MDedge Rheumatology

Telemedicine has had a profound effect upon the practice of rheumatology during the COVID-19 pandemic and will continue to do so afterward, speakers predicted at the 2021 Rheumatology Winter Clinical Symposium.

FatCamera/E+

“Telemedicine will change the way we do business. It already has,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University in Chicago.

“All of a sudden in March of last year we all turned on a dime and went 100% remote, and we made it work. And it has worked well. It’s not the same as seeing people in person, but I’m pretty sure that going forward probably somewhere in the range of 30% of our visits are going to be telemedicine. It’s an incredible way to deal with people who are stable and are driving in from an hour-and-a-half away to get their prescription refilled,” he said.

Conditions well suited for video patient visits are those where the physical exam isn’t informative or necessary, such as polymyalgia rheumatica, axial spondyloarthritis with axial disease only, childhood periodic fever syndromes, and even many cases of rheumatoid arthritis, in Dr. Ruderman’s view.

“People who are stable – maybe not in remission, but we’ve decided they’re at that their target – a lot of those visits can be done remotely. It’s way more efficient. Everybody loves it: We like it, the patients like it. But we have to get to where we can do it better. The technology is clumsy right now,” he said.

“We do need better and smarter platforms,” agreed Alvin F. Wells, MD, PhD, a telerheumatology pioneer who has been involved in digital/video communication with his patients for nearly 6 years. “But the biggest issue is connectivity. Not all of our patients can get on the Internet.”

The telerheumatology paradigm he has used during the pandemic and will continue to use afterward is to see every new patient in the office, then do the follow-up visits virtually.

“They don’t need to come back into the office in 4 weeks. I’ve done my physical exam, ordered the x-rays and lab work. At the virtual 4-week follow-up we go over everything and I tell them if they need to come in for training in giving their injections,” explained Dr. Wells, a rheumatologist in Franklin, Wisc.

“The telemedicine visit doesn’t take the place of an in-person visit, but it allows you to stratify, to say who needs to be seen sooner rather than later,” he added.

While he anticipates that physician-patient virtual visits will continue to be an important part of clinical practice post pandemic, he predicted the major growth areas for telerheumatology once COVID-19 is squashed will be in clinician-to-clinician interactions and remote patient monitoring using smart devices.

Dr. Wells hasn’t gone into the hospital once since the pandemic began. Initially, that was because he didn’t want to deal with the personal protective equipment shortage or expose himself to the virus. Now, it’s because it’s just a more efficient use of his time to conduct virtual – and billable – 15-minute e-consults with clinicians in the hospital.

“I’ve had a lot of appropriate consults with the hospitalists,” he said. He can walk a hospitalist through a real-time physical exam at a gout patient’s bedside and order the right laboratory tests.

“I don’t need to go into the hospital. The interventional radiologist can tap an ankle or toe as well as I can,” the rheumatologist said.

Dermatologist George Martin, MD, rose from the audience to say that while he recognizes that pandemic telemedicine has been a good fit for rheumatologists, it’s been a very different story in dermatology.

“I realize telemedicine works really well when you don’t have to lay your hands on a patient, or when you’re just doing a stable follow-up and talking about test results. But we in dermatology have found as a group that telemedicine is pretty worthless. When patients are trying to send you a video stream of what their melanoma looks like, or maybe it’s a benign seborrheic keratosis, you’re going to hang their life on that? Dermatology is a very hands-on, visual thing, and unless the camera work becomes better telemedicine is worthless, with the exception of a laboratory follow-up or a stable visit where a physical exam is not required,” declared Dr. Martin, who is in private practice in Maui.

Dr. Wells reported serving as a consultant to MiCare Path, a remote health and monitoring company.

[email protected]

Telemedicine has had a profound effect upon the practice of rheumatology during the COVID-19 pandemic and will continue to do so afterward, speakers predicted at the 2021 Rheumatology Winter Clinical Symposium.

FatCamera/E+

“Telemedicine will change the way we do business. It already has,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University in Chicago.

“All of a sudden in March of last year we all turned on a dime and went 100% remote, and we made it work. And it has worked well. It’s not the same as seeing people in person, but I’m pretty sure that going forward probably somewhere in the range of 30% of our visits are going to be telemedicine. It’s an incredible way to deal with people who are stable and are driving in from an hour-and-a-half away to get their prescription refilled,” he said.

Conditions well suited for video patient visits are those where the physical exam isn’t informative or necessary, such as polymyalgia rheumatica, axial spondyloarthritis with axial disease only, childhood periodic fever syndromes, and even many cases of rheumatoid arthritis, in Dr. Ruderman’s view.

“People who are stable – maybe not in remission, but we’ve decided they’re at that their target – a lot of those visits can be done remotely. It’s way more efficient. Everybody loves it: We like it, the patients like it. But we have to get to where we can do it better. The technology is clumsy right now,” he said.

“We do need better and smarter platforms,” agreed Alvin F. Wells, MD, PhD, a telerheumatology pioneer who has been involved in digital/video communication with his patients for nearly 6 years. “But the biggest issue is connectivity. Not all of our patients can get on the Internet.”

The telerheumatology paradigm he has used during the pandemic and will continue to use afterward is to see every new patient in the office, then do the follow-up visits virtually.

“They don’t need to come back into the office in 4 weeks. I’ve done my physical exam, ordered the x-rays and lab work. At the virtual 4-week follow-up we go over everything and I tell them if they need to come in for training in giving their injections,” explained Dr. Wells, a rheumatologist in Franklin, Wisc.

“The telemedicine visit doesn’t take the place of an in-person visit, but it allows you to stratify, to say who needs to be seen sooner rather than later,” he added.

While he anticipates that physician-patient virtual visits will continue to be an important part of clinical practice post pandemic, he predicted the major growth areas for telerheumatology once COVID-19 is squashed will be in clinician-to-clinician interactions and remote patient monitoring using smart devices.

Dr. Wells hasn’t gone into the hospital once since the pandemic began. Initially, that was because he didn’t want to deal with the personal protective equipment shortage or expose himself to the virus. Now, it’s because it’s just a more efficient use of his time to conduct virtual – and billable – 15-minute e-consults with clinicians in the hospital.

“I’ve had a lot of appropriate consults with the hospitalists,” he said. He can walk a hospitalist through a real-time physical exam at a gout patient’s bedside and order the right laboratory tests.

“I don’t need to go into the hospital. The interventional radiologist can tap an ankle or toe as well as I can,” the rheumatologist said.

Dermatologist George Martin, MD, rose from the audience to say that while he recognizes that pandemic telemedicine has been a good fit for rheumatologists, it’s been a very different story in dermatology.

“I realize telemedicine works really well when you don’t have to lay your hands on a patient, or when you’re just doing a stable follow-up and talking about test results. But we in dermatology have found as a group that telemedicine is pretty worthless. When patients are trying to send you a video stream of what their melanoma looks like, or maybe it’s a benign seborrheic keratosis, you’re going to hang their life on that? Dermatology is a very hands-on, visual thing, and unless the camera work becomes better telemedicine is worthless, with the exception of a laboratory follow-up or a stable visit where a physical exam is not required,” declared Dr. Martin, who is in private practice in Maui.

Dr. Wells reported serving as a consultant to MiCare Path, a remote health and monitoring company.

[email protected]

Telemedicine has had a profound effect upon the practice of rheumatology during the COVID-19 pandemic and will continue to do so afterward, speakers predicted at the 2021 Rheumatology Winter Clinical Symposium.

FatCamera/E+

“Telemedicine will change the way we do business. It already has,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University in Chicago.

“All of a sudden in March of last year we all turned on a dime and went 100% remote, and we made it work. And it has worked well. It’s not the same as seeing people in person, but I’m pretty sure that going forward probably somewhere in the range of 30% of our visits are going to be telemedicine. It’s an incredible way to deal with people who are stable and are driving in from an hour-and-a-half away to get their prescription refilled,” he said.

Conditions well suited for video patient visits are those where the physical exam isn’t informative or necessary, such as polymyalgia rheumatica, axial spondyloarthritis with axial disease only, childhood periodic fever syndromes, and even many cases of rheumatoid arthritis, in Dr. Ruderman’s view.

“People who are stable – maybe not in remission, but we’ve decided they’re at that their target – a lot of those visits can be done remotely. It’s way more efficient. Everybody loves it: We like it, the patients like it. But we have to get to where we can do it better. The technology is clumsy right now,” he said.

“We do need better and smarter platforms,” agreed Alvin F. Wells, MD, PhD, a telerheumatology pioneer who has been involved in digital/video communication with his patients for nearly 6 years. “But the biggest issue is connectivity. Not all of our patients can get on the Internet.”

The telerheumatology paradigm he has used during the pandemic and will continue to use afterward is to see every new patient in the office, then do the follow-up visits virtually.

“They don’t need to come back into the office in 4 weeks. I’ve done my physical exam, ordered the x-rays and lab work. At the virtual 4-week follow-up we go over everything and I tell them if they need to come in for training in giving their injections,” explained Dr. Wells, a rheumatologist in Franklin, Wisc.

“The telemedicine visit doesn’t take the place of an in-person visit, but it allows you to stratify, to say who needs to be seen sooner rather than later,” he added.

While he anticipates that physician-patient virtual visits will continue to be an important part of clinical practice post pandemic, he predicted the major growth areas for telerheumatology once COVID-19 is squashed will be in clinician-to-clinician interactions and remote patient monitoring using smart devices.

Dr. Wells hasn’t gone into the hospital once since the pandemic began. Initially, that was because he didn’t want to deal with the personal protective equipment shortage or expose himself to the virus. Now, it’s because it’s just a more efficient use of his time to conduct virtual – and billable – 15-minute e-consults with clinicians in the hospital.

“I’ve had a lot of appropriate consults with the hospitalists,” he said. He can walk a hospitalist through a real-time physical exam at a gout patient’s bedside and order the right laboratory tests.

“I don’t need to go into the hospital. The interventional radiologist can tap an ankle or toe as well as I can,” the rheumatologist said.

Dermatologist George Martin, MD, rose from the audience to say that while he recognizes that pandemic telemedicine has been a good fit for rheumatologists, it’s been a very different story in dermatology.

“I realize telemedicine works really well when you don’t have to lay your hands on a patient, or when you’re just doing a stable follow-up and talking about test results. But we in dermatology have found as a group that telemedicine is pretty worthless. When patients are trying to send you a video stream of what their melanoma looks like, or maybe it’s a benign seborrheic keratosis, you’re going to hang their life on that? Dermatology is a very hands-on, visual thing, and unless the camera work becomes better telemedicine is worthless, with the exception of a laboratory follow-up or a stable visit where a physical exam is not required,” declared Dr. Martin, who is in private practice in Maui.

Dr. Wells reported serving as a consultant to MiCare Path, a remote health and monitoring company.

[email protected]

Macrophages are among the most important inflammatory cells in the synovium of patients with rheumatoid arthritis, according to research discussed at the Canadian Arthritis Research Conference: Research with Impact.

Work conducted as part of the Accelerating Medicines Partnership (AMP) Rheumatoid Arthritis and Systemic Lupus Erythematosus (RA/SLE) Network suggests that not only do macrophages play an inflammatory role, but there may also be a subset of macrophages that have a predominantly anti-inflammatory effect.

“These are cells that are really activated and can produce a lot of proinflammatory cytokines, including TNF [tumor necrosis factor],” said Jennifer Howitt Anolik, MD, PhD, associate professor of medicine at the University of Rochester (N.Y.) and cochair of the AMP RA/SLE Network.

“In addition to inflammatory mediators there’s an anti-inflammatory population which may control the disease,” she added, at the virtual meeting, which was sponsored by The Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Health and Arthritis.

There are up to 15 different populations of macrophages found so far as part of a project by Fan Zhang of Brigham and Women’s Hospital and Harvard Medical School in Boston, Dr. Anolik revealed. Of these, three have been shown to be proinflammatory and five have been shown to be anti-inflammatory – including one of particular interest that expresses MERTK, which recent work suggests are lacking in people with RA, compared with a control population of people with osteoarthritis (OA).

Clearly, Dr. Anolik said, there is “lots more work to do to understand how those anti-inflammatory monocytes might work, understand the relationship to treatment response and treatment failure, and how to target them.”
 

AMP RA/SLE Network: Examining RA synovial tissue

What’s unique about the AMP’s work is that it is involving single-cell analytics in which individual cells derived from patients with RA are subjected to an array of RNA sequencing and molecular classification methods.

“If we’re able to define the cells that are driving the disease at the tissue level, this may lead to better therapeutics and more of like a precision medicine approach,” Dr. Anolik said. An important feature of the AMP’s work is that it is based on the use of existing and thus “very informative cohorts” for whom we know a lot about disease characteristics, she said.

The AMP RA/SLE Network officially formed in 2014 and is a public–private partnership between the National Institutes of Health, the Food and Drug Administration, several biopharmaceutical companies, and nonprofit organizations. The task was to try to accelerate discoveries that would lead to better patient care.

“The initial phase [Research Phase 0], was really about developing the procedures in a standardized way,” Dr. Anolik said. “Because we’re looking at patient joint tissue samples, we needed to access that tissue and that required developing needle biopsy approaches.” Synovial biopsy had been pioneered in the United Kingdom and become fairly standard to perform, she added, but this was not an approach that was routinely being used in the United States at the time.

In the next step, Research Phase I, researchers looked at the expression profiles of RA synovial cells in a small group of patients. In all, around 5,000 cells from the joints of up to 20 patients with RA were analyzed. What was apparent was that while there were fibroblasts, monocytes, T cells, and B cells all present to some degree, there was substantial heterogeneity among those subtypes.

“Within all the different immune cells and stromal cells, we found 18 different populations overall,” Dr. Anolik said, giving some of the top-level findings. Both single-cell RNA sequencing and mass cytometry revealed that there were greatly (16-fold) increased numbers of a population of sublining fibroblasts and a 3.3-fold increase in interleukin-1-beta-expressing proinflammatory monocytes. There was a threefold increase in a subset of B cells expressing CD11/T-bet, and a 2.4-fold increase in certain peripheral T cells.

“Interestingly, we were able to pinpoint which cells are making which kinds of inflammatory mediators like inflammatory cytokines,” Dr. Anolik said. Notably, one of the fibroblast populations and one of the B cells were prominent producers of interleukin-6.

The AMP RA/SLE Network is now in Research Phase II, looking at much greater numbers of cells (>5,000) in more than 100 samples from individual patients. It’s a “very comprehensive, big data look at RA,” according to Dr. Anolik.

Research Phase II will also see more rigorous groups of patients being examined, including those who have not had any or much exposure to disease-modifying antirheumatic drugs and those who have inadequately responded to methotrexate or anti-TNF drugs.

Recent AMP RA/SLE Network findings

Recent work by the AMP RA/SLE Network has shown that stromal fibroblasts can become highly inflammatory in RA.

“What’s becoming clear is that these are more than just lining of the joint or structure of the joint, they actually play an active role in the disease,” Dr. Anolik said.

There is a lot of diversity in these fibroblasts but they broadly fall into lining or sublining subtypes. Those that are proinflammatory tend to express markers such as HLA-DR and CD90, and one that is of notable interest is a subgroup of sublining fibroblasts that express Notch3. Indeed, it has been shown that the higher the number of Notch3-expressing fibroblasts there are in the joint, the greater the level of inflammation. Also, mice lacking Notch3 seem to get less arthritis than those with Notch3. This makes Notch3 an interesting potential target that no one had thought of before.

Dr. Anolik noted that some evolving concepts about T cells include evidence showing CD8-postive T cells are more abundant in the joint tissue than previously thought and, together with natural killer (NK) cells, are an important producer of interferon-gamma.

“There are some very interesting CD4 T-cell populations, including an expansion of T peripheral helper cells that may be very important in driving B-cell activation,” Dr. Anolik said. There are also many other clusters of T cells and NK cells that have unknown roles.

Over the past years, Dr. Anolik’s research had focused on the role B cells play in autoimmune disease, and one of the cells of interest are known as age-related B cells, or ABCs. High percentages of ABCs have been found in the RA synovium, and these seem to be related to disease activity as measured by the Disease Activity Score in 28 joints (DAS28). These cells also seem to cluster with some of the T helper cell populations found in the joint. Another interesting target could be B cells expressing a transcription factor known as T-bet. Work in mice suggests that the absence of T-bet B cells could be associated with reduced levels of arthritis.

