The new MDedge Dermatology podcast will feature Dr. Vincent A. DeLeo talking with colleagues about all things dermatology. The podcast will also feature news highlights.

Stop by our booth at AAD to chat with Dr. DeLeo!

Friday, March 1, 2019

2 pm to 3 pm

Booths 1721 and 1723

The new MDedge Dermatology podcast will feature Dr. Vincent A. DeLeo talking with colleagues about all things dermatology. The podcast will also feature news highlights.

Stop by our booth at AAD to chat with Dr. DeLeo!

Friday, March 1, 2019

2 pm to 3 pm

Booths 1721 and 1723

The new MDedge Dermatology podcast will feature Dr. Vincent A. DeLeo talking with colleagues about all things dermatology. The podcast will also feature news highlights.

Stop by our booth at AAD to chat with Dr. DeLeo!

Friday, March 1, 2019

2 pm to 3 pm

Booths 1721 and 1723

CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.

“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.

The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.

In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.

Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).

Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.

In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.

In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.

“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.

Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.

The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.

The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.

And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).

At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.

Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.

bjancin@mdedge.com

CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.

“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.

The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.

In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.

Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).

Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.

In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.

In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.

“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.

Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.

The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.

The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.

And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).

At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.

Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.

bjancin@mdedge.com

CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.

“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.

The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.

In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.

Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).

Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.

In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.

In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.

“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.

Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.

The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.

The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.

And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).

At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.

Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.

bjancin@mdedge.com

LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
 

Vidyard Video

In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).

The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).

The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.

“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.

Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.


Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.

PTCL cohort

The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.

The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.

Responses according to subtype were as follows:

• 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
• 2 CRs in PTCL not otherwise specified.
• 1 CR in gamma-delta T-cell lymphoma.
• 1 PR in ALK-negative anaplastic large-cell lymphoma.
• 1 CR and 1 PR in adult T-cell leukemia/lymphoma.

Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.

The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).

There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
 

CTCL cohort

The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.

The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.

Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.

“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.

The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).

“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”

She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.

“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.

She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
 

Vidyard Video

In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).

The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).

The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.

“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.

Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.


Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.

PTCL cohort

The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.

The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.

Responses according to subtype were as follows:

• 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
• 2 CRs in PTCL not otherwise specified.
• 1 CR in gamma-delta T-cell lymphoma.
• 1 PR in ALK-negative anaplastic large-cell lymphoma.
• 1 CR and 1 PR in adult T-cell leukemia/lymphoma.

Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.

The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).

There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
 

CTCL cohort

The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.

The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.

Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.

“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.

The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).

“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”

She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.

“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.

She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
 

Vidyard Video

In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).

The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).

The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.

“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.

Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.


Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.

PTCL cohort

The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.

The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.

Responses according to subtype were as follows:

• 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
• 2 CRs in PTCL not otherwise specified.
• 1 CR in gamma-delta T-cell lymphoma.
• 1 PR in ALK-negative anaplastic large-cell lymphoma.
• 1 CR and 1 PR in adult T-cell leukemia/lymphoma.

Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.

The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).

There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
 

CTCL cohort

The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.

The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.

Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.

“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.

The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).

“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”

She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.

“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.

She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

jensmith@mdedge.com

HIV/AIDS, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights of President Donald Trump’s second State of the Union address Feb. 5.

Courtesy whitehouse.gov

Mr. Trump promised to push for funds to end HIV/AIDS and childhood cancer within in 10 years. “In recent years, we have made remarkable progress in the fight against HIV and AIDS. Scientific breakthroughs have brought a once-distant dream within reach,” he said to assembled members of Congress and leaders of the executive and judicial branches of government. “My budget will ask Democrats and Republicans to make the needed commitment to eliminate the HIV epidemic in the United States within 10 years.”

Following the speech, Alex Azar, secretary of the Department of Health and Human Services, offered more details in a blog post on the agency’s website.

Funding for the initiative, dubbed “Ending the HIV Epidemic: A Plan for America,” will have three components.

The first involves increasing investments in “geographic hotspots” though existing programs like the Ryan White HIV/AIDS Program and a new community health center–based program to provide antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) to those at the highest risk of contracting the disease.

Second is the use of data to track where the disease is spreading most rapidly to help target prevention, care, and treatment at the local level. The third will provide funds for the creation of a local HIV HealthForce in these targeted areas to expand HIV prevention and treatment efforts.

A fact sheet on this initiative called for a 75% reduction in new cases of HIV infection in 5 years and at least a 90% reduction within 10 years.

President Trump called for similar efforts to address pediatric cancer.

“Tonight I am also asking you to join me in another fight that all American can get behind – the fight against childhood cancer,” he said, adding that his budget request will come with a line item of $500 million over 10 years to fund research. “Many childhood cancers have not seen new therapies in decades.”

President Trump also asked Congress to legislate a prohibition of late-term abortion.

“There could be no greater contrast to the beautiful image of a mother holding her infant child than the chilling displays our nation saw in recent days,” he said. “Lawmakers in New York cheered with delight upon the passage of legislation that would allow a baby to be ripped from the mother’s womb moments from birth. These are living, feeling beautiful babies who will never get the chance to share their love and their dreams with the world. ... Let us work together to build a culture that cherishes innocent life.”

He also touched on the recurring themes regarding lowering the cost of health care and prescription drugs, as well as protecting those with preexisting conditions, something he called a major priority.

“It’s unacceptable that Americans pay vastly more than people in other countries for the exact same drugs, often made in the exact same place. This is wrong. This is unfair and together we will stop it, and we will stop it fast,” he said.

He did not offer any specific policy recommendation on how to address prescription drug costs, other than a comment on the need for greater price transparency.

“I am asking Congress to pass legislation that finally takes on the problem of global freeloading and delivers fairness and price transparency for American patients,” he said.

“We should also require drug companies, insurance companies, and hospitals to disclose real prices to foster competition and bring costs way down.”

gtwachtman@mdedge.com

SOURCE: Trump D. State of the Union Address, Feb. 5, 2019.

HIV/AIDS, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights of President Donald Trump’s second State of the Union address Feb. 5.

Courtesy whitehouse.gov

Mr. Trump promised to push for funds to end HIV/AIDS and childhood cancer within in 10 years. “In recent years, we have made remarkable progress in the fight against HIV and AIDS. Scientific breakthroughs have brought a once-distant dream within reach,” he said to assembled members of Congress and leaders of the executive and judicial branches of government. “My budget will ask Democrats and Republicans to make the needed commitment to eliminate the HIV epidemic in the United States within 10 years.”

Following the speech, Alex Azar, secretary of the Department of Health and Human Services, offered more details in a blog post on the agency’s website.

Funding for the initiative, dubbed “Ending the HIV Epidemic: A Plan for America,” will have three components.

The first involves increasing investments in “geographic hotspots” though existing programs like the Ryan White HIV/AIDS Program and a new community health center–based program to provide antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) to those at the highest risk of contracting the disease.

