other outcomes of interest monitored during the study included the safety and tolerability of tocilizumab and change in use of topical corticosteroids. There were no serious adverse events associated with tocilizumab in this study, according to Dr. Ramanan.
SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2)265, Abstract LB0011.
MADRID – Tocilizumab was associated with improved vision in about half of 22 enrolled children with juvenile idiopathic arthritis (JIA) and uveitis refractory to tumor necrosis factor inhibitor (TNFi) therapy, based on results from an investigator-initiated phase 2 trial presented at the European Congress of Rheumatology.
At 12 weeks of treatment, 11 children in the study had some improvement in uveitis and 7 of them had achieved the primary study outcome, which was a two-step decrease in the level of inflammation as measured by the Standard of the Uveitis Nomenclature (SUN) criteria, Athimalaipet V. Ramanan, MBBS, of the department of paediatric rheumatology at the University Hospitals Bristol (England) NHS Foundation Trust, said. Ten of the 21 evaluable patients had no apparent response to tocilizumab. One study participant could not be included in the final analysis because of a violation in study protocol that involved use of disallowed concomitant medications.
“Although this study did not meet the prespecified criterion for efficacy (for most of those treated) ... almost half of those enrolled achieved some benefit,” reported Dr. Ramanan.
The multicenter investigator-initiated phase 2 trial conducted in the United Kingdom enrolled children with JIA and uveitis that was refractory to methotrexate and TNFi therapy. The study participants received methotrexate as well as 162 mg of tocilizumab administered subcutaneously every 2 weeks (those weighing less than 30 kg received tocilizumab treatment every 3 weeks).
Seven of 21 evaluable patients achieved the two-step reduction in inflammation that was the prespecified criterion for a response. For the study population overall, this fell short of statistical significance (P = .11).
However, Dr. Ramanan emphasized that another three patients achieved a one-step improvement, which he believes merits consideration as a sign of efficacy in a “very refractory group.” Moreover, three of four patients with macular edema at baseline had total resolution of this complication.
Other outcomes of interest monitored during the study included the safety and tolerability of tocilizumab and change in use of topical corticosteroids. There were no serious adverse events associated with tocilizumab in this study, according to Dr. Ramanan.
SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2)265, Abstract LB0011.
MADRID – Tocilizumab was associated with improved vision in about half of 22 enrolled children with juvenile idiopathic arthritis (JIA) and uveitis refractory to tumor necrosis factor inhibitor (TNFi) therapy, based on results from an investigator-initiated phase 2 trial presented at the European Congress of Rheumatology.
At 12 weeks of treatment, 11 children in the study had some improvement in uveitis and 7 of them had achieved the primary study outcome, which was a two-step decrease in the level of inflammation as measured by the Standard of the Uveitis Nomenclature (SUN) criteria, Athimalaipet V. Ramanan, MBBS, of the department of paediatric rheumatology at the University Hospitals Bristol (England) NHS Foundation Trust, said. Ten of the 21 evaluable patients had no apparent response to tocilizumab. One study participant could not be included in the final analysis because of a violation in study protocol that involved use of disallowed concomitant medications.
“Although this study did not meet the prespecified criterion for efficacy (for most of those treated) ... almost half of those enrolled achieved some benefit,” reported Dr. Ramanan.
The multicenter investigator-initiated phase 2 trial conducted in the United Kingdom enrolled children with JIA and uveitis that was refractory to methotrexate and TNFi therapy. The study participants received methotrexate as well as 162 mg of tocilizumab administered subcutaneously every 2 weeks (those weighing less than 30 kg received tocilizumab treatment every 3 weeks).
Seven of 21 evaluable patients achieved the two-step reduction in inflammation that was the prespecified criterion for a response. For the study population overall, this fell short of statistical significance (P = .11).
However, Dr. Ramanan emphasized that another three patients achieved a one-step improvement, which he believes merits consideration as a sign of efficacy in a “very refractory group.” Moreover, three of four patients with macular edema at baseline had total resolution of this complication.
Other outcomes of interest monitored during the study included the safety and tolerability of tocilizumab and change in use of topical corticosteroids. There were no serious adverse events associated with tocilizumab in this study, according to Dr. Ramanan.
SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2)265, Abstract LB0011.
REPORTING FROM EULAR 2019 Congress
Depressive symptoms linked to poor diet quality in men
Depressive symptoms may be linked to poor-quality diets in middle-aged and older men, according to findings from the Longitudinal Aging Study Amsterdam (LASA).
In a longitudinal study of 1,312 Dutch people aged 55 years or older, 52% of whom were women, depressive symptoms were associated with significantly lower diet quality scores on food quality questionnaires among men, Liset E.M. Elstgeest of the Amsterdam Public Health research institute at Vrije Universiteit Amsterdam and coauthors reported in the Journal of Affective Disorders.
Depressive symptoms were defined as a score of at least 16 on the Center for Epidemiologic Studies Depression scale (CES-D). Study participants were assessed in 2014-2015, and for five cycles of three times per year from 2001-2003 to 2015-2016. Diet quality was assessed in 2014 and 2015 using the Mediterranean Diet Score, Alternative Healthy Eating Index, and Dietary Approaches to Stop Hypertension (DASH) score.
The majority (84.8%) had no depressive symptoms in both cycles, while 5.4% experienced emerging, 4.6% remitted, and 5.1% chronic/recurrent depressive symptoms. For the history sample, the numbers with depressive symptoms were 69 (10.0%), 67(9.8%), 59 (8.6%), and 60 (8.7%) in the four regular cycles from 2001-2003 to 2011-2013. In total 144 participants (21.0%) ever had a CES-D of at least 16 from 2001-2003 to 2011-2013, of which 20 had an elevated CES-D score only in 2011-2013.
Compared with participants with CES-D scores less than 16, the 120 (9.7%) study participants with CES-D scores of at least 16 in 2011-2013 and the 130 (10.5%) study participants with elevated CES-D scores in 2015-2016 were more likely to have lower Mediterranean Diet Score and Alternative Healthy Eating Index scores. After adjustment for confounders, however, the association remained statistically significant only for men. Current depressive symptoms were also associated with a lower Alternative Healthy Eating Index score in men, but not in women.
More longitudinal studies are needed to confirm results, the investigators added. “Such studies should preferably include repeated diet measurements and investigate gender differences,” they concluded.
No conflicts of interest were reported.
SOURCE: Elstgeest L et al. 2019. J Affec Disord. doi: 10.1016/j.jad.2019.02.004.
Depressive symptoms may be linked to poor-quality diets in middle-aged and older men, according to findings from the Longitudinal Aging Study Amsterdam (LASA).
In a longitudinal study of 1,312 Dutch people aged 55 years or older, 52% of whom were women, depressive symptoms were associated with significantly lower diet quality scores on food quality questionnaires among men, Liset E.M. Elstgeest of the Amsterdam Public Health research institute at Vrije Universiteit Amsterdam and coauthors reported in the Journal of Affective Disorders.
Depressive symptoms were defined as a score of at least 16 on the Center for Epidemiologic Studies Depression scale (CES-D). Study participants were assessed in 2014-2015, and for five cycles of three times per year from 2001-2003 to 2015-2016. Diet quality was assessed in 2014 and 2015 using the Mediterranean Diet Score, Alternative Healthy Eating Index, and Dietary Approaches to Stop Hypertension (DASH) score.
The majority (84.8%) had no depressive symptoms in both cycles, while 5.4% experienced emerging, 4.6% remitted, and 5.1% chronic/recurrent depressive symptoms. For the history sample, the numbers with depressive symptoms were 69 (10.0%), 67(9.8%), 59 (8.6%), and 60 (8.7%) in the four regular cycles from 2001-2003 to 2011-2013. In total 144 participants (21.0%) ever had a CES-D of at least 16 from 2001-2003 to 2011-2013, of which 20 had an elevated CES-D score only in 2011-2013.
Compared with participants with CES-D scores less than 16, the 120 (9.7%) study participants with CES-D scores of at least 16 in 2011-2013 and the 130 (10.5%) study participants with elevated CES-D scores in 2015-2016 were more likely to have lower Mediterranean Diet Score and Alternative Healthy Eating Index scores. After adjustment for confounders, however, the association remained statistically significant only for men. Current depressive symptoms were also associated with a lower Alternative Healthy Eating Index score in men, but not in women.
More longitudinal studies are needed to confirm results, the investigators added. “Such studies should preferably include repeated diet measurements and investigate gender differences,” they concluded.
No conflicts of interest were reported.
SOURCE: Elstgeest L et al. 2019. J Affec Disord. doi: 10.1016/j.jad.2019.02.004.
Depressive symptoms may be linked to poor-quality diets in middle-aged and older men, according to findings from the Longitudinal Aging Study Amsterdam (LASA).
In a longitudinal study of 1,312 Dutch people aged 55 years or older, 52% of whom were women, depressive symptoms were associated with significantly lower diet quality scores on food quality questionnaires among men, Liset E.M. Elstgeest of the Amsterdam Public Health research institute at Vrije Universiteit Amsterdam and coauthors reported in the Journal of Affective Disorders.
