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Merkel cell carcinoma management undergoes revolution
LAHAINA, HAWAII – The , Paul Nghiem, MD, PhD, declared at the SDEF Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
That’s because dermatologists are typically the physicians who make the diagnosis of Merkel cell carcinoma (MCC), so they’re on the scene from the outset and well positioned to help direct early management of this particularly aggressive malignancy, explained Dr. Nghiem, professor and head of dermatology at the University of Washington, Seattle.
“The management of Merkel is pretty high stakes, and if you get it right at the beginning it makes a huge difference in the side effects, as well as the chances that the patient will have the disease under control,” said Dr. Nghiem, who is sometimes called “the Merkel man” because of his many pioneering contributions to the field.
Better early management
Getting early management right, he added, hinges upon ordering a baseline PET-CT scan to search for metastases before performing definitive surgical excision of the primary tumor.
“There are really important prognostic and therapeutic implications for a baseline scan in almost any patient with early Merkel – and that’s a very different situation than with melanoma,” the dermatologist said. “There’s at least a threefold higher likelihood that the cancer has spread asymptomatically at baseline with Merkel cell carcinoma than with melanoma.”
In a soon-to-be-published study by Dr. Nghiem and coworkers, baseline imaging resulted in prognostically important upstaging that led to an altered management strategy in 12% of 584 patients with MCC, or 1 in 8.
“You don’t want to overtreat locally a lesion that has already spread distantly; you want to start focusing on the distant disease. The local disease is secondary,” he said.
The surgical excision of the primary lesion should be thoughtfully wide without being aggressive or mutilating, and it should involve primary closure. “Definitely avoid flaps and grafts, which delay your further management with radiotherapy by months and months,” Dr. Nghiem advised.
Adjuvant radiotherapy of the primary tumor site is extremely effective at preventing recurrent MCC. In Dr. Nghiem’s view, almost everyone is a candidate: In a series of 803 patients in the Seattle MCC cohort, 92% received local adjuvant radiotherapy. The national rate, in contrast, is only about 50%, highlighting the need for additional physician education.
“A little bit of radiation – one dose – appears to be just as effective as 6 weeks in controlling microscopic disease. That’s probably something we’re going to be moving towards as a field,” he predicted.
Indeed, local adjuvant radiotherapy is so effective in MCC that the surgical margins make no difference. This was demonstrated in a study by Dr. Nghiem and his coinvestigators involving 70 patients with margins greater than 1 cm who received radiotherapy, 70 others with smaller or even positive margins who received radiotherapy, and 35 patients with margins of 1 cm or less who did not receive radiotherapy. There were no MCC recurrences in any of the radiotherapy recipients, regardless of their margin status. In contrast, 7 of the 35 patients who didn’t receive radiation therapy developed a cancer recurrence. Of note, the recurrence rate of MCC is historically about 40% – far greater than for any other skin cancer. Most recurrences happen within the first 2-3 years, Dr. Nghiem observed.
Immune therapy takes center stage
Another major transformation in MCC management has been the emergence of immune therapy as first-line systemic therapy. It has replaced chemotherapy, which is more toxic and has a much shorter average duration of response. Avelumab (Bavencio) and pembrolizumab (Keytruda), the two monoclonal antibodies directed against the protein programmed death–ligand 1 (PD-L1) receptor which are approved for MCC and have been incorporated into the National Comprehensive Cancer Network (NCCN) guidelines, provide a sixfold improvement in survival, compared with chemotherapy. For example, Dr. Nghiem was first author of a multicenter phase 2 study of pembrolizumab in which the 12- and 24-month overall survival rates in pembrolizumab responders were 85% and 79%, compared with just 12% and 6%, respectively, in historical controls on first-line chemotherapy (J Clin Oncol. 2019 Mar 20;37[9]:693-702).
“Merkel cell carcinoma is the most responsive solid tumor to immune therapy,” Dr. Nghiem commented.
Why MCC matters
Although rare, MCC is important because it’s five times more lethal than melanoma. Moreover, its incidence has been rising at a rate roughly twice that of the increase in melanoma since the turn of the century. There are now more than 3,000 new cases of MCC annually, about the same as for cutaneous T-cell lymphoma (CTCL).
“It’s just that you live a long time with CTCL and you don’t with Merkel cell carcinoma. You either get rid of Merkel fast or it gets rid of you,” the dermatologist observed.
It’s a fascinating malignancy, he continued. Eight of 10 cases are caused by Merkel cell polyomavirus, discovered in 2008. The virus is ubiquitously acquired in childhood and then lies dormant on the skin for the next 6 or 7 decades, at which point MCC rates shoot up dramatically, probably due to immunosenescence. Immunosuppressed patients are at 10-fold increased risk for MCC.
Given the rarity of MCC, it doesn’t make sense to actively hunt for it. But Dr. Nghiem and coworkers have developed a handy vowel-based mnemonic that serves to raise the index of suspicion: the “AEIOU” features.
- A = asymptomatic.
- E = expanding rapidly within past 3 months.
- I = immune-mediated.
- O = older than age 50.
- U = UV-exposed skin.
The investigators found in a series of 195 MCC patients that 89% of them possessed three or more of these features (J Am Acad Dermatol. 2008 Mar;58[3]:375-81). But while the AEIOU guide is quite sensitive, it’s not specific.
“If you have any three or more of these features, that lesion probably deserves a biopsy if it’s not readily explained. Even if it’s not a Merkel, it may turn out to be a different nonmelanoma skin cancer, something you want to know about,” Dr. Nghiem said.
A shift in surveillance strategy
Dr. Nghiem was senior author of a major study that validated the clinical utility of a Merkel polyomavirus serology test for monitoring the disease status of patients treated for MCC (Cancer. 2017 Apr 15;123[8]:1464-74). The test, which measures antibodies to Merkel cell polyomavirus oncoproteins, has been incorporated in NCCN guidelines. The blood test is used initially in newly diagnosed MCC to stratify patients into two subgroups: the half who are seropositive at baseline, and the other half who are seronegative. The seropositive group undergoes surveillance via repeat blood testing every 3 months. If antibody levels are low, there is a high degree of certainty that immune therapy is working and remission is present. Thus, the blood test spares patients in this group the expense and radiation exposure entailed in repeated surveillance scans. However, rising antibody levels indicate the cancer has already recurred or will do so within the next several months.
Unfortunately, the blood test cannot be used serially to track disease status in patients who are seronegative at baseline. That group is at 42% increased risk of MCC recurrence.
Immune therapy works in only about two-thirds of MCC patients with distant disease. Leaving the visible primary tumor in place to serve as a real-time window into immune treatment effectiveness is a useful contemporary surveillance strategy.
“By leaving the visible primary there, you will rapidly know if that patient is in the favorable two-thirds group or not,” he explained.
Historically, surgery and surveillance of MCC were based upon the melanoma model, and medical oncologists were trained to treat the malignancy as they would small cell lung cancer. These are now outmoded approaches, Dr. Nghiem said. That’s why a multidisciplinary approach is highly desirable for management of MCC, including dermatologists, pathologists, surgeons, radiation oncologists, medical oncologists, and imaging experts.
Dr. Nghiem and his colleagues have created a comprehensive source of information about Merkel cell carcinoma for physicians and patients at merkelcell.org.
He reported receiving research grants from Bristol-Myers Squibb and serving as a consultant to EMD Serono, Merck, Sanofi/Regeneron, and 4SC.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – The , Paul Nghiem, MD, PhD, declared at the SDEF Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
That’s because dermatologists are typically the physicians who make the diagnosis of Merkel cell carcinoma (MCC), so they’re on the scene from the outset and well positioned to help direct early management of this particularly aggressive malignancy, explained Dr. Nghiem, professor and head of dermatology at the University of Washington, Seattle.
“The management of Merkel is pretty high stakes, and if you get it right at the beginning it makes a huge difference in the side effects, as well as the chances that the patient will have the disease under control,” said Dr. Nghiem, who is sometimes called “the Merkel man” because of his many pioneering contributions to the field.
Better early management
Getting early management right, he added, hinges upon ordering a baseline PET-CT scan to search for metastases before performing definitive surgical excision of the primary tumor.
“There are really important prognostic and therapeutic implications for a baseline scan in almost any patient with early Merkel – and that’s a very different situation than with melanoma,” the dermatologist said. “There’s at least a threefold higher likelihood that the cancer has spread asymptomatically at baseline with Merkel cell carcinoma than with melanoma.”
In a soon-to-be-published study by Dr. Nghiem and coworkers, baseline imaging resulted in prognostically important upstaging that led to an altered management strategy in 12% of 584 patients with MCC, or 1 in 8.
“You don’t want to overtreat locally a lesion that has already spread distantly; you want to start focusing on the distant disease. The local disease is secondary,” he said.
The surgical excision of the primary lesion should be thoughtfully wide without being aggressive or mutilating, and it should involve primary closure. “Definitely avoid flaps and grafts, which delay your further management with radiotherapy by months and months,” Dr. Nghiem advised.
Adjuvant radiotherapy of the primary tumor site is extremely effective at preventing recurrent MCC. In Dr. Nghiem’s view, almost everyone is a candidate: In a series of 803 patients in the Seattle MCC cohort, 92% received local adjuvant radiotherapy. The national rate, in contrast, is only about 50%, highlighting the need for additional physician education.
“A little bit of radiation – one dose – appears to be just as effective as 6 weeks in controlling microscopic disease. That’s probably something we’re going to be moving towards as a field,” he predicted.
Indeed, local adjuvant radiotherapy is so effective in MCC that the surgical margins make no difference. This was demonstrated in a study by Dr. Nghiem and his coinvestigators involving 70 patients with margins greater than 1 cm who received radiotherapy, 70 others with smaller or even positive margins who received radiotherapy, and 35 patients with margins of 1 cm or less who did not receive radiotherapy. There were no MCC recurrences in any of the radiotherapy recipients, regardless of their margin status. In contrast, 7 of the 35 patients who didn’t receive radiation therapy developed a cancer recurrence. Of note, the recurrence rate of MCC is historically about 40% – far greater than for any other skin cancer. Most recurrences happen within the first 2-3 years, Dr. Nghiem observed.
Immune therapy takes center stage
Another major transformation in MCC management has been the emergence of immune therapy as first-line systemic therapy. It has replaced chemotherapy, which is more toxic and has a much shorter average duration of response. Avelumab (Bavencio) and pembrolizumab (Keytruda), the two monoclonal antibodies directed against the protein programmed death–ligand 1 (PD-L1) receptor which are approved for MCC and have been incorporated into the National Comprehensive Cancer Network (NCCN) guidelines, provide a sixfold improvement in survival, compared with chemotherapy. For example, Dr. Nghiem was first author of a multicenter phase 2 study of pembrolizumab in which the 12- and 24-month overall survival rates in pembrolizumab responders were 85% and 79%, compared with just 12% and 6%, respectively, in historical controls on first-line chemotherapy (J Clin Oncol. 2019 Mar 20;37[9]:693-702).
“Merkel cell carcinoma is the most responsive solid tumor to immune therapy,” Dr. Nghiem commented.
Why MCC matters
Although rare, MCC is important because it’s five times more lethal than melanoma. Moreover, its incidence has been rising at a rate roughly twice that of the increase in melanoma since the turn of the century. There are now more than 3,000 new cases of MCC annually, about the same as for cutaneous T-cell lymphoma (CTCL).
“It’s just that you live a long time with CTCL and you don’t with Merkel cell carcinoma. You either get rid of Merkel fast or it gets rid of you,” the dermatologist observed.
It’s a fascinating malignancy, he continued. Eight of 10 cases are caused by Merkel cell polyomavirus, discovered in 2008. The virus is ubiquitously acquired in childhood and then lies dormant on the skin for the next 6 or 7 decades, at which point MCC rates shoot up dramatically, probably due to immunosenescence. Immunosuppressed patients are at 10-fold increased risk for MCC.
Given the rarity of MCC, it doesn’t make sense to actively hunt for it. But Dr. Nghiem and coworkers have developed a handy vowel-based mnemonic that serves to raise the index of suspicion: the “AEIOU” features.
- A = asymptomatic.
- E = expanding rapidly within past 3 months.
- I = immune-mediated.
- O = older than age 50.
- U = UV-exposed skin.
The investigators found in a series of 195 MCC patients that 89% of them possessed three or more of these features (J Am Acad Dermatol. 2008 Mar;58[3]:375-81). But while the AEIOU guide is quite sensitive, it’s not specific.
“If you have any three or more of these features, that lesion probably deserves a biopsy if it’s not readily explained. Even if it’s not a Merkel, it may turn out to be a different nonmelanoma skin cancer, something you want to know about,” Dr. Nghiem said.