Second is the use of data to track where the disease is spreading most rapidly to help target prevention, care, and treatment at the local level. The third will provide funds for the creation of a local HIV HealthForce in these targeted areas to expand HIV prevention and treatment efforts.

A fact sheet on this initiative called for a 75% reduction in new cases of HIV infection in 5 years and at least a 90% reduction within 10 years.

President Trump called for similar efforts to address pediatric cancer.

“Tonight I am also asking you to join me in another fight that all American can get behind – the fight against childhood cancer,” he said, adding that his budget request will come with a line item of $500 million over 10 years to fund research. “Many childhood cancers have not seen new therapies in decades.”

President Trump also asked Congress to legislate a prohibition of late-term abortion.

“There could be no greater contrast to the beautiful image of a mother holding her infant child than the chilling displays our nation saw in recent days,” he said. “Lawmakers in New York cheered with delight upon the passage of legislation that would allow a baby to be ripped from the mother’s womb moments from birth. These are living, feeling beautiful babies who will never get the chance to share their love and their dreams with the world. ... Let us work together to build a culture that cherishes innocent life.”

He also touched on the recurring themes regarding lowering the cost of health care and prescription drugs, as well as protecting those with preexisting conditions, something he called a major priority.

“It’s unacceptable that Americans pay vastly more than people in other countries for the exact same drugs, often made in the exact same place. This is wrong. This is unfair and together we will stop it, and we will stop it fast,” he said.

He did not offer any specific policy recommendation on how to address prescription drug costs, other than a comment on the need for greater price transparency.

“I am asking Congress to pass legislation that finally takes on the problem of global freeloading and delivers fairness and price transparency for American patients,” he said.

“We should also require drug companies, insurance companies, and hospitals to disclose real prices to foster competition and bring costs way down.”

gtwachtman@mdedge.com

SOURCE: Trump D. State of the Union Address, Feb. 5, 2019.

HIV/AIDS, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights of President Donald Trump’s second State of the Union address Feb. 5.

Courtesy whitehouse.gov

Mr. Trump promised to push for funds to end HIV/AIDS and childhood cancer within in 10 years. “In recent years, we have made remarkable progress in the fight against HIV and AIDS. Scientific breakthroughs have brought a once-distant dream within reach,” he said to assembled members of Congress and leaders of the executive and judicial branches of government. “My budget will ask Democrats and Republicans to make the needed commitment to eliminate the HIV epidemic in the United States within 10 years.”

Following the speech, Alex Azar, secretary of the Department of Health and Human Services, offered more details in a blog post on the agency’s website.

Funding for the initiative, dubbed “Ending the HIV Epidemic: A Plan for America,” will have three components.

The first involves increasing investments in “geographic hotspots” though existing programs like the Ryan White HIV/AIDS Program and a new community health center–based program to provide antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) to those at the highest risk of contracting the disease.

Second is the use of data to track where the disease is spreading most rapidly to help target prevention, care, and treatment at the local level. The third will provide funds for the creation of a local HIV HealthForce in these targeted areas to expand HIV prevention and treatment efforts.

A fact sheet on this initiative called for a 75% reduction in new cases of HIV infection in 5 years and at least a 90% reduction within 10 years.

President Trump called for similar efforts to address pediatric cancer.

“Tonight I am also asking you to join me in another fight that all American can get behind – the fight against childhood cancer,” he said, adding that his budget request will come with a line item of $500 million over 10 years to fund research. “Many childhood cancers have not seen new therapies in decades.”

President Trump also asked Congress to legislate a prohibition of late-term abortion.

“There could be no greater contrast to the beautiful image of a mother holding her infant child than the chilling displays our nation saw in recent days,” he said. “Lawmakers in New York cheered with delight upon the passage of legislation that would allow a baby to be ripped from the mother’s womb moments from birth. These are living, feeling beautiful babies who will never get the chance to share their love and their dreams with the world. ... Let us work together to build a culture that cherishes innocent life.”

He also touched on the recurring themes regarding lowering the cost of health care and prescription drugs, as well as protecting those with preexisting conditions, something he called a major priority.

“It’s unacceptable that Americans pay vastly more than people in other countries for the exact same drugs, often made in the exact same place. This is wrong. This is unfair and together we will stop it, and we will stop it fast,” he said.

He did not offer any specific policy recommendation on how to address prescription drug costs, other than a comment on the need for greater price transparency.

“I am asking Congress to pass legislation that finally takes on the problem of global freeloading and delivers fairness and price transparency for American patients,” he said.

“We should also require drug companies, insurance companies, and hospitals to disclose real prices to foster competition and bring costs way down.”

gtwachtman@mdedge.com

SOURCE: Trump D. State of the Union Address, Feb. 5, 2019.

Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.

It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.

“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.

“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.

“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”

“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.

Focusing on patients with psoriasis

Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.

“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.

PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.

“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
 

Widening the PsA diagnostic net

What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.

The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.

“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.

“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”

“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.

“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”

Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.

“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
 

The earliest indicators of PsA

Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).

Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).

In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).

These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.

The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)

The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”

Weight loss and other interventions

Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.

Penn Medicine

Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”

“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.

“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.

At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).

Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).

Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.

“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.

Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.

mzoler@mdedge.com

Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.

It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.

“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.

“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.

“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”

“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.

Focusing on patients with psoriasis

Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.

“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.

PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.

“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
 

Widening the PsA diagnostic net

What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.

The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.

“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.

“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”

“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.

“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”

Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.

“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
 

The earliest indicators of PsA

Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).

Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).

In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).

These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.

The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)

The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”

Weight loss and other interventions

Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.

Penn Medicine

Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”

“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.

“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.

At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).

Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).

Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.

“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.

Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.

mzoler@mdedge.com

Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.

It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.

“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.

“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.

“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”

“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.

Focusing on patients with psoriasis

Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.

“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.

PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.

“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
 

Widening the PsA diagnostic net

What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.

The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.

“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.

“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”

“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.

“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”

Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.

“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
 

The earliest indicators of PsA

Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).

Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).

In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).

These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.

The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)

The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”

Weight loss and other interventions

Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.

Penn Medicine

Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”

“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.

“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.

At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).

Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).

Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.

“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.

Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.

mzoler@mdedge.com

An increased peripheral arterial stiffness index was associated with an increased rate of major adverse cardiac events (MACEs), independent of age, coronary artery disease, and Rutherford category, according to the results of a study of patients with peripheral arterial disease (PAD) presenting to the vascular surgery outpatient clinic at the San Francisco Veterans Affairs Medical Center.

copyright/pixologicstudio/Thinkstock

Seventy-two patients with PAD were recruited during 2011-2016 and each had baseline radial artery applanation tonometry performed at a baseline visit. Their central radial artery augmentation index (AIX), normalized to 75 beats/min, and the peripheral AIX were calculated using pulse wave analysis. Subsequent MACEs were identified by chart review in the Journal of Surgical Research.

The cohort was predominately male (96%) and white (69%), with an average age of 69.4 years.