Depressive symptoms were defined as a score of at least 16 on the Center for Epidemiologic Studies Depression scale (CES-D). Study participants were assessed in 2014-2015, and for five cycles of three times per year from 2001-2003 to 2015-2016. Diet quality was assessed in 2014 and 2015 using the Mediterranean Diet Score, Alternative Healthy Eating Index, and Dietary Approaches to Stop Hypertension (DASH) score.
The majority (84.8%) had no depressive symptoms in both cycles, while 5.4% experienced emerging, 4.6% remitted, and 5.1% chronic/recurrent depressive symptoms. For the history sample, the numbers with depressive symptoms were 69 (10.0%), 67(9.8%), 59 (8.6%), and 60 (8.7%) in the four regular cycles from 2001-2003 to 2011-2013. In total 144 participants (21.0%) ever had a CES-D of at least 16 from 2001-2003 to 2011-2013, of which 20 had an elevated CES-D score only in 2011-2013.
Compared with participants with CES-D scores less than 16, the 120 (9.7%) study participants with CES-D scores of at least 16 in 2011-2013 and the 130 (10.5%) study participants with elevated CES-D scores in 2015-2016 were more likely to have lower Mediterranean Diet Score and Alternative Healthy Eating Index scores. After adjustment for confounders, however, the association remained statistically significant only for men. Current depressive symptoms were also associated with a lower Alternative Healthy Eating Index score in men, but not in women.
More longitudinal studies are needed to confirm results, the investigators added. “Such studies should preferably include repeated diet measurements and investigate gender differences,” they concluded.
No conflicts of interest were reported.
SOURCE: Elstgeest L et al. 2019. J Affec Disord. doi: 10.1016/j.jad.2019.02.004.
FROM THE JOURNAL OF AFFECTIVE DISORDERS
BMI screening trigger for type 2 diabetes is unreliable for at-risk black, Hispanic adults
SAN FRANCISCO – according to findings presented at the annual scientific sessions of the American Diabetes Association.
The conclusions come from a review of 5,656 participants aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective cohort study. The participants had no signs of cardiovascular disease at enrollment.
The goal of the study reported at the meeting was to see if current ADA screening guidelines are appropriate across racial groups in an increasingly diverse United States. The guidelines recommend body mass index (BMI) as a trigger for screening for type 2 diabetes. The current advice is to screen any adult who has a BMI at or above 25 kg/m2 (23 kg/m2 for Asian Americans) and at least one risk factor for type 2 diabetes, such as hypertension, dyslipidemia, or physical inactivity.
Being black, Asian American, Hispanic, Pacific Islander, or American Indian is itself a risk factor, so “someone from a minority group just needs to meet the BMI criteria,” said lead investigator Luis Rodriguez, a PhD candidate in epidemiology at the University of California, San Francisco.
He and his colleagues focused on 2,383 white, 653 Chinese American, 1,459 black, and 1,161 Hispanic participants in MESA who did not have type 2 diabetes at baseline. Participants were in their early 60s at baseline, on average, and just more than half of them were women. They had five medical exams between 2000 and 2012. The investigators calculated the BMI at which each group hit a 10% risk of developing diabetes within the next 10 years.
In general, the lines crossed at a BMI of about 23 kg/m2 for Chinese Americans; 25 kg/m2 for black and Hispanic participants; and 27 kg/m2 for white participants, which is consistent with ADA advice. The guideline cut points are “appropriate for population-based screening where you may not know if the person in front of you has any diabetes risk factors,” Mr. Rodriguez said.
With known risk factors, however, BMI didn’t hold up. Black participants with one or more risk factor hit the 10% mark at a BMI of 24.7 kg/m2, Hispanics at 23.8 kg/m2, and Chinese Americans at 21.7 kg/m2, all of which are below the recommended cut-points.
“Almost 80%-90% of participants” in minority groups “who had one or more risk factors were above the 10% threshold, so if they have at least one factor, they should pretty much be screened for diabetes, regardless of BMI,” he said.
The 25-kg/m2 threshold worked for white participants; the investigators found that with one or more risk factors, white participants crossed the 10% line at a BMI of 26.2 kg/m2. In addition, white participants with no diabetes risk factors crossed the 10% mark at around a BMI of 30 kg/m2, which the investigators suggested as an appropriate screening trigger.
Participants were in their early 60s at baseline, on average, and just more than half of them were women. In all, 696 cases of type 2 diabetes were diagnosed over a median follow-up of about 9 years, which translated to an incidence rate of 11 cases per 1,000 person-years in white participants, 16 cases for Chinese Americans, 21 for black participants, and 22 for Hispanic participants. Well over half of the participants were overweight or obese at baseline, including about 80% of black and Hispanic participants.
The sample size reported in the abstract was smaller than that in the final presentation because the investigators did not adjust for diet in the final presentation, Mr. Rodriguez explained. Because some study participants did not report diet, by excluding diet from the model adjustment, the number of participants increased, as reflected in this text. Adjusting for diet did not alter the findings.
The National Heart, Lung, and Blood Institute sponsors MESA. Mr. Rodriguez was supported by a grant from the National Institutes of Health/National Institute of Diabetes and Kidney Disease. The other investigators reported having no disclosures.
SOURCE: Rodriguez L et al. ADA 2019, Abstract 115-OR.
SAN FRANCISCO – according to findings presented at the annual scientific sessions of the American Diabetes Association.
The conclusions come from a review of 5,656 participants aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective cohort study. The participants had no signs of cardiovascular disease at enrollment.
The goal of the study reported at the meeting was to see if current ADA screening guidelines are appropriate across racial groups in an increasingly diverse United States. The guidelines recommend body mass index (BMI) as a trigger for screening for type 2 diabetes. The current advice is to screen any adult who has a BMI at or above 25 kg/m2 (23 kg/m2 for Asian Americans) and at least one risk factor for type 2 diabetes, such as hypertension, dyslipidemia, or physical inactivity.
Being black, Asian American, Hispanic, Pacific Islander, or American Indian is itself a risk factor, so “someone from a minority group just needs to meet the BMI criteria,” said lead investigator Luis Rodriguez, a PhD candidate in epidemiology at the University of California, San Francisco.
He and his colleagues focused on 2,383 white, 653 Chinese American, 1,459 black, and 1,161 Hispanic participants in MESA who did not have type 2 diabetes at baseline. Participants were in their early 60s at baseline, on average, and just more than half of them were women. They had five medical exams between 2000 and 2012. The investigators calculated the BMI at which each group hit a 10% risk of developing diabetes within the next 10 years.
In general, the lines crossed at a BMI of about 23 kg/m2 for Chinese Americans; 25 kg/m2 for black and Hispanic participants; and 27 kg/m2 for white participants, which is consistent with ADA advice. The guideline cut points are “appropriate for population-based screening where you may not know if the person in front of you has any diabetes risk factors,” Mr. Rodriguez said.
With known risk factors, however, BMI didn’t hold up. Black participants with one or more risk factor hit the 10% mark at a BMI of 24.7 kg/m2, Hispanics at 23.8 kg/m2, and Chinese Americans at 21.7 kg/m2, all of which are below the recommended cut-points.
“Almost 80%-90% of participants” in minority groups “who had one or more risk factors were above the 10% threshold, so if they have at least one factor, they should pretty much be screened for diabetes, regardless of BMI,” he said.
The 25-kg/m2 threshold worked for white participants; the investigators found that with one or more risk factors, white participants crossed the 10% line at a BMI of 26.2 kg/m2. In addition, white participants with no diabetes risk factors crossed the 10% mark at around a BMI of 30 kg/m2, which the investigators suggested as an appropriate screening trigger.
Participants were in their early 60s at baseline, on average, and just more than half of them were women. In all, 696 cases of type 2 diabetes were diagnosed over a median follow-up of about 9 years, which translated to an incidence rate of 11 cases per 1,000 person-years in white participants, 16 cases for Chinese Americans, 21 for black participants, and 22 for Hispanic participants. Well over half of the participants were overweight or obese at baseline, including about 80% of black and Hispanic participants.
The sample size reported in the abstract was smaller than that in the final presentation because the investigators did not adjust for diet in the final presentation, Mr. Rodriguez explained. Because some study participants did not report diet, by excluding diet from the model adjustment, the number of participants increased, as reflected in this text. Adjusting for diet did not alter the findings.
The National Heart, Lung, and Blood Institute sponsors MESA. Mr. Rodriguez was supported by a grant from the National Institutes of Health/National Institute of Diabetes and Kidney Disease. The other investigators reported having no disclosures.
SOURCE: Rodriguez L et al. ADA 2019, Abstract 115-OR.
SAN FRANCISCO – according to findings presented at the annual scientific sessions of the American Diabetes Association.
The conclusions come from a review of 5,656 participants aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective cohort study. The participants had no signs of cardiovascular disease at enrollment.