A shift in surveillance strategy
Dr. Nghiem was senior author of a major study that validated the clinical utility of a Merkel polyomavirus serology test for monitoring the disease status of patients treated for MCC (Cancer. 2017 Apr 15;123[8]:1464-74). The test, which measures antibodies to Merkel cell polyomavirus oncoproteins, has been incorporated in NCCN guidelines. The blood test is used initially in newly diagnosed MCC to stratify patients into two subgroups: the half who are seropositive at baseline, and the other half who are seronegative. The seropositive group undergoes surveillance via repeat blood testing every 3 months. If antibody levels are low, there is a high degree of certainty that immune therapy is working and remission is present. Thus, the blood test spares patients in this group the expense and radiation exposure entailed in repeated surveillance scans. However, rising antibody levels indicate the cancer has already recurred or will do so within the next several months.
Unfortunately, the blood test cannot be used serially to track disease status in patients who are seronegative at baseline. That group is at 42% increased risk of MCC recurrence.
Immune therapy works in only about two-thirds of MCC patients with distant disease. Leaving the visible primary tumor in place to serve as a real-time window into immune treatment effectiveness is a useful contemporary surveillance strategy.
“By leaving the visible primary there, you will rapidly know if that patient is in the favorable two-thirds group or not,” he explained.
Historically, surgery and surveillance of MCC were based upon the melanoma model, and medical oncologists were trained to treat the malignancy as they would small cell lung cancer. These are now outmoded approaches, Dr. Nghiem said. That’s why a multidisciplinary approach is highly desirable for management of MCC, including dermatologists, pathologists, surgeons, radiation oncologists, medical oncologists, and imaging experts.
Dr. Nghiem and his colleagues have created a comprehensive source of information about Merkel cell carcinoma for physicians and patients at merkelcell.org.
He reported receiving research grants from Bristol-Myers Squibb and serving as a consultant to EMD Serono, Merck, Sanofi/Regeneron, and 4SC.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – The , Paul Nghiem, MD, PhD, declared at the SDEF Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
That’s because dermatologists are typically the physicians who make the diagnosis of Merkel cell carcinoma (MCC), so they’re on the scene from the outset and well positioned to help direct early management of this particularly aggressive malignancy, explained Dr. Nghiem, professor and head of dermatology at the University of Washington, Seattle.
“The management of Merkel is pretty high stakes, and if you get it right at the beginning it makes a huge difference in the side effects, as well as the chances that the patient will have the disease under control,” said Dr. Nghiem, who is sometimes called “the Merkel man” because of his many pioneering contributions to the field.
Better early management
Getting early management right, he added, hinges upon ordering a baseline PET-CT scan to search for metastases before performing definitive surgical excision of the primary tumor.
“There are really important prognostic and therapeutic implications for a baseline scan in almost any patient with early Merkel – and that’s a very different situation than with melanoma,” the dermatologist said. “There’s at least a threefold higher likelihood that the cancer has spread asymptomatically at baseline with Merkel cell carcinoma than with melanoma.”
In a soon-to-be-published study by Dr. Nghiem and coworkers, baseline imaging resulted in prognostically important upstaging that led to an altered management strategy in 12% of 584 patients with MCC, or 1 in 8.
“You don’t want to overtreat locally a lesion that has already spread distantly; you want to start focusing on the distant disease. The local disease is secondary,” he said.
The surgical excision of the primary lesion should be thoughtfully wide without being aggressive or mutilating, and it should involve primary closure. “Definitely avoid flaps and grafts, which delay your further management with radiotherapy by months and months,” Dr. Nghiem advised.
Adjuvant radiotherapy of the primary tumor site is extremely effective at preventing recurrent MCC. In Dr. Nghiem’s view, almost everyone is a candidate: In a series of 803 patients in the Seattle MCC cohort, 92% received local adjuvant radiotherapy. The national rate, in contrast, is only about 50%, highlighting the need for additional physician education.
“A little bit of radiation – one dose – appears to be just as effective as 6 weeks in controlling microscopic disease. That’s probably something we’re going to be moving towards as a field,” he predicted.
Indeed, local adjuvant radiotherapy is so effective in MCC that the surgical margins make no difference. This was demonstrated in a study by Dr. Nghiem and his coinvestigators involving 70 patients with margins greater than 1 cm who received radiotherapy, 70 others with smaller or even positive margins who received radiotherapy, and 35 patients with margins of 1 cm or less who did not receive radiotherapy. There were no MCC recurrences in any of the radiotherapy recipients, regardless of their margin status. In contrast, 7 of the 35 patients who didn’t receive radiation therapy developed a cancer recurrence. Of note, the recurrence rate of MCC is historically about 40% – far greater than for any other skin cancer. Most recurrences happen within the first 2-3 years, Dr. Nghiem observed.
Immune therapy takes center stage
Another major transformation in MCC management has been the emergence of immune therapy as first-line systemic therapy. It has replaced chemotherapy, which is more toxic and has a much shorter average duration of response. Avelumab (Bavencio) and pembrolizumab (Keytruda), the two monoclonal antibodies directed against the protein programmed death–ligand 1 (PD-L1) receptor which are approved for MCC and have been incorporated into the National Comprehensive Cancer Network (NCCN) guidelines, provide a sixfold improvement in survival, compared with chemotherapy. For example, Dr. Nghiem was first author of a multicenter phase 2 study of pembrolizumab in which the 12- and 24-month overall survival rates in pembrolizumab responders were 85% and 79%, compared with just 12% and 6%, respectively, in historical controls on first-line chemotherapy (J Clin Oncol. 2019 Mar 20;37[9]:693-702).
“Merkel cell carcinoma is the most responsive solid tumor to immune therapy,” Dr. Nghiem commented.
Why MCC matters
Although rare, MCC is important because it’s five times more lethal than melanoma. Moreover, its incidence has been rising at a rate roughly twice that of the increase in melanoma since the turn of the century. There are now more than 3,000 new cases of MCC annually, about the same as for cutaneous T-cell lymphoma (CTCL).
“It’s just that you live a long time with CTCL and you don’t with Merkel cell carcinoma. You either get rid of Merkel fast or it gets rid of you,” the dermatologist observed.
It’s a fascinating malignancy, he continued. Eight of 10 cases are caused by Merkel cell polyomavirus, discovered in 2008. The virus is ubiquitously acquired in childhood and then lies dormant on the skin for the next 6 or 7 decades, at which point MCC rates shoot up dramatically, probably due to immunosenescence. Immunosuppressed patients are at 10-fold increased risk for MCC.
Given the rarity of MCC, it doesn’t make sense to actively hunt for it. But Dr. Nghiem and coworkers have developed a handy vowel-based mnemonic that serves to raise the index of suspicion: the “AEIOU” features.
- A = asymptomatic.
- E = expanding rapidly within past 3 months.
- I = immune-mediated.
- O = older than age 50.
- U = UV-exposed skin.
The investigators found in a series of 195 MCC patients that 89% of them possessed three or more of these features (J Am Acad Dermatol. 2008 Mar;58[3]:375-81). But while the AEIOU guide is quite sensitive, it’s not specific.
“If you have any three or more of these features, that lesion probably deserves a biopsy if it’s not readily explained. Even if it’s not a Merkel, it may turn out to be a different nonmelanoma skin cancer, something you want to know about,” Dr. Nghiem said.
A shift in surveillance strategy
Dr. Nghiem was senior author of a major study that validated the clinical utility of a Merkel polyomavirus serology test for monitoring the disease status of patients treated for MCC (Cancer. 2017 Apr 15;123[8]:1464-74). The test, which measures antibodies to Merkel cell polyomavirus oncoproteins, has been incorporated in NCCN guidelines. The blood test is used initially in newly diagnosed MCC to stratify patients into two subgroups: the half who are seropositive at baseline, and the other half who are seronegative. The seropositive group undergoes surveillance via repeat blood testing every 3 months. If antibody levels are low, there is a high degree of certainty that immune therapy is working and remission is present. Thus, the blood test spares patients in this group the expense and radiation exposure entailed in repeated surveillance scans. However, rising antibody levels indicate the cancer has already recurred or will do so within the next several months.
Unfortunately, the blood test cannot be used serially to track disease status in patients who are seronegative at baseline. That group is at 42% increased risk of MCC recurrence.
Immune therapy works in only about two-thirds of MCC patients with distant disease. Leaving the visible primary tumor in place to serve as a real-time window into immune treatment effectiveness is a useful contemporary surveillance strategy.
“By leaving the visible primary there, you will rapidly know if that patient is in the favorable two-thirds group or not,” he explained.
Historically, surgery and surveillance of MCC were based upon the melanoma model, and medical oncologists were trained to treat the malignancy as they would small cell lung cancer. These are now outmoded approaches, Dr. Nghiem said. That’s why a multidisciplinary approach is highly desirable for management of MCC, including dermatologists, pathologists, surgeons, radiation oncologists, medical oncologists, and imaging experts.
Dr. Nghiem and his colleagues have created a comprehensive source of information about Merkel cell carcinoma for physicians and patients at merkelcell.org.
He reported receiving research grants from Bristol-Myers Squibb and serving as a consultant to EMD Serono, Merck, Sanofi/Regeneron, and 4SC.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM SDEF HAWAII DERMATOLOGY SEMINAR
Know the 15% rule in scleroderma
MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.
“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.
Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.
“It’s a good little rule of thumb,” Dr. Pope commented.
The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.
And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.
Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.
Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.
Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.
MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.
“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.
Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.
“It’s a good little rule of thumb,” Dr. Pope commented.
The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.
And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.
Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.
Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.
Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.
MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.
“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.
Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.
“It’s a good little rule of thumb,” Dr. Pope commented.
The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.
And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.
Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.
Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.
Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.
REPORTING FROM RWCS 2020
Advances in ankylosing spondylitis hailed as rheumatology’s story of the year
MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.
“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.
“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.
“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.
“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”
Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.
“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.
In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.
“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.
Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).
Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.
More biologics coming for nr-AxSpA
In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.
Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.
ACR/SAA/SPARTAN guidelines critiqued
The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.
“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.
Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.
“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.
He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.
“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.
Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.
“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.
Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.
MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.
“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.
“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.
“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.
“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”
Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.
“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.
In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.
“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.
Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).
Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.
More biologics coming for nr-AxSpA
In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.
Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.
ACR/SAA/SPARTAN guidelines critiqued
The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.
“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.
Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.
“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.
He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.
“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.
Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.
“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.
Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.
MAUI, HAWAII – Arguably the most important development in the field of rheumatology during the past year was the emergence of persuasive clinical trials data predictive of a bright future for the oral Janus kinase inhibitors as major new drugs for treating ankylosing spondylitis, two experts agreed at the 2020 Rheumatology Winter Clinical Symposium.
“These drugs are the first oral DMARDs [disease-modifying antirheumatic drugs], if you will, in AS [ankylosing spondylitis] ... I think obviously they are going to move forward to regulatory approval,” commented Arthur F. Kavanaugh, MD, professor of medicine at the University of California, San Diego, and the RWCS program director.
“I think they’re going to hit the ground running,” predicted Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Upon approval, the Janus kinase (JAK) inhibitors will quickly change the treatment paradigm in AS, the rheumatologists forecast.
“I think this is a way forward to go with strictly oral therapy without necessarily going first with parenteral therapy in these patients. It gives you an alternative, and my guess is, by the time these drugs are approved in this space, there’ll be more and more of their preferential use over biologics in rheumatoid arthritis and potentially in psoriatic arthritis, so people will be more familiar with them. A lot of patients are much happier taking a pill once a day with none of the tolerability issues that we have with shots,” Dr. Ruderman said.
“And they act fast,” noted Dr. Kavanaugh. “You can make a case for trying a JAK inhibitor for a month or 2, and then if you’re not better, then we go to the other option.”
Dr. Ruderman cautioned that the increased need for laboratory monitoring with the oral JAK inhibitors as compared with the annual monitoring with tumor necrosis factor inhibitors could be an issue, especially since AS patients tend to be on the younger side and often dislike coming in regularly for office visits and laboratory tests.
“There may be more of a headache in having to tell patients, ‘You’re not getting your JAK inhibitor refilled until you get your labs done,’ ” he said.
In December 2019, rheumatologists received a holiday present in the form of publication of the results of SELECT-AXIS 1, a multicenter, double-blind, randomized, placebo-controlled phase 2/3 trial in which 187 patients with active AS were randomized to placebo or to the JAK inhibitor upadacitinib (Rinvoq) at the same 15-mg dose approved by the FDA earlier in the year for rheumatoid arthritis. In SELECT-AXIS 1, upadacitinib not only demonstrated clinical efficacy, with a week-14 Assessment of SpondyloArthritis International Society-40 (ASAS 40) response rate of 52% – twice that for placebo – but the active treatment arm also experienced significantly reduced inflammatory disease activity as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores of the spine and sacroiliac joint. In contrast, MRI scores remained unchanged from baseline in the placebo arm.