“One of the things that we’re really interested in about B cells, in addition to their production of autoantibodies, is that they may be important for some of the structural damage that occurs with rheumatoid arthritis,” she said.

T-bet B cells seem to have an effect on both osteoclasts and osteoblasts – activating one while inhibiting the other to have a negative effect on bone overall, she explained. However, knocking out T-bet seems to resolve this, again suggesting that T-bet B cells may be another interesting subpopulation to target.

“Overall, the AMP has been a really interesting approach. This is a massive data set. We are putting the data together now to publish, and it will be available in the public domain,” Dr. Anolik said.

Members of the AMP RA/SLE Network include: AbbVie, the Arthritis Foundation, Bristol‐Myers Squibb, the Foundation for the NIH, the Lupus Foundation of America, the Lupus Research Alliance, Merck Sharp & Dohme, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, the Rheumatology Research Foundation, Sanofi, and Takeda Pharmaceuticals International.

Dr. Anolik had no disclosures.

Macrophages are among the most important inflammatory cells in the synovium of patients with rheumatoid arthritis, according to research discussed at the Canadian Arthritis Research Conference: Research with Impact.

Work conducted as part of the Accelerating Medicines Partnership (AMP) Rheumatoid Arthritis and Systemic Lupus Erythematosus (RA/SLE) Network suggests that not only do macrophages play an inflammatory role, but there may also be a subset of macrophages that have a predominantly anti-inflammatory effect.

“These are cells that are really activated and can produce a lot of proinflammatory cytokines, including TNF [tumor necrosis factor],” said Jennifer Howitt Anolik, MD, PhD, associate professor of medicine at the University of Rochester (N.Y.) and cochair of the AMP RA/SLE Network.

“In addition to inflammatory mediators there’s an anti-inflammatory population which may control the disease,” she added, at the virtual meeting, which was sponsored by The Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Health and Arthritis.

There are up to 15 different populations of macrophages found so far as part of a project by Fan Zhang of Brigham and Women’s Hospital and Harvard Medical School in Boston, Dr. Anolik revealed. Of these, three have been shown to be proinflammatory and five have been shown to be anti-inflammatory – including one of particular interest that expresses MERTK, which recent work suggests are lacking in people with RA, compared with a control population of people with osteoarthritis (OA).

Clearly, Dr. Anolik said, there is “lots more work to do to understand how those anti-inflammatory monocytes might work, understand the relationship to treatment response and treatment failure, and how to target them.”
 

AMP RA/SLE Network: Examining RA synovial tissue

What’s unique about the AMP’s work is that it is involving single-cell analytics in which individual cells derived from patients with RA are subjected to an array of RNA sequencing and molecular classification methods.

“If we’re able to define the cells that are driving the disease at the tissue level, this may lead to better therapeutics and more of like a precision medicine approach,” Dr. Anolik said. An important feature of the AMP’s work is that it is based on the use of existing and thus “very informative cohorts” for whom we know a lot about disease characteristics, she said.

The AMP RA/SLE Network officially formed in 2014 and is a public–private partnership between the National Institutes of Health, the Food and Drug Administration, several biopharmaceutical companies, and nonprofit organizations. The task was to try to accelerate discoveries that would lead to better patient care.

“The initial phase [Research Phase 0], was really about developing the procedures in a standardized way,” Dr. Anolik said. “Because we’re looking at patient joint tissue samples, we needed to access that tissue and that required developing needle biopsy approaches.” Synovial biopsy had been pioneered in the United Kingdom and become fairly standard to perform, she added, but this was not an approach that was routinely being used in the United States at the time.

In the next step, Research Phase I, researchers looked at the expression profiles of RA synovial cells in a small group of patients. In all, around 5,000 cells from the joints of up to 20 patients with RA were analyzed. What was apparent was that while there were fibroblasts, monocytes, T cells, and B cells all present to some degree, there was substantial heterogeneity among those subtypes.

“Within all the different immune cells and stromal cells, we found 18 different populations overall,” Dr. Anolik said, giving some of the top-level findings. Both single-cell RNA sequencing and mass cytometry revealed that there were greatly (16-fold) increased numbers of a population of sublining fibroblasts and a 3.3-fold increase in interleukin-1-beta-expressing proinflammatory monocytes. There was a threefold increase in a subset of B cells expressing CD11/T-bet, and a 2.4-fold increase in certain peripheral T cells.

“Interestingly, we were able to pinpoint which cells are making which kinds of inflammatory mediators like inflammatory cytokines,” Dr. Anolik said. Notably, one of the fibroblast populations and one of the B cells were prominent producers of interleukin-6.

The AMP RA/SLE Network is now in Research Phase II, looking at much greater numbers of cells (>5,000) in more than 100 samples from individual patients. It’s a “very comprehensive, big data look at RA,” according to Dr. Anolik.

Research Phase II will also see more rigorous groups of patients being examined, including those who have not had any or much exposure to disease-modifying antirheumatic drugs and those who have inadequately responded to methotrexate or anti-TNF drugs.

Recent AMP RA/SLE Network findings

Recent work by the AMP RA/SLE Network has shown that stromal fibroblasts can become highly inflammatory in RA.

“What’s becoming clear is that these are more than just lining of the joint or structure of the joint, they actually play an active role in the disease,” Dr. Anolik said.

There is a lot of diversity in these fibroblasts but they broadly fall into lining or sublining subtypes. Those that are proinflammatory tend to express markers such as HLA-DR and CD90, and one that is of notable interest is a subgroup of sublining fibroblasts that express Notch3. Indeed, it has been shown that the higher the number of Notch3-expressing fibroblasts there are in the joint, the greater the level of inflammation. Also, mice lacking Notch3 seem to get less arthritis than those with Notch3. This makes Notch3 an interesting potential target that no one had thought of before.

Dr. Anolik noted that some evolving concepts about T cells include evidence showing CD8-postive T cells are more abundant in the joint tissue than previously thought and, together with natural killer (NK) cells, are an important producer of interferon-gamma.

“There are some very interesting CD4 T-cell populations, including an expansion of T peripheral helper cells that may be very important in driving B-cell activation,” Dr. Anolik said. There are also many other clusters of T cells and NK cells that have unknown roles.

Over the past years, Dr. Anolik’s research had focused on the role B cells play in autoimmune disease, and one of the cells of interest are known as age-related B cells, or ABCs. High percentages of ABCs have been found in the RA synovium, and these seem to be related to disease activity as measured by the Disease Activity Score in 28 joints (DAS28). These cells also seem to cluster with some of the T helper cell populations found in the joint. Another interesting target could be B cells expressing a transcription factor known as T-bet. Work in mice suggests that the absence of T-bet B cells could be associated with reduced levels of arthritis.

“One of the things that we’re really interested in about B cells, in addition to their production of autoantibodies, is that they may be important for some of the structural damage that occurs with rheumatoid arthritis,” she said.

T-bet B cells seem to have an effect on both osteoclasts and osteoblasts – activating one while inhibiting the other to have a negative effect on bone overall, she explained. However, knocking out T-bet seems to resolve this, again suggesting that T-bet B cells may be another interesting subpopulation to target.

“Overall, the AMP has been a really interesting approach. This is a massive data set. We are putting the data together now to publish, and it will be available in the public domain,” Dr. Anolik said.

Members of the AMP RA/SLE Network include: AbbVie, the Arthritis Foundation, Bristol‐Myers Squibb, the Foundation for the NIH, the Lupus Foundation of America, the Lupus Research Alliance, Merck Sharp & Dohme, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, the Rheumatology Research Foundation, Sanofi, and Takeda Pharmaceuticals International.

Dr. Anolik had no disclosures.

Macrophages are among the most important inflammatory cells in the synovium of patients with rheumatoid arthritis, according to research discussed at the Canadian Arthritis Research Conference: Research with Impact.

Work conducted as part of the Accelerating Medicines Partnership (AMP) Rheumatoid Arthritis and Systemic Lupus Erythematosus (RA/SLE) Network suggests that not only do macrophages play an inflammatory role, but there may also be a subset of macrophages that have a predominantly anti-inflammatory effect.

“These are cells that are really activated and can produce a lot of proinflammatory cytokines, including TNF [tumor necrosis factor],” said Jennifer Howitt Anolik, MD, PhD, associate professor of medicine at the University of Rochester (N.Y.) and cochair of the AMP RA/SLE Network.

“In addition to inflammatory mediators there’s an anti-inflammatory population which may control the disease,” she added, at the virtual meeting, which was sponsored by The Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Health and Arthritis.

There are up to 15 different populations of macrophages found so far as part of a project by Fan Zhang of Brigham and Women’s Hospital and Harvard Medical School in Boston, Dr. Anolik revealed. Of these, three have been shown to be proinflammatory and five have been shown to be anti-inflammatory – including one of particular interest that expresses MERTK, which recent work suggests are lacking in people with RA, compared with a control population of people with osteoarthritis (OA).

Clearly, Dr. Anolik said, there is “lots more work to do to understand how those anti-inflammatory monocytes might work, understand the relationship to treatment response and treatment failure, and how to target them.”
 

AMP RA/SLE Network: Examining RA synovial tissue

What’s unique about the AMP’s work is that it is involving single-cell analytics in which individual cells derived from patients with RA are subjected to an array of RNA sequencing and molecular classification methods.

“If we’re able to define the cells that are driving the disease at the tissue level, this may lead to better therapeutics and more of like a precision medicine approach,” Dr. Anolik said. An important feature of the AMP’s work is that it is based on the use of existing and thus “very informative cohorts” for whom we know a lot about disease characteristics, she said.

The AMP RA/SLE Network officially formed in 2014 and is a public–private partnership between the National Institutes of Health, the Food and Drug Administration, several biopharmaceutical companies, and nonprofit organizations. The task was to try to accelerate discoveries that would lead to better patient care.

“The initial phase [Research Phase 0], was really about developing the procedures in a standardized way,” Dr. Anolik said. “Because we’re looking at patient joint tissue samples, we needed to access that tissue and that required developing needle biopsy approaches.” Synovial biopsy had been pioneered in the United Kingdom and become fairly standard to perform, she added, but this was not an approach that was routinely being used in the United States at the time.

In the next step, Research Phase I, researchers looked at the expression profiles of RA synovial cells in a small group of patients. In all, around 5,000 cells from the joints of up to 20 patients with RA were analyzed. What was apparent was that while there were fibroblasts, monocytes, T cells, and B cells all present to some degree, there was substantial heterogeneity among those subtypes.

“Within all the different immune cells and stromal cells, we found 18 different populations overall,” Dr. Anolik said, giving some of the top-level findings. Both single-cell RNA sequencing and mass cytometry revealed that there were greatly (16-fold) increased numbers of a population of sublining fibroblasts and a 3.3-fold increase in interleukin-1-beta-expressing proinflammatory monocytes. There was a threefold increase in a subset of B cells expressing CD11/T-bet, and a 2.4-fold increase in certain peripheral T cells.

“Interestingly, we were able to pinpoint which cells are making which kinds of inflammatory mediators like inflammatory cytokines,” Dr. Anolik said. Notably, one of the fibroblast populations and one of the B cells were prominent producers of interleukin-6.

The AMP RA/SLE Network is now in Research Phase II, looking at much greater numbers of cells (>5,000) in more than 100 samples from individual patients. It’s a “very comprehensive, big data look at RA,” according to Dr. Anolik.

Research Phase II will also see more rigorous groups of patients being examined, including those who have not had any or much exposure to disease-modifying antirheumatic drugs and those who have inadequately responded to methotrexate or anti-TNF drugs.

Recent AMP RA/SLE Network findings

Recent work by the AMP RA/SLE Network has shown that stromal fibroblasts can become highly inflammatory in RA.

“What’s becoming clear is that these are more than just lining of the joint or structure of the joint, they actually play an active role in the disease,” Dr. Anolik said.

There is a lot of diversity in these fibroblasts but they broadly fall into lining or sublining subtypes. Those that are proinflammatory tend to express markers such as HLA-DR and CD90, and one that is of notable interest is a subgroup of sublining fibroblasts that express Notch3. Indeed, it has been shown that the higher the number of Notch3-expressing fibroblasts there are in the joint, the greater the level of inflammation. Also, mice lacking Notch3 seem to get less arthritis than those with Notch3. This makes Notch3 an interesting potential target that no one had thought of before.

Dr. Anolik noted that some evolving concepts about T cells include evidence showing CD8-postive T cells are more abundant in the joint tissue than previously thought and, together with natural killer (NK) cells, are an important producer of interferon-gamma.

“There are some very interesting CD4 T-cell populations, including an expansion of T peripheral helper cells that may be very important in driving B-cell activation,” Dr. Anolik said. There are also many other clusters of T cells and NK cells that have unknown roles.

Over the past years, Dr. Anolik’s research had focused on the role B cells play in autoimmune disease, and one of the cells of interest are known as age-related B cells, or ABCs. High percentages of ABCs have been found in the RA synovium, and these seem to be related to disease activity as measured by the Disease Activity Score in 28 joints (DAS28). These cells also seem to cluster with some of the T helper cell populations found in the joint. Another interesting target could be B cells expressing a transcription factor known as T-bet. Work in mice suggests that the absence of T-bet B cells could be associated with reduced levels of arthritis.

“One of the things that we’re really interested in about B cells, in addition to their production of autoantibodies, is that they may be important for some of the structural damage that occurs with rheumatoid arthritis,” she said.

T-bet B cells seem to have an effect on both osteoclasts and osteoblasts – activating one while inhibiting the other to have a negative effect on bone overall, she explained. However, knocking out T-bet seems to resolve this, again suggesting that T-bet B cells may be another interesting subpopulation to target.

“Overall, the AMP has been a really interesting approach. This is a massive data set. We are putting the data together now to publish, and it will be available in the public domain,” Dr. Anolik said.

Members of the AMP RA/SLE Network include: AbbVie, the Arthritis Foundation, Bristol‐Myers Squibb, the Foundation for the NIH, the Lupus Foundation of America, the Lupus Research Alliance, Merck Sharp & Dohme, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, the Rheumatology Research Foundation, Sanofi, and Takeda Pharmaceuticals International.

Dr. Anolik had no disclosures.

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

Sub-subspecialization would be counterproductive: Orrin M. Troum, MD

The much-discussed looming rheumatology workforce shortage is actually here already. And it’s going to worsen rapidly. Add to that the striking geographic maldistribution of rheumatologists across the United States, and it makes little sense for some rheumatologists to declare they’re only going to see patients with psoriatic arthritis, or gout, or lupus. Such sub-subspecialization will only worsen the workforce problem, Orrin M. Troum, MD, asserted at the 2021 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Besides, surveys indicate that most rheumatologists like what they do now, despite their status as the lowest-paid subspecialists within internal medicine. They enjoy a sense of satisfaction stemming from their ability to help patients with chronic debilitating diseases turn their lives around as a result of revolutionary treatment advances in the last 2 decades, said Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica.

The 2015 American College of Rheumatology Workforce Study concluded that the demand for adult rheumatology services already outstripped the supply by 12.9% in 2015. And as current rheumatologists retire in tandem with a growing aged general population saddled with an accompanying burgeoning prevalence of rheumatic and musculoskeletal diseases, demand is expected to exceed supply by a whopping 102% in 2030.

The Workforce Study also highlighted the geographic maldistribution problem, with 21% of all adult rheumatologists now practicing in the Northeast and only 3.9% in the Southwest. Rheumatologists are also few and far between across large swaths of the South Central, North Central, and Northwest United States.

Today rheumatologists spend about half their working hours seeing patients with rheumatic diseases, one-quarter of their time in administrative tasks, 20% seeing patients with nonrheumatic diseases such as osteoarthritis, and the rest in teaching or research. It could be argued that, if rheumatologists declined to see patients with osteoarthritis, a nonrheumatic disease, it would put a sizeable dent in the workforce shortage, but it’s clear that nonrheumatologists can’t reliably differentiate inflammatory from noninflammatory arthritis. And there’s another problem with the idea of rheumatologists barring the office door to patients with nonrheumatic diseases: imagine a young clinical rheumatologist going out into practice and trying to tell referring internists, family physicians, and orthopedists that he or she doesn’t want to see patients with osteoarthritis, noninflammatory back pain, or fibromyalgia.