The goal of the study reported at the meeting was to see if current ADA screening guidelines are appropriate across racial groups in an increasingly diverse United States. The guidelines recommend body mass index (BMI) as a trigger for screening for type 2 diabetes. The current advice is to screen any adult who has a BMI at or above 25 kg/m2 (23 kg/m2 for Asian Americans) and at least one risk factor for type 2 diabetes, such as hypertension, dyslipidemia, or physical inactivity.
Being black, Asian American, Hispanic, Pacific Islander, or American Indian is itself a risk factor, so “someone from a minority group just needs to meet the BMI criteria,” said lead investigator Luis Rodriguez, a PhD candidate in epidemiology at the University of California, San Francisco.
He and his colleagues focused on 2,383 white, 653 Chinese American, 1,459 black, and 1,161 Hispanic participants in MESA who did not have type 2 diabetes at baseline. Participants were in their early 60s at baseline, on average, and just more than half of them were women. They had five medical exams between 2000 and 2012. The investigators calculated the BMI at which each group hit a 10% risk of developing diabetes within the next 10 years.
In general, the lines crossed at a BMI of about 23 kg/m2 for Chinese Americans; 25 kg/m2 for black and Hispanic participants; and 27 kg/m2 for white participants, which is consistent with ADA advice. The guideline cut points are “appropriate for population-based screening where you may not know if the person in front of you has any diabetes risk factors,” Mr. Rodriguez said.
With known risk factors, however, BMI didn’t hold up. Black participants with one or more risk factor hit the 10% mark at a BMI of 24.7 kg/m2, Hispanics at 23.8 kg/m2, and Chinese Americans at 21.7 kg/m2, all of which are below the recommended cut-points.
“Almost 80%-90% of participants” in minority groups “who had one or more risk factors were above the 10% threshold, so if they have at least one factor, they should pretty much be screened for diabetes, regardless of BMI,” he said.
The 25-kg/m2 threshold worked for white participants; the investigators found that with one or more risk factors, white participants crossed the 10% line at a BMI of 26.2 kg/m2. In addition, white participants with no diabetes risk factors crossed the 10% mark at around a BMI of 30 kg/m2, which the investigators suggested as an appropriate screening trigger.
Participants were in their early 60s at baseline, on average, and just more than half of them were women. In all, 696 cases of type 2 diabetes were diagnosed over a median follow-up of about 9 years, which translated to an incidence rate of 11 cases per 1,000 person-years in white participants, 16 cases for Chinese Americans, 21 for black participants, and 22 for Hispanic participants. Well over half of the participants were overweight or obese at baseline, including about 80% of black and Hispanic participants.
The sample size reported in the abstract was smaller than that in the final presentation because the investigators did not adjust for diet in the final presentation, Mr. Rodriguez explained. Because some study participants did not report diet, by excluding diet from the model adjustment, the number of participants increased, as reflected in this text. Adjusting for diet did not alter the findings.
The National Heart, Lung, and Blood Institute sponsors MESA. Mr. Rodriguez was supported by a grant from the National Institutes of Health/National Institute of Diabetes and Kidney Disease. The other investigators reported having no disclosures.
SOURCE: Rodriguez L et al. ADA 2019, Abstract 115-OR.
REPORTING FROM ADA 2019
Key clinical point:
Major finding: Black participants with one or more risk factors had a 10% or greater risk of type 2 diabetes at a BMI of 24.7 kg/m2; Hispanic participants had the same risk at 23.8 kg/m2; and Chinese Americans at 21.7 kg/mg2, all of which are below the BMI cut points recommended by the ADA.
Study details: Review of 5,656 participants in the Multi-Ethnic Study of Atherosclerosis .
Disclosures: The National Heart, Lung, and Blood Institute sponsors MESA. Mr. Rodriguez was supported by grant from the National Institutes of Health/National Institute of Diabetes and Kidney Disease. The other investigators reported having no disclosures.
Source: Rodriguez L et al. ADA 2019, Abstract 115-OR.
Frontline pembro + chemo shows superiority against NSCLC
A combination of pembrolizumab and platinum chemotherapy is the most effective frontline treatment for patients with non–small cell lung cancer (NSCLC), according to a retrospective analysis of more than 16,000 patients.
The study showed that responses to therapy are best predicted by an aggregate of tumor mutational burden (TMB), programmed cell death ligand 1 (PD-L1) expression, and proportion of CD8+ T-cell tumor-infiltrating lymphocytes (TILs), reported Yunfang Yu, MD, of Sun Yat-sen University, Guangzhou, China, and colleagues.
“[I]mmunotherapy has produced inconsistent results in previous randomized clinical trials,” the investigators wrote, citing inconsistent survival outcomes in CheckMate-026 and publications by Takayama and Wu. “Moreover, independent immune-related biomarkers that are currently used, such as PD-L1 and TMB, have achieved clinical relevance for a selection of patients to some extent, but to our knowledge, they are still far from clear and established.” The report is in JAMA Network Open.
To gain clarity, the investigators performed a large-scale meta-analysis (n = 14,395) and individual patient-level study (n = 1,833) involving patients with NSCLC. Data were drawn from a variety of sources, including PubMed, EMBASE, Cochrane, conference proceedings, and others. Primary outcomes were median overall survival and progression-free survival. Secondary outcomes were objective response rate and durable clinical benefit. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was used as a reporting guideline.
Analysis showed the superiority of immunotherapy to conventional therapy with significantly extended median overall survival and progression-free survival, both with an immunotherapy-favoring hazard ratio (HR) of 0.76 (P less than .001). Immunotherapy survival advantages were also reported individually for checkpoint inhibitors (HR, 0.75), tumor vaccines (HR, 0.83), and cellular immunotherapy (HR, 0.40). Of these three, checkpoint inhibitors and tumor vaccines showed superiority for progression-free survival. For first-line therapy, a combination of a pembrolizumab and chemotherapy was associated with better progression-free and overall survival than were other immunotherapies.
For patients treated with checkpoint inhibitors, higher levels of PD-L1 expression, TMB, or neo-antigen burden (NAB) were each prognostically valuable; however, the most powerful predictive tool was a combination of PD-L1 expression, TMB, and proportion of CD8+ T-cell TILs, with a 3-year overall survival area under the curve of 0.659. In addition, RYR1 and MGAM mutations were independently associated with durable clinical benefits.
“Future development of an optimized, integrated predictive model for immunotherapy should consider the integration of multiple approaches involving biomarkers associated with the T cell–inflamed tumor microenvironment, such as PD-L1 expression, ICs, and those associated with tumor neoepitope burden,” the investigators wrote.
The study was funded by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, and Guangzhou Science and Technology Program. The investigators disclosed no conflicts of interest.
SOURCE: Yu et al. JAMA Open. 2019 Jul 10. doi: 10.1001/jamanetworkopen.2019.6879.
A combination of pembrolizumab and platinum chemotherapy is the most effective frontline treatment for patients with non–small cell lung cancer (NSCLC), according to a retrospective analysis of more than 16,000 patients.
The study showed that responses to therapy are best predicted by an aggregate of tumor mutational burden (TMB), programmed cell death ligand 1 (PD-L1) expression, and proportion of CD8+ T-cell tumor-infiltrating lymphocytes (TILs), reported Yunfang Yu, MD, of Sun Yat-sen University, Guangzhou, China, and colleagues.
“[I]mmunotherapy has produced inconsistent results in previous randomized clinical trials,” the investigators wrote, citing inconsistent survival outcomes in CheckMate-026 and publications by Takayama and Wu. “Moreover, independent immune-related biomarkers that are currently used, such as PD-L1 and TMB, have achieved clinical relevance for a selection of patients to some extent, but to our knowledge, they are still far from clear and established.” The report is in JAMA Network Open.
To gain clarity, the investigators performed a large-scale meta-analysis (n = 14,395) and individual patient-level study (n = 1,833) involving patients with NSCLC. Data were drawn from a variety of sources, including PubMed, EMBASE, Cochrane, conference proceedings, and others. Primary outcomes were median overall survival and progression-free survival. Secondary outcomes were objective response rate and durable clinical benefit. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was used as a reporting guideline.
Analysis showed the superiority of immunotherapy to conventional therapy with significantly extended median overall survival and progression-free survival, both with an immunotherapy-favoring hazard ratio (HR) of 0.76 (P less than .001). Immunotherapy survival advantages were also reported individually for checkpoint inhibitors (HR, 0.75), tumor vaccines (HR, 0.83), and cellular immunotherapy (HR, 0.40). Of these three, checkpoint inhibitors and tumor vaccines showed superiority for progression-free survival. For first-line therapy, a combination of a pembrolizumab and chemotherapy was associated with better progression-free and overall survival than were other immunotherapies.
For patients treated with checkpoint inhibitors, higher levels of PD-L1 expression, TMB, or neo-antigen burden (NAB) were each prognostically valuable; however, the most powerful predictive tool was a combination of PD-L1 expression, TMB, and proportion of CD8+ T-cell TILs, with a 3-year overall survival area under the curve of 0.659. In addition, RYR1 and MGAM mutations were independently associated with durable clinical benefits.