“This suggests a biologic effect, a hook beyond clinical disease. And the time of onset was pretty impressive, much like with our experience with JAK inhibitors in RA. Within 2 weeks, there was significant separation from placebo on the ASDAS [Ankylosing Spondylitis Disease Activity Score],” Dr. Ruderman noted.
Positive clinical trials in AS have also been reported for the oral JAK inhibitors filgotinib and tofacitinib (Xeljanz).
Dr. Ruderman and Dr. Kavanaugh also touched on other major developments in AS within the past year, including the landmark FDA approval of certolizumab pegol (Cimzia) as the first-ever drug for treatment of nonradiographic axial spondyloarthritis (nr-axSpA). Also, Dr. Kavanaugh and Dr. Ruderman gave two thumbs down to the 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.
More biologics coming for nr-AxSpA
In order to gain an indication for treatment of nr-axSpA, the FDA requires completion of a 52-week, randomized, placebo-controlled clinical trial. That’s what UCB did with the company’s TNF inhibitor, certolizumab. Similarly, Eli Lilly sprang for the mandated 52-week trial in 303 nr-axSpA patients for its interleukin-17 inhibitor ixekizumab (Taltz), with positive findings (Lancet. 2020 Jan 4;395[10217]:53-64). And Novartis has done so with its IL-17 inhibitor secukinumab (Cosentyx) in the 555-patient PREVENT trial, again with positive outcomes. So the two IL-17 inhibitors, which are already approved for AS, are seemingly a lock for approval in nr-axSpA as well.
Will the makers of other TNF inhibitors already approved for AS fork over the considerable money entailed in a 52-week randomized trial, or will they ride on certolizumab’s coattails? Dr. Ruderman said he doesn’t know the answer, but it’s certain that, if they don’t complete the trial, they can’t market their biologic for nr-axSpA in the United States, even though there might well be a drug class effect at work.
ACR/SAA/SPARTAN guidelines critiqued
The two panelists had plenty to say about the 2019 update of the guidelines, none of it favorable. Among their criticisms: The guidelines are already out of date several months after their release, they are based heavily on opinion rather than on evidence, they appear to take medication cost into consideration when they’re not supposed to, they are complicated, and they are just not practical or useful.
“I don’t know when these guidelines would potentially be used,” Dr. Kavanaugh commented in response to an audience question.
Specifically, the guidelines strongly recommend a TNF inhibitor over the IL-17 inhibitors secukinumab or ixekizumab as the first-line biologic in AS patients with active disease while on NSAIDs, guidance that is already out of date.
“You’d almost think it would have been better just to wait a few months to see the published literature, which I think is going to have a tremendous impact on practice,” Dr. Kavanaugh said.
He also said he was troubled by the strong recommendation against switching to a TNF inhibitor–biosimilar after receiving treatment with an originator TNF inhibitor. That’s something rheumatologists all across Europe are routinely doing now for economic reasons without known harm, with the caveat that patients must be switched to a biosimilar of a different TNF inhibitor than the originator.
“There’s absolutely no data to support a recommendation against switching. I think they’re going out on a limb a little bit,” he added.
Dr. Ruderman said he struggles with the guideline development methodology, which involves posing a series of key questions at the outset, with a strict charge to provide answers.
“They always have to have an answer to the question. And in the event that there’s no data to support an answer, then it becomes a matter of the expert opinion of the people on the committee. I think many rheumatologists would say, ‘Why are they any more expert than a clinical rheumatologist who’s been seeing AS patients for 20 years?’ And the answer is they’re probably not. The fact that most of these are conditional recommendations, meaning they’re not supported by strong evidence, makes them less useful,” according to Dr. Ruderman.
Both he and Dr. Kavanaugh reported receiving research funding from and/or serving as a consultant to numerous pharmaceutical companies.
REPORTING FROM RWCS 2020
Effective osteoarthritis therapy remains elusive
MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.
“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Several audience members were less restrained in their assessments.
“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.
“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.
Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”
That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.
Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.
A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
In the OA pipeline
“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.
Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.
“I’m not sure this is going anywhere,” Dr. Ruderman commented.
Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.
“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.
This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.
Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)
Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.
“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.
Welcome to the wild, wild West
Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.
“It’s the wild, wild West out there,” the rheumatologist warned.
He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.
As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.
These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.
“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.
The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.
Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.
“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”
On a brighter note
Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.
Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.
“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”
As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.
“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.
He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.
Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.
Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.
MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.
“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Several audience members were less restrained in their assessments.
“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.
“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.
Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”
That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.
Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.
A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
In the OA pipeline
“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.
Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.
“I’m not sure this is going anywhere,” Dr. Ruderman commented.
Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.
“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.
This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.
Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)
Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.
“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.
Welcome to the wild, wild West
Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.
“It’s the wild, wild West out there,” the rheumatologist warned.
He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.
As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.
These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.
“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.
The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.
Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.
“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”
On a brighter note
Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.
Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.
“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”
As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.
“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.
He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.
Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.
Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.
MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.
“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Several audience members were less restrained in their assessments.
“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.
“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.
Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”
That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.
Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.
A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
In the OA pipeline
“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.
Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.
“I’m not sure this is going anywhere,” Dr. Ruderman commented.
Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.
“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.
This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.
Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)
Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.
“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.
Welcome to the wild, wild West
Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.
“It’s the wild, wild West out there,” the rheumatologist warned.
He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.
As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.
These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.
“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.
The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.
Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.
“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”
On a brighter note
Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.
Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.
“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”
As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.
“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.
He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.
Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.
Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2020
Short-course calcipotriol plus 5-FU for AKs: potential major public health impact
LAHAINA, HAWAII – The most intriguing recent development in the treatment of actinic keratosis is a study in which a short-course of topical field therapy with , with a resultant markedly reduced risk of developing squamous cell carcinoma within the next 3 years, Kishwer S. Nehal, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
The annual cost of treating actinic keratoses (AKs) exceeds $1 billion in the United States, so the billion-dollar question in dermatology is, does AK reduction lead to long-term protection against cancer? And this 3-year study by investigators at Washington University in St. Louis and Massachusetts General Hospital in Boston suggests the answer may be yes – when topical immunotherapy is utilized to induce robust T cell immunity, said Dr. Nehal, director of Mohs micrographic and dermatologic surgery, and codirector of the multidisciplinary skin cancer management program at Memorial Sloan Kettering Cancer Center in New York.
The investigators previously conducted a randomized, double-blind clinical trial in which 130 participants with a substantial AK burden received a 4-day course of 0.005% calcipotriol ointment plus 5% 5-FU cream or Vaseline plus 5-FU. The combination therapy proved more effective than the comparator in eliminating AKs at 8 weeks of follow-up. Moreover, tissue analysis pointed to the mechanism of benefit: The combination treatment induced keratinocyte expression of thymic stromal lymphopoietin (TSLP) cytokine, which led to a powerful CD4+ T cell response against AKs.
The researchers’ follow-up study addressed two key questions: Whether this epidermal T cell immunity persists long term, and if it actually achieves a reduced risk of squamous cell carcinoma (SCC) over time. The answers were yes and yes.
Seventy of the original 130 patients were prospectively followed for 3 years. Only 2 of 30 (7%) in the short-course combination therapy group developed SCC in treated areas of the face and scalp, compared with 11 of 40 controls (28%), a statistically significant difference, which constitutes a 79% relative risk reduction. This chemopreventive effect was long lasting at the cellular level, as the combination therapy group still retained measurable T cell immunity in the skin at the 3-year mark. As expected, the topical therapy had no impact on the development of basal cell carcinoma. The question now becomes how long the chemopreventive effect extends beyond 3 years.
“These remarkable findings substantiate the use of immunotherapeutic agents with minimal side effects and high efficacy against precancerous lesions in order to reduce the risk of cancer development and recurrence, which may be broadly applicable to skin and internal malignancies,” the investigators wrote in the study (JCI Insight. 2019 Mar 21;4(6). pii: 125476. doi: 10.1172/jci.insight.125476). Dr. Nehal said that this study requires confirmation in light of its post hoc design and the relatively small numbers of patients and SCCs. But the potential public health implications are profound, since roughly 40 million Americans have AKs, subclinical AKs are 10 times more common than visible ones, AKs are known precursors for SCC, and high-risk SCC is the cause of roughly 10,000 deaths per year, an underappreciated mortality burden that’s actually comparable to that of melanoma.
While awaiting further studies, this short-course combination therapy also offers the ready appeal of a field therapy without much downtime due to treatment-induced inflammation. In the study, 4 days of combo therapy resulted in moderate inflammation which quickly resolved.
“Does treatment duration and severity affect patient compliance? I would argue that in 2020 it does. People have very active, busy lives and they don’t want a lot of downtime. I can tell you that in Manhattan they want no downtime,” said Dr. Nehal, professor of dermatology at Weill Cornell Medicine, New York.
Even though a traditional 4-week, twice-daily course of 5% 5-FU cream has been convincingly shown in a recent large randomized Dutch trial (N Engl J Med. 2019 Mar 7;380[10]:935-46) to be the most effective field therapy for eradicating AKs – outperforming in descending order of efficacy at 12 months of follow-up imiquimod (Zyclara), photodynamic therapy, and ingenol mebutate (Picato) – Dr. Nehal finds few takers for 5-FU. People balk at the downtime. Her female patients with a significant AK burden typically opt for photodynamic therapy because of the aesthetic side benefit and shorter downtime, while the men – even those who’ve already had a large SCC – are more likely to prefer a watch-and-wait approach, dealing with an SCC if and when it arises.
“I love the science behind using calcipotriol with 5-FU, but I wish it was more friendly to dermatologists,” said fellow panelist Paul Nghiem, MD, PhD. “Of all the things we should have a combination product for, the pharmaceutical industry should really prepare a [calcipotriol/5-FU] cream and market it with the improved efficacy data.”
He added that he has no use for the conventional 2- to 4-week, twice-daily 5-FU regimens employed by many dermatologists.
“I don’t understand this need to feel like you’ve got to treat patients until they look like they’ve fallen off a motorcycle at 50 mph. I just can’t see that,” said Dr. Nghiem, professor and chair of dermatology at the University of Washington, Seattle.
Instead, he routinely utilizes the nearly 3-decade-old Pearlman technique of weekly pulsed dosing of topical 5-FU (J Am Acad Dermatol. 1991 Oct;25[4]:665-7).
“I almost never even ask my patients, ‘Are you OK with having a bunch of downtime?’ I just say, ‘Treat with the 5-FU until you get some erythema, until you’re bothered by it, and then stop for a while,’ ” he explained. “I’ve treated many patients with that technique over the years. It might not be quite as effective, but I hardly have to do any treatment with liquid nitrogen.”
Session chair Ashfaq A. Marghoob, MD, is of a similar mind.
“I also don’t go to the point that you’re fire engine red. Once the irritation sets in, we stop,” said Dr. Marghoob, director of clinical dermatology, Memorial Sloan Kettering Skin Cancer Center Hauppauge (New York).
Neither Dr. Nehal nor Dr. Nghiem has used short-course calcipotriol plus 5-FU therapy. When they polled the large audience as to who has, only a few hands went up.
“I feel like residents who are keeping up with the literature are using it,” Dr. Nehal observed. “My fellows say, ‘Yup, that’s what we’re doing,’ but I’m not using it.”
“I use it,” volunteered fellow panelist Trilokraj Tejasvi, MBBS. “I was educated by one of my residents, and now I use it all the time, especially in my VA population. I’ve been using it for a year. Things get red, but it clears fast,” said Dr. Tejasvi, director of the cutaneous lymphoma program and director of teledermatology services at the University of Michigan, Ann Arbor, and chief of the dermatology service at Ann Arbor Veteran Affairs Hospital.
Dr. Nehal reported having no conflicts of interest regarding her presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – The most intriguing recent development in the treatment of actinic keratosis is a study in which a short-course of topical field therapy with , with a resultant markedly reduced risk of developing squamous cell carcinoma within the next 3 years, Kishwer S. Nehal, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
The annual cost of treating actinic keratoses (AKs) exceeds $1 billion in the United States, so the billion-dollar question in dermatology is, does AK reduction lead to long-term protection against cancer? And this 3-year study by investigators at Washington University in St. Louis and Massachusetts General Hospital in Boston suggests the answer may be yes – when topical immunotherapy is utilized to induce robust T cell immunity, said Dr. Nehal, director of Mohs micrographic and dermatologic surgery, and codirector of the multidisciplinary skin cancer management program at Memorial Sloan Kettering Cancer Center in New York.
The investigators previously conducted a randomized, double-blind clinical trial in which 130 participants with a substantial AK burden received a 4-day course of 0.005% calcipotriol ointment plus 5% 5-FU cream or Vaseline plus 5-FU. The combination therapy proved more effective than the comparator in eliminating AKs at 8 weeks of follow-up. Moreover, tissue analysis pointed to the mechanism of benefit: The combination treatment induced keratinocyte expression of thymic stromal lymphopoietin (TSLP) cytokine, which led to a powerful CD4+ T cell response against AKs.