During a median follow-up period of 34 months, 14 patients experienced a MACE (19%). These events included eight myocardial infarctions or coronary revascularizations, four deaths from a cardiac cause, one stroke, and one transient ischemic attack. Unadjusted Cox proportional hazards models identified a significant association between the peripheral AIX and rate of MACE (hazard ratio, 1.54; 95% confidence interval, 1.06-2.22; P less than .02).

“These findings suggest that increased stiffness of the peripheral arteries may play a predictive role in patients with PAD. Furthermore, these findings inform future studies and suggest that the peripheral AIX may be used to risk stratify patients with PAD,” the researchers concluded.

The study was funded by public institutions including the National Institutes of Heath, the University of California, San Francisco, and a Society for Vascular Surgery Seed Grant and Career Development Award. The authors reported that they had no disclosures.

mlesney@mdedge.com

SOURCE: Ramirez JL et al. J Surg Res 2019;235:250-7.

An increased peripheral arterial stiffness index was associated with an increased rate of major adverse cardiac events (MACEs), independent of age, coronary artery disease, and Rutherford category, according to the results of a study of patients with peripheral arterial disease (PAD) presenting to the vascular surgery outpatient clinic at the San Francisco Veterans Affairs Medical Center.

copyright/pixologicstudio/Thinkstock

Seventy-two patients with PAD were recruited during 2011-2016 and each had baseline radial artery applanation tonometry performed at a baseline visit. Their central radial artery augmentation index (AIX), normalized to 75 beats/min, and the peripheral AIX were calculated using pulse wave analysis. Subsequent MACEs were identified by chart review in the Journal of Surgical Research.

The cohort was predominately male (96%) and white (69%), with an average age of 69.4 years.

During a median follow-up period of 34 months, 14 patients experienced a MACE (19%). These events included eight myocardial infarctions or coronary revascularizations, four deaths from a cardiac cause, one stroke, and one transient ischemic attack. Unadjusted Cox proportional hazards models identified a significant association between the peripheral AIX and rate of MACE (hazard ratio, 1.54; 95% confidence interval, 1.06-2.22; P less than .02).

“These findings suggest that increased stiffness of the peripheral arteries may play a predictive role in patients with PAD. Furthermore, these findings inform future studies and suggest that the peripheral AIX may be used to risk stratify patients with PAD,” the researchers concluded.

The study was funded by public institutions including the National Institutes of Heath, the University of California, San Francisco, and a Society for Vascular Surgery Seed Grant and Career Development Award. The authors reported that they had no disclosures.

mlesney@mdedge.com

SOURCE: Ramirez JL et al. J Surg Res 2019;235:250-7.

An increased peripheral arterial stiffness index was associated with an increased rate of major adverse cardiac events (MACEs), independent of age, coronary artery disease, and Rutherford category, according to the results of a study of patients with peripheral arterial disease (PAD) presenting to the vascular surgery outpatient clinic at the San Francisco Veterans Affairs Medical Center.

copyright/pixologicstudio/Thinkstock

Seventy-two patients with PAD were recruited during 2011-2016 and each had baseline radial artery applanation tonometry performed at a baseline visit. Their central radial artery augmentation index (AIX), normalized to 75 beats/min, and the peripheral AIX were calculated using pulse wave analysis. Subsequent MACEs were identified by chart review in the Journal of Surgical Research.

The cohort was predominately male (96%) and white (69%), with an average age of 69.4 years.

During a median follow-up period of 34 months, 14 patients experienced a MACE (19%). These events included eight myocardial infarctions or coronary revascularizations, four deaths from a cardiac cause, one stroke, and one transient ischemic attack. Unadjusted Cox proportional hazards models identified a significant association between the peripheral AIX and rate of MACE (hazard ratio, 1.54; 95% confidence interval, 1.06-2.22; P less than .02).

“These findings suggest that increased stiffness of the peripheral arteries may play a predictive role in patients with PAD. Furthermore, these findings inform future studies and suggest that the peripheral AIX may be used to risk stratify patients with PAD,” the researchers concluded.

The study was funded by public institutions including the National Institutes of Heath, the University of California, San Francisco, and a Society for Vascular Surgery Seed Grant and Career Development Award. The authors reported that they had no disclosures.

mlesney@mdedge.com

SOURCE: Ramirez JL et al. J Surg Res 2019;235:250-7.

Nearly 80% of veterans are overweight or obese. According to researchers from Walter Reed National Military Medical Center in Maryland and Yale School of Medicine in Connecticut, obesity is more common among veterans with posttraumatic stress disorder (PTSD) compared with that in other veterans in the VHA (47% vs 41%). Moreover, they say, veterans with PTSD lose less weight during weight-loss treatment than do those without comorbid mental health conditions. PTSD also has been associated with night eating, food addiction, binge eating, and eating as a coping strategy. In a national survey, veterans who self-reported a diagnosis of PTSD were more likely to endorse eating because of emotions or stress.

The researchers conducted a study of 126 veterans referred to the MOVE! Weight Management Program at VA Connecticut Healthcare System. Although it replicates and extends findings from other studies, they believe theirs is the first study examining emotional eating among veterans seeking obesity treatment.

The veterans were given the Yale Emotional Overeating Questionnaire (YEOQ), which assesses how often the respondent has eaten an unusually large amount of food in response to anxiety, sadness, loneliness, tiredness, anger, happiness, boredom, guilt, and physical pain. The researchers also used the Primary Care PTSD Screen to test for PTSD.

A positive PTSD screen was associated with significantly higher scores on the YEOQ overall as well as higher scores on each individual item. Higher scores on the PTSD screen also were associated with more frequent emotional eating for all emotions.

The researchers note that findings about the predictive validity of emotional eating questionnaires have been mixed. Although emotions may influence eating patterns, other mechanisms could be at work, such as general concern about, or lack of control over, eating.

However, the researchers suggest that veterans with PTSD may need specific attention given to alternative coping strategies when facing difficult emotions as part of weight loss treatment.

Nearly 80% of veterans are overweight or obese. According to researchers from Walter Reed National Military Medical Center in Maryland and Yale School of Medicine in Connecticut, obesity is more common among veterans with posttraumatic stress disorder (PTSD) compared with that in other veterans in the VHA (47% vs 41%). Moreover, they say, veterans with PTSD lose less weight during weight-loss treatment than do those without comorbid mental health conditions. PTSD also has been associated with night eating, food addiction, binge eating, and eating as a coping strategy. In a national survey, veterans who self-reported a diagnosis of PTSD were more likely to endorse eating because of emotions or stress.

The researchers conducted a study of 126 veterans referred to the MOVE! Weight Management Program at VA Connecticut Healthcare System. Although it replicates and extends findings from other studies, they believe theirs is the first study examining emotional eating among veterans seeking obesity treatment.

The veterans were given the Yale Emotional Overeating Questionnaire (YEOQ), which assesses how often the respondent has eaten an unusually large amount of food in response to anxiety, sadness, loneliness, tiredness, anger, happiness, boredom, guilt, and physical pain. The researchers also used the Primary Care PTSD Screen to test for PTSD.

A positive PTSD screen was associated with significantly higher scores on the YEOQ overall as well as higher scores on each individual item. Higher scores on the PTSD screen also were associated with more frequent emotional eating for all emotions.