“Future development of an optimized, integrated predictive model for immunotherapy should consider the integration of multiple approaches involving biomarkers associated with the T cell–inflamed tumor microenvironment, such as PD-L1 expression, ICs, and those associated with tumor neoepitope burden,” the investigators wrote.
The study was funded by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, and Guangzhou Science and Technology Program. The investigators disclosed no conflicts of interest.
SOURCE: Yu et al. JAMA Open. 2019 Jul 10. doi: 10.1001/jamanetworkopen.2019.6879.
A combination of pembrolizumab and platinum chemotherapy is the most effective frontline treatment for patients with non–small cell lung cancer (NSCLC), according to a retrospective analysis of more than 16,000 patients.
The study showed that responses to therapy are best predicted by an aggregate of tumor mutational burden (TMB), programmed cell death ligand 1 (PD-L1) expression, and proportion of CD8+ T-cell tumor-infiltrating lymphocytes (TILs), reported Yunfang Yu, MD, of Sun Yat-sen University, Guangzhou, China, and colleagues.
“[I]mmunotherapy has produced inconsistent results in previous randomized clinical trials,” the investigators wrote, citing inconsistent survival outcomes in CheckMate-026 and publications by Takayama and Wu. “Moreover, independent immune-related biomarkers that are currently used, such as PD-L1 and TMB, have achieved clinical relevance for a selection of patients to some extent, but to our knowledge, they are still far from clear and established.” The report is in JAMA Network Open.
To gain clarity, the investigators performed a large-scale meta-analysis (n = 14,395) and individual patient-level study (n = 1,833) involving patients with NSCLC. Data were drawn from a variety of sources, including PubMed, EMBASE, Cochrane, conference proceedings, and others. Primary outcomes were median overall survival and progression-free survival. Secondary outcomes were objective response rate and durable clinical benefit. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was used as a reporting guideline.
Analysis showed the superiority of immunotherapy to conventional therapy with significantly extended median overall survival and progression-free survival, both with an immunotherapy-favoring hazard ratio (HR) of 0.76 (P less than .001). Immunotherapy survival advantages were also reported individually for checkpoint inhibitors (HR, 0.75), tumor vaccines (HR, 0.83), and cellular immunotherapy (HR, 0.40). Of these three, checkpoint inhibitors and tumor vaccines showed superiority for progression-free survival. For first-line therapy, a combination of a pembrolizumab and chemotherapy was associated with better progression-free and overall survival than were other immunotherapies.
For patients treated with checkpoint inhibitors, higher levels of PD-L1 expression, TMB, or neo-antigen burden (NAB) were each prognostically valuable; however, the most powerful predictive tool was a combination of PD-L1 expression, TMB, and proportion of CD8+ T-cell TILs, with a 3-year overall survival area under the curve of 0.659. In addition, RYR1 and MGAM mutations were independently associated with durable clinical benefits.
“Future development of an optimized, integrated predictive model for immunotherapy should consider the integration of multiple approaches involving biomarkers associated with the T cell–inflamed tumor microenvironment, such as PD-L1 expression, ICs, and those associated with tumor neoepitope burden,” the investigators wrote.
The study was funded by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, and Guangzhou Science and Technology Program. The investigators disclosed no conflicts of interest.
SOURCE: Yu et al. JAMA Open. 2019 Jul 10. doi: 10.1001/jamanetworkopen.2019.6879.
FROM JAMA NETWORK OPEN
Thelarche and menarche are associated with increased prevalence of migraine
PHILADELPHIA – , according to research presented at the annual meeting of the American Headache Society. The results suggest that earlier exposure to estrogen increases the risk for migraine in adolescent girls, said Vincent Martin, MD, director of the Headache and Facial Pain Center at the University of Cincinnati Gardner Neuroscience Institute.
Previous studies observed an association between earlier onset of menarche and greater prevalence of migraine in adolescent girls, but no investigators had examined the relationship between earlier stages of pubertal development, such as thelarche and pubarche, and migraine.
Dr. Martin and colleagues included participants in the Breast Cancer and Environment Research Program puberty cohort in their study. Physicians examined the girls every 6 to 12 months from the time that they were aged 6-8 years to the time of late adolescence. During the last examination, participants responded to a validated questionnaire to determine whether they met International Classification of Headache Disorders–3 criteria for a diagnosis of migraine. Dr. Martin and colleagues performed logistic regression to examine whether age at thelarche, pubarche, or menarche predicted migraine.
Of 761 girls included in this study, 85 (11.2%) received a diagnosis of migraine. The mean age at which the questionnaire was administered was 15.6 years. After adjusting the data for potential confounders, the researchers found that an earlier age of onset of thelarche and menarche was associated with a higher prevalence of migraine. A 1-year decrease in the age of onset of thelarche or menarche was associated with a 32.8% or 33.8% increase in the odds of migraine headache, respectively. Pubarche was not associated with migraine.
Dr. Martin had no relevant disclosures.
PHILADELPHIA – , according to research presented at the annual meeting of the American Headache Society. The results suggest that earlier exposure to estrogen increases the risk for migraine in adolescent girls, said Vincent Martin, MD, director of the Headache and Facial Pain Center at the University of Cincinnati Gardner Neuroscience Institute.
Previous studies observed an association between earlier onset of menarche and greater prevalence of migraine in adolescent girls, but no investigators had examined the relationship between earlier stages of pubertal development, such as thelarche and pubarche, and migraine.
Dr. Martin and colleagues included participants in the Breast Cancer and Environment Research Program puberty cohort in their study. Physicians examined the girls every 6 to 12 months from the time that they were aged 6-8 years to the time of late adolescence. During the last examination, participants responded to a validated questionnaire to determine whether they met International Classification of Headache Disorders–3 criteria for a diagnosis of migraine. Dr. Martin and colleagues performed logistic regression to examine whether age at thelarche, pubarche, or menarche predicted migraine.
Of 761 girls included in this study, 85 (11.2%) received a diagnosis of migraine. The mean age at which the questionnaire was administered was 15.6 years. After adjusting the data for potential confounders, the researchers found that an earlier age of onset of thelarche and menarche was associated with a higher prevalence of migraine. A 1-year decrease in the age of onset of thelarche or menarche was associated with a 32.8% or 33.8% increase in the odds of migraine headache, respectively. Pubarche was not associated with migraine.
Dr. Martin had no relevant disclosures.
PHILADELPHIA – , according to research presented at the annual meeting of the American Headache Society. The results suggest that earlier exposure to estrogen increases the risk for migraine in adolescent girls, said Vincent Martin, MD, director of the Headache and Facial Pain Center at the University of Cincinnati Gardner Neuroscience Institute.
Previous studies observed an association between earlier onset of menarche and greater prevalence of migraine in adolescent girls, but no investigators had examined the relationship between earlier stages of pubertal development, such as thelarche and pubarche, and migraine.
Dr. Martin and colleagues included participants in the Breast Cancer and Environment Research Program puberty cohort in their study. Physicians examined the girls every 6 to 12 months from the time that they were aged 6-8 years to the time of late adolescence. During the last examination, participants responded to a validated questionnaire to determine whether they met International Classification of Headache Disorders–3 criteria for a diagnosis of migraine. Dr. Martin and colleagues performed logistic regression to examine whether age at thelarche, pubarche, or menarche predicted migraine.
Of 761 girls included in this study, 85 (11.2%) received a diagnosis of migraine. The mean age at which the questionnaire was administered was 15.6 years. After adjusting the data for potential confounders, the researchers found that an earlier age of onset of thelarche and menarche was associated with a higher prevalence of migraine. A 1-year decrease in the age of onset of thelarche or menarche was associated with a 32.8% or 33.8% increase in the odds of migraine headache, respectively. Pubarche was not associated with migraine.
Dr. Martin had no relevant disclosures.
EXPERT ANALYSIS FROM AHS 2019
Abnormal uterine bleeding: When can you forgo biopsy?
NASHVILLE, TENN. – Ultrasound is a reasonable first step for the evaluation of postmenopausal women with abnormal uterine bleeding and endometrial thickness up to 5 mm, according to James Shwayder, MD, JD.
About a third of such patients presenting with abnormal uterine bleeding (AUB) will have an endometrial polyp or submucous myoma, Dr. Shwayder explained during a presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
However, recurrent bleeding warrants further work-up, he said.
The 5-mm value is based on a number of studies, which, in sum, show that the negative predictive value for cancer for endometrial thickness less than 4 mm is greater than 99%, said Dr. Shwayder, chief of the division of gynecology and director of the fellowship in advanced endoscopy obstetrics, gynecology, and women’s health at the University of Louisville (Ky.).
“In fact ... the risk of cancer is 1 in 917,” he added. “That’s pretty good ... that’s a great screening tool.”
The question is whether one can feel comfortable foregoing biopsy in such cases, he said, describing a 61-year-old patient with a 3.9-mm endometrium and AUB for 3 days, 3 weeks prior to her visit.
There are two possibilities: The patient will either have no further bleeding, or she will continue to bleed, he said, noting that a 2003 Swedish study provides some guidance in the case of continued bleeding (Am J Obstet Gynecol. 2003;188:401-8).