The researchers’ follow-up study addressed two key questions: Whether this epidermal T cell immunity persists long term, and if it actually achieves a reduced risk of squamous cell carcinoma (SCC) over time. The answers were yes and yes.
Seventy of the original 130 patients were prospectively followed for 3 years. Only 2 of 30 (7%) in the short-course combination therapy group developed SCC in treated areas of the face and scalp, compared with 11 of 40 controls (28%), a statistically significant difference, which constitutes a 79% relative risk reduction. This chemopreventive effect was long lasting at the cellular level, as the combination therapy group still retained measurable T cell immunity in the skin at the 3-year mark. As expected, the topical therapy had no impact on the development of basal cell carcinoma. The question now becomes how long the chemopreventive effect extends beyond 3 years.
“These remarkable findings substantiate the use of immunotherapeutic agents with minimal side effects and high efficacy against precancerous lesions in order to reduce the risk of cancer development and recurrence, which may be broadly applicable to skin and internal malignancies,” the investigators wrote in the study (JCI Insight. 2019 Mar 21;4(6). pii: 125476. doi: 10.1172/jci.insight.125476). Dr. Nehal said that this study requires confirmation in light of its post hoc design and the relatively small numbers of patients and SCCs. But the potential public health implications are profound, since roughly 40 million Americans have AKs, subclinical AKs are 10 times more common than visible ones, AKs are known precursors for SCC, and high-risk SCC is the cause of roughly 10,000 deaths per year, an underappreciated mortality burden that’s actually comparable to that of melanoma.
While awaiting further studies, this short-course combination therapy also offers the ready appeal of a field therapy without much downtime due to treatment-induced inflammation. In the study, 4 days of combo therapy resulted in moderate inflammation which quickly resolved.
“Does treatment duration and severity affect patient compliance? I would argue that in 2020 it does. People have very active, busy lives and they don’t want a lot of downtime. I can tell you that in Manhattan they want no downtime,” said Dr. Nehal, professor of dermatology at Weill Cornell Medicine, New York.
Even though a traditional 4-week, twice-daily course of 5% 5-FU cream has been convincingly shown in a recent large randomized Dutch trial (N Engl J Med. 2019 Mar 7;380[10]:935-46) to be the most effective field therapy for eradicating AKs – outperforming in descending order of efficacy at 12 months of follow-up imiquimod (Zyclara), photodynamic therapy, and ingenol mebutate (Picato) – Dr. Nehal finds few takers for 5-FU. People balk at the downtime. Her female patients with a significant AK burden typically opt for photodynamic therapy because of the aesthetic side benefit and shorter downtime, while the men – even those who’ve already had a large SCC – are more likely to prefer a watch-and-wait approach, dealing with an SCC if and when it arises.
“I love the science behind using calcipotriol with 5-FU, but I wish it was more friendly to dermatologists,” said fellow panelist Paul Nghiem, MD, PhD. “Of all the things we should have a combination product for, the pharmaceutical industry should really prepare a [calcipotriol/5-FU] cream and market it with the improved efficacy data.”
He added that he has no use for the conventional 2- to 4-week, twice-daily 5-FU regimens employed by many dermatologists.
“I don’t understand this need to feel like you’ve got to treat patients until they look like they’ve fallen off a motorcycle at 50 mph. I just can’t see that,” said Dr. Nghiem, professor and chair of dermatology at the University of Washington, Seattle.
Instead, he routinely utilizes the nearly 3-decade-old Pearlman technique of weekly pulsed dosing of topical 5-FU (J Am Acad Dermatol. 1991 Oct;25[4]:665-7).
“I almost never even ask my patients, ‘Are you OK with having a bunch of downtime?’ I just say, ‘Treat with the 5-FU until you get some erythema, until you’re bothered by it, and then stop for a while,’ ” he explained. “I’ve treated many patients with that technique over the years. It might not be quite as effective, but I hardly have to do any treatment with liquid nitrogen.”
Session chair Ashfaq A. Marghoob, MD, is of a similar mind.
“I also don’t go to the point that you’re fire engine red. Once the irritation sets in, we stop,” said Dr. Marghoob, director of clinical dermatology, Memorial Sloan Kettering Skin Cancer Center Hauppauge (New York).
Neither Dr. Nehal nor Dr. Nghiem has used short-course calcipotriol plus 5-FU therapy. When they polled the large audience as to who has, only a few hands went up.
“I feel like residents who are keeping up with the literature are using it,” Dr. Nehal observed. “My fellows say, ‘Yup, that’s what we’re doing,’ but I’m not using it.”
“I use it,” volunteered fellow panelist Trilokraj Tejasvi, MBBS. “I was educated by one of my residents, and now I use it all the time, especially in my VA population. I’ve been using it for a year. Things get red, but it clears fast,” said Dr. Tejasvi, director of the cutaneous lymphoma program and director of teledermatology services at the University of Michigan, Ann Arbor, and chief of the dermatology service at Ann Arbor Veteran Affairs Hospital.
Dr. Nehal reported having no conflicts of interest regarding her presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – The most intriguing recent development in the treatment of actinic keratosis is a study in which a short-course of topical field therapy with , with a resultant markedly reduced risk of developing squamous cell carcinoma within the next 3 years, Kishwer S. Nehal, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
The annual cost of treating actinic keratoses (AKs) exceeds $1 billion in the United States, so the billion-dollar question in dermatology is, does AK reduction lead to long-term protection against cancer? And this 3-year study by investigators at Washington University in St. Louis and Massachusetts General Hospital in Boston suggests the answer may be yes – when topical immunotherapy is utilized to induce robust T cell immunity, said Dr. Nehal, director of Mohs micrographic and dermatologic surgery, and codirector of the multidisciplinary skin cancer management program at Memorial Sloan Kettering Cancer Center in New York.
The investigators previously conducted a randomized, double-blind clinical trial in which 130 participants with a substantial AK burden received a 4-day course of 0.005% calcipotriol ointment plus 5% 5-FU cream or Vaseline plus 5-FU. The combination therapy proved more effective than the comparator in eliminating AKs at 8 weeks of follow-up. Moreover, tissue analysis pointed to the mechanism of benefit: The combination treatment induced keratinocyte expression of thymic stromal lymphopoietin (TSLP) cytokine, which led to a powerful CD4+ T cell response against AKs.
The researchers’ follow-up study addressed two key questions: Whether this epidermal T cell immunity persists long term, and if it actually achieves a reduced risk of squamous cell carcinoma (SCC) over time. The answers were yes and yes.
Seventy of the original 130 patients were prospectively followed for 3 years. Only 2 of 30 (7%) in the short-course combination therapy group developed SCC in treated areas of the face and scalp, compared with 11 of 40 controls (28%), a statistically significant difference, which constitutes a 79% relative risk reduction. This chemopreventive effect was long lasting at the cellular level, as the combination therapy group still retained measurable T cell immunity in the skin at the 3-year mark. As expected, the topical therapy had no impact on the development of basal cell carcinoma. The question now becomes how long the chemopreventive effect extends beyond 3 years.
“These remarkable findings substantiate the use of immunotherapeutic agents with minimal side effects and high efficacy against precancerous lesions in order to reduce the risk of cancer development and recurrence, which may be broadly applicable to skin and internal malignancies,” the investigators wrote in the study (JCI Insight. 2019 Mar 21;4(6). pii: 125476. doi: 10.1172/jci.insight.125476). Dr. Nehal said that this study requires confirmation in light of its post hoc design and the relatively small numbers of patients and SCCs. But the potential public health implications are profound, since roughly 40 million Americans have AKs, subclinical AKs are 10 times more common than visible ones, AKs are known precursors for SCC, and high-risk SCC is the cause of roughly 10,000 deaths per year, an underappreciated mortality burden that’s actually comparable to that of melanoma.
While awaiting further studies, this short-course combination therapy also offers the ready appeal of a field therapy without much downtime due to treatment-induced inflammation. In the study, 4 days of combo therapy resulted in moderate inflammation which quickly resolved.
“Does treatment duration and severity affect patient compliance? I would argue that in 2020 it does. People have very active, busy lives and they don’t want a lot of downtime. I can tell you that in Manhattan they want no downtime,” said Dr. Nehal, professor of dermatology at Weill Cornell Medicine, New York.
Even though a traditional 4-week, twice-daily course of 5% 5-FU cream has been convincingly shown in a recent large randomized Dutch trial (N Engl J Med. 2019 Mar 7;380[10]:935-46) to be the most effective field therapy for eradicating AKs – outperforming in descending order of efficacy at 12 months of follow-up imiquimod (Zyclara), photodynamic therapy, and ingenol mebutate (Picato) – Dr. Nehal finds few takers for 5-FU. People balk at the downtime. Her female patients with a significant AK burden typically opt for photodynamic therapy because of the aesthetic side benefit and shorter downtime, while the men – even those who’ve already had a large SCC – are more likely to prefer a watch-and-wait approach, dealing with an SCC if and when it arises.
“I love the science behind using calcipotriol with 5-FU, but I wish it was more friendly to dermatologists,” said fellow panelist Paul Nghiem, MD, PhD. “Of all the things we should have a combination product for, the pharmaceutical industry should really prepare a [calcipotriol/5-FU] cream and market it with the improved efficacy data.”
He added that he has no use for the conventional 2- to 4-week, twice-daily 5-FU regimens employed by many dermatologists.
“I don’t understand this need to feel like you’ve got to treat patients until they look like they’ve fallen off a motorcycle at 50 mph. I just can’t see that,” said Dr. Nghiem, professor and chair of dermatology at the University of Washington, Seattle.
Instead, he routinely utilizes the nearly 3-decade-old Pearlman technique of weekly pulsed dosing of topical 5-FU (J Am Acad Dermatol. 1991 Oct;25[4]:665-7).
“I almost never even ask my patients, ‘Are you OK with having a bunch of downtime?’ I just say, ‘Treat with the 5-FU until you get some erythema, until you’re bothered by it, and then stop for a while,’ ” he explained. “I’ve treated many patients with that technique over the years. It might not be quite as effective, but I hardly have to do any treatment with liquid nitrogen.”
Session chair Ashfaq A. Marghoob, MD, is of a similar mind.
“I also don’t go to the point that you’re fire engine red. Once the irritation sets in, we stop,” said Dr. Marghoob, director of clinical dermatology, Memorial Sloan Kettering Skin Cancer Center Hauppauge (New York).
Neither Dr. Nehal nor Dr. Nghiem has used short-course calcipotriol plus 5-FU therapy. When they polled the large audience as to who has, only a few hands went up.
“I feel like residents who are keeping up with the literature are using it,” Dr. Nehal observed. “My fellows say, ‘Yup, that’s what we’re doing,’ but I’m not using it.”
“I use it,” volunteered fellow panelist Trilokraj Tejasvi, MBBS. “I was educated by one of my residents, and now I use it all the time, especially in my VA population. I’ve been using it for a year. Things get red, but it clears fast,” said Dr. Tejasvi, director of the cutaneous lymphoma program and director of teledermatology services at the University of Michigan, Ann Arbor, and chief of the dermatology service at Ann Arbor Veteran Affairs Hospital.
Dr. Nehal reported having no conflicts of interest regarding her presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM SDEF HAWAII DERMATOLOGY SEMINAR
Is telerheumatology the future of rheumatology?
MAUI, HAWAII – Alvin F. Wells, MD, PhD, believes he’s seen the future of rheumatology. So he’s taken a deep dive into telerheumatology, going all in.
“Whether you’re in academic, private, or hospital-based practice, in 2020 if you are not thinking about telerheumatology, you and your practice will not be able to compete with growing patient demands, expectations, and need for clinical monitoring. If you do not have a digital/virtual strategy, you do not have a health care strategy,” he asserted at the 2020 Rheumatology Winter Clinical Symposium.
“Begin now,” the rheumatologist advised.
In pursuit of his own telerheumatology strategy, he holds licenses to practice medicine in five states and has licensure pending in five others.
“My goal is to cover 20% of the U.S., so if the local guys can’t see the patients, I can see them virtually,” he explained. “The days of waiting 4-6 months to be seen by a rheumatologist are gone.”
Rheumatologists are already in short supply in most of the country, and a major shortage looms ahead as older practitioners retire. Telerheumatology can help fill that unmet need. But the specialty is behind the curve. In a survey that rated the medical specialties most engaged in telemedicine, the top three spots were held by radiology, psychiatry, and internal medicine. Rheumatology didn’t even crack the top 10, noted Dr. Wells, director of the Rheumatology and Immunotherapy Center in Franklin, Wisc., and a part-time faculty member at Duke University, the Medical College of Wisconsin, and the Karolinska Institute.