The researchers note that findings about the predictive validity of emotional eating questionnaires have been mixed. Although emotions may influence eating patterns, other mechanisms could be at work, such as general concern about, or lack of control over, eating.

However, the researchers suggest that veterans with PTSD may need specific attention given to alternative coping strategies when facing difficult emotions as part of weight loss treatment.

Nearly 80% of veterans are overweight or obese. According to researchers from Walter Reed National Military Medical Center in Maryland and Yale School of Medicine in Connecticut, obesity is more common among veterans with posttraumatic stress disorder (PTSD) compared with that in other veterans in the VHA (47% vs 41%). Moreover, they say, veterans with PTSD lose less weight during weight-loss treatment than do those without comorbid mental health conditions. PTSD also has been associated with night eating, food addiction, binge eating, and eating as a coping strategy. In a national survey, veterans who self-reported a diagnosis of PTSD were more likely to endorse eating because of emotions or stress.

The researchers conducted a study of 126 veterans referred to the MOVE! Weight Management Program at VA Connecticut Healthcare System. Although it replicates and extends findings from other studies, they believe theirs is the first study examining emotional eating among veterans seeking obesity treatment.

The veterans were given the Yale Emotional Overeating Questionnaire (YEOQ), which assesses how often the respondent has eaten an unusually large amount of food in response to anxiety, sadness, loneliness, tiredness, anger, happiness, boredom, guilt, and physical pain. The researchers also used the Primary Care PTSD Screen to test for PTSD.

A positive PTSD screen was associated with significantly higher scores on the YEOQ overall as well as higher scores on each individual item. Higher scores on the PTSD screen also were associated with more frequent emotional eating for all emotions.

The researchers note that findings about the predictive validity of emotional eating questionnaires have been mixed. Although emotions may influence eating patterns, other mechanisms could be at work, such as general concern about, or lack of control over, eating.

However, the researchers suggest that veterans with PTSD may need specific attention given to alternative coping strategies when facing difficult emotions as part of weight loss treatment.

In this episode of the MDedge Psychcast, we join Jeffrey R. Strawn, MD, at the Psychopharmacology Update meeting in Cincinnati, for a lecture on using benzodiazapines for patients with anxiety disorders. Also in this episode, what happens when you have plans to get some work done, but Alexa has other ideas? Dr. RK offers her thoughts on just such a situation – and on practicing what she preaches. You can contact the Psychcast by emailing podcasts@mdedge.com.

Amazon

Apple Podcasts

Google Podcasts

Spotify


 

In this episode of the MDedge Psychcast, we join Jeffrey R. Strawn, MD, at the Psychopharmacology Update meeting in Cincinnati, for a lecture on using benzodiazapines for patients with anxiety disorders. Also in this episode, what happens when you have plans to get some work done, but Alexa has other ideas? Dr. RK offers her thoughts on just such a situation – and on practicing what she preaches. You can contact the Psychcast by emailing podcasts@mdedge.com.

Amazon

Apple Podcasts

Google Podcasts

Spotify


 

In this episode of the MDedge Psychcast, we join Jeffrey R. Strawn, MD, at the Psychopharmacology Update meeting in Cincinnati, for a lecture on using benzodiazapines for patients with anxiety disorders. Also in this episode, what happens when you have plans to get some work done, but Alexa has other ideas? Dr. RK offers her thoughts on just such a situation – and on practicing what she preaches. You can contact the Psychcast by emailing podcasts@mdedge.com.

Amazon

Apple Podcasts

Google Podcasts

Spotify


 

Automated office blood pressure readings appear to be more accurate than routine office readings and BP readings in research settings. Also today, a positive fecal immunochemical test should prompt colonoscopy, mild aerobic exercise speeds recovery for sports concussions, and phase 2 studies of the antiamyloid Alzheimer’s drug crenezumab are stopped.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Automated office blood pressure readings appear to be more accurate than routine office readings and BP readings in research settings. Also today, a positive fecal immunochemical test should prompt colonoscopy, mild aerobic exercise speeds recovery for sports concussions, and phase 2 studies of the antiamyloid Alzheimer’s drug crenezumab are stopped.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Automated office blood pressure readings appear to be more accurate than routine office readings and BP readings in research settings. Also today, a positive fecal immunochemical test should prompt colonoscopy, mild aerobic exercise speeds recovery for sports concussions, and phase 2 studies of the antiamyloid Alzheimer’s drug crenezumab are stopped.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Lung cancer is the most frequent cause of cancer-related mortality worldwide.¹ The most prevalent type of lung cancer is non-small cell lung cancer (NSCLC), which comprises about 85% of lung cancer cases.² As there are no cost-effective approaches to screening for lung cancer, most lung cancers are identified at an advanced stage (stage IIIB or IV).

New approaches to managing advanced lung cancer have emerged in recent years, including drugs designed to target specific genetic mutations in some tumors.³ The National Comprehensive Cancer Network (NCCN) recommends erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) for first-line treatment of advanced NSCLC with EGFR mutation.⁴ Crizotinib is recommended to treat cancers that test positive for the anaplastic lymphoma kinase (ALK) mutation.⁴ Utilization of targeting agents has been found to extend the survival times for patients with the specified mutations.⁵ Both erlotinib and crizotinib are available at the VHA.

Previous research showed that VHA providers expressed overall favorable attitudes about genomic medicine.⁶ Providers perceived genomic medicine to have an important and possibly transformative role in medicine. Barriers to utilization of genomic medicine involved concerns about coordination of care, changes in workload, and increased length of patient visits. In addition to these system-level barriers, many providers had concerns about the proficiency of VHA-based practitioners to appropriately use genomic medicine.

Previous research has evaluated utilization of genomic testing and genomic-based targeted therapy (GBTT) in VA and community settings.^5-8 It is unclear whether VHA-based providers are following clinical guidelines regarding genomic testing and utilization of GBTT.⁴ The authors set out to identify factors that impede and encourage guideline-consistent care in the management of NSCLC at the VHA. The authors specifically sought information about oncologists’ perceptions and experiences with EGFR and ALK mutation testing in patients with advanced NSCLC, as well as use of erlotinib and crizotinib in treating such patients.

Methods

This study was approved by the institutional review boards at Michael E. DeBakey VAMC in Houston, Texas and Baylor College of Medicine. In-depth qualitative interviews were conducted with VHA oncologists to examine their reported barriers and facilitators to mutation testing and prescribing of genomic-based treatment in patients with advanced NSCLC.

The sample of participants was recruited from a list of VHA medical oncologists, compiled by the study project coordinator. Investigators stratified the list by American College of Surgeons Commission on Cancer (CoC) accreditation status (yes/no) and used a stratified purposive sampling technique to recruit participants from CoC-accredited facilities and nonaccredited facilities. Recruitment and data collection occurred between March 2015 and February 2016. Oncologists were considered for inclusion if they (1) were specialists in oncology; (2) practiced at the VHA during the time of recruitment; and (3) had experience treating lung cancer at a VHA facility. During recruitment, potential participants were told that the investigators were interested in learning about oncologists’ experiences and decisions about using GBTT to treat advanced lung cancer in the VHA. Participants were scheduled for telephone-based interviews, and verbal consent was obtained prior to all interviews. Interviews ranged from 19 to 90 minutes (average, 40 min).