The investigators initially looked at histology associated with endometrial thickness in 394 postmenopausal women referred for AUB between 1987 and 1990. Both transvaginal ultrasound and dilatation and curettage were performed, and the findings were correlated.
“But they had the rare opportunity to take patients who had benign evaluations and bring them back 10 years later,” Dr. Shwayder said. “What they found was that, regardless of the endometrial thickness, if it was benign initially and they did not bleed over that 10-year period, no one had cancer.”
However, among the patients followed for 10 years who had recurrent bleeding, 10% had cancer and 12% had hyperplasia. Thus, deciding against a biopsy in this case is supported by good data; if the patient doesn’t bleed, she has an “incredibly low risk of cancer,” he said.
“If they bleed again, you’ve gotta work ‘em up,” he stressed. “Don’t continue to say, ‘Well, let me repeat the ultrasound and see if it’s thinner or thicker.’ No. They need to be evaluated.”
Keep in mind that if a biopsy is performed as the first step, the chances of the results coming back as tissue insufficient for diagnosis (TIFD) are increased, and a repeat biopsy will be necessary because of the inconclusive findings, Dr. Shwayder said. It helps to warn a patient in advance that their thin endometrium makes it highly likely that a repeat biopsy will be necessary, as 90% come back as TIFD or atrophy.
Importantly, though, ACOG says endometrial sampling should be performed first line in patients over age 45 years with AUB.
“I’ll be honest – I use ultrasound in these patients because of the fact that a third will have some sort of structural defect, and the focal abnormalities are things we’re not going to be able to pick up with a straight biopsy, but we have to be cognizant that the college recommends biopsy in this population,” Dr. Shwayder said.
Asymptomatic endometrial thickening
Postmenopausal women are increasingly being referred for asymptomatic endometrial thickening that is found incidentally during an unrelated evaluation, Dr. Shwayder said, noting that evidence to date on how to approach such cases is conflicting.
Although ACOG is working on a recommendation, none is currently available, he said.
However, a 2001 study comparing 123 asymptomatic patients with 90 symptomatic patients, all with an endometrial thickness of greater than 10 mm, found no prognostic advantage to screening versus waiting until bleeding occurred, he noted (Euro J Cancer. 2001;37:64-71).
Overall, 13% of the patients had cancer, 50% had polyps, and 17% had hyperplasia.
“But what they emphasized was ... the length [of time] the patients complained of abnormal uterine bleeding. If it was less than 8 weeks ... there was no statistical difference in outcome, but if it was over 8 weeks there was a statistically significant difference in the grade of disease – a prognostic advantage for those patients who were screened versus symptomatic.”
The overall 5-year disease-free survival was 86% for asymptomatic versus 77% for symptomatic patients; for those with bleeding for less than 8 weeks, it was 98% versus 83%, respectively. The differences were not statistically different. However, for those with bleeding for 8-16 weeks it was 90% versus 74%, and for those with bleeding for more than 16 weeks it was 69% versus 62%, respectively, and those differences were statistically significant.
The problem is that many patients put off coming in for a long time, which means they are in a category with a worse prognosis when they do come in, Dr. Shwayder said. That’s not to say everyone should be screened, but there is no prognostic advantage to screening asymptomatic patients versus symptomatic patients who had bleeding for less than 8 weeks.
“It’s a little clarification, but I think an important one,” he noted.
Another study of 1,607 patients with endometrial thickening, including 233 who were asymptomatic and 1,374 who were symptomatic, found a lower rate of deep invasion with stage 1 disease, but no difference in the rate of more advanced disease, and no association with a more favorable outcome between the groups. (Am J Obstet Gynecol. 2018;219[2]:183e1-6).
Additionally, a study of 42 asymptomatic patients, 95 symptomatic patients with bleeding for less than 3 months, and 83 symptomatic patients with bleeding for more than 3 months showed a nonsignificant trend toward poorer 5-year survival in patients with a longer history of bleeding prior to surgery (Arch Gynecol Obstet 2013;288:1361-4).
“So now the question becomes how thick is too thick [and whether there is] some threshold where we ought to be evaluating patients and some threshold where we’re not,” he said.
The risk of malignancy among symptomatic postmenopausal women with an endometrial thickness greater than 5 mm is 7.3%, and the risk is similar at 6.7% in asymptomatic patients with an endometrial thickness of 11 mm or greater, according to a 2004 study by Smith-Bindman et al. (Ultrasound Obstet Gynecol. 2004;24:558-65).
“So the thought process here is that if a patient is asymptomatic, but the endometrium is over 11 mm, maybe we ought to evaluate that patient, because her risk of cancer is equivalent to that of someone who presents with postmenopausal bleeding and has an endometrium greater than 5 mm,” he explained.
In fact, a practice guideline from the Society of Obstetricians and Gynecologists of Canada recommends that women with endometrial thickness over 11 mm and other risk factors for cancer – such as obesity, hypertension, or late menopause – should be referred to a gynecologist for investigation, Dr. Shwayder said, adding that he also considers increased vascularity, heterogeneity in the endometrium, and fluid seen on a scan as cause for further evaluation.
“But endometrial sampling without bleeding should not be routinely performed,” he said. “So don’t routinely [sample] but based on risk factors and ultrasound findings, you may want to consider evaluating these patients further.”
Dr. Shwayder is a consultant for GE Ultrasound.
NASHVILLE, TENN. – Ultrasound is a reasonable first step for the evaluation of postmenopausal women with abnormal uterine bleeding and endometrial thickness up to 5 mm, according to James Shwayder, MD, JD.
About a third of such patients presenting with abnormal uterine bleeding (AUB) will have an endometrial polyp or submucous myoma, Dr. Shwayder explained during a presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
However, recurrent bleeding warrants further work-up, he said.
The 5-mm value is based on a number of studies, which, in sum, show that the negative predictive value for cancer for endometrial thickness less than 4 mm is greater than 99%, said Dr. Shwayder, chief of the division of gynecology and director of the fellowship in advanced endoscopy obstetrics, gynecology, and women’s health at the University of Louisville (Ky.).
“In fact ... the risk of cancer is 1 in 917,” he added. “That’s pretty good ... that’s a great screening tool.”
The question is whether one can feel comfortable foregoing biopsy in such cases, he said, describing a 61-year-old patient with a 3.9-mm endometrium and AUB for 3 days, 3 weeks prior to her visit.
There are two possibilities: The patient will either have no further bleeding, or she will continue to bleed, he said, noting that a 2003 Swedish study provides some guidance in the case of continued bleeding (Am J Obstet Gynecol. 2003;188:401-8).
The investigators initially looked at histology associated with endometrial thickness in 394 postmenopausal women referred for AUB between 1987 and 1990. Both transvaginal ultrasound and dilatation and curettage were performed, and the findings were correlated.
“But they had the rare opportunity to take patients who had benign evaluations and bring them back 10 years later,” Dr. Shwayder said. “What they found was that, regardless of the endometrial thickness, if it was benign initially and they did not bleed over that 10-year period, no one had cancer.”
However, among the patients followed for 10 years who had recurrent bleeding, 10% had cancer and 12% had hyperplasia. Thus, deciding against a biopsy in this case is supported by good data; if the patient doesn’t bleed, she has an “incredibly low risk of cancer,” he said.
“If they bleed again, you’ve gotta work ‘em up,” he stressed. “Don’t continue to say, ‘Well, let me repeat the ultrasound and see if it’s thinner or thicker.’ No. They need to be evaluated.”
Keep in mind that if a biopsy is performed as the first step, the chances of the results coming back as tissue insufficient for diagnosis (TIFD) are increased, and a repeat biopsy will be necessary because of the inconclusive findings, Dr. Shwayder said. It helps to warn a patient in advance that their thin endometrium makes it highly likely that a repeat biopsy will be necessary, as 90% come back as TIFD or atrophy.
Importantly, though, ACOG says endometrial sampling should be performed first line in patients over age 45 years with AUB.
“I’ll be honest – I use ultrasound in these patients because of the fact that a third will have some sort of structural defect, and the focal abnormalities are things we’re not going to be able to pick up with a straight biopsy, but we have to be cognizant that the college recommends biopsy in this population,” Dr. Shwayder said.
Asymptomatic endometrial thickening
Postmenopausal women are increasingly being referred for asymptomatic endometrial thickening that is found incidentally during an unrelated evaluation, Dr. Shwayder said, noting that evidence to date on how to approach such cases is conflicting.
Although ACOG is working on a recommendation, none is currently available, he said.
However, a 2001 study comparing 123 asymptomatic patients with 90 symptomatic patients, all with an endometrial thickness of greater than 10 mm, found no prognostic advantage to screening versus waiting until bleeding occurred, he noted (Euro J Cancer. 2001;37:64-71).
Overall, 13% of the patients had cancer, 50% had polyps, and 17% had hyperplasia.
“But what they emphasized was ... the length [of time] the patients complained of abnormal uterine bleeding. If it was less than 8 weeks ... there was no statistical difference in outcome, but if it was over 8 weeks there was a statistically significant difference in the grade of disease – a prognostic advantage for those patients who were screened versus symptomatic.”