Yet telemedicine is primed for rheumatologic takeoff. Notably, the 2019 update of the American College of Rheumatology recommendations on rheumatoid arthritis disease activity measures incorporates the RAPID3 (Routine Assessment of Patient Index Data) as an endorsed three-question clinical assessment that doesn’t involve a physical exam or laboratory work. The ACR update is recognition that, while every rheumatology patient needs an initial physical exam along with follow-up physical exams at various rates, many patients with well-controlled disease don’t need a physical exam at every physician encounter, he said.
Telerheumatology saves time for both patient and physician. The patient saves travel time, doesn’t miss work, avoids having to arrange for child care in order to make a face-to-face clinic visit, and can schedule more frequent virtual follow-up visits. For the practitioner, telerheumatology means additional consults and – here’s the big one – “You never run behind,” according to Dr. Wells. “For a 15-minute appointment, the patient gets a 5-minute warning, then a 2-minute warning, and at 15 minutes the link is cut. If the fibromyalgia patients want 30 minutes, they pay for 30 minutes.”
He sees the strictly enforced, impersonally delivered electronic time limits as key to running an efficient practice.
“The patients with osteoarthritis who hate the nodules, the fibromyalgia patients because they’re hurting all over, the patients with back pain – you’ve really got to limit those patients because otherwise you’ll be running 30-40 minutes behind for a scheduled 15-minute visit,” he explained.
One rheumatologist’s telemedicine practice
Dr. Wells currently utilizes the Epic electronic health record integrated with a Zoom videoconferencing platform for real-time virtual patient encounters. But he noted that other virtual platforms are available, including Health Tap, American Well, MySpecialistMD, MDLIVE, and TelaDoc. The American Telemedicine Association is a valuable resource for state-by-state medicolegal, reimbursement, and how-to-do-it questions.
At present, he reserves two daily time slots for telerheumatology: one at 8:30-9:00 a.m., the other at 4:30-5:00 p.m. These can be filled with four 15-minute live consults or two 30-minute consults. His goal is to eventually make telerheumatology 20% of his patient load of about 100 patients per week.
His typical 15-minute virtual visit proceeds as follows: It begins with a 3-minute subjective patient assessment, followed by a 5-minute objective assessment which includes the RAPID3, a brief Health Assessment Questionnaire (HAQ) addressing the patient’s pain and overall satisfaction, a virtual joint inspection, the use of high-quality teleultrasound and other technology when warranted, and capture of relevant still photos. This is followed by 5 minutes to relay the treatment plan, and finally a 2-minute recap and summary.
“No niceties. We cut right to the chase,” he noted.
He documents the patient encounter as he goes, dictating his notes throughout the visit.
“When I walk out of the room, I’m done. It’s on to the next patient,” Dr. Wells said.
The reimbursement picture is improving, although major hurdles remain. At present, 48 states and the District of Columbia reimburse for live video telemedicine through Medicaid. And in January 2020, Aetna announced it covers reimbursement for telemedicine in all of its fully insured health plans via the Teladoc platform. Dr. Wells’ patients pay for their telerheumatology out of pocket if their insurance doesn’t cover it.
Telemedicine caveats
Dr. Wells shared his telerheumatology experience as the first half of a point/counterpoint session on telemedicine’s future in the specialty. His debate opponent, Orrin M. Troum, MD, announced at the outset that he is quite interested in getting into telerheumatology; however, while looking into it he has come across issues that for now give him pause and that other rheumatologists need to be aware of.
Legal risks. The telemedicine movement has gotten big enough to draw the scrutiny of federal prosecutors and regulatory enforcement officials. In April 2018, the Department of Health & Human Services Office of the Inspector General (OIG) issued a report that concluded that one-third of all examined telemedicine claims were improper.
“Just imagine who might come knocking on your door,” he said.
Among the most common offenses, according to the OIG, were claims for services outside the limited range currently covered; lack of the requisite HIPAA-compliant two-way audio and visual communication technology with fully encrypted data transmission; services billed by institutional providers not defined by Medicare as telemedicine-eligible; and claims for services received by patients who weren’t located in an officially designated Health Professional Shortage Area or in a rural county as determined by the U.S. Census Bureau.
Telemedicine is no panacea for out-of-control health care costs. A RAND study of participants in the California Public Employees’ Retirement System (CalPERS) concluded that only 12% of beneficiaries who used direct-to-consumer telemedicine did so to replace provider visits. The other 88% added on telemedicine as an additional service. So while telemedicine increased patient access to health care, it also increased the overall cost, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica, Calif.
Talk to your attorney and malpractice insurer before embarking on telerheumatology. Physicians could potentially lose their medical malpractice insurance if they use telemedicine to treat patients located in states where they aren’t licensed to practice, even if through inadvertent error.
Telemedicine isn’t appropriate for all patients. Nearly a decade ago, rheumatologists at Dartmouth-Hitchcock Medical Center launched a telerheumatology service in order to bring specialty care to the largely rural populations of New Hampshire and Vermont. In a review of the experience that included interviews with both patients and providers, investigators concluded that telerheumatology successfully increased access to specialty care in underserved locations and got good satisfaction scores from both providers and beneficiaries. However, fully 19% of patients were found to be inappropriate for their telerheumatology visit, mainly because their disease was too complex or the underlying diagnosis was unclear.
“Almost one-fifth of their patients were inappropriate for telerheumatology. The question is, how are you supposed to know that ahead of time?” Dr. Troum asked.
Patient satisfaction. Dr. Troum’s reading of the literature on patient satisfaction with telerheumatology, coupled with his own extensive experience in clinical practice, makes him think that many of his younger patients with less disease activity might welcome a telerheumatology option, even with strict time boundaries. But his older patients with more disease activity are a different story.
“Typically my middle-aged and older patients won’t accept that without a lot of convincing,” he commented.
Dr. Wells and Dr. Troum had no relevant disclosures regarding their presentations.
MAUI, HAWAII – Alvin F. Wells, MD, PhD, believes he’s seen the future of rheumatology. So he’s taken a deep dive into telerheumatology, going all in.
“Whether you’re in academic, private, or hospital-based practice, in 2020 if you are not thinking about telerheumatology, you and your practice will not be able to compete with growing patient demands, expectations, and need for clinical monitoring. If you do not have a digital/virtual strategy, you do not have a health care strategy,” he asserted at the 2020 Rheumatology Winter Clinical Symposium.
“Begin now,” the rheumatologist advised.
In pursuit of his own telerheumatology strategy, he holds licenses to practice medicine in five states and has licensure pending in five others.
“My goal is to cover 20% of the U.S., so if the local guys can’t see the patients, I can see them virtually,” he explained. “The days of waiting 4-6 months to be seen by a rheumatologist are gone.”
Rheumatologists are already in short supply in most of the country, and a major shortage looms ahead as older practitioners retire. Telerheumatology can help fill that unmet need. But the specialty is behind the curve. In a survey that rated the medical specialties most engaged in telemedicine, the top three spots were held by radiology, psychiatry, and internal medicine. Rheumatology didn’t even crack the top 10, noted Dr. Wells, director of the Rheumatology and Immunotherapy Center in Franklin, Wisc., and a part-time faculty member at Duke University, the Medical College of Wisconsin, and the Karolinska Institute.
Yet telemedicine is primed for rheumatologic takeoff. Notably, the 2019 update of the American College of Rheumatology recommendations on rheumatoid arthritis disease activity measures incorporates the RAPID3 (Routine Assessment of Patient Index Data) as an endorsed three-question clinical assessment that doesn’t involve a physical exam or laboratory work. The ACR update is recognition that, while every rheumatology patient needs an initial physical exam along with follow-up physical exams at various rates, many patients with well-controlled disease don’t need a physical exam at every physician encounter, he said.
Telerheumatology saves time for both patient and physician. The patient saves travel time, doesn’t miss work, avoids having to arrange for child care in order to make a face-to-face clinic visit, and can schedule more frequent virtual follow-up visits. For the practitioner, telerheumatology means additional consults and – here’s the big one – “You never run behind,” according to Dr. Wells. “For a 15-minute appointment, the patient gets a 5-minute warning, then a 2-minute warning, and at 15 minutes the link is cut. If the fibromyalgia patients want 30 minutes, they pay for 30 minutes.”
He sees the strictly enforced, impersonally delivered electronic time limits as key to running an efficient practice.
“The patients with osteoarthritis who hate the nodules, the fibromyalgia patients because they’re hurting all over, the patients with back pain – you’ve really got to limit those patients because otherwise you’ll be running 30-40 minutes behind for a scheduled 15-minute visit,” he explained.
One rheumatologist’s telemedicine practice
Dr. Wells currently utilizes the Epic electronic health record integrated with a Zoom videoconferencing platform for real-time virtual patient encounters. But he noted that other virtual platforms are available, including Health Tap, American Well, MySpecialistMD, MDLIVE, and TelaDoc. The American Telemedicine Association is a valuable resource for state-by-state medicolegal, reimbursement, and how-to-do-it questions.
At present, he reserves two daily time slots for telerheumatology: one at 8:30-9:00 a.m., the other at 4:30-5:00 p.m. These can be filled with four 15-minute live consults or two 30-minute consults. His goal is to eventually make telerheumatology 20% of his patient load of about 100 patients per week.
His typical 15-minute virtual visit proceeds as follows: It begins with a 3-minute subjective patient assessment, followed by a 5-minute objective assessment which includes the RAPID3, a brief Health Assessment Questionnaire (HAQ) addressing the patient’s pain and overall satisfaction, a virtual joint inspection, the use of high-quality teleultrasound and other technology when warranted, and capture of relevant still photos. This is followed by 5 minutes to relay the treatment plan, and finally a 2-minute recap and summary.
“No niceties. We cut right to the chase,” he noted.
He documents the patient encounter as he goes, dictating his notes throughout the visit.
“When I walk out of the room, I’m done. It’s on to the next patient,” Dr. Wells said.
The reimbursement picture is improving, although major hurdles remain. At present, 48 states and the District of Columbia reimburse for live video telemedicine through Medicaid. And in January 2020, Aetna announced it covers reimbursement for telemedicine in all of its fully insured health plans via the Teladoc platform. Dr. Wells’ patients pay for their telerheumatology out of pocket if their insurance doesn’t cover it.
Telemedicine caveats
Dr. Wells shared his telerheumatology experience as the first half of a point/counterpoint session on telemedicine’s future in the specialty. His debate opponent, Orrin M. Troum, MD, announced at the outset that he is quite interested in getting into telerheumatology; however, while looking into it he has come across issues that for now give him pause and that other rheumatologists need to be aware of.
Legal risks. The telemedicine movement has gotten big enough to draw the scrutiny of federal prosecutors and regulatory enforcement officials. In April 2018, the Department of Health & Human Services Office of the Inspector General (OIG) issued a report that concluded that one-third of all examined telemedicine claims were improper.
“Just imagine who might come knocking on your door,” he said.
Among the most common offenses, according to the OIG, were claims for services outside the limited range currently covered; lack of the requisite HIPAA-compliant two-way audio and visual communication technology with fully encrypted data transmission; services billed by institutional providers not defined by Medicare as telemedicine-eligible; and claims for services received by patients who weren’t located in an officially designated Health Professional Shortage Area or in a rural county as determined by the U.S. Census Bureau.
Telemedicine is no panacea for out-of-control health care costs. A RAND study of participants in the California Public Employees’ Retirement System (CalPERS) concluded that only 12% of beneficiaries who used direct-to-consumer telemedicine did so to replace provider visits. The other 88% added on telemedicine as an additional service. So while telemedicine increased patient access to health care, it also increased the overall cost, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica, Calif.
Talk to your attorney and malpractice insurer before embarking on telerheumatology. Physicians could potentially lose their medical malpractice insurance if they use telemedicine to treat patients located in states where they aren’t licensed to practice, even if through inadvertent error.
Telemedicine isn’t appropriate for all patients. Nearly a decade ago, rheumatologists at Dartmouth-Hitchcock Medical Center launched a telerheumatology service in order to bring specialty care to the largely rural populations of New Hampshire and Vermont. In a review of the experience that included interviews with both patients and providers, investigators concluded that telerheumatology successfully increased access to specialty care in underserved locations and got good satisfaction scores from both providers and beneficiaries. However, fully 19% of patients were found to be inappropriate for their telerheumatology visit, mainly because their disease was too complex or the underlying diagnosis was unclear.
“Almost one-fifth of their patients were inappropriate for telerheumatology. The question is, how are you supposed to know that ahead of time?” Dr. Troum asked.
Patient satisfaction. Dr. Troum’s reading of the literature on patient satisfaction with telerheumatology, coupled with his own extensive experience in clinical practice, makes him think that many of his younger patients with less disease activity might welcome a telerheumatology option, even with strict time boundaries. But his older patients with more disease activity are a different story.