Recruitment was stopped at the point of thematic saturation, defined a priori as the point when 2 independent coders agreed that 3 consecutive transcripts for a given interview category (see below) rendered no new thematic concepts.^9,10 Consistent with the theoretical framework developed by Cabana and colleagues, interviews were designed to elicit information about oncologists’ knowledge, attitudes, intent to use GBTT, and perceived facilitators and barriers to using GBTT in the VHA.¹¹ Additional findings are presented elsewhere.¹² The interview guide was pilot tested and revised prior to initiating data collection. All interviews were recorded, transcribed, and analyzed for content.

Analysis

Data were analyzed using framework analysis methodology, which allows for the inclusion of existing concepts as well as emergent themes within an established theoretical framework.¹³ Two independent coders with expertise in framework analysis independently created codes and indexed the data using Atlas.ti 6.2 (Scientific Software Development, Berlin, Germany). Disagreements about coding decisions were resolved through group consensus. Coding centered on 2 themes:

• Barriers and facilitators to mutation testing. This includes system or facility factors and testing weaknesses that act as barriers to ordering mutation testing, system or facility factors that facilitate ordering mutation testing, and oncologists’ suggestions for ways to encourage more testing in the VHA.
• Barriers and facilitators to prescribing GBTT. This includes system or facility factors that act as barriers to prescribing GBTT, system or facility factors that facilitate prescribing GBTT, and oncologists’ suggestions for ways to encourage more prescribing of GBTT in the VHA.

Thirty medical oncologists were interviewed. Participant demographics are presented in the Table.

Barriers to testing

The 2 most commonly cited barriers to ordering mutation testing can be considered weaknesses in the testing process: lack of tissue and wait time for results. Almost all providers identified lack of tissue as a barrier to ordering a mutation test.

Another frequently cited testing weakness involved the wait time for results. Because the mutation analysis is not conducted in the VHA facility, providers often must wait 2 to 4 weeks to receive results. This can present a problem because some providers do not want to wait for the results before recommending a course of treatment.

Several providers cited system and facility factors as barriers to mutation testing. The most common of these involves the ordering process. Oncology providers often remarked that ordering the mutation test is cumbersome or inconvenient because there is no ordering mechanism in the Computerized Patient Record System (CPRS). Many different approaches for ordering a mutation test exist, including e-mailing the pathology department, calling to place the order, or requesting the test in person. As providers can order many, if not most, other tests via CPRS, it is clear that this presents an inconvenient exception.

Budgetary constraints were another frequently cited system or facility-level barrier. Providers sometimes were unable to access the test due to the cost. Several providers informed the interviewers that the cost of the test is deducted from the pathology department’s budget, and this could present a major constraint to testing. A less commonly cited system or facility level barrier involves the inability to biopsy at the VHA. This was mentioned by only 2 providers who, due to lack of equipment or lack of personnel, were unable to acquire additional tissue samples at their facilities.

Finally, several providers noted that in some cases patients did not wish to undergo a biopsy. Thus, patient preference can act as a barrier to mutation testing. Some patients wish to forgo treatment, which eliminates the need for a mutation test. Other patients believe that due to their smoking history, they are unlikely to have an ALK or EGFR mutation and instead immediately opt for chemotherapy. Only a small minority of participants identified no barriers to mutation testing.

Facilitators for Testing

Many providers complimented the availability of the mutation test. Interestingly, while some providers mentioned that lack of CPRS ordering was a barrier to testing, several also listed access to a CPRS order as a facilitator. These providers commented that ordering a test was streamlined and easy, given the mechanism in CPRS. Some VHA facilities offer CPRS order capabilities, and others do not. Other oncologists commented more generally on the cooperativeness of the pathology department in ordering mutation tests. It seems that facilities may use different ordering procedures, but in most of these facilities, a high degree of cooperation exists between departments to send out for tests that are requested.

Providers offered many ideas for ways to improve mutation testing or to facilitate the testing. By far, the most commonly cited way to improve the testing process was to make mutation testing reflexive for metastatic nonsquamous NSCLC. Some acknowledged that to achieve this would require a change to the budgeting process such that the test would not drain the pathology department’s budget. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address several of the barriers that were identified in this study. Other providers recommended standardizing the ordering procedure and location of results. Specifically, providers recommended creating a button in CPRS for ordering and always reporting the results in the same place in CPRS.

Barriers to GBTT Prescribing

The clear majority of providers identified no barriers to prescribing GBTTs. A few mentioned that they were required to submit a nonformulary consult. A representative quote described this as “more out of a formality, and the pharmacist basically is there with me and he approves it on the spot and provides the prescription on the day, right when I’m seeing the patient.” Only a very small minority of providers identified medication cost as a barrier, but even those respondents did not indicate that cost prevented them from offering GBTTs to their patients. Rather, cost consciousness simply made them more mindful and judicious when making decisions about prescribing GBTTs.

Facilitators to GBTT Prescribing

Several providers listed availability of the costly medication in the VHA as a facilitator to prescribing. Veterans can obtain GBTTs with little to no insurance cost or copayment, which is not always the case outside the VHA.

One recommendation for further facilitating prescribing of GBTTs involved eliminating the preauthorization requirement, particularly in first-line use for patients testing positive for ALK or EGFR mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

Discussion

Although in some cases, testing weaknesses (lack of tissue, wait time to receive results) can interrupt a treatment trajectory, many of the barriers identified in this study are modifiable. Overwhelmingly, oncologists recommended making mutation testing reflexive for metastatic nonsquamous NSCLC. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address issues related to variable utilization of genomic testing in VHA.¹² Additionally, in response to system and facility barriers to mutation testing, other providers recommended standardizing the ordering procedure and location of results. Utilization of GBTT can be facilitated by eliminating the preauthorization requirement, particularly in first-line use for patients with positive mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

This study extends previous research that identified underuse of genomic testing in community-based practices. The authors sought to interview a broad sample of providers from various facilities (small, large, CoC accredited, nonaccredited) to understand the range of conditions faced by VA providers. Some providers face more barriers than do others, whereas some face few or no barriers. This wide range of experiences can help to better understand the factors that facilitate guideline-adherent care.

Limitations

The authors recognize that availability of resources and testing and prescribing practices are constantly evolving and perhaps have improved since the data were collected. Thus, the age of the study data might be a limitation to the study. Like most qualitative studies, these findings are limited in their generalizability beyond the study population. Additionally, the authors were limited to recruiting oncologists with reliable contact information listed in the VHA directory. Although this could have introduced some degree of sampling bias, the authors are confident that the sample sufficiently represents the population of VHA-based medical oncologists who treat lung cancer. Despite these limitations, these findings provide novel perspectives on barriers and facilitators to genomic testing GBTT prescribing in the VHA. The authors identify modifiable barriers to testing and prescribing that can be addressed to improve and standardize care of advanced lung cancer in the VHA.