“How busy do you think you’re going to be, ever, if you tell the referring docs that you’re not going to see patients they think they need help with? And who’s going to make the correct diagnosis if we don’t at least see these patients initially?” Dr. Troum asked.

The case for sub-subspecialization: Martin J. Bergman, MD

Think about how many patients you’re treating for vasculitis, systemic lupus erythematosus, Behçet’s disease, or systemic sclerosis. Do you think you’re doing the best job that’s possible when you’re seeing just a handful of these patients, or would outcomes be better if they were seen at centers where the focus is specifically on these somewhat rare diseases? asked Martin J. Bergman, MD, a rheumatologist at Drexel University, Philadelphia, and in private practice in Ridley Park, Pa.

Bruce Jancin/MDedge News

We can take a lesson from other specialties. It’s well-documented that higher surgical volume brings better care and better outcomes for cardiovascular and cancer surgery. Specialized high-level trauma centers achieve 20%-30% better outcomes. And outcomes are also improved when joint replacement surgery is done at specialty centers. Why would we expect rheumatology to be any different?

Actually, there is already evidence from within our own field to support this concept. A longitudinal study of 150 consecutive SLE patients – half treated at the general rheumatology clinic at Rush University, Chicago, and the other half at the medical center’s specialized lupus clinic – showed demonstrably better quality-of-care outcomes for the patients seen in the dedicated lupus clinic. They were roughly twice as likely to undergo antiphospholipid antibody testing and were also significantly more likely to have bone mineral density testing, pneumococcal vaccination, and sunscreen counseling.

Look, I get it. This is not going to be possible everywhere. In underserved geographic areas, it may not be feasible. But I would think that, even in places where you can’t have sub-subspecialty clinics, maybe it’s time for rheumatologists to start thinking in terms of sub-specializing their own practice and getting out of areas where we can make little or no impact beyond what other physicians can accomplish. Most of us provide very little value for patients with fibromyalgia and chronic fatigue syndrome. We have only so much time, and rather than taking care of anybody who has an ache or a pain we should focus on where we can make the most impact, and that’s inflammatory disease.

The speakers reported having no financial conflicts regarding their presentations.

[email protected]

Sub-subspecialization would be counterproductive: Orrin M. Troum, MD

The much-discussed looming rheumatology workforce shortage is actually here already. And it’s going to worsen rapidly. Add to that the striking geographic maldistribution of rheumatologists across the United States, and it makes little sense for some rheumatologists to declare they’re only going to see patients with psoriatic arthritis, or gout, or lupus. Such sub-subspecialization will only worsen the workforce problem, Orrin M. Troum, MD, asserted at the 2021 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Besides, surveys indicate that most rheumatologists like what they do now, despite their status as the lowest-paid subspecialists within internal medicine. They enjoy a sense of satisfaction stemming from their ability to help patients with chronic debilitating diseases turn their lives around as a result of revolutionary treatment advances in the last 2 decades, said Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica.

The 2015 American College of Rheumatology Workforce Study concluded that the demand for adult rheumatology services already outstripped the supply by 12.9% in 2015. And as current rheumatologists retire in tandem with a growing aged general population saddled with an accompanying burgeoning prevalence of rheumatic and musculoskeletal diseases, demand is expected to exceed supply by a whopping 102% in 2030.

The Workforce Study also highlighted the geographic maldistribution problem, with 21% of all adult rheumatologists now practicing in the Northeast and only 3.9% in the Southwest. Rheumatologists are also few and far between across large swaths of the South Central, North Central, and Northwest United States.

Today rheumatologists spend about half their working hours seeing patients with rheumatic diseases, one-quarter of their time in administrative tasks, 20% seeing patients with nonrheumatic diseases such as osteoarthritis, and the rest in teaching or research. It could be argued that, if rheumatologists declined to see patients with osteoarthritis, a nonrheumatic disease, it would put a sizeable dent in the workforce shortage, but it’s clear that nonrheumatologists can’t reliably differentiate inflammatory from noninflammatory arthritis. And there’s another problem with the idea of rheumatologists barring the office door to patients with nonrheumatic diseases: imagine a young clinical rheumatologist going out into practice and trying to tell referring internists, family physicians, and orthopedists that he or she doesn’t want to see patients with osteoarthritis, noninflammatory back pain, or fibromyalgia.

“How busy do you think you’re going to be, ever, if you tell the referring docs that you’re not going to see patients they think they need help with? And who’s going to make the correct diagnosis if we don’t at least see these patients initially?” Dr. Troum asked.

The case for sub-subspecialization: Martin J. Bergman, MD

Think about how many patients you’re treating for vasculitis, systemic lupus erythematosus, Behçet’s disease, or systemic sclerosis. Do you think you’re doing the best job that’s possible when you’re seeing just a handful of these patients, or would outcomes be better if they were seen at centers where the focus is specifically on these somewhat rare diseases? asked Martin J. Bergman, MD, a rheumatologist at Drexel University, Philadelphia, and in private practice in Ridley Park, Pa.

Bruce Jancin/MDedge News

We can take a lesson from other specialties. It’s well-documented that higher surgical volume brings better care and better outcomes for cardiovascular and cancer surgery. Specialized high-level trauma centers achieve 20%-30% better outcomes. And outcomes are also improved when joint replacement surgery is done at specialty centers. Why would we expect rheumatology to be any different?

Actually, there is already evidence from within our own field to support this concept. A longitudinal study of 150 consecutive SLE patients – half treated at the general rheumatology clinic at Rush University, Chicago, and the other half at the medical center’s specialized lupus clinic – showed demonstrably better quality-of-care outcomes for the patients seen in the dedicated lupus clinic. They were roughly twice as likely to undergo antiphospholipid antibody testing and were also significantly more likely to have bone mineral density testing, pneumococcal vaccination, and sunscreen counseling.

Look, I get it. This is not going to be possible everywhere. In underserved geographic areas, it may not be feasible. But I would think that, even in places where you can’t have sub-subspecialty clinics, maybe it’s time for rheumatologists to start thinking in terms of sub-specializing their own practice and getting out of areas where we can make little or no impact beyond what other physicians can accomplish. Most of us provide very little value for patients with fibromyalgia and chronic fatigue syndrome. We have only so much time, and rather than taking care of anybody who has an ache or a pain we should focus on where we can make the most impact, and that’s inflammatory disease.

The speakers reported having no financial conflicts regarding their presentations.

[email protected]

Sub-subspecialization would be counterproductive: Orrin M. Troum, MD

The much-discussed looming rheumatology workforce shortage is actually here already. And it’s going to worsen rapidly. Add to that the striking geographic maldistribution of rheumatologists across the United States, and it makes little sense for some rheumatologists to declare they’re only going to see patients with psoriatic arthritis, or gout, or lupus. Such sub-subspecialization will only worsen the workforce problem, Orrin M. Troum, MD, asserted at the 2021 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Besides, surveys indicate that most rheumatologists like what they do now, despite their status as the lowest-paid subspecialists within internal medicine. They enjoy a sense of satisfaction stemming from their ability to help patients with chronic debilitating diseases turn their lives around as a result of revolutionary treatment advances in the last 2 decades, said Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica.

The 2015 American College of Rheumatology Workforce Study concluded that the demand for adult rheumatology services already outstripped the supply by 12.9% in 2015. And as current rheumatologists retire in tandem with a growing aged general population saddled with an accompanying burgeoning prevalence of rheumatic and musculoskeletal diseases, demand is expected to exceed supply by a whopping 102% in 2030.

The Workforce Study also highlighted the geographic maldistribution problem, with 21% of all adult rheumatologists now practicing in the Northeast and only 3.9% in the Southwest. Rheumatologists are also few and far between across large swaths of the South Central, North Central, and Northwest United States.

Today rheumatologists spend about half their working hours seeing patients with rheumatic diseases, one-quarter of their time in administrative tasks, 20% seeing patients with nonrheumatic diseases such as osteoarthritis, and the rest in teaching or research. It could be argued that, if rheumatologists declined to see patients with osteoarthritis, a nonrheumatic disease, it would put a sizeable dent in the workforce shortage, but it’s clear that nonrheumatologists can’t reliably differentiate inflammatory from noninflammatory arthritis. And there’s another problem with the idea of rheumatologists barring the office door to patients with nonrheumatic diseases: imagine a young clinical rheumatologist going out into practice and trying to tell referring internists, family physicians, and orthopedists that he or she doesn’t want to see patients with osteoarthritis, noninflammatory back pain, or fibromyalgia.

“How busy do you think you’re going to be, ever, if you tell the referring docs that you’re not going to see patients they think they need help with? And who’s going to make the correct diagnosis if we don’t at least see these patients initially?” Dr. Troum asked.

The case for sub-subspecialization: Martin J. Bergman, MD

Think about how many patients you’re treating for vasculitis, systemic lupus erythematosus, Behçet’s disease, or systemic sclerosis. Do you think you’re doing the best job that’s possible when you’re seeing just a handful of these patients, or would outcomes be better if they were seen at centers where the focus is specifically on these somewhat rare diseases? asked Martin J. Bergman, MD, a rheumatologist at Drexel University, Philadelphia, and in private practice in Ridley Park, Pa.

Bruce Jancin/MDedge News

We can take a lesson from other specialties. It’s well-documented that higher surgical volume brings better care and better outcomes for cardiovascular and cancer surgery. Specialized high-level trauma centers achieve 20%-30% better outcomes. And outcomes are also improved when joint replacement surgery is done at specialty centers. Why would we expect rheumatology to be any different?

Actually, there is already evidence from within our own field to support this concept. A longitudinal study of 150 consecutive SLE patients – half treated at the general rheumatology clinic at Rush University, Chicago, and the other half at the medical center’s specialized lupus clinic – showed demonstrably better quality-of-care outcomes for the patients seen in the dedicated lupus clinic. They were roughly twice as likely to undergo antiphospholipid antibody testing and were also significantly more likely to have bone mineral density testing, pneumococcal vaccination, and sunscreen counseling.

Look, I get it. This is not going to be possible everywhere. In underserved geographic areas, it may not be feasible. But I would think that, even in places where you can’t have sub-subspecialty clinics, maybe it’s time for rheumatologists to start thinking in terms of sub-specializing their own practice and getting out of areas where we can make little or no impact beyond what other physicians can accomplish. Most of us provide very little value for patients with fibromyalgia and chronic fatigue syndrome. We have only so much time, and rather than taking care of anybody who has an ache or a pain we should focus on where we can make the most impact, and that’s inflammatory disease.

The speakers reported having no financial conflicts regarding their presentations.

[email protected]

Most checkpoint inhibitor–induced rheumatic complications in cancer patients can be treated successfully with corticosteroids, albeit often at considerably higher doses than rheumatologists typically use in managing rheumatoid arthritis, Eric M. Ruderman, MD, observed at the 2021 Rheumatology Winter Clinical Symposium.

“In RA, we’re all used to the idea that 5 or 10 mg of corticosteroids per day can make a tremendous difference. That’s not always the case here. Patients who develop rheumatic immunotherapy-related adverse events often require 20-30 mg/day to get symptoms under control,” according to Dr. Ruderman, professor of medicine (rheumatology) at Northwestern University, Chicago.

This may be in part because oncologists typically don’t refer affected patients to rheumatologists early on. Guidelines from the National Comprehensive Cancer Network and other oncology groups suggest referral only once a patient develops grade 3 immunotherapy-related rheumatic adverse events, meaning the symptoms significantly impair daily activities, he explained.

Checkpoint inhibitors, which induce T-cell activation to fight the patient’s malignancy, can produce a plethora of off-target effects. These adverse events may involve the skin, heart, lungs, kidneys, eyes, blood, GI tract, and endocrine organs. The drugs also can cause rheumatic or neurologic complications. The most common of these adverse events are colitis and rash. Next most common are arthritis and arthralgia. Rheumatic side effects are most common as a consequence of immunotherapy using a CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor, but can also occur in association with programmed cell death protein 1 (PD-1) inhibitors and PD-ligand 1 inhibitors. Arthritis and other rheumatic adverse events are more common in patients undergoing combination therapy.

Some form of frank inflammatory arthritis occurs in 5%-10% of cancer patients undergoing checkpoint inhibitor therapy. This can manifest as an RA-like polyarthritis, spondyloarthritis, polymyalgia rheumatica, necrotizing myositis, or vasculitis. Arthralgia occurs in up to 40% of treated patients.

This immunotherapy-related arthritis is typically more inflammatory than RA. It also has a much more abrupt onset. It is usually seronegative and has no gender predisposition, and the limited available evidence to date suggests there is no increased risk of this complication in checkpoint inhibitor–treated patients with a history of prior rheumatic disease, according to Dr. Ruderman.
 

Delayed onset and resolution of rheumatologic immune-related adverse events

“Onset and resolution of rheumatologic adverse events with immunotherapy may be delayed. This is an important point: While skin rash and colitis often show up pretty early in the course of immunotherapy, some of the arthritic events can happen later. They can actually continue after the immunotherapy is stopped,” the rheumatologist said.

Indeed, a retrospective nationwide Canadian study of 117 patients at nine academic centers who developed 136 rheumatic immune-related adverse events in conjunction with cancer immunotherapy found that the mean time to the first such event was 6.8 months into checkpoint inhibitor therapy. The most common rheumatic complication was symmetric polyarthritis, affecting 45 patients. Other rheumatologic immune-related complications included polymyalgia rheumatica in 17 patients, noninflammatory musculoskeletal symptoms in 18, and myositis in 9.

Seventy-six patients were treated with prednisone for a mean of 8.4 months at a maximum dose of 60 mg/day. Forty-two moved up the treatment ladder to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to manage their symptoms. Only two patients required escalation to biologic therapy. A reassuring finding in this relatively small study was that treatment of the patients’ rheumatic complications didn’t appear to worsen the tumor response to immunotherapy: Twenty-three patients experienced tumor progression prior to treatment of their rheumatic disorder, and 14 did so following treatment.
 

Flares of preexisting rheumatic diseases

These tend to occur much earlier in the course of immune checkpoint inhibitor therapy for cancer than de novo immunotherapy-related rheumatic adverse events. In a retrospective Australian study of 12 cancer patients with preexisting rheumatic disease before going on a PD-1 inhibitor and 24 others with no such history, all of whom developed rheumatic adverse events while on the checkpoint inhibitor, the mean time to a flare of preexisting rheumatic disease was 6.2 weeks, compared to 21.5 weeks in patients who experienced a de novo rheumatic adverse event.

Dr. Ruderman supports recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the management of rheumatic immune-related adverse events due to cancer immunotherapy, even though the underlying level of evidence is fairly weak. The recommendations call for the use of csDMARDs when corticosteroids don’t adequately control symptoms. And when the response to csDMARDs is insufficient, the next step is a biologic, preferably a tumor necrosis factor inhibitor or interleukin-6 inhibitor.

“At our institution, the oncologists are a little bit nervous about using biologics in cancer patients, but I think more and more they’re going to have to accept it. And so far there isn’t a ton of evidence that suggests the addition of biologics interferes with the efficacy of the immunotherapy,” the rheumatologist said.

He underscored the critical importance of one of the overarching principles of the EULAR guidelines: the need for interdisciplinary coordination between rheumatologists and oncologists regarding the problem of rheumatologic immune-related adverse events.

“Oncologists aren’t good at managing inflammatory arthritis. I think they really need us,” he said.

Dr. Ruderman reported serving as a consultant to and/or receiving a research grant from nine pharmaceutical companies.

[email protected]

Most checkpoint inhibitor–induced rheumatic complications in cancer patients can be treated successfully with corticosteroids, albeit often at considerably higher doses than rheumatologists typically use in managing rheumatoid arthritis, Eric M. Ruderman, MD, observed at the 2021 Rheumatology Winter Clinical Symposium.

“In RA, we’re all used to the idea that 5 or 10 mg of corticosteroids per day can make a tremendous difference. That’s not always the case here. Patients who develop rheumatic immunotherapy-related adverse events often require 20-30 mg/day to get symptoms under control,” according to Dr. Ruderman, professor of medicine (rheumatology) at Northwestern University, Chicago.

This may be in part because oncologists typically don’t refer affected patients to rheumatologists early on. Guidelines from the National Comprehensive Cancer Network and other oncology groups suggest referral only once a patient develops grade 3 immunotherapy-related rheumatic adverse events, meaning the symptoms significantly impair daily activities, he explained.