“Typically my middle-aged and older patients won’t accept that without a lot of convincing,” he commented.
Dr. Wells and Dr. Troum had no relevant disclosures regarding their presentations.
MAUI, HAWAII – Alvin F. Wells, MD, PhD, believes he’s seen the future of rheumatology. So he’s taken a deep dive into telerheumatology, going all in.
“Whether you’re in academic, private, or hospital-based practice, in 2020 if you are not thinking about telerheumatology, you and your practice will not be able to compete with growing patient demands, expectations, and need for clinical monitoring. If you do not have a digital/virtual strategy, you do not have a health care strategy,” he asserted at the 2020 Rheumatology Winter Clinical Symposium.
“Begin now,” the rheumatologist advised.
In pursuit of his own telerheumatology strategy, he holds licenses to practice medicine in five states and has licensure pending in five others.
“My goal is to cover 20% of the U.S., so if the local guys can’t see the patients, I can see them virtually,” he explained. “The days of waiting 4-6 months to be seen by a rheumatologist are gone.”
Rheumatologists are already in short supply in most of the country, and a major shortage looms ahead as older practitioners retire. Telerheumatology can help fill that unmet need. But the specialty is behind the curve. In a survey that rated the medical specialties most engaged in telemedicine, the top three spots were held by radiology, psychiatry, and internal medicine. Rheumatology didn’t even crack the top 10, noted Dr. Wells, director of the Rheumatology and Immunotherapy Center in Franklin, Wisc., and a part-time faculty member at Duke University, the Medical College of Wisconsin, and the Karolinska Institute.
Yet telemedicine is primed for rheumatologic takeoff. Notably, the 2019 update of the American College of Rheumatology recommendations on rheumatoid arthritis disease activity measures incorporates the RAPID3 (Routine Assessment of Patient Index Data) as an endorsed three-question clinical assessment that doesn’t involve a physical exam or laboratory work. The ACR update is recognition that, while every rheumatology patient needs an initial physical exam along with follow-up physical exams at various rates, many patients with well-controlled disease don’t need a physical exam at every physician encounter, he said.
Telerheumatology saves time for both patient and physician. The patient saves travel time, doesn’t miss work, avoids having to arrange for child care in order to make a face-to-face clinic visit, and can schedule more frequent virtual follow-up visits. For the practitioner, telerheumatology means additional consults and – here’s the big one – “You never run behind,” according to Dr. Wells. “For a 15-minute appointment, the patient gets a 5-minute warning, then a 2-minute warning, and at 15 minutes the link is cut. If the fibromyalgia patients want 30 minutes, they pay for 30 minutes.”
He sees the strictly enforced, impersonally delivered electronic time limits as key to running an efficient practice.
“The patients with osteoarthritis who hate the nodules, the fibromyalgia patients because they’re hurting all over, the patients with back pain – you’ve really got to limit those patients because otherwise you’ll be running 30-40 minutes behind for a scheduled 15-minute visit,” he explained.
One rheumatologist’s telemedicine practice
Dr. Wells currently utilizes the Epic electronic health record integrated with a Zoom videoconferencing platform for real-time virtual patient encounters. But he noted that other virtual platforms are available, including Health Tap, American Well, MySpecialistMD, MDLIVE, and TelaDoc. The American Telemedicine Association is a valuable resource for state-by-state medicolegal, reimbursement, and how-to-do-it questions.
At present, he reserves two daily time slots for telerheumatology: one at 8:30-9:00 a.m., the other at 4:30-5:00 p.m. These can be filled with four 15-minute live consults or two 30-minute consults. His goal is to eventually make telerheumatology 20% of his patient load of about 100 patients per week.
His typical 15-minute virtual visit proceeds as follows: It begins with a 3-minute subjective patient assessment, followed by a 5-minute objective assessment which includes the RAPID3, a brief Health Assessment Questionnaire (HAQ) addressing the patient’s pain and overall satisfaction, a virtual joint inspection, the use of high-quality teleultrasound and other technology when warranted, and capture of relevant still photos. This is followed by 5 minutes to relay the treatment plan, and finally a 2-minute recap and summary.
“No niceties. We cut right to the chase,” he noted.
He documents the patient encounter as he goes, dictating his notes throughout the visit.
“When I walk out of the room, I’m done. It’s on to the next patient,” Dr. Wells said.
The reimbursement picture is improving, although major hurdles remain. At present, 48 states and the District of Columbia reimburse for live video telemedicine through Medicaid. And in January 2020, Aetna announced it covers reimbursement for telemedicine in all of its fully insured health plans via the Teladoc platform. Dr. Wells’ patients pay for their telerheumatology out of pocket if their insurance doesn’t cover it.
Telemedicine caveats
Dr. Wells shared his telerheumatology experience as the first half of a point/counterpoint session on telemedicine’s future in the specialty. His debate opponent, Orrin M. Troum, MD, announced at the outset that he is quite interested in getting into telerheumatology; however, while looking into it he has come across issues that for now give him pause and that other rheumatologists need to be aware of.
Legal risks. The telemedicine movement has gotten big enough to draw the scrutiny of federal prosecutors and regulatory enforcement officials. In April 2018, the Department of Health & Human Services Office of the Inspector General (OIG) issued a report that concluded that one-third of all examined telemedicine claims were improper.
“Just imagine who might come knocking on your door,” he said.
Among the most common offenses, according to the OIG, were claims for services outside the limited range currently covered; lack of the requisite HIPAA-compliant two-way audio and visual communication technology with fully encrypted data transmission; services billed by institutional providers not defined by Medicare as telemedicine-eligible; and claims for services received by patients who weren’t located in an officially designated Health Professional Shortage Area or in a rural county as determined by the U.S. Census Bureau.
Telemedicine is no panacea for out-of-control health care costs. A RAND study of participants in the California Public Employees’ Retirement System (CalPERS) concluded that only 12% of beneficiaries who used direct-to-consumer telemedicine did so to replace provider visits. The other 88% added on telemedicine as an additional service. So while telemedicine increased patient access to health care, it also increased the overall cost, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica, Calif.
Talk to your attorney and malpractice insurer before embarking on telerheumatology. Physicians could potentially lose their medical malpractice insurance if they use telemedicine to treat patients located in states where they aren’t licensed to practice, even if through inadvertent error.
Telemedicine isn’t appropriate for all patients. Nearly a decade ago, rheumatologists at Dartmouth-Hitchcock Medical Center launched a telerheumatology service in order to bring specialty care to the largely rural populations of New Hampshire and Vermont. In a review of the experience that included interviews with both patients and providers, investigators concluded that telerheumatology successfully increased access to specialty care in underserved locations and got good satisfaction scores from both providers and beneficiaries. However, fully 19% of patients were found to be inappropriate for their telerheumatology visit, mainly because their disease was too complex or the underlying diagnosis was unclear.
“Almost one-fifth of their patients were inappropriate for telerheumatology. The question is, how are you supposed to know that ahead of time?” Dr. Troum asked.
Patient satisfaction. Dr. Troum’s reading of the literature on patient satisfaction with telerheumatology, coupled with his own extensive experience in clinical practice, makes him think that many of his younger patients with less disease activity might welcome a telerheumatology option, even with strict time boundaries. But his older patients with more disease activity are a different story.
“Typically my middle-aged and older patients won’t accept that without a lot of convincing,” he commented.
Dr. Wells and Dr. Troum had no relevant disclosures regarding their presentations.
REPORTING FROM RWCS 2020
RA magnifies fragility fracture risk in ESRD
MAUI, HAWAII – Comorbid rheumatoid arthritis is a force multiplier for fragility fracture risk in patients with end-stage renal disease, Renée Peterkin-McCalman, MD, reported at the 2020 Rheumatology Winter Clinical Symposium.
“Patients with RA and ESRD are at substantially increased risk of osteoporotic fragility fractures compared to the overall population of ESRD patients. So fracture prevention prior to initiation of dialysis should be a focus of care in patients with RA,” said Dr. Peterkin-McCalman, a rheumatology fellow at the Medical College of Georgia, Augusta.
She presented a retrospective cohort study of 10,706 adults who initiated hemodialysis or peritoneal dialysis for ESRD during 2005-2008, including 1,040 who also had RA. All subjects were drawn from the United States Renal Data System. The impetus for the study, Dr. Peterkin-McCalman explained in an interview, was that although prior studies have established that RA and ESRD are independent risk factors for osteoporotic fractures, the interplay between the two was previously unknown.
The risk of incident osteoporotic fractures during the first 3 years after going on renal dialysis was 14.7% in patients with ESRD only, vaulting to 25.6% in those with comorbid RA. Individuals with both RA and ESRD were at an adjusted 1.83-fold increased overall risk for new fragility fractures and at 1.85-fold increased risk for hip fracture, compared to those without RA.
Far and away the strongest risk factor for incident osteoporotic fractures in the group with RA plus ESRD was a history of a fracture sustained within 5 years prior to initiation of dialysis, with an associated 11.5-fold increased fracture risk overall and an 8.2-fold increased risk of hip fracture.
“The reason that’s important is we don’t really have any medications to reduce fracture risk once you get to ESRD. Of course, we have bisphosphonates and Prolia (denosumab) and things like that, but that’s in patients with milder CKD [chronic kidney disease] or no renal disease at all. So the goal is to identify the patients early who are at higher risk so that we can protect those bones before they get to ESRD and we have nothing left to treat them with,” she said.
In addition to a history of prevalent fracture prior to starting ESRD, the other risk factors for fracture in patients with ESRD and comorbid RA Dr. Peterkin-McCalman identified in her study included age greater than 50 years at the start of dialysis and female gender, which was associated with a twofold greater fracture risk than in men. Black patients with ESRD and RA were 64% less likely than whites to experience an incident fragility fracture. And the fracture risk was higher in patients on hemodialysis than with peritoneal dialysis.
Her study was supported by the Medical College of Georgia and a research grant from Dialysis Clinic Inc.
SOURCE: Peterkin-McCalman R et al. RWCS 2020.
MAUI, HAWAII – Comorbid rheumatoid arthritis is a force multiplier for fragility fracture risk in patients with end-stage renal disease, Renée Peterkin-McCalman, MD, reported at the 2020 Rheumatology Winter Clinical Symposium.
“Patients with RA and ESRD are at substantially increased risk of osteoporotic fragility fractures compared to the overall population of ESRD patients. So fracture prevention prior to initiation of dialysis should be a focus of care in patients with RA,” said Dr. Peterkin-McCalman, a rheumatology fellow at the Medical College of Georgia, Augusta.
She presented a retrospective cohort study of 10,706 adults who initiated hemodialysis or peritoneal dialysis for ESRD during 2005-2008, including 1,040 who also had RA. All subjects were drawn from the United States Renal Data System. The impetus for the study, Dr. Peterkin-McCalman explained in an interview, was that although prior studies have established that RA and ESRD are independent risk factors for osteoporotic fractures, the interplay between the two was previously unknown.
The risk of incident osteoporotic fractures during the first 3 years after going on renal dialysis was 14.7% in patients with ESRD only, vaulting to 25.6% in those with comorbid RA. Individuals with both RA and ESRD were at an adjusted 1.83-fold increased overall risk for new fragility fractures and at 1.85-fold increased risk for hip fracture, compared to those without RA.
Far and away the strongest risk factor for incident osteoporotic fractures in the group with RA plus ESRD was a history of a fracture sustained within 5 years prior to initiation of dialysis, with an associated 11.5-fold increased fracture risk overall and an 8.2-fold increased risk of hip fracture.
“The reason that’s important is we don’t really have any medications to reduce fracture risk once you get to ESRD. Of course, we have bisphosphonates and Prolia (denosumab) and things like that, but that’s in patients with milder CKD [chronic kidney disease] or no renal disease at all. So the goal is to identify the patients early who are at higher risk so that we can protect those bones before they get to ESRD and we have nothing left to treat them with,” she said.
In addition to a history of prevalent fracture prior to starting ESRD, the other risk factors for fracture in patients with ESRD and comorbid RA Dr. Peterkin-McCalman identified in her study included age greater than 50 years at the start of dialysis and female gender, which was associated with a twofold greater fracture risk than in men. Black patients with ESRD and RA were 64% less likely than whites to experience an incident fragility fracture. And the fracture risk was higher in patients on hemodialysis than with peritoneal dialysis.
Her study was supported by the Medical College of Georgia and a research grant from Dialysis Clinic Inc.
SOURCE: Peterkin-McCalman R et al. RWCS 2020.
MAUI, HAWAII – Comorbid rheumatoid arthritis is a force multiplier for fragility fracture risk in patients with end-stage renal disease, Renée Peterkin-McCalman, MD, reported at the 2020 Rheumatology Winter Clinical Symposium.