Conclusion

Efforts should be made to address modifiable barriers to mutation testing and guideline-consistent prescribing of GBTT in the VA setting. Implementation of specific practices like reflexive testing for all metastatic nonsquamous NSCLC, standardization of the mutation test ordering procedure, standardization of results reporting, and elimination of the preauthorization to prescribe GBTT could impact the utilization of GBTT in VHA.

Click here to read the digital edition.

Lung cancer is the most frequent cause of cancer-related mortality worldwide.¹ The most prevalent type of lung cancer is non-small cell lung cancer (NSCLC), which comprises about 85% of lung cancer cases.² As there are no cost-effective approaches to screening for lung cancer, most lung cancers are identified at an advanced stage (stage IIIB or IV).

New approaches to managing advanced lung cancer have emerged in recent years, including drugs designed to target specific genetic mutations in some tumors.³ The National Comprehensive Cancer Network (NCCN) recommends erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) for first-line treatment of advanced NSCLC with EGFR mutation.⁴ Crizotinib is recommended to treat cancers that test positive for the anaplastic lymphoma kinase (ALK) mutation.⁴ Utilization of targeting agents has been found to extend the survival times for patients with the specified mutations.⁵ Both erlotinib and crizotinib are available at the VHA.

Previous research showed that VHA providers expressed overall favorable attitudes about genomic medicine.⁶ Providers perceived genomic medicine to have an important and possibly transformative role in medicine. Barriers to utilization of genomic medicine involved concerns about coordination of care, changes in workload, and increased length of patient visits. In addition to these system-level barriers, many providers had concerns about the proficiency of VHA-based practitioners to appropriately use genomic medicine.

Previous research has evaluated utilization of genomic testing and genomic-based targeted therapy (GBTT) in VA and community settings.^5-8 It is unclear whether VHA-based providers are following clinical guidelines regarding genomic testing and utilization of GBTT.⁴ The authors set out to identify factors that impede and encourage guideline-consistent care in the management of NSCLC at the VHA. The authors specifically sought information about oncologists’ perceptions and experiences with EGFR and ALK mutation testing in patients with advanced NSCLC, as well as use of erlotinib and crizotinib in treating such patients.

Methods

This study was approved by the institutional review boards at Michael E. DeBakey VAMC in Houston, Texas and Baylor College of Medicine. In-depth qualitative interviews were conducted with VHA oncologists to examine their reported barriers and facilitators to mutation testing and prescribing of genomic-based treatment in patients with advanced NSCLC.

The sample of participants was recruited from a list of VHA medical oncologists, compiled by the study project coordinator. Investigators stratified the list by American College of Surgeons Commission on Cancer (CoC) accreditation status (yes/no) and used a stratified purposive sampling technique to recruit participants from CoC-accredited facilities and nonaccredited facilities. Recruitment and data collection occurred between March 2015 and February 2016. Oncologists were considered for inclusion if they (1) were specialists in oncology; (2) practiced at the VHA during the time of recruitment; and (3) had experience treating lung cancer at a VHA facility. During recruitment, potential participants were told that the investigators were interested in learning about oncologists’ experiences and decisions about using GBTT to treat advanced lung cancer in the VHA. Participants were scheduled for telephone-based interviews, and verbal consent was obtained prior to all interviews. Interviews ranged from 19 to 90 minutes (average, 40 min).

Recruitment was stopped at the point of thematic saturation, defined a priori as the point when 2 independent coders agreed that 3 consecutive transcripts for a given interview category (see below) rendered no new thematic concepts.^9,10 Consistent with the theoretical framework developed by Cabana and colleagues, interviews were designed to elicit information about oncologists’ knowledge, attitudes, intent to use GBTT, and perceived facilitators and barriers to using GBTT in the VHA.¹¹ Additional findings are presented elsewhere.¹² The interview guide was pilot tested and revised prior to initiating data collection. All interviews were recorded, transcribed, and analyzed for content.

Analysis

Data were analyzed using framework analysis methodology, which allows for the inclusion of existing concepts as well as emergent themes within an established theoretical framework.¹³ Two independent coders with expertise in framework analysis independently created codes and indexed the data using Atlas.ti 6.2 (Scientific Software Development, Berlin, Germany). Disagreements about coding decisions were resolved through group consensus. Coding centered on 2 themes:

• Barriers and facilitators to mutation testing. This includes system or facility factors and testing weaknesses that act as barriers to ordering mutation testing, system or facility factors that facilitate ordering mutation testing, and oncologists’ suggestions for ways to encourage more testing in the VHA.
• Barriers and facilitators to prescribing GBTT. This includes system or facility factors that act as barriers to prescribing GBTT, system or facility factors that facilitate prescribing GBTT, and oncologists’ suggestions for ways to encourage more prescribing of GBTT in the VHA.

Thirty medical oncologists were interviewed. Participant demographics are presented in the Table.

Barriers to testing

The 2 most commonly cited barriers to ordering mutation testing can be considered weaknesses in the testing process: lack of tissue and wait time for results. Almost all providers identified lack of tissue as a barrier to ordering a mutation test.

Another frequently cited testing weakness involved the wait time for results. Because the mutation analysis is not conducted in the VHA facility, providers often must wait 2 to 4 weeks to receive results. This can present a problem because some providers do not want to wait for the results before recommending a course of treatment.

Several providers cited system and facility factors as barriers to mutation testing. The most common of these involves the ordering process. Oncology providers often remarked that ordering the mutation test is cumbersome or inconvenient because there is no ordering mechanism in the Computerized Patient Record System (CPRS). Many different approaches for ordering a mutation test exist, including e-mailing the pathology department, calling to place the order, or requesting the test in person. As providers can order many, if not most, other tests via CPRS, it is clear that this presents an inconvenient exception.

Budgetary constraints were another frequently cited system or facility-level barrier. Providers sometimes were unable to access the test due to the cost. Several providers informed the interviewers that the cost of the test is deducted from the pathology department’s budget, and this could present a major constraint to testing. A less commonly cited system or facility level barrier involves the inability to biopsy at the VHA. This was mentioned by only 2 providers who, due to lack of equipment or lack of personnel, were unable to acquire additional tissue samples at their facilities.

Finally, several providers noted that in some cases patients did not wish to undergo a biopsy. Thus, patient preference can act as a barrier to mutation testing. Some patients wish to forgo treatment, which eliminates the need for a mutation test. Other patients believe that due to their smoking history, they are unlikely to have an ALK or EGFR mutation and instead immediately opt for chemotherapy. Only a small minority of participants identified no barriers to mutation testing.

Facilitators for Testing

Many providers complimented the availability of the mutation test. Interestingly, while some providers mentioned that lack of CPRS ordering was a barrier to testing, several also listed access to a CPRS order as a facilitator. These providers commented that ordering a test was streamlined and easy, given the mechanism in CPRS. Some VHA facilities offer CPRS order capabilities, and others do not. Other oncologists commented more generally on the cooperativeness of the pathology department in ordering mutation tests. It seems that facilities may use different ordering procedures, but in most of these facilities, a high degree of cooperation exists between departments to send out for tests that are requested.