Checkpoint inhibitors, which induce T-cell activation to fight the patient’s malignancy, can produce a plethora of off-target effects. These adverse events may involve the skin, heart, lungs, kidneys, eyes, blood, GI tract, and endocrine organs. The drugs also can cause rheumatic or neurologic complications. The most common of these adverse events are colitis and rash. Next most common are arthritis and arthralgia. Rheumatic side effects are most common as a consequence of immunotherapy using a CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor, but can also occur in association with programmed cell death protein 1 (PD-1) inhibitors and PD-ligand 1 inhibitors. Arthritis and other rheumatic adverse events are more common in patients undergoing combination therapy.

Some form of frank inflammatory arthritis occurs in 5%-10% of cancer patients undergoing checkpoint inhibitor therapy. This can manifest as an RA-like polyarthritis, spondyloarthritis, polymyalgia rheumatica, necrotizing myositis, or vasculitis. Arthralgia occurs in up to 40% of treated patients.

This immunotherapy-related arthritis is typically more inflammatory than RA. It also has a much more abrupt onset. It is usually seronegative and has no gender predisposition, and the limited available evidence to date suggests there is no increased risk of this complication in checkpoint inhibitor–treated patients with a history of prior rheumatic disease, according to Dr. Ruderman.
 

Delayed onset and resolution of rheumatologic immune-related adverse events

“Onset and resolution of rheumatologic adverse events with immunotherapy may be delayed. This is an important point: While skin rash and colitis often show up pretty early in the course of immunotherapy, some of the arthritic events can happen later. They can actually continue after the immunotherapy is stopped,” the rheumatologist said.

Indeed, a retrospective nationwide Canadian study of 117 patients at nine academic centers who developed 136 rheumatic immune-related adverse events in conjunction with cancer immunotherapy found that the mean time to the first such event was 6.8 months into checkpoint inhibitor therapy. The most common rheumatic complication was symmetric polyarthritis, affecting 45 patients. Other rheumatologic immune-related complications included polymyalgia rheumatica in 17 patients, noninflammatory musculoskeletal symptoms in 18, and myositis in 9.

Seventy-six patients were treated with prednisone for a mean of 8.4 months at a maximum dose of 60 mg/day. Forty-two moved up the treatment ladder to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to manage their symptoms. Only two patients required escalation to biologic therapy. A reassuring finding in this relatively small study was that treatment of the patients’ rheumatic complications didn’t appear to worsen the tumor response to immunotherapy: Twenty-three patients experienced tumor progression prior to treatment of their rheumatic disorder, and 14 did so following treatment.
 

Flares of preexisting rheumatic diseases

These tend to occur much earlier in the course of immune checkpoint inhibitor therapy for cancer than de novo immunotherapy-related rheumatic adverse events. In a retrospective Australian study of 12 cancer patients with preexisting rheumatic disease before going on a PD-1 inhibitor and 24 others with no such history, all of whom developed rheumatic adverse events while on the checkpoint inhibitor, the mean time to a flare of preexisting rheumatic disease was 6.2 weeks, compared to 21.5 weeks in patients who experienced a de novo rheumatic adverse event.

Dr. Ruderman supports recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the management of rheumatic immune-related adverse events due to cancer immunotherapy, even though the underlying level of evidence is fairly weak. The recommendations call for the use of csDMARDs when corticosteroids don’t adequately control symptoms. And when the response to csDMARDs is insufficient, the next step is a biologic, preferably a tumor necrosis factor inhibitor or interleukin-6 inhibitor.

“At our institution, the oncologists are a little bit nervous about using biologics in cancer patients, but I think more and more they’re going to have to accept it. And so far there isn’t a ton of evidence that suggests the addition of biologics interferes with the efficacy of the immunotherapy,” the rheumatologist said.

He underscored the critical importance of one of the overarching principles of the EULAR guidelines: the need for interdisciplinary coordination between rheumatologists and oncologists regarding the problem of rheumatologic immune-related adverse events.

“Oncologists aren’t good at managing inflammatory arthritis. I think they really need us,” he said.

Dr. Ruderman reported serving as a consultant to and/or receiving a research grant from nine pharmaceutical companies.

[email protected]

Most checkpoint inhibitor–induced rheumatic complications in cancer patients can be treated successfully with corticosteroids, albeit often at considerably higher doses than rheumatologists typically use in managing rheumatoid arthritis, Eric M. Ruderman, MD, observed at the 2021 Rheumatology Winter Clinical Symposium.

“In RA, we’re all used to the idea that 5 or 10 mg of corticosteroids per day can make a tremendous difference. That’s not always the case here. Patients who develop rheumatic immunotherapy-related adverse events often require 20-30 mg/day to get symptoms under control,” according to Dr. Ruderman, professor of medicine (rheumatology) at Northwestern University, Chicago.

This may be in part because oncologists typically don’t refer affected patients to rheumatologists early on. Guidelines from the National Comprehensive Cancer Network and other oncology groups suggest referral only once a patient develops grade 3 immunotherapy-related rheumatic adverse events, meaning the symptoms significantly impair daily activities, he explained.

Checkpoint inhibitors, which induce T-cell activation to fight the patient’s malignancy, can produce a plethora of off-target effects. These adverse events may involve the skin, heart, lungs, kidneys, eyes, blood, GI tract, and endocrine organs. The drugs also can cause rheumatic or neurologic complications. The most common of these adverse events are colitis and rash. Next most common are arthritis and arthralgia. Rheumatic side effects are most common as a consequence of immunotherapy using a CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor, but can also occur in association with programmed cell death protein 1 (PD-1) inhibitors and PD-ligand 1 inhibitors. Arthritis and other rheumatic adverse events are more common in patients undergoing combination therapy.

Some form of frank inflammatory arthritis occurs in 5%-10% of cancer patients undergoing checkpoint inhibitor therapy. This can manifest as an RA-like polyarthritis, spondyloarthritis, polymyalgia rheumatica, necrotizing myositis, or vasculitis. Arthralgia occurs in up to 40% of treated patients.

This immunotherapy-related arthritis is typically more inflammatory than RA. It also has a much more abrupt onset. It is usually seronegative and has no gender predisposition, and the limited available evidence to date suggests there is no increased risk of this complication in checkpoint inhibitor–treated patients with a history of prior rheumatic disease, according to Dr. Ruderman.
 

Delayed onset and resolution of rheumatologic immune-related adverse events

“Onset and resolution of rheumatologic adverse events with immunotherapy may be delayed. This is an important point: While skin rash and colitis often show up pretty early in the course of immunotherapy, some of the arthritic events can happen later. They can actually continue after the immunotherapy is stopped,” the rheumatologist said.

Indeed, a retrospective nationwide Canadian study of 117 patients at nine academic centers who developed 136 rheumatic immune-related adverse events in conjunction with cancer immunotherapy found that the mean time to the first such event was 6.8 months into checkpoint inhibitor therapy. The most common rheumatic complication was symmetric polyarthritis, affecting 45 patients. Other rheumatologic immune-related complications included polymyalgia rheumatica in 17 patients, noninflammatory musculoskeletal symptoms in 18, and myositis in 9.

Seventy-six patients were treated with prednisone for a mean of 8.4 months at a maximum dose of 60 mg/day. Forty-two moved up the treatment ladder to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to manage their symptoms. Only two patients required escalation to biologic therapy. A reassuring finding in this relatively small study was that treatment of the patients’ rheumatic complications didn’t appear to worsen the tumor response to immunotherapy: Twenty-three patients experienced tumor progression prior to treatment of their rheumatic disorder, and 14 did so following treatment.
 

Flares of preexisting rheumatic diseases

These tend to occur much earlier in the course of immune checkpoint inhibitor therapy for cancer than de novo immunotherapy-related rheumatic adverse events. In a retrospective Australian study of 12 cancer patients with preexisting rheumatic disease before going on a PD-1 inhibitor and 24 others with no such history, all of whom developed rheumatic adverse events while on the checkpoint inhibitor, the mean time to a flare of preexisting rheumatic disease was 6.2 weeks, compared to 21.5 weeks in patients who experienced a de novo rheumatic adverse event.

Dr. Ruderman supports recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the management of rheumatic immune-related adverse events due to cancer immunotherapy, even though the underlying level of evidence is fairly weak. The recommendations call for the use of csDMARDs when corticosteroids don’t adequately control symptoms. And when the response to csDMARDs is insufficient, the next step is a biologic, preferably a tumor necrosis factor inhibitor or interleukin-6 inhibitor.

“At our institution, the oncologists are a little bit nervous about using biologics in cancer patients, but I think more and more they’re going to have to accept it. And so far there isn’t a ton of evidence that suggests the addition of biologics interferes with the efficacy of the immunotherapy,” the rheumatologist said.

He underscored the critical importance of one of the overarching principles of the EULAR guidelines: the need for interdisciplinary coordination between rheumatologists and oncologists regarding the problem of rheumatologic immune-related adverse events.

“Oncologists aren’t good at managing inflammatory arthritis. I think they really need us,” he said.

Dr. Ruderman reported serving as a consultant to and/or receiving a research grant from nine pharmaceutical companies.

[email protected]

Patients with rheumatoid arthritis are often eager to try dietary interventions in an effort to improve their symptoms. For guidance, they turn to their rheumatologists, who typically can offer little in terms of concrete evidence-based recommendations. That’s because their training didn’t emphasize the role of nutrients in rheumatic diseases, the scientific evidence has historically been sketchy, and the topic of diet and disease is rife with fad diets, inflated Internet claims, and hucksterism.

Bruce Jancin/MDedge News

But that’s changing. Indeed, recent annual meetings of the American College of Rheumatology have featured randomized, controlled trials that bring welcome rigor to the field and provide findings of practical interest to clinicians and their patients, Orrin M. Troum, MD, said at the 2021 Rheumatology Winter Clinical Symposium.

He highlighted some of this work, including positive randomized trials of the dietary supplements Biqi – a traditional Chinese herbal medicine – as well as turmeric, along with reported progress in efforts to design a palatable anti-inflammatory diet that favorably alters the gut microbiome and systemic metabolome while improving clinical outcomes in patients with RA.

Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica, described a typical patient encounter in his clinic that appeared to resonate with his audience from throughout the country: “You can tell people to take another medicine and they’ll start shaking their head no before you’re finished. But when you say there are natural supplements that can help you, they’re saying ‘Yes!’ ”
 

RA improvement on an ITIS diet

Many physicians recommend a Mediterranean-style diet, first popularized in the landmark Seven Countries Study launched by the late Dr. Ancel Keys. This familiar plant-based regimen emphasizes liberal consumption of extra-virgin olive oil, legumes, fruits and vegetables, whole grains, fish, nuts, and moderate alcohol intake, with very limited intake of red and processed meats, refined grains, and sugar. There is strong evidence that the Mediterranean diet is cardioprotective, which is relevant to patients with RA since they are known to be at elevated cardiovascular risk.

However, investigators at the University of California, San Diego, became convinced that the Mediterranean diet is lacking in key anti-inflammatory ingredients from other parts of the world. These include ginger, green tea, black pepper, turmeric, miso, flax seeds, and tahini, all of which are backed by evidence – from animal models and/or interventional diet studies in patients – that suggests beneficial effects in pain and joint swelling in RA. The researchers also suspected that certain vegetables embraced in the Mediterranean diet – notably eggplant, tomatoes, and potatoes – might be problematic for RA patients because they contain solanine, thought to increase intestinal permeability, which might have arthritogenic effects on the gut microbiome.

The investigators set out to develop an anti-inflammatory diet they call the ITIS diet, essentially tweaking the Mediterranean-style diet by incorporating these additions and subtractions. Importantly, they designed the ITIS diet in conjunction with a multiracial local group of RA patients strongly enthusiastic about the potential for dietary interventions aimed at improving their symptoms. The patients provided feedback that enabled the investigators to fine-tune the anti-inflammatory diet so as to boost palatability and acceptance.

As an illustrative example of the ITIS diet, a typical day might start off with a homemade smoothie of parsley, pineapple, strawberries, and water, followed by a breakfast consisting of one or two corn tortillas spread with avocado, linseed oil, and sesame seeds, accompanied by green tea. Following a mid-morning snack of plain Greek-style yogurt, lunch might be a choice of a large salad, legumes with vegetables, or whole grains with vegetables. For the afternoon snack: four walnuts plus mango, banana, pear, papaya, apple, or pineapple. And for dinner, the options are vegetable soup and a protein; salad plus a protein; or miso soup, cooked vegetables, and a protein.

At the 2020 ACR annual meeting, Roxana Coras, MD, presented the positive findings of an open-label, pilot study of the ITIS diet in which 17 patients with active RA involving at least three tender and three swollen joints adopted the diet for 2 weeks . The ITIS diet turned out to be not too much of a stretch for Southern California RA patients interested in dietary complementary and alternative medicine. Many had already adopted some elements of the anti-inflammatory diet. Dietary adherence in the study was good, as monitored in food logs and by mass spectrometry metabolic profiling of fecal and plasma samples.

Eleven patients were categorized as responders to the anti-inflammatory diet as defined by at least a 50% improvement in pain scores from baseline to 2 weeks; six patients were nonresponders. In the overall study population, mean pain scores on a 0-10 visual analog scale improved from 3.9 to 2.45. Scores on the Clinical Disease Activity Index (CDAI) also improved significantly on the ITIS diet, from 29 to 12.7, reported Dr. Coras, a rheumatologist at the University of California, San Diego.

The mechanisms for the clinical improvement on the diet are under study. Significant differences in the gut microbiome and metabolome were seen between the responders and nonresponders. For example, Mollicutes were increased and Coriobacteriales decreased in clinical responders versus nonresponders. A significant increase in circulating levels of anti-inflammatory oxylipins was also seen in responders. Longer-term controlled studies of the ITIS diet are planned.

Biqi is big in China, gaining ground in the U.S.

Ayurvedic medicine in India and Chinese traditional herbal medicine have richly documented 4,500-year histories.

“It’s so common in my neck of the woods, where there are large Asian communities, for Chinese or Korean or Japanese or Indian medicines to be combined with our medicines. And if you don’t ask about them, you’re never going to find out what these patients are taking,” Dr. Troum said.

If they’re taking Biqi capsules, readily available on the Internet, be advised that there is randomized trial evidence to show that they’re using an efficacious and safe herbal medicine for RA. In China, the combination of Biqi capsules and a conventional disease-modifying antirheumatic drug such as methotrexate is now widely used for treatment of RA. And at the 2019 ACR annual meeting, Runyue Huang, MD, of Guangzhou University of Chinese Medicine, presented the results of a 24-week, randomized, multicenter, open-label clinical trial in which 70 RA patients were assigned to methotrexate plus a 1.2-g Biqi capsule twice daily or to methotrexate plus leflunomide (Arava) at 20 mg/day. The primary outcome – achievement of a 20% improvement in the ACR criteria, or ACR20 response, at week 24 – was achieved in 77% of the Biqi group, not significantly different from the 83% rate in the comparator group. However, the Biqi plus methotrexate group had significantly fewer adverse events and the combination was better tolerated than was leflunomide plus methotrexate.

In addition, a systematic review of earlier clinical trials concluded that Biqi in combination with methotrexate was more effective and had fewer adverse events than methotrexate alone.

“Biqi capsule with methotrexate appears to be a promising combination for RA if you can rest assured that what’s found in the Biqi capsule is exactly what they say. And that’s the main issue: You don’t really know what you’re getting unless it’s in a trial,” Dr. Troum said.

American RA patients embrace turmeric

Turmeric has played a prominent role in Ayurvedic medicine for millenia. The most medicinally important component of turmeric root is curcumin, which has potent anti-inflammatory and antioxidant properties. Americans with RA have gotten on the bandwagon, as demonstrated in a survey of 291 patients with RA or psoriatic arthritis presented at ACR 2020 by investigators from the University of Central Florida, Orlando. Among the respondents, 37% reported having taken curcumin, with no predilection based upon age, gender, or diagnosis. Fifty-nine percent took their curcumin in the form of capsules, with the rest took it as an oil or powder. Fifty-four percent got their curcumin at a local store.

Thirty-six percent of curcumin users reported improvement in pain after going on the herbal supplement. Twenty-five percent reported reduced swelling, 23% had less stiffness, and 16% reported improvement in fatigue. Patients taking 200-1,000 mg/day reported significantly greater improvement in symptoms than that of those taking less than 200 mg/day. Onset of benefits was slow: Patients on curcumin for a year or longer reported greater symptomatic improvement than did those on the supplement for less time.