The overall 5-year disease-free survival was 86% for asymptomatic versus 77% for symptomatic patients; for those with bleeding for less than 8 weeks, it was 98% versus 83%, respectively. The differences were not statistically different. However, for those with bleeding for 8-16 weeks it was 90% versus 74%, and for those with bleeding for more than 16 weeks it was 69% versus 62%, respectively, and those differences were statistically significant.
The problem is that many patients put off coming in for a long time, which means they are in a category with a worse prognosis when they do come in, Dr. Shwayder said. That’s not to say everyone should be screened, but there is no prognostic advantage to screening asymptomatic patients versus symptomatic patients who had bleeding for less than 8 weeks.
“It’s a little clarification, but I think an important one,” he noted.
Another study of 1,607 patients with endometrial thickening, including 233 who were asymptomatic and 1,374 who were symptomatic, found a lower rate of deep invasion with stage 1 disease, but no difference in the rate of more advanced disease, and no association with a more favorable outcome between the groups. (Am J Obstet Gynecol. 2018;219[2]:183e1-6).
Additionally, a study of 42 asymptomatic patients, 95 symptomatic patients with bleeding for less than 3 months, and 83 symptomatic patients with bleeding for more than 3 months showed a nonsignificant trend toward poorer 5-year survival in patients with a longer history of bleeding prior to surgery (Arch Gynecol Obstet 2013;288:1361-4).
“So now the question becomes how thick is too thick [and whether there is] some threshold where we ought to be evaluating patients and some threshold where we’re not,” he said.
The risk of malignancy among symptomatic postmenopausal women with an endometrial thickness greater than 5 mm is 7.3%, and the risk is similar at 6.7% in asymptomatic patients with an endometrial thickness of 11 mm or greater, according to a 2004 study by Smith-Bindman et al. (Ultrasound Obstet Gynecol. 2004;24:558-65).
“So the thought process here is that if a patient is asymptomatic, but the endometrium is over 11 mm, maybe we ought to evaluate that patient, because her risk of cancer is equivalent to that of someone who presents with postmenopausal bleeding and has an endometrium greater than 5 mm,” he explained.
In fact, a practice guideline from the Society of Obstetricians and Gynecologists of Canada recommends that women with endometrial thickness over 11 mm and other risk factors for cancer – such as obesity, hypertension, or late menopause – should be referred to a gynecologist for investigation, Dr. Shwayder said, adding that he also considers increased vascularity, heterogeneity in the endometrium, and fluid seen on a scan as cause for further evaluation.
“But endometrial sampling without bleeding should not be routinely performed,” he said. “So don’t routinely [sample] but based on risk factors and ultrasound findings, you may want to consider evaluating these patients further.”
Dr. Shwayder is a consultant for GE Ultrasound.
NASHVILLE, TENN. – Ultrasound is a reasonable first step for the evaluation of postmenopausal women with abnormal uterine bleeding and endometrial thickness up to 5 mm, according to James Shwayder, MD, JD.
About a third of such patients presenting with abnormal uterine bleeding (AUB) will have an endometrial polyp or submucous myoma, Dr. Shwayder explained during a presentation at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
However, recurrent bleeding warrants further work-up, he said.
The 5-mm value is based on a number of studies, which, in sum, show that the negative predictive value for cancer for endometrial thickness less than 4 mm is greater than 99%, said Dr. Shwayder, chief of the division of gynecology and director of the fellowship in advanced endoscopy obstetrics, gynecology, and women’s health at the University of Louisville (Ky.).
“In fact ... the risk of cancer is 1 in 917,” he added. “That’s pretty good ... that’s a great screening tool.”
The question is whether one can feel comfortable foregoing biopsy in such cases, he said, describing a 61-year-old patient with a 3.9-mm endometrium and AUB for 3 days, 3 weeks prior to her visit.
There are two possibilities: The patient will either have no further bleeding, or she will continue to bleed, he said, noting that a 2003 Swedish study provides some guidance in the case of continued bleeding (Am J Obstet Gynecol. 2003;188:401-8).
The investigators initially looked at histology associated with endometrial thickness in 394 postmenopausal women referred for AUB between 1987 and 1990. Both transvaginal ultrasound and dilatation and curettage were performed, and the findings were correlated.
“But they had the rare opportunity to take patients who had benign evaluations and bring them back 10 years later,” Dr. Shwayder said. “What they found was that, regardless of the endometrial thickness, if it was benign initially and they did not bleed over that 10-year period, no one had cancer.”
However, among the patients followed for 10 years who had recurrent bleeding, 10% had cancer and 12% had hyperplasia. Thus, deciding against a biopsy in this case is supported by good data; if the patient doesn’t bleed, she has an “incredibly low risk of cancer,” he said.
“If they bleed again, you’ve gotta work ‘em up,” he stressed. “Don’t continue to say, ‘Well, let me repeat the ultrasound and see if it’s thinner or thicker.’ No. They need to be evaluated.”
Keep in mind that if a biopsy is performed as the first step, the chances of the results coming back as tissue insufficient for diagnosis (TIFD) are increased, and a repeat biopsy will be necessary because of the inconclusive findings, Dr. Shwayder said. It helps to warn a patient in advance that their thin endometrium makes it highly likely that a repeat biopsy will be necessary, as 90% come back as TIFD or atrophy.
Importantly, though, ACOG says endometrial sampling should be performed first line in patients over age 45 years with AUB.
“I’ll be honest – I use ultrasound in these patients because of the fact that a third will have some sort of structural defect, and the focal abnormalities are things we’re not going to be able to pick up with a straight biopsy, but we have to be cognizant that the college recommends biopsy in this population,” Dr. Shwayder said.
Asymptomatic endometrial thickening
Postmenopausal women are increasingly being referred for asymptomatic endometrial thickening that is found incidentally during an unrelated evaluation, Dr. Shwayder said, noting that evidence to date on how to approach such cases is conflicting.
Although ACOG is working on a recommendation, none is currently available, he said.
However, a 2001 study comparing 123 asymptomatic patients with 90 symptomatic patients, all with an endometrial thickness of greater than 10 mm, found no prognostic advantage to screening versus waiting until bleeding occurred, he noted (Euro J Cancer. 2001;37:64-71).
Overall, 13% of the patients had cancer, 50% had polyps, and 17% had hyperplasia.
“But what they emphasized was ... the length [of time] the patients complained of abnormal uterine bleeding. If it was less than 8 weeks ... there was no statistical difference in outcome, but if it was over 8 weeks there was a statistically significant difference in the grade of disease – a prognostic advantage for those patients who were screened versus symptomatic.”
The overall 5-year disease-free survival was 86% for asymptomatic versus 77% for symptomatic patients; for those with bleeding for less than 8 weeks, it was 98% versus 83%, respectively. The differences were not statistically different. However, for those with bleeding for 8-16 weeks it was 90% versus 74%, and for those with bleeding for more than 16 weeks it was 69% versus 62%, respectively, and those differences were statistically significant.
The problem is that many patients put off coming in for a long time, which means they are in a category with a worse prognosis when they do come in, Dr. Shwayder said. That’s not to say everyone should be screened, but there is no prognostic advantage to screening asymptomatic patients versus symptomatic patients who had bleeding for less than 8 weeks.
“It’s a little clarification, but I think an important one,” he noted.
Another study of 1,607 patients with endometrial thickening, including 233 who were asymptomatic and 1,374 who were symptomatic, found a lower rate of deep invasion with stage 1 disease, but no difference in the rate of more advanced disease, and no association with a more favorable outcome between the groups. (Am J Obstet Gynecol. 2018;219[2]:183e1-6).
Additionally, a study of 42 asymptomatic patients, 95 symptomatic patients with bleeding for less than 3 months, and 83 symptomatic patients with bleeding for more than 3 months showed a nonsignificant trend toward poorer 5-year survival in patients with a longer history of bleeding prior to surgery (Arch Gynecol Obstet 2013;288:1361-4).
“So now the question becomes how thick is too thick [and whether there is] some threshold where we ought to be evaluating patients and some threshold where we’re not,” he said.
The risk of malignancy among symptomatic postmenopausal women with an endometrial thickness greater than 5 mm is 7.3%, and the risk is similar at 6.7% in asymptomatic patients with an endometrial thickness of 11 mm or greater, according to a 2004 study by Smith-Bindman et al. (Ultrasound Obstet Gynecol. 2004;24:558-65).
“So the thought process here is that if a patient is asymptomatic, but the endometrium is over 11 mm, maybe we ought to evaluate that patient, because her risk of cancer is equivalent to that of someone who presents with postmenopausal bleeding and has an endometrium greater than 5 mm,” he explained.
In fact, a practice guideline from the Society of Obstetricians and Gynecologists of Canada recommends that women with endometrial thickness over 11 mm and other risk factors for cancer – such as obesity, hypertension, or late menopause – should be referred to a gynecologist for investigation, Dr. Shwayder said, adding that he also considers increased vascularity, heterogeneity in the endometrium, and fluid seen on a scan as cause for further evaluation.