“Patients with RA and ESRD are at substantially increased risk of osteoporotic fragility fractures compared to the overall population of ESRD patients. So fracture prevention prior to initiation of dialysis should be a focus of care in patients with RA,” said Dr. Peterkin-McCalman, a rheumatology fellow at the Medical College of Georgia, Augusta.
She presented a retrospective cohort study of 10,706 adults who initiated hemodialysis or peritoneal dialysis for ESRD during 2005-2008, including 1,040 who also had RA. All subjects were drawn from the United States Renal Data System. The impetus for the study, Dr. Peterkin-McCalman explained in an interview, was that although prior studies have established that RA and ESRD are independent risk factors for osteoporotic fractures, the interplay between the two was previously unknown.
The risk of incident osteoporotic fractures during the first 3 years after going on renal dialysis was 14.7% in patients with ESRD only, vaulting to 25.6% in those with comorbid RA. Individuals with both RA and ESRD were at an adjusted 1.83-fold increased overall risk for new fragility fractures and at 1.85-fold increased risk for hip fracture, compared to those without RA.
Far and away the strongest risk factor for incident osteoporotic fractures in the group with RA plus ESRD was a history of a fracture sustained within 5 years prior to initiation of dialysis, with an associated 11.5-fold increased fracture risk overall and an 8.2-fold increased risk of hip fracture.
“The reason that’s important is we don’t really have any medications to reduce fracture risk once you get to ESRD. Of course, we have bisphosphonates and Prolia (denosumab) and things like that, but that’s in patients with milder CKD [chronic kidney disease] or no renal disease at all. So the goal is to identify the patients early who are at higher risk so that we can protect those bones before they get to ESRD and we have nothing left to treat them with,” she said.
In addition to a history of prevalent fracture prior to starting ESRD, the other risk factors for fracture in patients with ESRD and comorbid RA Dr. Peterkin-McCalman identified in her study included age greater than 50 years at the start of dialysis and female gender, which was associated with a twofold greater fracture risk than in men. Black patients with ESRD and RA were 64% less likely than whites to experience an incident fragility fracture. And the fracture risk was higher in patients on hemodialysis than with peritoneal dialysis.
Her study was supported by the Medical College of Georgia and a research grant from Dialysis Clinic Inc.
SOURCE: Peterkin-McCalman R et al. RWCS 2020.
REPORTING FROM RWCS 2020
Meta-analysis highlights safety concerns with interleukin inhibition
MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.
The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.
“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.
The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.
For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.
Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.
He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”
The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.
Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.
“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.
A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.
Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).
MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.
The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.
“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.
The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.
For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.
Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.
He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”
The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.
Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.
“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.
A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.
Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).
MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.
The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.
“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.
The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.
For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.
Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.
He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”
The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.
Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.
“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.
A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.
Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).
REPORTING FROM RWCS 2020
Keep your eye on tapinarof, a topical antipsoriatic therapy
LAHAINA, HAWAII – Tapinarof is an investigational drug whose novel mechanism of action – and encouraging performance in phase 2 studies – are making waves for the topical treatment of both psoriasis and atopic dermatitis, Linda F. Stein Gold, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Tapinarof is a first-in-class agonist of the aryl hydrocarbon receptor.
“An aryl hydrocarbon receptor agonist – what in the world does that mean? It means that this drug actually acts at the receptor level inside the cell, and it does a lot of different things,” explained Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.
For one, tapinarof down-regulates Th17 cytokines, an attribute that positions the drug very well as a potential topical treatment for psoriasis. But in addition, the drug has a skin barrier repair element through up-regulation of the filaggrin and involucrin genes in keratinocytes, and it also down-regulates Th2 cytokines, actions desirable in a treatment for atopic dermatitis.
Dr. Stein Gold focused mainly on tapinarof’s potential as a novel treatment for psoriasis, a disease that hasn’t seen approval of a new nonsteroidal topical therapy in decades. There is a huge unmet need for safe and effective new topical therapies for this disease; despite all the attention devoted to biologics and other systemic therapies, the great majority of psoriasis patients are managed via topical therapy only.
The definitive trial was initiated based upon the results of a phase 2b, double-blind, six-arm study including 141 adults with body surface involvement of 1%-15% and a baseline Physician Global Assessment (PGA) score of 2 or more who were assigned to tapinarof at 0.5% or 1% once or twice daily or placebo. The phase 2b results, she commented, were very encouraging.
“When we look at the clinical efficacy, it looks like this drug has legs. It does work even as monotherapy to get patients clear,” she said.
The phase 2b, dose-finding study showed dose-dependent treatment efficacy. At week 12, the proportion of participants with a PGA of 0-1 and at least a 2-grade improvement – that is, clear or almost clear – was 36% with tapinarof monotherapy at 0.5% once daily, 46% with 0.5% twice daily, 56% with 1% once daily, and 65% with 1% twice daily, compared with 5% in controls on once-daily application of vehicle and 11% with twice-daily vehicle. Moreover, the improvement was maintained for 4 weeks post treatment. The drug was well tolerated other than some mild to moderate folliculitis and contact dermatitis (J Am Acad Dermatol. 2019 Mar;80[3]:714-21).
“With such small numbers in phase 2, we don’t necessarily need to see statistical significance, but we want to see a trend in the right direction. But every one of the active treatment arms was statistically significantly better than with vehicle. And at higher concentrations, greater efficacy,” noted Dr. Stein Gold.
A phase 2 study of tapinarof cream has also been completed in adults and adolescents with atopic dermatitis, again with positive results. A phase 3 study in atopic dermatitis is still in the planning stages.
Dr. Stein Gold wasn’t involved in the tapinarof psoriasis phase 2b study, sponsored by GlaxoSmithKline. She reported research funding from nine other pharmaceutical companies and serves as a consultant and/or scientific to more than a dozen companies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – Tapinarof is an investigational drug whose novel mechanism of action – and encouraging performance in phase 2 studies – are making waves for the topical treatment of both psoriasis and atopic dermatitis, Linda F. Stein Gold, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Tapinarof is a first-in-class agonist of the aryl hydrocarbon receptor.
“An aryl hydrocarbon receptor agonist – what in the world does that mean? It means that this drug actually acts at the receptor level inside the cell, and it does a lot of different things,” explained Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.
For one, tapinarof down-regulates Th17 cytokines, an attribute that positions the drug very well as a potential topical treatment for psoriasis. But in addition, the drug has a skin barrier repair element through up-regulation of the filaggrin and involucrin genes in keratinocytes, and it also down-regulates Th2 cytokines, actions desirable in a treatment for atopic dermatitis.
Dr. Stein Gold focused mainly on tapinarof’s potential as a novel treatment for psoriasis, a disease that hasn’t seen approval of a new nonsteroidal topical therapy in decades. There is a huge unmet need for safe and effective new topical therapies for this disease; despite all the attention devoted to biologics and other systemic therapies, the great majority of psoriasis patients are managed via topical therapy only.
The definitive trial was initiated based upon the results of a phase 2b, double-blind, six-arm study including 141 adults with body surface involvement of 1%-15% and a baseline Physician Global Assessment (PGA) score of 2 or more who were assigned to tapinarof at 0.5% or 1% once or twice daily or placebo. The phase 2b results, she commented, were very encouraging.
“When we look at the clinical efficacy, it looks like this drug has legs. It does work even as monotherapy to get patients clear,” she said.
The phase 2b, dose-finding study showed dose-dependent treatment efficacy. At week 12, the proportion of participants with a PGA of 0-1 and at least a 2-grade improvement – that is, clear or almost clear – was 36% with tapinarof monotherapy at 0.5% once daily, 46% with 0.5% twice daily, 56% with 1% once daily, and 65% with 1% twice daily, compared with 5% in controls on once-daily application of vehicle and 11% with twice-daily vehicle. Moreover, the improvement was maintained for 4 weeks post treatment. The drug was well tolerated other than some mild to moderate folliculitis and contact dermatitis (J Am Acad Dermatol. 2019 Mar;80[3]:714-21).
“With such small numbers in phase 2, we don’t necessarily need to see statistical significance, but we want to see a trend in the right direction. But every one of the active treatment arms was statistically significantly better than with vehicle. And at higher concentrations, greater efficacy,” noted Dr. Stein Gold.
A phase 2 study of tapinarof cream has also been completed in adults and adolescents with atopic dermatitis, again with positive results. A phase 3 study in atopic dermatitis is still in the planning stages.
Dr. Stein Gold wasn’t involved in the tapinarof psoriasis phase 2b study, sponsored by GlaxoSmithKline. She reported research funding from nine other pharmaceutical companies and serves as a consultant and/or scientific to more than a dozen companies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
LAHAINA, HAWAII – Tapinarof is an investigational drug whose novel mechanism of action – and encouraging performance in phase 2 studies – are making waves for the topical treatment of both psoriasis and atopic dermatitis, Linda F. Stein Gold, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Tapinarof is a first-in-class agonist of the aryl hydrocarbon receptor.
“An aryl hydrocarbon receptor agonist – what in the world does that mean? It means that this drug actually acts at the receptor level inside the cell, and it does a lot of different things,” explained Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.
For one, tapinarof down-regulates Th17 cytokines, an attribute that positions the drug very well as a potential topical treatment for psoriasis. But in addition, the drug has a skin barrier repair element through up-regulation of the filaggrin and involucrin genes in keratinocytes, and it also down-regulates Th2 cytokines, actions desirable in a treatment for atopic dermatitis.
Dr. Stein Gold focused mainly on tapinarof’s potential as a novel treatment for psoriasis, a disease that hasn’t seen approval of a new nonsteroidal topical therapy in decades. There is a huge unmet need for safe and effective new topical therapies for this disease; despite all the attention devoted to biologics and other systemic therapies, the great majority of psoriasis patients are managed via topical therapy only.
The definitive trial was initiated based upon the results of a phase 2b, double-blind, six-arm study including 141 adults with body surface involvement of 1%-15% and a baseline Physician Global Assessment (PGA) score of 2 or more who were assigned to tapinarof at 0.5% or 1% once or twice daily or placebo. The phase 2b results, she commented, were very encouraging.
“When we look at the clinical efficacy, it looks like this drug has legs. It does work even as monotherapy to get patients clear,” she said.
The phase 2b, dose-finding study showed dose-dependent treatment efficacy. At week 12, the proportion of participants with a PGA of 0-1 and at least a 2-grade improvement – that is, clear or almost clear – was 36% with tapinarof monotherapy at 0.5% once daily, 46% with 0.5% twice daily, 56% with 1% once daily, and 65% with 1% twice daily, compared with 5% in controls on once-daily application of vehicle and 11% with twice-daily vehicle. Moreover, the improvement was maintained for 4 weeks post treatment. The drug was well tolerated other than some mild to moderate folliculitis and contact dermatitis (J Am Acad Dermatol. 2019 Mar;80[3]:714-21).
“With such small numbers in phase 2, we don’t necessarily need to see statistical significance, but we want to see a trend in the right direction. But every one of the active treatment arms was statistically significantly better than with vehicle. And at higher concentrations, greater efficacy,” noted Dr. Stein Gold.
A phase 2 study of tapinarof cream has also been completed in adults and adolescents with atopic dermatitis, again with positive results. A phase 3 study in atopic dermatitis is still in the planning stages.
Dr. Stein Gold wasn’t involved in the tapinarof psoriasis phase 2b study, sponsored by GlaxoSmithKline. She reported research funding from nine other pharmaceutical companies and serves as a consultant and/or scientific to more than a dozen companies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM THE SDEF HAWAII DERMATOLOGY SEMINAR
Secukinumab outperforms adalimumab overall for PsA
MAUI, HAWAII – The interleukin-17A inhibitor secukinumab made a strong showing versus the tumor necrosis factor inhibitor adalimumab for the treatment of psoriatic arthritis in the 52-week, randomized, head-to-head phase 3b EXCEED study, Arthur Kavanaugh, MD, reported at the 2020 Rheumatology Winter Clinical Symposium.
EXCEED was the first double-blind, randomized comparison of an IL-17A inhibitor versus a tumor necrosis factor inhibitor as first-line biologic monotherapy in 853 psoriatic arthritis (PsA) patients with an inadequate response to conventional disease-modifying antirheumatic drugs. And while secukinumab (Cosentyx) narrowly failed to demonstrate superiority over adalimumab (Humira) on the primary endpoint of at least a 20% improvement over baseline on American College of Rheumatology disease criteria at 52 weeks, or ACR20 response, the IL-17A inhibitor demonstrated far greater efficacy for the skin disease, noted Dr. Kavanaugh, a rheumatologist who is professor of medicine at the University of California, San Diego, and RWCS program director. Patients received standard dosing of either drug: secukinumab at 300 mg every 4 weeks or adalimumab at 40 mg every 2 weeks.