Asked what he recommends to his RA patients who express interest in supplements aimed at achieving symptomatic improvement, Dr. Troum replied that he’s comfortable suggesting curcumin capsules at 500 mg twice daily, which should be labeled as containing black pepper extract to aid in absorption. He also recommends fish oil both for its cardioprotective benefits and because of randomized trial evidence that it enhances the chances of achieving ACR remission in patients on conventional disease-modifying antirheumatic drugs.
 

What about osteoarthritis?

Investigators with the National Institutes of Health–sponsored Osteoarthritis Initiative found in an analysis of the dietary patterns of 2,757 patients with mild to moderate knee OA who were followed annually for 6 years that participants could be grouped into two broad categories: Those who consumed what was termed the prudent diet, with high intake of fruits and vegetables, legumes, fish, and whole grains; and fans of the Western diet, characterized by lots of red meat, refined grains, and liberal consumption of French fries. Knee symptoms increased over time in dose-response fashion with greater adherence to the Western diet and decreased with higher prudent diet scores.

Also at ACR 2019, Australian investigators presented the results of the double-blind CurKOA trial, in which 70 participants with knee OA and moderate baseline effusion/synovitis by ultrasound were randomized to take a capsule containing 500 mg of turmeric root extract or identical placebo twice daily for 12 weeks. The group on turmeric plant extract experienced 9.11-mm greater reduction in knee pain on a 0- to 100-mm visual analog scale than did controls, which translates to a moderate standard effect size deemed by investigators to be “greater than other conventional pharmacologic therapies.” Overall, 63% of the turmeric group achieved a treatment response by OARSI-OMERACT criteria, a significantly better outcome than the 38% rate in controls. However, there was no significant between-group difference in knee structural measures as assessed by MRI in this relatively brief trial.

Anne M. Stevens, MD, PhD, senior director of immunology translational medicine at Janssen Pharmaceuticals and a pediatric rheumatologist at Seattle Children’s Hospital, rose from the audience to share that she recommends that her patients on high-dose curcumin not take NSAIDs because the two share a similar mechanism of action involving COX-2 inhibition, and the combination might therefore increase bleeding risk. But Dr. Troum said he hasn’t seen any increase in bleeding in his patients on both agents.

Dr. Troum has financial relationships with numerous pharmaceutical companies, but reported having no financial conflicts of interest regarding his presentation.
 

[email protected]

Patients with rheumatoid arthritis are often eager to try dietary interventions in an effort to improve their symptoms. For guidance, they turn to their rheumatologists, who typically can offer little in terms of concrete evidence-based recommendations. That’s because their training didn’t emphasize the role of nutrients in rheumatic diseases, the scientific evidence has historically been sketchy, and the topic of diet and disease is rife with fad diets, inflated Internet claims, and hucksterism.

Bruce Jancin/MDedge News

But that’s changing. Indeed, recent annual meetings of the American College of Rheumatology have featured randomized, controlled trials that bring welcome rigor to the field and provide findings of practical interest to clinicians and their patients, Orrin M. Troum, MD, said at the 2021 Rheumatology Winter Clinical Symposium.

He highlighted some of this work, including positive randomized trials of the dietary supplements Biqi – a traditional Chinese herbal medicine – as well as turmeric, along with reported progress in efforts to design a palatable anti-inflammatory diet that favorably alters the gut microbiome and systemic metabolome while improving clinical outcomes in patients with RA.

Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica, described a typical patient encounter in his clinic that appeared to resonate with his audience from throughout the country: “You can tell people to take another medicine and they’ll start shaking their head no before you’re finished. But when you say there are natural supplements that can help you, they’re saying ‘Yes!’ ”
 

RA improvement on an ITIS diet

Many physicians recommend a Mediterranean-style diet, first popularized in the landmark Seven Countries Study launched by the late Dr. Ancel Keys. This familiar plant-based regimen emphasizes liberal consumption of extra-virgin olive oil, legumes, fruits and vegetables, whole grains, fish, nuts, and moderate alcohol intake, with very limited intake of red and processed meats, refined grains, and sugar. There is strong evidence that the Mediterranean diet is cardioprotective, which is relevant to patients with RA since they are known to be at elevated cardiovascular risk.

However, investigators at the University of California, San Diego, became convinced that the Mediterranean diet is lacking in key anti-inflammatory ingredients from other parts of the world. These include ginger, green tea, black pepper, turmeric, miso, flax seeds, and tahini, all of which are backed by evidence – from animal models and/or interventional diet studies in patients – that suggests beneficial effects in pain and joint swelling in RA. The researchers also suspected that certain vegetables embraced in the Mediterranean diet – notably eggplant, tomatoes, and potatoes – might be problematic for RA patients because they contain solanine, thought to increase intestinal permeability, which might have arthritogenic effects on the gut microbiome.

The investigators set out to develop an anti-inflammatory diet they call the ITIS diet, essentially tweaking the Mediterranean-style diet by incorporating these additions and subtractions. Importantly, they designed the ITIS diet in conjunction with a multiracial local group of RA patients strongly enthusiastic about the potential for dietary interventions aimed at improving their symptoms. The patients provided feedback that enabled the investigators to fine-tune the anti-inflammatory diet so as to boost palatability and acceptance.

As an illustrative example of the ITIS diet, a typical day might start off with a homemade smoothie of parsley, pineapple, strawberries, and water, followed by a breakfast consisting of one or two corn tortillas spread with avocado, linseed oil, and sesame seeds, accompanied by green tea. Following a mid-morning snack of plain Greek-style yogurt, lunch might be a choice of a large salad, legumes with vegetables, or whole grains with vegetables. For the afternoon snack: four walnuts plus mango, banana, pear, papaya, apple, or pineapple. And for dinner, the options are vegetable soup and a protein; salad plus a protein; or miso soup, cooked vegetables, and a protein.

At the 2020 ACR annual meeting, Roxana Coras, MD, presented the positive findings of an open-label, pilot study of the ITIS diet in which 17 patients with active RA involving at least three tender and three swollen joints adopted the diet for 2 weeks . The ITIS diet turned out to be not too much of a stretch for Southern California RA patients interested in dietary complementary and alternative medicine. Many had already adopted some elements of the anti-inflammatory diet. Dietary adherence in the study was good, as monitored in food logs and by mass spectrometry metabolic profiling of fecal and plasma samples.

Eleven patients were categorized as responders to the anti-inflammatory diet as defined by at least a 50% improvement in pain scores from baseline to 2 weeks; six patients were nonresponders. In the overall study population, mean pain scores on a 0-10 visual analog scale improved from 3.9 to 2.45. Scores on the Clinical Disease Activity Index (CDAI) also improved significantly on the ITIS diet, from 29 to 12.7, reported Dr. Coras, a rheumatologist at the University of California, San Diego.

The mechanisms for the clinical improvement on the diet are under study. Significant differences in the gut microbiome and metabolome were seen between the responders and nonresponders. For example, Mollicutes were increased and Coriobacteriales decreased in clinical responders versus nonresponders. A significant increase in circulating levels of anti-inflammatory oxylipins was also seen in responders. Longer-term controlled studies of the ITIS diet are planned.

Biqi is big in China, gaining ground in the U.S.

Ayurvedic medicine in India and Chinese traditional herbal medicine have richly documented 4,500-year histories.

“It’s so common in my neck of the woods, where there are large Asian communities, for Chinese or Korean or Japanese or Indian medicines to be combined with our medicines. And if you don’t ask about them, you’re never going to find out what these patients are taking,” Dr. Troum said.

If they’re taking Biqi capsules, readily available on the Internet, be advised that there is randomized trial evidence to show that they’re using an efficacious and safe herbal medicine for RA. In China, the combination of Biqi capsules and a conventional disease-modifying antirheumatic drug such as methotrexate is now widely used for treatment of RA. And at the 2019 ACR annual meeting, Runyue Huang, MD, of Guangzhou University of Chinese Medicine, presented the results of a 24-week, randomized, multicenter, open-label clinical trial in which 70 RA patients were assigned to methotrexate plus a 1.2-g Biqi capsule twice daily or to methotrexate plus leflunomide (Arava) at 20 mg/day. The primary outcome – achievement of a 20% improvement in the ACR criteria, or ACR20 response, at week 24 – was achieved in 77% of the Biqi group, not significantly different from the 83% rate in the comparator group. However, the Biqi plus methotrexate group had significantly fewer adverse events and the combination was better tolerated than was leflunomide plus methotrexate.

In addition, a systematic review of earlier clinical trials concluded that Biqi in combination with methotrexate was more effective and had fewer adverse events than methotrexate alone.

“Biqi capsule with methotrexate appears to be a promising combination for RA if you can rest assured that what’s found in the Biqi capsule is exactly what they say. And that’s the main issue: You don’t really know what you’re getting unless it’s in a trial,” Dr. Troum said.

American RA patients embrace turmeric

Turmeric has played a prominent role in Ayurvedic medicine for millenia. The most medicinally important component of turmeric root is curcumin, which has potent anti-inflammatory and antioxidant properties. Americans with RA have gotten on the bandwagon, as demonstrated in a survey of 291 patients with RA or psoriatic arthritis presented at ACR 2020 by investigators from the University of Central Florida, Orlando. Among the respondents, 37% reported having taken curcumin, with no predilection based upon age, gender, or diagnosis. Fifty-nine percent took their curcumin in the form of capsules, with the rest took it as an oil or powder. Fifty-four percent got their curcumin at a local store.

Thirty-six percent of curcumin users reported improvement in pain after going on the herbal supplement. Twenty-five percent reported reduced swelling, 23% had less stiffness, and 16% reported improvement in fatigue. Patients taking 200-1,000 mg/day reported significantly greater improvement in symptoms than that of those taking less than 200 mg/day. Onset of benefits was slow: Patients on curcumin for a year or longer reported greater symptomatic improvement than did those on the supplement for less time.

Asked what he recommends to his RA patients who express interest in supplements aimed at achieving symptomatic improvement, Dr. Troum replied that he’s comfortable suggesting curcumin capsules at 500 mg twice daily, which should be labeled as containing black pepper extract to aid in absorption. He also recommends fish oil both for its cardioprotective benefits and because of randomized trial evidence that it enhances the chances of achieving ACR remission in patients on conventional disease-modifying antirheumatic drugs.
 

What about osteoarthritis?

Investigators with the National Institutes of Health–sponsored Osteoarthritis Initiative found in an analysis of the dietary patterns of 2,757 patients with mild to moderate knee OA who were followed annually for 6 years that participants could be grouped into two broad categories: Those who consumed what was termed the prudent diet, with high intake of fruits and vegetables, legumes, fish, and whole grains; and fans of the Western diet, characterized by lots of red meat, refined grains, and liberal consumption of French fries. Knee symptoms increased over time in dose-response fashion with greater adherence to the Western diet and decreased with higher prudent diet scores.

Also at ACR 2019, Australian investigators presented the results of the double-blind CurKOA trial, in which 70 participants with knee OA and moderate baseline effusion/synovitis by ultrasound were randomized to take a capsule containing 500 mg of turmeric root extract or identical placebo twice daily for 12 weeks. The group on turmeric plant extract experienced 9.11-mm greater reduction in knee pain on a 0- to 100-mm visual analog scale than did controls, which translates to a moderate standard effect size deemed by investigators to be “greater than other conventional pharmacologic therapies.” Overall, 63% of the turmeric group achieved a treatment response by OARSI-OMERACT criteria, a significantly better outcome than the 38% rate in controls. However, there was no significant between-group difference in knee structural measures as assessed by MRI in this relatively brief trial.

Anne M. Stevens, MD, PhD, senior director of immunology translational medicine at Janssen Pharmaceuticals and a pediatric rheumatologist at Seattle Children’s Hospital, rose from the audience to share that she recommends that her patients on high-dose curcumin not take NSAIDs because the two share a similar mechanism of action involving COX-2 inhibition, and the combination might therefore increase bleeding risk. But Dr. Troum said he hasn’t seen any increase in bleeding in his patients on both agents.

Dr. Troum has financial relationships with numerous pharmaceutical companies, but reported having no financial conflicts of interest regarding his presentation.
 

[email protected]

Patients with rheumatoid arthritis are often eager to try dietary interventions in an effort to improve their symptoms. For guidance, they turn to their rheumatologists, who typically can offer little in terms of concrete evidence-based recommendations. That’s because their training didn’t emphasize the role of nutrients in rheumatic diseases, the scientific evidence has historically been sketchy, and the topic of diet and disease is rife with fad diets, inflated Internet claims, and hucksterism.

Bruce Jancin/MDedge News

But that’s changing. Indeed, recent annual meetings of the American College of Rheumatology have featured randomized, controlled trials that bring welcome rigor to the field and provide findings of practical interest to clinicians and their patients, Orrin M. Troum, MD, said at the 2021 Rheumatology Winter Clinical Symposium.

He highlighted some of this work, including positive randomized trials of the dietary supplements Biqi – a traditional Chinese herbal medicine – as well as turmeric, along with reported progress in efforts to design a palatable anti-inflammatory diet that favorably alters the gut microbiome and systemic metabolome while improving clinical outcomes in patients with RA.

Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica, described a typical patient encounter in his clinic that appeared to resonate with his audience from throughout the country: “You can tell people to take another medicine and they’ll start shaking their head no before you’re finished. But when you say there are natural supplements that can help you, they’re saying ‘Yes!’ ”
 

RA improvement on an ITIS diet

Many physicians recommend a Mediterranean-style diet, first popularized in the landmark Seven Countries Study launched by the late Dr. Ancel Keys. This familiar plant-based regimen emphasizes liberal consumption of extra-virgin olive oil, legumes, fruits and vegetables, whole grains, fish, nuts, and moderate alcohol intake, with very limited intake of red and processed meats, refined grains, and sugar. There is strong evidence that the Mediterranean diet is cardioprotective, which is relevant to patients with RA since they are known to be at elevated cardiovascular risk.

However, investigators at the University of California, San Diego, became convinced that the Mediterranean diet is lacking in key anti-inflammatory ingredients from other parts of the world. These include ginger, green tea, black pepper, turmeric, miso, flax seeds, and tahini, all of which are backed by evidence – from animal models and/or interventional diet studies in patients – that suggests beneficial effects in pain and joint swelling in RA. The researchers also suspected that certain vegetables embraced in the Mediterranean diet – notably eggplant, tomatoes, and potatoes – might be problematic for RA patients because they contain solanine, thought to increase intestinal permeability, which might have arthritogenic effects on the gut microbiome.

The investigators set out to develop an anti-inflammatory diet they call the ITIS diet, essentially tweaking the Mediterranean-style diet by incorporating these additions and subtractions. Importantly, they designed the ITIS diet in conjunction with a multiracial local group of RA patients strongly enthusiastic about the potential for dietary interventions aimed at improving their symptoms. The patients provided feedback that enabled the investigators to fine-tune the anti-inflammatory diet so as to boost palatability and acceptance.

As an illustrative example of the ITIS diet, a typical day might start off with a homemade smoothie of parsley, pineapple, strawberries, and water, followed by a breakfast consisting of one or two corn tortillas spread with avocado, linseed oil, and sesame seeds, accompanied by green tea. Following a mid-morning snack of plain Greek-style yogurt, lunch might be a choice of a large salad, legumes with vegetables, or whole grains with vegetables. For the afternoon snack: four walnuts plus mango, banana, pear, papaya, apple, or pineapple. And for dinner, the options are vegetable soup and a protein; salad plus a protein; or miso soup, cooked vegetables, and a protein.

At the 2020 ACR annual meeting, Roxana Coras, MD, presented the positive findings of an open-label, pilot study of the ITIS diet in which 17 patients with active RA involving at least three tender and three swollen joints adopted the diet for 2 weeks . The ITIS diet turned out to be not too much of a stretch for Southern California RA patients interested in dietary complementary and alternative medicine. Many had already adopted some elements of the anti-inflammatory diet. Dietary adherence in the study was good, as monitored in food logs and by mass spectrometry metabolic profiling of fecal and plasma samples.

Eleven patients were categorized as responders to the anti-inflammatory diet as defined by at least a 50% improvement in pain scores from baseline to 2 weeks; six patients were nonresponders. In the overall study population, mean pain scores on a 0-10 visual analog scale improved from 3.9 to 2.45. Scores on the Clinical Disease Activity Index (CDAI) also improved significantly on the ITIS diet, from 29 to 12.7, reported Dr. Coras, a rheumatologist at the University of California, San Diego.