Providers offered many ideas for ways to improve mutation testing or to facilitate the testing. By far, the most commonly cited way to improve the testing process was to make mutation testing reflexive for metastatic nonsquamous NSCLC. Some acknowledged that to achieve this would require a change to the budgeting process such that the test would not drain the pathology department’s budget. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address several of the barriers that were identified in this study. Other providers recommended standardizing the ordering procedure and location of results. Specifically, providers recommended creating a button in CPRS for ordering and always reporting the results in the same place in CPRS.

Barriers to GBTT Prescribing

The clear majority of providers identified no barriers to prescribing GBTTs. A few mentioned that they were required to submit a nonformulary consult. A representative quote described this as “more out of a formality, and the pharmacist basically is there with me and he approves it on the spot and provides the prescription on the day, right when I’m seeing the patient.” Only a very small minority of providers identified medication cost as a barrier, but even those respondents did not indicate that cost prevented them from offering GBTTs to their patients. Rather, cost consciousness simply made them more mindful and judicious when making decisions about prescribing GBTTs.

Facilitators to GBTT Prescribing

Several providers listed availability of the costly medication in the VHA as a facilitator to prescribing. Veterans can obtain GBTTs with little to no insurance cost or copayment, which is not always the case outside the VHA.

One recommendation for further facilitating prescribing of GBTTs involved eliminating the preauthorization requirement, particularly in first-line use for patients testing positive for ALK or EGFR mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

Discussion

Although in some cases, testing weaknesses (lack of tissue, wait time to receive results) can interrupt a treatment trajectory, many of the barriers identified in this study are modifiable. Overwhelmingly, oncologists recommended making mutation testing reflexive for metastatic nonsquamous NSCLC. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address issues related to variable utilization of genomic testing in VHA.¹² Additionally, in response to system and facility barriers to mutation testing, other providers recommended standardizing the ordering procedure and location of results. Utilization of GBTT can be facilitated by eliminating the preauthorization requirement, particularly in first-line use for patients with positive mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

This study extends previous research that identified underuse of genomic testing in community-based practices. The authors sought to interview a broad sample of providers from various facilities (small, large, CoC accredited, nonaccredited) to understand the range of conditions faced by VA providers. Some providers face more barriers than do others, whereas some face few or no barriers. This wide range of experiences can help to better understand the factors that facilitate guideline-adherent care.

Limitations

The authors recognize that availability of resources and testing and prescribing practices are constantly evolving and perhaps have improved since the data were collected. Thus, the age of the study data might be a limitation to the study. Like most qualitative studies, these findings are limited in their generalizability beyond the study population. Additionally, the authors were limited to recruiting oncologists with reliable contact information listed in the VHA directory. Although this could have introduced some degree of sampling bias, the authors are confident that the sample sufficiently represents the population of VHA-based medical oncologists who treat lung cancer. Despite these limitations, these findings provide novel perspectives on barriers and facilitators to genomic testing GBTT prescribing in the VHA. The authors identify modifiable barriers to testing and prescribing that can be addressed to improve and standardize care of advanced lung cancer in the VHA.

Conclusion

Efforts should be made to address modifiable barriers to mutation testing and guideline-consistent prescribing of GBTT in the VA setting. Implementation of specific practices like reflexive testing for all metastatic nonsquamous NSCLC, standardization of the mutation test ordering procedure, standardization of results reporting, and elimination of the preauthorization to prescribe GBTT could impact the utilization of GBTT in VHA.

Click here to read the digital edition.

Lung cancer is the most frequent cause of cancer-related mortality worldwide.¹ The most prevalent type of lung cancer is non-small cell lung cancer (NSCLC), which comprises about 85% of lung cancer cases.² As there are no cost-effective approaches to screening for lung cancer, most lung cancers are identified at an advanced stage (stage IIIB or IV).

New approaches to managing advanced lung cancer have emerged in recent years, including drugs designed to target specific genetic mutations in some tumors.³ The National Comprehensive Cancer Network (NCCN) recommends erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) for first-line treatment of advanced NSCLC with EGFR mutation.⁴ Crizotinib is recommended to treat cancers that test positive for the anaplastic lymphoma kinase (ALK) mutation.⁴ Utilization of targeting agents has been found to extend the survival times for patients with the specified mutations.⁵ Both erlotinib and crizotinib are available at the VHA.

Previous research showed that VHA providers expressed overall favorable attitudes about genomic medicine.⁶ Providers perceived genomic medicine to have an important and possibly transformative role in medicine. Barriers to utilization of genomic medicine involved concerns about coordination of care, changes in workload, and increased length of patient visits. In addition to these system-level barriers, many providers had concerns about the proficiency of VHA-based practitioners to appropriately use genomic medicine.

Previous research has evaluated utilization of genomic testing and genomic-based targeted therapy (GBTT) in VA and community settings.^5-8 It is unclear whether VHA-based providers are following clinical guidelines regarding genomic testing and utilization of GBTT.⁴ The authors set out to identify factors that impede and encourage guideline-consistent care in the management of NSCLC at the VHA. The authors specifically sought information about oncologists’ perceptions and experiences with EGFR and ALK mutation testing in patients with advanced NSCLC, as well as use of erlotinib and crizotinib in treating such patients.

Methods

This study was approved by the institutional review boards at Michael E. DeBakey VAMC in Houston, Texas and Baylor College of Medicine. In-depth qualitative interviews were conducted with VHA oncologists to examine their reported barriers and facilitators to mutation testing and prescribing of genomic-based treatment in patients with advanced NSCLC.

The sample of participants was recruited from a list of VHA medical oncologists, compiled by the study project coordinator. Investigators stratified the list by American College of Surgeons Commission on Cancer (CoC) accreditation status (yes/no) and used a stratified purposive sampling technique to recruit participants from CoC-accredited facilities and nonaccredited facilities. Recruitment and data collection occurred between March 2015 and February 2016. Oncologists were considered for inclusion if they (1) were specialists in oncology; (2) practiced at the VHA during the time of recruitment; and (3) had experience treating lung cancer at a VHA facility. During recruitment, potential participants were told that the investigators were interested in learning about oncologists’ experiences and decisions about using GBTT to treat advanced lung cancer in the VHA. Participants were scheduled for telephone-based interviews, and verbal consent was obtained prior to all interviews. Interviews ranged from 19 to 90 minutes (average, 40 min).

Recruitment was stopped at the point of thematic saturation, defined a priori as the point when 2 independent coders agreed that 3 consecutive transcripts for a given interview category (see below) rendered no new thematic concepts.^9,10 Consistent with the theoretical framework developed by Cabana and colleagues, interviews were designed to elicit information about oncologists’ knowledge, attitudes, intent to use GBTT, and perceived facilitators and barriers to using GBTT in the VHA.¹¹ Additional findings are presented elsewhere.¹² The interview guide was pilot tested and revised prior to initiating data collection. All interviews were recorded, transcribed, and analyzed for content.