“But endometrial sampling without bleeding should not be routinely performed,” he said. “So don’t routinely [sample] but based on risk factors and ultrasound findings, you may want to consider evaluating these patients further.”
Dr. Shwayder is a consultant for GE Ultrasound.
EXPERT ANALYSIS FROM ACOG 2019
Patients with AD should routinely be asked about conjunctivitis
according to a recent position statement from the International Eczema Council.
Patients with AD who develop conjunctivitis during dupilumab treatment may experience “bilateral inflammation of the anterior conjunctiva and hyperaemia of the limbus, which may cause nodular swelling.”according to the statement, which pertains to conjunctivitis in AD patients, “with and without dupilumab therapy.” (J Eur Acad Dermatol Venereol. 2019 May 6. doi: 10.1111/jdv.15608). Currently, there are no predictive factors of conjunctivitis and no guidance in the literature on how to manage conjunctivitis associated with dupilumab, which in some cases can make it necessary to stop treatment, the authors wrote.
The International Eczema Council (IEC) polled 86 dermatologists in 22 countries who are experts in AD; 46 members responded from 19 countries, including dermatologists from Australia, Canada, Denmark, France, Germany, Japan, Korea, the Netherlands, the United Kingdom, and the United States. The questions centered on the diagnosis and management of conjunctivitis in AD patients, and whether to refer cases to an ophthalmologist. Consensus was achieved if less than 30% of participants disagreed with a statement. IEC members then met in person at a European Academy of Dermatology and Venereology meeting in Paris to discuss the results of the survey. Survey respondents noted they had seen dupilumab-associated conjunctivitis in both pediatric and adult patients.
The IEC members recommended that:
- Patients should be informed about the risks of conjunctivitis before being prescribed dupilumab.
- AD patients should be asked “routinely” about ocular complaints or symptoms.
- AD patients with conjunctivitis should be referred to an ophthalmologist for diagnosis and treatment.
- AD patients with new-onset conjunctivitis during dupilumab treatment always should be referred to an ophthalmologist, especially in more severe cases such as when they do not respond to treatment with antihistamine or artificial tears.
- Dermatologists also should rule out keratoconjunctivitis before treating with dupilumab, as it may cause keratitis and blindness.
- Patients who have had keratoconjunctivitis in the past should not be precluded from treatment with dupilumab, and those who develop conjunctivitis during treatment should be referred to an ophthalmologist – but should stay on treatment while waiting for the consult.
“It was stressed that at this moment there are also no reliable data on the course of atopic keratoconjunctivitis and vernal keratoconjunctivitis during dupilumab treatment,” according to Jacob P. Thyssen, MD, PhD, Herlev and Gentofte Hospital, Hellerup, Denmark, and coauthors. These patients “should be carefully monitored by an ophthalmologist before and during treatment with dupilumab.”
The recommendations also centered around which treatments should be initiated by dermatologists, and which should be referred to ophthalmologists. Those patients with conjunctivitis should receive eye drops, eye ointment, or oral antihistamines from their dermatologists before an ophthalmology referral, the IEC members said. Dermatologists also should perform, or refer patients for, skin prick testing or specific IgE testing for aeroallergens in patients with AD who have conjunctivitis, and patch testing with an “ophthalmologic series, and native eye drops/ointments to diagnose possible delayed type hypersensitivity reactions to topical ingredients,” they added.
Among the treatments for conjunctivitis best left to ophthalmologists are cyclosporine, tacrolimus, or corticosteroid eye drops.
“Despite the more limited experience with eye drops by dermatologists, rapid access to ophthalmological service may be difficult, sometimes warranting a short course of corticosteroid eye drops without ophthalmological consultations,” Dr. Thyssen and associates said. “However, persistent or recurrent conjunctivitis requiring repeated or prolonged use of corticosteroid, tacrolimus, and ciclosporin-containing eye drops, must be managed by an ophthalmologist, given the risk of glaucoma, cataract, and infections.”
“The AD severity, conjunctivitis severity, possible contraindications, possible effect of dupilumab therapy on concomitant asthma or other comorbidities, as well as other treatment options, should be considered on an individual patient basis,” the authors concluded.
The IEC survey was limited by the small survey response and reliance on expert opinion.
The authors reported personal and institutional relationships in the form of grants, corporate sponsorships, advisory board memberships, investigator appointments, speakers bureau positions, and consultancies for a variety of pharmaceutical companies, agencies, societies, and other organizations. No funding was obtained for the study.
This article was updated 7/17/19.
according to a recent position statement from the International Eczema Council.
Patients with AD who develop conjunctivitis during dupilumab treatment may experience “bilateral inflammation of the anterior conjunctiva and hyperaemia of the limbus, which may cause nodular swelling.”according to the statement, which pertains to conjunctivitis in AD patients, “with and without dupilumab therapy.” (J Eur Acad Dermatol Venereol. 2019 May 6. doi: 10.1111/jdv.15608). Currently, there are no predictive factors of conjunctivitis and no guidance in the literature on how to manage conjunctivitis associated with dupilumab, which in some cases can make it necessary to stop treatment, the authors wrote.
The International Eczema Council (IEC) polled 86 dermatologists in 22 countries who are experts in AD; 46 members responded from 19 countries, including dermatologists from Australia, Canada, Denmark, France, Germany, Japan, Korea, the Netherlands, the United Kingdom, and the United States. The questions centered on the diagnosis and management of conjunctivitis in AD patients, and whether to refer cases to an ophthalmologist. Consensus was achieved if less than 30% of participants disagreed with a statement. IEC members then met in person at a European Academy of Dermatology and Venereology meeting in Paris to discuss the results of the survey. Survey respondents noted they had seen dupilumab-associated conjunctivitis in both pediatric and adult patients.
The IEC members recommended that:
- Patients should be informed about the risks of conjunctivitis before being prescribed dupilumab.
- AD patients should be asked “routinely” about ocular complaints or symptoms.
- AD patients with conjunctivitis should be referred to an ophthalmologist for diagnosis and treatment.
- AD patients with new-onset conjunctivitis during dupilumab treatment always should be referred to an ophthalmologist, especially in more severe cases such as when they do not respond to treatment with antihistamine or artificial tears.
- Dermatologists also should rule out keratoconjunctivitis before treating with dupilumab, as it may cause keratitis and blindness.
- Patients who have had keratoconjunctivitis in the past should not be precluded from treatment with dupilumab, and those who develop conjunctivitis during treatment should be referred to an ophthalmologist – but should stay on treatment while waiting for the consult.
“It was stressed that at this moment there are also no reliable data on the course of atopic keratoconjunctivitis and vernal keratoconjunctivitis during dupilumab treatment,” according to Jacob P. Thyssen, MD, PhD, Herlev and Gentofte Hospital, Hellerup, Denmark, and coauthors. These patients “should be carefully monitored by an ophthalmologist before and during treatment with dupilumab.”
The recommendations also centered around which treatments should be initiated by dermatologists, and which should be referred to ophthalmologists. Those patients with conjunctivitis should receive eye drops, eye ointment, or oral antihistamines from their dermatologists before an ophthalmology referral, the IEC members said. Dermatologists also should perform, or refer patients for, skin prick testing or specific IgE testing for aeroallergens in patients with AD who have conjunctivitis, and patch testing with an “ophthalmologic series, and native eye drops/ointments to diagnose possible delayed type hypersensitivity reactions to topical ingredients,” they added.
Among the treatments for conjunctivitis best left to ophthalmologists are cyclosporine, tacrolimus, or corticosteroid eye drops.
“Despite the more limited experience with eye drops by dermatologists, rapid access to ophthalmological service may be difficult, sometimes warranting a short course of corticosteroid eye drops without ophthalmological consultations,” Dr. Thyssen and associates said. “However, persistent or recurrent conjunctivitis requiring repeated or prolonged use of corticosteroid, tacrolimus, and ciclosporin-containing eye drops, must be managed by an ophthalmologist, given the risk of glaucoma, cataract, and infections.”
“The AD severity, conjunctivitis severity, possible contraindications, possible effect of dupilumab therapy on concomitant asthma or other comorbidities, as well as other treatment options, should be considered on an individual patient basis,” the authors concluded.
The IEC survey was limited by the small survey response and reliance on expert opinion.
The authors reported personal and institutional relationships in the form of grants, corporate sponsorships, advisory board memberships, investigator appointments, speakers bureau positions, and consultancies for a variety of pharmaceutical companies, agencies, societies, and other organizations. No funding was obtained for the study.
This article was updated 7/17/19.
according to a recent position statement from the International Eczema Council.
Patients with AD who develop conjunctivitis during dupilumab treatment may experience “bilateral inflammation of the anterior conjunctiva and hyperaemia of the limbus, which may cause nodular swelling.”according to the statement, which pertains to conjunctivitis in AD patients, “with and without dupilumab therapy.” (J Eur Acad Dermatol Venereol. 2019 May 6. doi: 10.1111/jdv.15608). Currently, there are no predictive factors of conjunctivitis and no guidance in the literature on how to manage conjunctivitis associated with dupilumab, which in some cases can make it necessary to stop treatment, the authors wrote.