The mechanisms for the clinical improvement on the diet are under study. Significant differences in the gut microbiome and metabolome were seen between the responders and nonresponders. For example, Mollicutes were increased and Coriobacteriales decreased in clinical responders versus nonresponders. A significant increase in circulating levels of anti-inflammatory oxylipins was also seen in responders. Longer-term controlled studies of the ITIS diet are planned.

Biqi is big in China, gaining ground in the U.S.

Ayurvedic medicine in India and Chinese traditional herbal medicine have richly documented 4,500-year histories.

“It’s so common in my neck of the woods, where there are large Asian communities, for Chinese or Korean or Japanese or Indian medicines to be combined with our medicines. And if you don’t ask about them, you’re never going to find out what these patients are taking,” Dr. Troum said.

If they’re taking Biqi capsules, readily available on the Internet, be advised that there is randomized trial evidence to show that they’re using an efficacious and safe herbal medicine for RA. In China, the combination of Biqi capsules and a conventional disease-modifying antirheumatic drug such as methotrexate is now widely used for treatment of RA. And at the 2019 ACR annual meeting, Runyue Huang, MD, of Guangzhou University of Chinese Medicine, presented the results of a 24-week, randomized, multicenter, open-label clinical trial in which 70 RA patients were assigned to methotrexate plus a 1.2-g Biqi capsule twice daily or to methotrexate plus leflunomide (Arava) at 20 mg/day. The primary outcome – achievement of a 20% improvement in the ACR criteria, or ACR20 response, at week 24 – was achieved in 77% of the Biqi group, not significantly different from the 83% rate in the comparator group. However, the Biqi plus methotrexate group had significantly fewer adverse events and the combination was better tolerated than was leflunomide plus methotrexate.

In addition, a systematic review of earlier clinical trials concluded that Biqi in combination with methotrexate was more effective and had fewer adverse events than methotrexate alone.

“Biqi capsule with methotrexate appears to be a promising combination for RA if you can rest assured that what’s found in the Biqi capsule is exactly what they say. And that’s the main issue: You don’t really know what you’re getting unless it’s in a trial,” Dr. Troum said.

American RA patients embrace turmeric

Turmeric has played a prominent role in Ayurvedic medicine for millenia. The most medicinally important component of turmeric root is curcumin, which has potent anti-inflammatory and antioxidant properties. Americans with RA have gotten on the bandwagon, as demonstrated in a survey of 291 patients with RA or psoriatic arthritis presented at ACR 2020 by investigators from the University of Central Florida, Orlando. Among the respondents, 37% reported having taken curcumin, with no predilection based upon age, gender, or diagnosis. Fifty-nine percent took their curcumin in the form of capsules, with the rest took it as an oil or powder. Fifty-four percent got their curcumin at a local store.

Thirty-six percent of curcumin users reported improvement in pain after going on the herbal supplement. Twenty-five percent reported reduced swelling, 23% had less stiffness, and 16% reported improvement in fatigue. Patients taking 200-1,000 mg/day reported significantly greater improvement in symptoms than that of those taking less than 200 mg/day. Onset of benefits was slow: Patients on curcumin for a year or longer reported greater symptomatic improvement than did those on the supplement for less time.

Asked what he recommends to his RA patients who express interest in supplements aimed at achieving symptomatic improvement, Dr. Troum replied that he’s comfortable suggesting curcumin capsules at 500 mg twice daily, which should be labeled as containing black pepper extract to aid in absorption. He also recommends fish oil both for its cardioprotective benefits and because of randomized trial evidence that it enhances the chances of achieving ACR remission in patients on conventional disease-modifying antirheumatic drugs.
 

What about osteoarthritis?

Investigators with the National Institutes of Health–sponsored Osteoarthritis Initiative found in an analysis of the dietary patterns of 2,757 patients with mild to moderate knee OA who were followed annually for 6 years that participants could be grouped into two broad categories: Those who consumed what was termed the prudent diet, with high intake of fruits and vegetables, legumes, fish, and whole grains; and fans of the Western diet, characterized by lots of red meat, refined grains, and liberal consumption of French fries. Knee symptoms increased over time in dose-response fashion with greater adherence to the Western diet and decreased with higher prudent diet scores.

Also at ACR 2019, Australian investigators presented the results of the double-blind CurKOA trial, in which 70 participants with knee OA and moderate baseline effusion/synovitis by ultrasound were randomized to take a capsule containing 500 mg of turmeric root extract or identical placebo twice daily for 12 weeks. The group on turmeric plant extract experienced 9.11-mm greater reduction in knee pain on a 0- to 100-mm visual analog scale than did controls, which translates to a moderate standard effect size deemed by investigators to be “greater than other conventional pharmacologic therapies.” Overall, 63% of the turmeric group achieved a treatment response by OARSI-OMERACT criteria, a significantly better outcome than the 38% rate in controls. However, there was no significant between-group difference in knee structural measures as assessed by MRI in this relatively brief trial.

Anne M. Stevens, MD, PhD, senior director of immunology translational medicine at Janssen Pharmaceuticals and a pediatric rheumatologist at Seattle Children’s Hospital, rose from the audience to share that she recommends that her patients on high-dose curcumin not take NSAIDs because the two share a similar mechanism of action involving COX-2 inhibition, and the combination might therefore increase bleeding risk. But Dr. Troum said he hasn’t seen any increase in bleeding in his patients on both agents.

Dr. Troum has financial relationships with numerous pharmaceutical companies, but reported having no financial conflicts of interest regarding his presentation.
 

[email protected]

Pursuing fellowship training is often financially costly in terms of lifetime earnings, compared with starting a career as a general pediatrician immediately after residency, a report suggests.

Researchers found that most pediatric subspecialists – including those practicing neurology, pulmonology, and adolescent medicine – do not see a financial return from additional training because of the delays in receiving increased compensation and the repayment of educational debt.

“Most pediatric subspecialists don’t experience a relative increase in compensation after training compared to a general pediatrician, so there isn’t a financial benefit to additional training,” lead author Eva Catenaccio, MD, from the division of pediatric neurology, department of neurology, Johns Hopkins University, Baltimore, told this news organization.

The findings, published online March 8 in Pediatrics, contribute to the ongoing debate about the length of pediatric fellowship training programs. The data also provide evidence for the potential effect of a pediatric subspecialty loan repayment program.
 

Pediatric subspecialty training rarely pays off

However, not all practitioners in pediatric subspecialties would find themselves in the red relative to their generalist peers. Three subspecialties had a positive financial return: cardiology, critical care, and neonatology. Dr. Catenaccio explained that this may be because these subspecialties tend to be “inpatient procedure oriented, which are often more [lucrative] than outpatient cognitive–oriented subspecialties, such as pediatric infectious diseases, endocrinology, or adolescent medicine.”

Enrolling in a pediatric fellowship program resulted in lifetime financial returns that ranged from an increase of $852,129 for cardiology, relative to general pediatrics, to a loss of $1,594,366 for adolescent medicine, researchers found.

For the study, researchers calculated the financial returns of 15 pediatric subspecialties – emergency medicine, neurology, cardiology, critical care, neonatology, hematology and oncology, pulmonology, hospitalist medicine, allergy and immunology, gastroenterology, rheumatology, nephrology, adolescent medicine, infectious diseases, and endocrinology – in comparison with returns of private practice general pediatrics on the basis of 2018-2019 data on fellowship stipends, compensation, and educational debt.

They obtained most of the data from the Association of American Medical Colleges Survey of Resident/Fellow Stipends and Benefits, AAMC’s annual Medical School Faculty Salary Report, and the AAMC Medical School Graduation Questionnaire.

Richard Mink, MD, department of pediatrics, Harbor-UCLA Medical Center, Torrance, Calif., noted that it would have been helpful to have also compared the lifetime earnings of practitioners in pediatric subspecialties to academic general pediatricians and not just those in private practice.
 

The financial gap has worsened

To better understand which aspects of fellowship training have the greatest effect on lifetime compensation, Dr. Catenaccio and colleagues evaluated the potential effects of shortening fellowship length, eliminating school debt, and implementing a federal loan repayment plan. These changes enhanced the returns of cardiology, critical care, and neonatology – subspecialties that had already seen financial returns before these changes – and resulted in a positive financial return for emergency medicine.

The changes also narrowed the financial gap between subspecialties and general pediatrics. However, the remaining subspecialties still earned less than private practice pediatrics.

The new study is an update to a 2011 report, which reflected 2007-2008 data for 11 subspecialties. This time around, the researchers included the subspecialty of hospitalist medicine, which was approved as a board-certified subspecialty by the American Board of Pediatrics in 2014, as well as neurology, allergy and immunology, and adolescent medicine.

“I was most surprised that the additional pediatric subspecialties we included since the 2011 report followed the same general trend, with pediatric subspecialty training having a lower lifetime earning potential than general pediatrics,” Dr. Catenaccio said.

Comparing results from the two study periods showed that the financial gap between general pediatrics and subspecialty pediatrics worsened over time. For example, the financial return for pediatric endocrinology decreased an additional $500,000 between 2007 and 2018.

The researchers believe a combination of increased educational debt burden, slow growth in compensation, and changing interest rates over time have caused the financial differences between general pediatrics and subspecialty pediatrics to become more pronounced.
 

‘Pediatric subspecialty training is worth it!’

Despite the financial gaps, Dr. Catenaccio and colleagues say pediatric subspecialty training is still worthwhile but that policymakers should address these financial differences to help guide workforce distribution in a way that meets the needs of patients.

“I think pediatric subspecialty training is worth it,” said Dr. Catenaccio, who’s pursuing pediatric subspecialty training. “There are so many factors that go into choosing a specialty or subspecialty in medicine, including the desire to care for a particular patient population, interest in certain diseases or organ systems, lifestyle considerations, and research opportunities.”

But it’s also important for trainees to be aware of economic considerations in their decision-making.

Dr. Mink, who wrote an accompanying commentary, agrees that young clinicians should not make career decisions on the basis of metrics such as lifetime earning measures.

“I think people who go into pediatrics have decided that money is not the driving force,” said Dr. Mink. He noted that pediatricians are usually not paid well, compared with other specialists. “To me the important thing is you have to like what you’re doing.”

A 2020 study found that trainees who chose a career in pediatric pulmonology, a subspecialty, said that financial considerations were not the driving factor in their decision-making. Nevertheless, Dr. Mink also believes young clinicians should take into account their educational debt.

The further widening of the financial gap between general pediatrics and pediatric subspecialties could lead to shortages in the pediatric subspecialty workforce.

The authors and Dr. Mink have disclosed no relevant financial relationships.

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

Pursuing fellowship training is often financially costly in terms of lifetime earnings, compared with starting a career as a general pediatrician immediately after residency, a report suggests.

Researchers found that most pediatric subspecialists – including those practicing neurology, pulmonology, and adolescent medicine – do not see a financial return from additional training because of the delays in receiving increased compensation and the repayment of educational debt.

“Most pediatric subspecialists don’t experience a relative increase in compensation after training compared to a general pediatrician, so there isn’t a financial benefit to additional training,” lead author Eva Catenaccio, MD, from the division of pediatric neurology, department of neurology, Johns Hopkins University, Baltimore, told this news organization.

The findings, published online March 8 in Pediatrics, contribute to the ongoing debate about the length of pediatric fellowship training programs. The data also provide evidence for the potential effect of a pediatric subspecialty loan repayment program.
 

Pediatric subspecialty training rarely pays off

However, not all practitioners in pediatric subspecialties would find themselves in the red relative to their generalist peers. Three subspecialties had a positive financial return: cardiology, critical care, and neonatology. Dr. Catenaccio explained that this may be because these subspecialties tend to be “inpatient procedure oriented, which are often more [lucrative] than outpatient cognitive–oriented subspecialties, such as pediatric infectious diseases, endocrinology, or adolescent medicine.”

Enrolling in a pediatric fellowship program resulted in lifetime financial returns that ranged from an increase of $852,129 for cardiology, relative to general pediatrics, to a loss of $1,594,366 for adolescent medicine, researchers found.

For the study, researchers calculated the financial returns of 15 pediatric subspecialties – emergency medicine, neurology, cardiology, critical care, neonatology, hematology and oncology, pulmonology, hospitalist medicine, allergy and immunology, gastroenterology, rheumatology, nephrology, adolescent medicine, infectious diseases, and endocrinology – in comparison with returns of private practice general pediatrics on the basis of 2018-2019 data on fellowship stipends, compensation, and educational debt.

They obtained most of the data from the Association of American Medical Colleges Survey of Resident/Fellow Stipends and Benefits, AAMC’s annual Medical School Faculty Salary Report, and the AAMC Medical School Graduation Questionnaire.

Richard Mink, MD, department of pediatrics, Harbor-UCLA Medical Center, Torrance, Calif., noted that it would have been helpful to have also compared the lifetime earnings of practitioners in pediatric subspecialties to academic general pediatricians and not just those in private practice.
 

The financial gap has worsened

To better understand which aspects of fellowship training have the greatest effect on lifetime compensation, Dr. Catenaccio and colleagues evaluated the potential effects of shortening fellowship length, eliminating school debt, and implementing a federal loan repayment plan. These changes enhanced the returns of cardiology, critical care, and neonatology – subspecialties that had already seen financial returns before these changes – and resulted in a positive financial return for emergency medicine.

The changes also narrowed the financial gap between subspecialties and general pediatrics. However, the remaining subspecialties still earned less than private practice pediatrics.

The new study is an update to a 2011 report, which reflected 2007-2008 data for 11 subspecialties. This time around, the researchers included the subspecialty of hospitalist medicine, which was approved as a board-certified subspecialty by the American Board of Pediatrics in 2014, as well as neurology, allergy and immunology, and adolescent medicine.

“I was most surprised that the additional pediatric subspecialties we included since the 2011 report followed the same general trend, with pediatric subspecialty training having a lower lifetime earning potential than general pediatrics,” Dr. Catenaccio said.

Comparing results from the two study periods showed that the financial gap between general pediatrics and subspecialty pediatrics worsened over time. For example, the financial return for pediatric endocrinology decreased an additional $500,000 between 2007 and 2018.

The researchers believe a combination of increased educational debt burden, slow growth in compensation, and changing interest rates over time have caused the financial differences between general pediatrics and subspecialty pediatrics to become more pronounced.
 

‘Pediatric subspecialty training is worth it!’

Despite the financial gaps, Dr. Catenaccio and colleagues say pediatric subspecialty training is still worthwhile but that policymakers should address these financial differences to help guide workforce distribution in a way that meets the needs of patients.

“I think pediatric subspecialty training is worth it,” said Dr. Catenaccio, who’s pursuing pediatric subspecialty training. “There are so many factors that go into choosing a specialty or subspecialty in medicine, including the desire to care for a particular patient population, interest in certain diseases or organ systems, lifestyle considerations, and research opportunities.”

But it’s also important for trainees to be aware of economic considerations in their decision-making.

Dr. Mink, who wrote an accompanying commentary, agrees that young clinicians should not make career decisions on the basis of metrics such as lifetime earning measures.

“I think people who go into pediatrics have decided that money is not the driving force,” said Dr. Mink. He noted that pediatricians are usually not paid well, compared with other specialists. “To me the important thing is you have to like what you’re doing.”

A 2020 study found that trainees who chose a career in pediatric pulmonology, a subspecialty, said that financial considerations were not the driving factor in their decision-making. Nevertheless, Dr. Mink also believes young clinicians should take into account their educational debt.

The further widening of the financial gap between general pediatrics and pediatric subspecialties could lead to shortages in the pediatric subspecialty workforce.

The authors and Dr. Mink have disclosed no relevant financial relationships.

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

Pursuing fellowship training is often financially costly in terms of lifetime earnings, compared with starting a career as a general pediatrician immediately after residency, a report suggests.

Researchers found that most pediatric subspecialists – including those practicing neurology, pulmonology, and adolescent medicine – do not see a financial return from additional training because of the delays in receiving increased compensation and the repayment of educational debt.

“Most pediatric subspecialists don’t experience a relative increase in compensation after training compared to a general pediatrician, so there isn’t a financial benefit to additional training,” lead author Eva Catenaccio, MD, from the division of pediatric neurology, department of neurology, Johns Hopkins University, Baltimore, told this news organization.