Analysis

Data were analyzed using framework analysis methodology, which allows for the inclusion of existing concepts as well as emergent themes within an established theoretical framework.¹³ Two independent coders with expertise in framework analysis independently created codes and indexed the data using Atlas.ti 6.2 (Scientific Software Development, Berlin, Germany). Disagreements about coding decisions were resolved through group consensus. Coding centered on 2 themes:

• Barriers and facilitators to mutation testing. This includes system or facility factors and testing weaknesses that act as barriers to ordering mutation testing, system or facility factors that facilitate ordering mutation testing, and oncologists’ suggestions for ways to encourage more testing in the VHA.
• Barriers and facilitators to prescribing GBTT. This includes system or facility factors that act as barriers to prescribing GBTT, system or facility factors that facilitate prescribing GBTT, and oncologists’ suggestions for ways to encourage more prescribing of GBTT in the VHA.

Thirty medical oncologists were interviewed. Participant demographics are presented in the Table.

Barriers to testing

The 2 most commonly cited barriers to ordering mutation testing can be considered weaknesses in the testing process: lack of tissue and wait time for results. Almost all providers identified lack of tissue as a barrier to ordering a mutation test.

Another frequently cited testing weakness involved the wait time for results. Because the mutation analysis is not conducted in the VHA facility, providers often must wait 2 to 4 weeks to receive results. This can present a problem because some providers do not want to wait for the results before recommending a course of treatment.

Several providers cited system and facility factors as barriers to mutation testing. The most common of these involves the ordering process. Oncology providers often remarked that ordering the mutation test is cumbersome or inconvenient because there is no ordering mechanism in the Computerized Patient Record System (CPRS). Many different approaches for ordering a mutation test exist, including e-mailing the pathology department, calling to place the order, or requesting the test in person. As providers can order many, if not most, other tests via CPRS, it is clear that this presents an inconvenient exception.

Budgetary constraints were another frequently cited system or facility-level barrier. Providers sometimes were unable to access the test due to the cost. Several providers informed the interviewers that the cost of the test is deducted from the pathology department’s budget, and this could present a major constraint to testing. A less commonly cited system or facility level barrier involves the inability to biopsy at the VHA. This was mentioned by only 2 providers who, due to lack of equipment or lack of personnel, were unable to acquire additional tissue samples at their facilities.

Finally, several providers noted that in some cases patients did not wish to undergo a biopsy. Thus, patient preference can act as a barrier to mutation testing. Some patients wish to forgo treatment, which eliminates the need for a mutation test. Other patients believe that due to their smoking history, they are unlikely to have an ALK or EGFR mutation and instead immediately opt for chemotherapy. Only a small minority of participants identified no barriers to mutation testing.

Facilitators for Testing

Many providers complimented the availability of the mutation test. Interestingly, while some providers mentioned that lack of CPRS ordering was a barrier to testing, several also listed access to a CPRS order as a facilitator. These providers commented that ordering a test was streamlined and easy, given the mechanism in CPRS. Some VHA facilities offer CPRS order capabilities, and others do not. Other oncologists commented more generally on the cooperativeness of the pathology department in ordering mutation tests. It seems that facilities may use different ordering procedures, but in most of these facilities, a high degree of cooperation exists between departments to send out for tests that are requested.

Providers offered many ideas for ways to improve mutation testing or to facilitate the testing. By far, the most commonly cited way to improve the testing process was to make mutation testing reflexive for metastatic nonsquamous NSCLC. Some acknowledged that to achieve this would require a change to the budgeting process such that the test would not drain the pathology department’s budget. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address several of the barriers that were identified in this study. Other providers recommended standardizing the ordering procedure and location of results. Specifically, providers recommended creating a button in CPRS for ordering and always reporting the results in the same place in CPRS.

Barriers to GBTT Prescribing

The clear majority of providers identified no barriers to prescribing GBTTs. A few mentioned that they were required to submit a nonformulary consult. A representative quote described this as “more out of a formality, and the pharmacist basically is there with me and he approves it on the spot and provides the prescription on the day, right when I’m seeing the patient.” Only a very small minority of providers identified medication cost as a barrier, but even those respondents did not indicate that cost prevented them from offering GBTTs to their patients. Rather, cost consciousness simply made them more mindful and judicious when making decisions about prescribing GBTTs.

Facilitators to GBTT Prescribing

Several providers listed availability of the costly medication in the VHA as a facilitator to prescribing. Veterans can obtain GBTTs with little to no insurance cost or copayment, which is not always the case outside the VHA.

One recommendation for further facilitating prescribing of GBTTs involved eliminating the preauthorization requirement, particularly in first-line use for patients testing positive for ALK or EGFR mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

Discussion

Although in some cases, testing weaknesses (lack of tissue, wait time to receive results) can interrupt a treatment trajectory, many of the barriers identified in this study are modifiable. Overwhelmingly, oncologists recommended making mutation testing reflexive for metastatic nonsquamous NSCLC. Implementing reflexive testing of patients, as recommended by guidelines, would understandably address issues related to variable utilization of genomic testing in VHA.¹² Additionally, in response to system and facility barriers to mutation testing, other providers recommended standardizing the ordering procedure and location of results. Utilization of GBTT can be facilitated by eliminating the preauthorization requirement, particularly in first-line use for patients with positive mutations. Although the preauthorization was not seen as a significant barrier, removal of this formality could make prescribing easier.

This study extends previous research that identified underuse of genomic testing in community-based practices. The authors sought to interview a broad sample of providers from various facilities (small, large, CoC accredited, nonaccredited) to understand the range of conditions faced by VA providers. Some providers face more barriers than do others, whereas some face few or no barriers. This wide range of experiences can help to better understand the factors that facilitate guideline-adherent care.

Limitations

The authors recognize that availability of resources and testing and prescribing practices are constantly evolving and perhaps have improved since the data were collected. Thus, the age of the study data might be a limitation to the study. Like most qualitative studies, these findings are limited in their generalizability beyond the study population. Additionally, the authors were limited to recruiting oncologists with reliable contact information listed in the VHA directory. Although this could have introduced some degree of sampling bias, the authors are confident that the sample sufficiently represents the population of VHA-based medical oncologists who treat lung cancer. Despite these limitations, these findings provide novel perspectives on barriers and facilitators to genomic testing GBTT prescribing in the VHA. The authors identify modifiable barriers to testing and prescribing that can be addressed to improve and standardize care of advanced lung cancer in the VHA.

Conclusion

Efforts should be made to address modifiable barriers to mutation testing and guideline-consistent prescribing of GBTT in the VA setting. Implementation of specific practices like reflexive testing for all metastatic nonsquamous NSCLC, standardization of the mutation test ordering procedure, standardization of results reporting, and elimination of the preauthorization to prescribe GBTT could impact the utilization of GBTT in VHA.

Click here to read the digital edition.