Dr. Kavanaugh, an EXCEED coinvestigator, characterized the articular outcomes as similar in the two study arms. The ACR20 primary outcome rate was 67.4% in the secukinumab-treated patients and 61.5% with adalimumab, a difference that didn’t quite reach statistical significance (P = .07). However, in a prespecified secondary analysis of ACR20 rates based upon nonresponder imputation – the most conservative method of statistical analysis, in which all subjects who don’t complete the full study period are counted as treatment failures – secukinumab proved superior to adalimumab by a margin of 66.9% versus 59.5% (P = .02). That result was heavily influenced by the significantly higher dropout rate in the adalimumab group: 23.7%, compared with 14.2% in the secukinumab group.
The ACR50 response rate was 49% in the secukinumab group and 44.6% with adalimumab, a nonsignificant difference. Enthesitis resolution rates at 52 weeks were 60.5% and 54.2%, respectively, also a nonsignificant difference. The mean improvement in Health Assessment Questionnaire–Disability Index scores was closely similar in the two groups. However, a 90% improvement in Psoriasis Area and Severity Index scores, or PASI90 response, was achieved in 65.4% of the secukinumab group, far better than the 43.2% rate with adalimumab.
Dr. Kavanaugh observed that the EXCEED outcomes are consistent with the recently published 24-week results of the SPIRIT-H2H trial, an open-label, assessor-blinded randomized comparison of adalimumab versus another IL-17A inhibitor, ixekizumab (Taltz), in 566 PsA patients. Ixekizumab proved superior to adalimumab for the primary composite endpoint composed of an ACR50 response and simultaneous achievement of a PASI100 response, with rates of 36% and 28%, respectively. The ACR50 rates were similar for the two biologics, while the skin results were superior with ixekizumab.
Eric M. Ruderman, MD, said that, taken together, the EXCEED and SPIRIT-H2H results raise an important issue for clinical practice: Even though both secukinumab and ixekizumab are approved for the treatment of PsA, rheumatologists tend to reflexively reach for a TNF inhibitor as the first biologic in affected patients.
“I don’t know that that necessarily needs to be so. There’s absolutely no reason why an IL-17 inhibitor shouldn’t be equally an option as first-line treatment when you think about starting a biologic in these patients. It’s inertia: We like what we like, we do what we’ve been doing for a long time,” said Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Indeed, an IL-17A inhibitor may actually be a better first-line option in certain circumstances, such as in the PsA patient with more extensive skin involvement, he continued. Also, there is a possibility that the IL-17A inhibitors are less immunogenic than the anti-TNF biologics, which may result in a more durable response. This concept, while still speculative, is supported by the recently published results of the long-term extension of the phase 3 FUTURE 1 study, in which 82% of patients randomized to secukinumab were still on the biologic after 5 years. That’s a far better retention rate than is seen with TNF inhibitors, he noted.
In addition, SPIRIT-H2H participants randomized to ixekizumab didn’t derive added benefit from concomitant methotrexate, while those on adalimumab did. Thus, PsA patients who desire a simpler, methotrexate-free regimen may prefer an IL-17A inhibitor, Dr. Ruderman said.
Dr. Kavanaugh noted that differences in the side effect profiles of the two classes of biologics may be relevant in treatment decisions. The TNF inhibitors have a higher risk of serious infections than do the IL-17A inhibitors, which in turn are associated with more Candida infections.
Dr. Kavanaugh reported receiving research funding from and serving as a consultant to Novartis, which sponsored EXCEED, as well as more than a dozen other pharmaceutical companies. Dr. Ruderman reported serving as a consultant to Pfizer.
MAUI, HAWAII – The interleukin-17A inhibitor secukinumab made a strong showing versus the tumor necrosis factor inhibitor adalimumab for the treatment of psoriatic arthritis in the 52-week, randomized, head-to-head phase 3b EXCEED study, Arthur Kavanaugh, MD, reported at the 2020 Rheumatology Winter Clinical Symposium.
EXCEED was the first double-blind, randomized comparison of an IL-17A inhibitor versus a tumor necrosis factor inhibitor as first-line biologic monotherapy in 853 psoriatic arthritis (PsA) patients with an inadequate response to conventional disease-modifying antirheumatic drugs. And while secukinumab (Cosentyx) narrowly failed to demonstrate superiority over adalimumab (Humira) on the primary endpoint of at least a 20% improvement over baseline on American College of Rheumatology disease criteria at 52 weeks, or ACR20 response, the IL-17A inhibitor demonstrated far greater efficacy for the skin disease, noted Dr. Kavanaugh, a rheumatologist who is professor of medicine at the University of California, San Diego, and RWCS program director. Patients received standard dosing of either drug: secukinumab at 300 mg every 4 weeks or adalimumab at 40 mg every 2 weeks.
Dr. Kavanaugh, an EXCEED coinvestigator, characterized the articular outcomes as similar in the two study arms. The ACR20 primary outcome rate was 67.4% in the secukinumab-treated patients and 61.5% with adalimumab, a difference that didn’t quite reach statistical significance (P = .07). However, in a prespecified secondary analysis of ACR20 rates based upon nonresponder imputation – the most conservative method of statistical analysis, in which all subjects who don’t complete the full study period are counted as treatment failures – secukinumab proved superior to adalimumab by a margin of 66.9% versus 59.5% (P = .02). That result was heavily influenced by the significantly higher dropout rate in the adalimumab group: 23.7%, compared with 14.2% in the secukinumab group.
The ACR50 response rate was 49% in the secukinumab group and 44.6% with adalimumab, a nonsignificant difference. Enthesitis resolution rates at 52 weeks were 60.5% and 54.2%, respectively, also a nonsignificant difference. The mean improvement in Health Assessment Questionnaire–Disability Index scores was closely similar in the two groups. However, a 90% improvement in Psoriasis Area and Severity Index scores, or PASI90 response, was achieved in 65.4% of the secukinumab group, far better than the 43.2% rate with adalimumab.
Dr. Kavanaugh observed that the EXCEED outcomes are consistent with the recently published 24-week results of the SPIRIT-H2H trial, an open-label, assessor-blinded randomized comparison of adalimumab versus another IL-17A inhibitor, ixekizumab (Taltz), in 566 PsA patients. Ixekizumab proved superior to adalimumab for the primary composite endpoint composed of an ACR50 response and simultaneous achievement of a PASI100 response, with rates of 36% and 28%, respectively. The ACR50 rates were similar for the two biologics, while the skin results were superior with ixekizumab.
Eric M. Ruderman, MD, said that, taken together, the EXCEED and SPIRIT-H2H results raise an important issue for clinical practice: Even though both secukinumab and ixekizumab are approved for the treatment of PsA, rheumatologists tend to reflexively reach for a TNF inhibitor as the first biologic in affected patients.
“I don’t know that that necessarily needs to be so. There’s absolutely no reason why an IL-17 inhibitor shouldn’t be equally an option as first-line treatment when you think about starting a biologic in these patients. It’s inertia: We like what we like, we do what we’ve been doing for a long time,” said Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Indeed, an IL-17A inhibitor may actually be a better first-line option in certain circumstances, such as in the PsA patient with more extensive skin involvement, he continued. Also, there is a possibility that the IL-17A inhibitors are less immunogenic than the anti-TNF biologics, which may result in a more durable response. This concept, while still speculative, is supported by the recently published results of the long-term extension of the phase 3 FUTURE 1 study, in which 82% of patients randomized to secukinumab were still on the biologic after 5 years. That’s a far better retention rate than is seen with TNF inhibitors, he noted.
In addition, SPIRIT-H2H participants randomized to ixekizumab didn’t derive added benefit from concomitant methotrexate, while those on adalimumab did. Thus, PsA patients who desire a simpler, methotrexate-free regimen may prefer an IL-17A inhibitor, Dr. Ruderman said.
Dr. Kavanaugh noted that differences in the side effect profiles of the two classes of biologics may be relevant in treatment decisions. The TNF inhibitors have a higher risk of serious infections than do the IL-17A inhibitors, which in turn are associated with more Candida infections.
Dr. Kavanaugh reported receiving research funding from and serving as a consultant to Novartis, which sponsored EXCEED, as well as more than a dozen other pharmaceutical companies. Dr. Ruderman reported serving as a consultant to Pfizer.
MAUI, HAWAII – The interleukin-17A inhibitor secukinumab made a strong showing versus the tumor necrosis factor inhibitor adalimumab for the treatment of psoriatic arthritis in the 52-week, randomized, head-to-head phase 3b EXCEED study, Arthur Kavanaugh, MD, reported at the 2020 Rheumatology Winter Clinical Symposium.
EXCEED was the first double-blind, randomized comparison of an IL-17A inhibitor versus a tumor necrosis factor inhibitor as first-line biologic monotherapy in 853 psoriatic arthritis (PsA) patients with an inadequate response to conventional disease-modifying antirheumatic drugs. And while secukinumab (Cosentyx) narrowly failed to demonstrate superiority over adalimumab (Humira) on the primary endpoint of at least a 20% improvement over baseline on American College of Rheumatology disease criteria at 52 weeks, or ACR20 response, the IL-17A inhibitor demonstrated far greater efficacy for the skin disease, noted Dr. Kavanaugh, a rheumatologist who is professor of medicine at the University of California, San Diego, and RWCS program director. Patients received standard dosing of either drug: secukinumab at 300 mg every 4 weeks or adalimumab at 40 mg every 2 weeks.
Dr. Kavanaugh, an EXCEED coinvestigator, characterized the articular outcomes as similar in the two study arms. The ACR20 primary outcome rate was 67.4% in the secukinumab-treated patients and 61.5% with adalimumab, a difference that didn’t quite reach statistical significance (P = .07). However, in a prespecified secondary analysis of ACR20 rates based upon nonresponder imputation – the most conservative method of statistical analysis, in which all subjects who don’t complete the full study period are counted as treatment failures – secukinumab proved superior to adalimumab by a margin of 66.9% versus 59.5% (P = .02). That result was heavily influenced by the significantly higher dropout rate in the adalimumab group: 23.7%, compared with 14.2% in the secukinumab group.
The ACR50 response rate was 49% in the secukinumab group and 44.6% with adalimumab, a nonsignificant difference. Enthesitis resolution rates at 52 weeks were 60.5% and 54.2%, respectively, also a nonsignificant difference. The mean improvement in Health Assessment Questionnaire–Disability Index scores was closely similar in the two groups. However, a 90% improvement in Psoriasis Area and Severity Index scores, or PASI90 response, was achieved in 65.4% of the secukinumab group, far better than the 43.2% rate with adalimumab.
Dr. Kavanaugh observed that the EXCEED outcomes are consistent with the recently published 24-week results of the SPIRIT-H2H trial, an open-label, assessor-blinded randomized comparison of adalimumab versus another IL-17A inhibitor, ixekizumab (Taltz), in 566 PsA patients. Ixekizumab proved superior to adalimumab for the primary composite endpoint composed of an ACR50 response and simultaneous achievement of a PASI100 response, with rates of 36% and 28%, respectively. The ACR50 rates were similar for the two biologics, while the skin results were superior with ixekizumab.
Eric M. Ruderman, MD, said that, taken together, the EXCEED and SPIRIT-H2H results raise an important issue for clinical practice: Even though both secukinumab and ixekizumab are approved for the treatment of PsA, rheumatologists tend to reflexively reach for a TNF inhibitor as the first biologic in affected patients.
“I don’t know that that necessarily needs to be so. There’s absolutely no reason why an IL-17 inhibitor shouldn’t be equally an option as first-line treatment when you think about starting a biologic in these patients. It’s inertia: We like what we like, we do what we’ve been doing for a long time,” said Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Indeed, an IL-17A inhibitor may actually be a better first-line option in certain circumstances, such as in the PsA patient with more extensive skin involvement, he continued. Also, there is a possibility that the IL-17A inhibitors are less immunogenic than the anti-TNF biologics, which may result in a more durable response. This concept, while still speculative, is supported by the recently published results of the long-term extension of the phase 3 FUTURE 1 study, in which 82% of patients randomized to secukinumab were still on the biologic after 5 years. That’s a far better retention rate than is seen with TNF inhibitors, he noted.
In addition, SPIRIT-H2H participants randomized to ixekizumab didn’t derive added benefit from concomitant methotrexate, while those on adalimumab did. Thus, PsA patients who desire a simpler, methotrexate-free regimen may prefer an IL-17A inhibitor, Dr. Ruderman said.
Dr. Kavanaugh noted that differences in the side effect profiles of the two classes of biologics may be relevant in treatment decisions. The TNF inhibitors have a higher risk of serious infections than do the IL-17A inhibitors, which in turn are associated with more Candida infections.
Dr. Kavanaugh reported receiving research funding from and serving as a consultant to Novartis, which sponsored EXCEED, as well as more than a dozen other pharmaceutical companies. Dr. Ruderman reported serving as a consultant to Pfizer.
REPORTING FROM RWCS 2020