The findings, published online March 8 in Pediatrics, contribute to the ongoing debate about the length of pediatric fellowship training programs. The data also provide evidence for the potential effect of a pediatric subspecialty loan repayment program.
 

Pediatric subspecialty training rarely pays off

However, not all practitioners in pediatric subspecialties would find themselves in the red relative to their generalist peers. Three subspecialties had a positive financial return: cardiology, critical care, and neonatology. Dr. Catenaccio explained that this may be because these subspecialties tend to be “inpatient procedure oriented, which are often more [lucrative] than outpatient cognitive–oriented subspecialties, such as pediatric infectious diseases, endocrinology, or adolescent medicine.”

Enrolling in a pediatric fellowship program resulted in lifetime financial returns that ranged from an increase of $852,129 for cardiology, relative to general pediatrics, to a loss of $1,594,366 for adolescent medicine, researchers found.

For the study, researchers calculated the financial returns of 15 pediatric subspecialties – emergency medicine, neurology, cardiology, critical care, neonatology, hematology and oncology, pulmonology, hospitalist medicine, allergy and immunology, gastroenterology, rheumatology, nephrology, adolescent medicine, infectious diseases, and endocrinology – in comparison with returns of private practice general pediatrics on the basis of 2018-2019 data on fellowship stipends, compensation, and educational debt.

They obtained most of the data from the Association of American Medical Colleges Survey of Resident/Fellow Stipends and Benefits, AAMC’s annual Medical School Faculty Salary Report, and the AAMC Medical School Graduation Questionnaire.

Richard Mink, MD, department of pediatrics, Harbor-UCLA Medical Center, Torrance, Calif., noted that it would have been helpful to have also compared the lifetime earnings of practitioners in pediatric subspecialties to academic general pediatricians and not just those in private practice.
 

The financial gap has worsened

To better understand which aspects of fellowship training have the greatest effect on lifetime compensation, Dr. Catenaccio and colleagues evaluated the potential effects of shortening fellowship length, eliminating school debt, and implementing a federal loan repayment plan. These changes enhanced the returns of cardiology, critical care, and neonatology – subspecialties that had already seen financial returns before these changes – and resulted in a positive financial return for emergency medicine.

The changes also narrowed the financial gap between subspecialties and general pediatrics. However, the remaining subspecialties still earned less than private practice pediatrics.

The new study is an update to a 2011 report, which reflected 2007-2008 data for 11 subspecialties. This time around, the researchers included the subspecialty of hospitalist medicine, which was approved as a board-certified subspecialty by the American Board of Pediatrics in 2014, as well as neurology, allergy and immunology, and adolescent medicine.

“I was most surprised that the additional pediatric subspecialties we included since the 2011 report followed the same general trend, with pediatric subspecialty training having a lower lifetime earning potential than general pediatrics,” Dr. Catenaccio said.

Comparing results from the two study periods showed that the financial gap between general pediatrics and subspecialty pediatrics worsened over time. For example, the financial return for pediatric endocrinology decreased an additional $500,000 between 2007 and 2018.

The researchers believe a combination of increased educational debt burden, slow growth in compensation, and changing interest rates over time have caused the financial differences between general pediatrics and subspecialty pediatrics to become more pronounced.
 

‘Pediatric subspecialty training is worth it!’

Despite the financial gaps, Dr. Catenaccio and colleagues say pediatric subspecialty training is still worthwhile but that policymakers should address these financial differences to help guide workforce distribution in a way that meets the needs of patients.

“I think pediatric subspecialty training is worth it,” said Dr. Catenaccio, who’s pursuing pediatric subspecialty training. “There are so many factors that go into choosing a specialty or subspecialty in medicine, including the desire to care for a particular patient population, interest in certain diseases or organ systems, lifestyle considerations, and research opportunities.”

But it’s also important for trainees to be aware of economic considerations in their decision-making.

Dr. Mink, who wrote an accompanying commentary, agrees that young clinicians should not make career decisions on the basis of metrics such as lifetime earning measures.

“I think people who go into pediatrics have decided that money is not the driving force,” said Dr. Mink. He noted that pediatricians are usually not paid well, compared with other specialists. “To me the important thing is you have to like what you’re doing.”

A 2020 study found that trainees who chose a career in pediatric pulmonology, a subspecialty, said that financial considerations were not the driving factor in their decision-making. Nevertheless, Dr. Mink also believes young clinicians should take into account their educational debt.

The further widening of the financial gap between general pediatrics and pediatric subspecialties could lead to shortages in the pediatric subspecialty workforce.

The authors and Dr. Mink have disclosed no relevant financial relationships.

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

Only about 30% or fewer of patients with psoriatic arthritis (PsA) on therapy achieve disease remission by any definition. One reason for this may be inadequate attention to common comorbid conditions, Alexis Ogdie, MD, MSCE, declared at the 2021 Rheumatology Winter Clinical Symposium.

Courtesy Dr. Alexis Ogdie

“I believe that addressing off-target aspects of disease is really important to improving the patient experience of their disease. We might need to target these directly in order to improve outcomes,” said Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia, who coauthored the current American College of Rheumatology/National Psoriasis Foundation PsA guidelines.

Since rheumatologists are by now well informed about the increased cardiovascular risk associated with PsA, she focused on two common comorbidities that get less attention, both of which are associated with worse clinical outcomes in PsA: obesity and mental health issues.
 

Anxiety and depression

Dr. Ogdie was first author of a large, population-based, longitudinal cohort study of cause-specific mortality in 8,706 U.K. patients with PsA, 41,752 with RA, and more than 81,000 controls. Particularly striking was the finding of elevated mortality because of suicide in the rheumatic disease patients: a 203% increased risk in the PsA population, compared with the general population, and a 147% greater risk in patients with RA.

Overall, 30%-40% of PsA patients have comorbid depression and/or anxiety.

“That’s pretty striking. It’s also true for rheumatoid arthritis and axial spondyloarthritis. And if you’re depressed, you’re much less likely to respond to therapy in the way that we are measuring response to therapy,” Dr. Ogdie said.

Her approach to screening for depression and anxiety in her PsA patients, and indeed in all her other patients, is to begin by normalizing the topic, explaining to them that these affective disorders are common among patients with these disorders. She lets her patients know they can talk to her about it. And she informs them that, while effective treatment of their rheumatic disease may improve their depression or anxiety, managing those is also important for improving their disease. Additionally, understanding whether depression is present is important prior to prescribing certain medications. Apremilast (Otezla), for example, can worsen preexisting depression.

“Ask about signs and symptoms of depression,” Dr. Ogdie urged her colleagues. “I do this at every single visit in my review of symptoms. This is one I don’t skip. I ask: ‘Do you have any symptoms of depression or anxiety?’ ”

Structured evidence-based screening tools, many of which are well suited for completion during a patient’s preappointment check-in survey, include the Patient Health Questionnaire–2, the PHQ-9, the Patient-Reported Outcomes Measure Information System–10, PROMIS–Depression, and Routine Assessment of Patient Index Data 3.

“I also really like the PROMIS-29. It covers many domains of interest: depression and anxiety, sleep, fatigue, pain, physical function. It gives a lot of information about what’s going on in a patient’s life right now,” according to the rheumatologist.

The main thing is to regularly screen for anxiety and depression and then refer symptomatic patients for further assessment and treatment. This is not something that all rheumatologists have been trained to do.

Obesity

Dr. Ogdie was lead author of a national CORRONA Registry study which concluded that obese patients with PsA were only half as likely to achieve remission on a tumor necrosis factor (TNF) inhibitor, compared with nonobese patients. She believes the same holds true for all other types of therapy: Across the board, obesity is associated with a poor response. And obesity is much more common in PsA patients than the general population in every age group. Moreover, obesity is associated with risk factors for cardiovascular disease and is associated with fatty liver disease, two other major comorbid conditions in the PsA population.

The CORRONA Registry findings are supportive of an earlier Italian prospective, observational study of 135 obese and an equal number of normal-weight PsA patients, all of whom started on a TNF inhibitor and were followed for 24 months. In a multivariate-adjusted analysis, obesity was independently associated with a 390% higher risk of not achieving minimal disease activity.

The same Italian group subsequently conducted a prospective dietary intervention study in 138 overweight or obese patients with PsA starting anti-TNF therapy. A total of 59% of participants randomized to either of the two dietary interventions experienced at least a 5% weight loss at 6 months. The key study finding: Compared with the subjects with less than 5% weight loss, those with 5%-10% weight loss were 275% more likely to achieve minimal disease activity at 6 months, and in those with greater than 10% weight loss the likelihood of attaining minimal disease activity increased by 567%.

“We’re talking about a disease where treatments tested in clinical trials have odds ratios in the 1.2 range, compared with other therapies, so this is a really striking difference,” she observed.

Several studies have demonstrated that obesity in psoriasis patients is a risk factor for developing PsA. Recently, U.K. investigators took things a step further, reporting in a huge observational study that obese or overweight psoriasis patients who reduced their body mass index over a 10-year period had a corresponding reduction in the risk of developing PsA, compared with overweight or obese psoriasis patients whose BMI remained steady over the same period.

What’s needed now is access to programs to help patients with PsA lose weight. Health insurers are often unwilling to provide coverage. “We have a really tough time getting the patients in to see a nutritionist unless they’re willing to pay out of pocket,” Dr. Ogdie said.

Physical activity is an important element in successful weight loss. It also is recommended in practice guidelines for patients with inflammatory arthritis because of its salutary effects on disease activity scores, pain and stiffness, sleep, and quality of life. But a recent survey conducted by Dr. Ogdie and coworkers concluded that patients with PsA and other forms of inflammatory arthritis don’t receive much exercise guidance from their rheumatologists. About 60% of subjects were inactive. Those who were physically active typically engaged in aerobic exercise but were much less likely to do the other guideline-recommended forms of exercise, namely flexibility, balance, and resistance training. The patients’ report of low engagement of their physicians “suggests an opportunity for more prescriptive exercise discussions,” according to the investigators.

Diabetes, a critical risk factor for cardiovascular disease, occurs at an increased incidence in PsA. This was demonstrated in a U.K. cohort study coauthored by Dr. Ogdie. The study, which included nearly 4,200 individuals with PsA, concluded that they had a 43% greater incidence of diabetes than the general population in an analysis adjusted for body mass index, smoking, alcohol use, and demographics.

New-onset diabetes can be readily picked up by rheumatologists based upon the laboratory work they often order at patient office visits, or during their review of symptoms, she noted, and added that the U.S. Preventive Services Task Force recommends ordering a hemoglobin A1c test every 3 years.

Dr. Ogdie reported receiving research grants and/or consulting fees from numerous pharmaceutical companies. Her research is also funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, and the National Psoriasis Foundation.

[email protected]

Only about 30% or fewer of patients with psoriatic arthritis (PsA) on therapy achieve disease remission by any definition. One reason for this may be inadequate attention to common comorbid conditions, Alexis Ogdie, MD, MSCE, declared at the 2021 Rheumatology Winter Clinical Symposium.

Courtesy Dr. Alexis Ogdie

“I believe that addressing off-target aspects of disease is really important to improving the patient experience of their disease. We might need to target these directly in order to improve outcomes,” said Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia, who coauthored the current American College of Rheumatology/National Psoriasis Foundation PsA guidelines.

Since rheumatologists are by now well informed about the increased cardiovascular risk associated with PsA, she focused on two common comorbidities that get less attention, both of which are associated with worse clinical outcomes in PsA: obesity and mental health issues.
 

Anxiety and depression

Dr. Ogdie was first author of a large, population-based, longitudinal cohort study of cause-specific mortality in 8,706 U.K. patients with PsA, 41,752 with RA, and more than 81,000 controls. Particularly striking was the finding of elevated mortality because of suicide in the rheumatic disease patients: a 203% increased risk in the PsA population, compared with the general population, and a 147% greater risk in patients with RA.

Overall, 30%-40% of PsA patients have comorbid depression and/or anxiety.

“That’s pretty striking. It’s also true for rheumatoid arthritis and axial spondyloarthritis. And if you’re depressed, you’re much less likely to respond to therapy in the way that we are measuring response to therapy,” Dr. Ogdie said.

Her approach to screening for depression and anxiety in her PsA patients, and indeed in all her other patients, is to begin by normalizing the topic, explaining to them that these affective disorders are common among patients with these disorders. She lets her patients know they can talk to her about it. And she informs them that, while effective treatment of their rheumatic disease may improve their depression or anxiety, managing those is also important for improving their disease. Additionally, understanding whether depression is present is important prior to prescribing certain medications. Apremilast (Otezla), for example, can worsen preexisting depression.

“Ask about signs and symptoms of depression,” Dr. Ogdie urged her colleagues. “I do this at every single visit in my review of symptoms. This is one I don’t skip. I ask: ‘Do you have any symptoms of depression or anxiety?’ ”

Structured evidence-based screening tools, many of which are well suited for completion during a patient’s preappointment check-in survey, include the Patient Health Questionnaire–2, the PHQ-9, the Patient-Reported Outcomes Measure Information System–10, PROMIS–Depression, and Routine Assessment of Patient Index Data 3.

“I also really like the PROMIS-29. It covers many domains of interest: depression and anxiety, sleep, fatigue, pain, physical function. It gives a lot of information about what’s going on in a patient’s life right now,” according to the rheumatologist.

The main thing is to regularly screen for anxiety and depression and then refer symptomatic patients for further assessment and treatment. This is not something that all rheumatologists have been trained to do.

Obesity

Dr. Ogdie was lead author of a national CORRONA Registry study which concluded that obese patients with PsA were only half as likely to achieve remission on a tumor necrosis factor (TNF) inhibitor, compared with nonobese patients. She believes the same holds true for all other types of therapy: Across the board, obesity is associated with a poor response. And obesity is much more common in PsA patients than the general population in every age group. Moreover, obesity is associated with risk factors for cardiovascular disease and is associated with fatty liver disease, two other major comorbid conditions in the PsA population.

The CORRONA Registry findings are supportive of an earlier Italian prospective, observational study of 135 obese and an equal number of normal-weight PsA patients, all of whom started on a TNF inhibitor and were followed for 24 months. In a multivariate-adjusted analysis, obesity was independently associated with a 390% higher risk of not achieving minimal disease activity.

The same Italian group subsequently conducted a prospective dietary intervention study in 138 overweight or obese patients with PsA starting anti-TNF therapy. A total of 59% of participants randomized to either of the two dietary interventions experienced at least a 5% weight loss at 6 months. The key study finding: Compared with the subjects with less than 5% weight loss, those with 5%-10% weight loss were 275% more likely to achieve minimal disease activity at 6 months, and in those with greater than 10% weight loss the likelihood of attaining minimal disease activity increased by 567%.

“We’re talking about a disease where treatments tested in clinical trials have odds ratios in the 1.2 range, compared with other therapies, so this is a really striking difference,” she observed.

Several studies have demonstrated that obesity in psoriasis patients is a risk factor for developing PsA. Recently, U.K. investigators took things a step further, reporting in a huge observational study that obese or overweight psoriasis patients who reduced their body mass index over a 10-year period had a corresponding reduction in the risk of developing PsA, compared with overweight or obese psoriasis patients whose BMI remained steady over the same period.

What’s needed now is access to programs to help patients with PsA lose weight. Health insurers are often unwilling to provide coverage. “We have a really tough time getting the patients in to see a nutritionist unless they’re willing to pay out of pocket,” Dr. Ogdie said.

Physical activity is an important element in successful weight loss. It also is recommended in practice guidelines for patients with inflammatory arthritis because of its salutary effects on disease activity scores, pain and stiffness, sleep, and quality of life. But a recent survey conducted by Dr. Ogdie and coworkers concluded that patients with PsA and other forms of inflammatory arthritis don’t receive much exercise guidance from their rheumatologists. About 60% of subjects were inactive. Those who were physically active typically engaged in aerobic exercise but were much less likely to do the other guideline-recommended forms of exercise, namely flexibility, balance, and resistance training. The patients’ report of low engagement of their physicians “suggests an opportunity for more prescriptive exercise discussions,” according to the investigators.

Diabetes, a critical risk factor for cardiovascular disease, occurs at an increased incidence in PsA. This was demonstrated in a U.K. cohort study coauthored by Dr. Ogdie. The study, which included nearly 4,200 individuals with PsA, concluded that they had a 43% greater incidence of diabetes than the general population in an analysis adjusted for body mass index, smoking, alcohol use, and demographics.