The International Eczema Council (IEC) polled 86 dermatologists in 22 countries who are experts in AD; 46 members responded from 19 countries, including dermatologists from Australia, Canada, Denmark, France, Germany, Japan, Korea, the Netherlands, the United Kingdom, and the United States. The questions centered on the diagnosis and management of conjunctivitis in AD patients, and whether to refer cases to an ophthalmologist. Consensus was achieved if less than 30% of participants disagreed with a statement. IEC members then met in person at a European Academy of Dermatology and Venereology meeting in Paris to discuss the results of the survey. Survey respondents noted they had seen dupilumab-associated conjunctivitis in both pediatric and adult patients.
The IEC members recommended that:
- Patients should be informed about the risks of conjunctivitis before being prescribed dupilumab.
- AD patients should be asked “routinely” about ocular complaints or symptoms.
- AD patients with conjunctivitis should be referred to an ophthalmologist for diagnosis and treatment.
- AD patients with new-onset conjunctivitis during dupilumab treatment always should be referred to an ophthalmologist, especially in more severe cases such as when they do not respond to treatment with antihistamine or artificial tears.
- Dermatologists also should rule out keratoconjunctivitis before treating with dupilumab, as it may cause keratitis and blindness.
- Patients who have had keratoconjunctivitis in the past should not be precluded from treatment with dupilumab, and those who develop conjunctivitis during treatment should be referred to an ophthalmologist – but should stay on treatment while waiting for the consult.
“It was stressed that at this moment there are also no reliable data on the course of atopic keratoconjunctivitis and vernal keratoconjunctivitis during dupilumab treatment,” according to Jacob P. Thyssen, MD, PhD, Herlev and Gentofte Hospital, Hellerup, Denmark, and coauthors. These patients “should be carefully monitored by an ophthalmologist before and during treatment with dupilumab.”
The recommendations also centered around which treatments should be initiated by dermatologists, and which should be referred to ophthalmologists. Those patients with conjunctivitis should receive eye drops, eye ointment, or oral antihistamines from their dermatologists before an ophthalmology referral, the IEC members said. Dermatologists also should perform, or refer patients for, skin prick testing or specific IgE testing for aeroallergens in patients with AD who have conjunctivitis, and patch testing with an “ophthalmologic series, and native eye drops/ointments to diagnose possible delayed type hypersensitivity reactions to topical ingredients,” they added.
Among the treatments for conjunctivitis best left to ophthalmologists are cyclosporine, tacrolimus, or corticosteroid eye drops.
“Despite the more limited experience with eye drops by dermatologists, rapid access to ophthalmological service may be difficult, sometimes warranting a short course of corticosteroid eye drops without ophthalmological consultations,” Dr. Thyssen and associates said. “However, persistent or recurrent conjunctivitis requiring repeated or prolonged use of corticosteroid, tacrolimus, and ciclosporin-containing eye drops, must be managed by an ophthalmologist, given the risk of glaucoma, cataract, and infections.”
“The AD severity, conjunctivitis severity, possible contraindications, possible effect of dupilumab therapy on concomitant asthma or other comorbidities, as well as other treatment options, should be considered on an individual patient basis,” the authors concluded.
The IEC survey was limited by the small survey response and reliance on expert opinion.
The authors reported personal and institutional relationships in the form of grants, corporate sponsorships, advisory board memberships, investigator appointments, speakers bureau positions, and consultancies for a variety of pharmaceutical companies, agencies, societies, and other organizations. No funding was obtained for the study.
This article was updated 7/17/19.
FROM THE JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Smartphone-based system rivals clinical assessments of anxiety in bipolar disorder
In patients with bipolar disorder currently in partial or full remission, self-reporting of anxiety to a smartphone-based system matched clinical evaluations of anxiety, according to Maria Faurholt-Jepsen, MD, and her associates.
A total of 84 patients with bipolar disorder who participated in the randomized, controlled, single-blind, parallel-group MONARCA II trial were included in the study, reported Dr. Faurholt-Jepsen of Rigshospitalet in Copenhagen, and her associates. All patients reported their anxiety to the smartphone-based system every day for a 9-month period; all patients underwent clinical evaluations of anxiety, functioning, patient-reported stress, and quality of life at five fixed time points over the study period. The study was published online by the Journal of Affective Disorders.
Self-reported anxiety was mild, with 19.3% of patients reporting anxiety during the study period, and 2.6% reporting severe anxiety. No association was seen between gender and anxiety days, or between bipolar disorder type and anxiety days. Patients reported depressed mood on 43.2% of the days when anxiety was also reported, and reported mania on 48.0% of the days when anxiety was reported.
Self-reported anxiety scores were positively associated with the anxiety subitems on a key rating scale (P = .0001). In addition, self-reported anxiety was associated with perceived stress, quality of life, and functioning (P = .0001 for all three).
“ Frequent fine-grained monitoring in clinical, high-risk and epidemiological populations provides an opportunity to gain a better understanding of the nature, correlates, and clinical implications of [bipolar disorder],” the investigators wrote.
Three coauthors reported consulting with Eli Lilly, Astra Zeneca, Servier, Bristol-Myers Squibb, Lundbeck, Sunovion, and Medilink. Two coauthors are cofounders and shareholders in Monsenso.
SOURCE: Faurholt-Jepsen M et al. J Affect Disord. 2019. doi: 10.1016/j.jad.2019.07.029.
In patients with bipolar disorder currently in partial or full remission, self-reporting of anxiety to a smartphone-based system matched clinical evaluations of anxiety, according to Maria Faurholt-Jepsen, MD, and her associates.
A total of 84 patients with bipolar disorder who participated in the randomized, controlled, single-blind, parallel-group MONARCA II trial were included in the study, reported Dr. Faurholt-Jepsen of Rigshospitalet in Copenhagen, and her associates. All patients reported their anxiety to the smartphone-based system every day for a 9-month period; all patients underwent clinical evaluations of anxiety, functioning, patient-reported stress, and quality of life at five fixed time points over the study period. The study was published online by the Journal of Affective Disorders.
Self-reported anxiety was mild, with 19.3% of patients reporting anxiety during the study period, and 2.6% reporting severe anxiety. No association was seen between gender and anxiety days, or between bipolar disorder type and anxiety days. Patients reported depressed mood on 43.2% of the days when anxiety was also reported, and reported mania on 48.0% of the days when anxiety was reported.
Self-reported anxiety scores were positively associated with the anxiety subitems on a key rating scale (P = .0001). In addition, self-reported anxiety was associated with perceived stress, quality of life, and functioning (P = .0001 for all three).
“ Frequent fine-grained monitoring in clinical, high-risk and epidemiological populations provides an opportunity to gain a better understanding of the nature, correlates, and clinical implications of [bipolar disorder],” the investigators wrote.
Three coauthors reported consulting with Eli Lilly, Astra Zeneca, Servier, Bristol-Myers Squibb, Lundbeck, Sunovion, and Medilink. Two coauthors are cofounders and shareholders in Monsenso.
SOURCE: Faurholt-Jepsen M et al. J Affect Disord. 2019. doi: 10.1016/j.jad.2019.07.029.
In patients with bipolar disorder currently in partial or full remission, self-reporting of anxiety to a smartphone-based system matched clinical evaluations of anxiety, according to Maria Faurholt-Jepsen, MD, and her associates.
A total of 84 patients with bipolar disorder who participated in the randomized, controlled, single-blind, parallel-group MONARCA II trial were included in the study, reported Dr. Faurholt-Jepsen of Rigshospitalet in Copenhagen, and her associates. All patients reported their anxiety to the smartphone-based system every day for a 9-month period; all patients underwent clinical evaluations of anxiety, functioning, patient-reported stress, and quality of life at five fixed time points over the study period. The study was published online by the Journal of Affective Disorders.
Self-reported anxiety was mild, with 19.3% of patients reporting anxiety during the study period, and 2.6% reporting severe anxiety. No association was seen between gender and anxiety days, or between bipolar disorder type and anxiety days. Patients reported depressed mood on 43.2% of the days when anxiety was also reported, and reported mania on 48.0% of the days when anxiety was reported.
Self-reported anxiety scores were positively associated with the anxiety subitems on a key rating scale (P = .0001). In addition, self-reported anxiety was associated with perceived stress, quality of life, and functioning (P = .0001 for all three).
“ Frequent fine-grained monitoring in clinical, high-risk and epidemiological populations provides an opportunity to gain a better understanding of the nature, correlates, and clinical implications of [bipolar disorder],” the investigators wrote.
Three coauthors reported consulting with Eli Lilly, Astra Zeneca, Servier, Bristol-Myers Squibb, Lundbeck, Sunovion, and Medilink. Two coauthors are cofounders and shareholders in Monsenso.
SOURCE: Faurholt-Jepsen M et al. J Affect Disord. 2019. doi: 10.1016/j.jad.2019.07.029.
FROM THE JOURNAL OF AFFECTIVE DISORDERS