New-onset diabetes can be readily picked up by rheumatologists based upon the laboratory work they often order at patient office visits, or during their review of symptoms, she noted, and added that the U.S. Preventive Services Task Force recommends ordering a hemoglobin A1c test every 3 years.

Dr. Ogdie reported receiving research grants and/or consulting fees from numerous pharmaceutical companies. Her research is also funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, and the National Psoriasis Foundation.

[email protected]

Only about 30% or fewer of patients with psoriatic arthritis (PsA) on therapy achieve disease remission by any definition. One reason for this may be inadequate attention to common comorbid conditions, Alexis Ogdie, MD, MSCE, declared at the 2021 Rheumatology Winter Clinical Symposium.

Courtesy Dr. Alexis Ogdie

“I believe that addressing off-target aspects of disease is really important to improving the patient experience of their disease. We might need to target these directly in order to improve outcomes,” said Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia, who coauthored the current American College of Rheumatology/National Psoriasis Foundation PsA guidelines.

Since rheumatologists are by now well informed about the increased cardiovascular risk associated with PsA, she focused on two common comorbidities that get less attention, both of which are associated with worse clinical outcomes in PsA: obesity and mental health issues.
 

Anxiety and depression

Dr. Ogdie was first author of a large, population-based, longitudinal cohort study of cause-specific mortality in 8,706 U.K. patients with PsA, 41,752 with RA, and more than 81,000 controls. Particularly striking was the finding of elevated mortality because of suicide in the rheumatic disease patients: a 203% increased risk in the PsA population, compared with the general population, and a 147% greater risk in patients with RA.

Overall, 30%-40% of PsA patients have comorbid depression and/or anxiety.

“That’s pretty striking. It’s also true for rheumatoid arthritis and axial spondyloarthritis. And if you’re depressed, you’re much less likely to respond to therapy in the way that we are measuring response to therapy,” Dr. Ogdie said.

Her approach to screening for depression and anxiety in her PsA patients, and indeed in all her other patients, is to begin by normalizing the topic, explaining to them that these affective disorders are common among patients with these disorders. She lets her patients know they can talk to her about it. And she informs them that, while effective treatment of their rheumatic disease may improve their depression or anxiety, managing those is also important for improving their disease. Additionally, understanding whether depression is present is important prior to prescribing certain medications. Apremilast (Otezla), for example, can worsen preexisting depression.

“Ask about signs and symptoms of depression,” Dr. Ogdie urged her colleagues. “I do this at every single visit in my review of symptoms. This is one I don’t skip. I ask: ‘Do you have any symptoms of depression or anxiety?’ ”

Structured evidence-based screening tools, many of which are well suited for completion during a patient’s preappointment check-in survey, include the Patient Health Questionnaire–2, the PHQ-9, the Patient-Reported Outcomes Measure Information System–10, PROMIS–Depression, and Routine Assessment of Patient Index Data 3.

“I also really like the PROMIS-29. It covers many domains of interest: depression and anxiety, sleep, fatigue, pain, physical function. It gives a lot of information about what’s going on in a patient’s life right now,” according to the rheumatologist.

The main thing is to regularly screen for anxiety and depression and then refer symptomatic patients for further assessment and treatment. This is not something that all rheumatologists have been trained to do.

Obesity

Dr. Ogdie was lead author of a national CORRONA Registry study which concluded that obese patients with PsA were only half as likely to achieve remission on a tumor necrosis factor (TNF) inhibitor, compared with nonobese patients. She believes the same holds true for all other types of therapy: Across the board, obesity is associated with a poor response. And obesity is much more common in PsA patients than the general population in every age group. Moreover, obesity is associated with risk factors for cardiovascular disease and is associated with fatty liver disease, two other major comorbid conditions in the PsA population.

The CORRONA Registry findings are supportive of an earlier Italian prospective, observational study of 135 obese and an equal number of normal-weight PsA patients, all of whom started on a TNF inhibitor and were followed for 24 months. In a multivariate-adjusted analysis, obesity was independently associated with a 390% higher risk of not achieving minimal disease activity.

The same Italian group subsequently conducted a prospective dietary intervention study in 138 overweight or obese patients with PsA starting anti-TNF therapy. A total of 59% of participants randomized to either of the two dietary interventions experienced at least a 5% weight loss at 6 months. The key study finding: Compared with the subjects with less than 5% weight loss, those with 5%-10% weight loss were 275% more likely to achieve minimal disease activity at 6 months, and in those with greater than 10% weight loss the likelihood of attaining minimal disease activity increased by 567%.

“We’re talking about a disease where treatments tested in clinical trials have odds ratios in the 1.2 range, compared with other therapies, so this is a really striking difference,” she observed.

Several studies have demonstrated that obesity in psoriasis patients is a risk factor for developing PsA. Recently, U.K. investigators took things a step further, reporting in a huge observational study that obese or overweight psoriasis patients who reduced their body mass index over a 10-year period had a corresponding reduction in the risk of developing PsA, compared with overweight or obese psoriasis patients whose BMI remained steady over the same period.

What’s needed now is access to programs to help patients with PsA lose weight. Health insurers are often unwilling to provide coverage. “We have a really tough time getting the patients in to see a nutritionist unless they’re willing to pay out of pocket,” Dr. Ogdie said.

Physical activity is an important element in successful weight loss. It also is recommended in practice guidelines for patients with inflammatory arthritis because of its salutary effects on disease activity scores, pain and stiffness, sleep, and quality of life. But a recent survey conducted by Dr. Ogdie and coworkers concluded that patients with PsA and other forms of inflammatory arthritis don’t receive much exercise guidance from their rheumatologists. About 60% of subjects were inactive. Those who were physically active typically engaged in aerobic exercise but were much less likely to do the other guideline-recommended forms of exercise, namely flexibility, balance, and resistance training. The patients’ report of low engagement of their physicians “suggests an opportunity for more prescriptive exercise discussions,” according to the investigators.

Diabetes, a critical risk factor for cardiovascular disease, occurs at an increased incidence in PsA. This was demonstrated in a U.K. cohort study coauthored by Dr. Ogdie. The study, which included nearly 4,200 individuals with PsA, concluded that they had a 43% greater incidence of diabetes than the general population in an analysis adjusted for body mass index, smoking, alcohol use, and demographics.

New-onset diabetes can be readily picked up by rheumatologists based upon the laboratory work they often order at patient office visits, or during their review of symptoms, she noted, and added that the U.S. Preventive Services Task Force recommends ordering a hemoglobin A1c test every 3 years.

Dr. Ogdie reported receiving research grants and/or consulting fees from numerous pharmaceutical companies. Her research is also funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, and the National Psoriasis Foundation.

[email protected]

Novel therapies have transformed the treatment of hemophilia in recent decades, but these new approaches also raise new challenges for clinicians who monitor joint health in persons with hemophilia, a specialist said.

“Patient-reported outcomes should be combined with other, more objective outcome measures for joint health monitoring, and joint ultrasound is a promising tool for objective joint health monitoring, although, due to its relatively recent introduction in clinical practice, we lack objective data and standardization,” said Roberta Gualtierotti, MD, PhD, from the Università Degli Studi of Milan.

She reviewed the challenges and approaches to monitoring joint health in persons with hemophilia during the annual congress of the European Association for Haemophilia and Allied Disorders.

Over the last decades the target of hemophilia treatment has shifted from prolonging survival to improving joint health and quality of life, and care has improved with the introduction of novel therapies such as extended half-life replacement products, nonreplacement therapies, and gene therapy, she noted.

However, “due to different pharmacodynamics and pharmacokinetics profiles, the currently available therapies cannot be compared to each other on several levels,” Dr. Gualtierotti said.

Laboratory monitoring of replacement therapies with standard coagulation assays may be unreliable, and depending on the mechanism of action and type of administration of nonreplacement agents, patients may experience breakthrough bleeding, especially after traumatic injury, she said.

Until the specific noncoagulatory effects of factor VIII on bone and joint health is better understood, close monitoring of patients will be required, she added.
 

Outcome measures

Subjective measures of joint health include patient-reported bleeding rates and health-related quality of life. These are practical for home management, but patients may not be able to distinguish symptoms of acute joint bleeding from chronic arthritis pain, with the potential for either under- or overtreatment, and subjective reporting is likely to miss subclinical bleeding that can occur even when patients are on prophylaxis.

Health-related quality of life tools, whether generic or specific for hemophilia, are not sensitive to small improvements, and they are not always used in routine clinical practice.

Objective measures include physical examination with scoring according to the World Federation of Hemophilia (Gilbert Scale) score or Hemophilia Joint Health Score, but these measures have limited ability to identify early or subclinical joint abnormalities.

“Therefore, joint physical examination on its own is not a sufficient measure of treatment efficacy, and it should be used in combination with other tools more objective, such as imaging,” Dr. Gualtierotti said.
 

Get the picture?

Imaging with x-rays, MRI, and, recently in some centers, point-of-care ultrasound can provide clinicians with important real-time information about the joint stability and health.

Point-of-care ultrasound in particular offers promise as a practical tool, with no ionizing radiation and high sensitivity for synovial hyperplasia subclinical joint effusion. It’s relatively inexpensive, can be used to image multiple joints, and allows for ease of follow-up, she said. The technique requires specialized training, however, and there is a lack of prospective data about its utility in hemophilia.

Various ultrasound scoring systems have been proposed, and home-based ultrasound is currently being explored in several clinical trials, Dr. Gualtierotti noted.

Other avenues for remote joint health monitoring under consideration are serum or synovial biomarkers for joint bleeding and arthropathy that could be employed at bedside or at home, smartphone apps for breakthrough bleeding and patient-reported outcomes, and sensors for detecting abnormalities in gait that may signal joint dysfunction, she said.
 

Best practice

In the question-and-answer session following the talk, Fernando Zikan, MD, from the Federal University of Rio de Janeiro noted that, “in underdeveloped countries, we still find it very difficult to guide good practices for joint health control by the patient and family members. Which strategy do you think is fundamental for the patient to feel safe to notice changes in his body?”

“It would be useful to educate patients to come to the center whenever the patient has trauma and whenever an increase in his physical activity occurs. If this is far, a bedside ultrasound evaluation by the general practitioner could help avoid joint damage. Finally, a correct rehabilitation is fundamental,” Dr. Gualtierotti replied.

Asked by several others whether she used ultrasound in her daily practice, Dr. Gualtierotti said that “we use joint ultrasound in our clinical practice in the regular annual check-up examination and whenever the patient suspects and reports hemarthrosis.”

Dr. Gualtierotti reported participation in advisory boards for Biomarin, Pfizer, Bayer, and Takeda, and in educational seminars sponsored by Pfizer, Sobi, and Roche. She has received support for congress travel and/or attendance by Bayer and Pfizer. Dr. Zikan reported no relevant disclosures.

Novel therapies have transformed the treatment of hemophilia in recent decades, but these new approaches also raise new challenges for clinicians who monitor joint health in persons with hemophilia, a specialist said.

“Patient-reported outcomes should be combined with other, more objective outcome measures for joint health monitoring, and joint ultrasound is a promising tool for objective joint health monitoring, although, due to its relatively recent introduction in clinical practice, we lack objective data and standardization,” said Roberta Gualtierotti, MD, PhD, from the Università Degli Studi of Milan.

She reviewed the challenges and approaches to monitoring joint health in persons with hemophilia during the annual congress of the European Association for Haemophilia and Allied Disorders.

Over the last decades the target of hemophilia treatment has shifted from prolonging survival to improving joint health and quality of life, and care has improved with the introduction of novel therapies such as extended half-life replacement products, nonreplacement therapies, and gene therapy, she noted.

However, “due to different pharmacodynamics and pharmacokinetics profiles, the currently available therapies cannot be compared to each other on several levels,” Dr. Gualtierotti said.

Laboratory monitoring of replacement therapies with standard coagulation assays may be unreliable, and depending on the mechanism of action and type of administration of nonreplacement agents, patients may experience breakthrough bleeding, especially after traumatic injury, she said.

Until the specific noncoagulatory effects of factor VIII on bone and joint health is better understood, close monitoring of patients will be required, she added.
 

Outcome measures

Subjective measures of joint health include patient-reported bleeding rates and health-related quality of life. These are practical for home management, but patients may not be able to distinguish symptoms of acute joint bleeding from chronic arthritis pain, with the potential for either under- or overtreatment, and subjective reporting is likely to miss subclinical bleeding that can occur even when patients are on prophylaxis.

Health-related quality of life tools, whether generic or specific for hemophilia, are not sensitive to small improvements, and they are not always used in routine clinical practice.

Objective measures include physical examination with scoring according to the World Federation of Hemophilia (Gilbert Scale) score or Hemophilia Joint Health Score, but these measures have limited ability to identify early or subclinical joint abnormalities.

“Therefore, joint physical examination on its own is not a sufficient measure of treatment efficacy, and it should be used in combination with other tools more objective, such as imaging,” Dr. Gualtierotti said.
 

Get the picture?

Imaging with x-rays, MRI, and, recently in some centers, point-of-care ultrasound can provide clinicians with important real-time information about the joint stability and health.

Point-of-care ultrasound in particular offers promise as a practical tool, with no ionizing radiation and high sensitivity for synovial hyperplasia subclinical joint effusion. It’s relatively inexpensive, can be used to image multiple joints, and allows for ease of follow-up, she said. The technique requires specialized training, however, and there is a lack of prospective data about its utility in hemophilia.

Various ultrasound scoring systems have been proposed, and home-based ultrasound is currently being explored in several clinical trials, Dr. Gualtierotti noted.

Other avenues for remote joint health monitoring under consideration are serum or synovial biomarkers for joint bleeding and arthropathy that could be employed at bedside or at home, smartphone apps for breakthrough bleeding and patient-reported outcomes, and sensors for detecting abnormalities in gait that may signal joint dysfunction, she said.
 

Best practice

In the question-and-answer session following the talk, Fernando Zikan, MD, from the Federal University of Rio de Janeiro noted that, “in underdeveloped countries, we still find it very difficult to guide good practices for joint health control by the patient and family members. Which strategy do you think is fundamental for the patient to feel safe to notice changes in his body?”

“It would be useful to educate patients to come to the center whenever the patient has trauma and whenever an increase in his physical activity occurs. If this is far, a bedside ultrasound evaluation by the general practitioner could help avoid joint damage. Finally, a correct rehabilitation is fundamental,” Dr. Gualtierotti replied.

Asked by several others whether she used ultrasound in her daily practice, Dr. Gualtierotti said that “we use joint ultrasound in our clinical practice in the regular annual check-up examination and whenever the patient suspects and reports hemarthrosis.”

Dr. Gualtierotti reported participation in advisory boards for Biomarin, Pfizer, Bayer, and Takeda, and in educational seminars sponsored by Pfizer, Sobi, and Roche. She has received support for congress travel and/or attendance by Bayer and Pfizer. Dr. Zikan reported no relevant disclosures.

Novel therapies have transformed the treatment of hemophilia in recent decades, but these new approaches also raise new challenges for clinicians who monitor joint health in persons with hemophilia, a specialist said.

“Patient-reported outcomes should be combined with other, more objective outcome measures for joint health monitoring, and joint ultrasound is a promising tool for objective joint health monitoring, although, due to its relatively recent introduction in clinical practice, we lack objective data and standardization,” said Roberta Gualtierotti, MD, PhD, from the Università Degli Studi of Milan.

She reviewed the challenges and approaches to monitoring joint health in persons with hemophilia during the annual congress of the European Association for Haemophilia and Allied Disorders.

Over the last decades the target of hemophilia treatment has shifted from prolonging survival to improving joint health and quality of life, and care has improved with the introduction of novel therapies such as extended half-life replacement products, nonreplacement therapies, and gene therapy, she noted.

However, “due to different pharmacodynamics and pharmacokinetics profiles, the currently available therapies cannot be compared to each other on several levels,” Dr. Gualtierotti said.

Laboratory monitoring of replacement therapies with standard coagulation assays may be unreliable, and depending on the mechanism of action and type of administration of nonreplacement agents, patients may experience breakthrough bleeding, especially after traumatic injury, she said.

Until the specific noncoagulatory effects of factor VIII on bone and joint health is better understood, close monitoring of patients will be required, she added.
 

Outcome measures

Subjective measures of joint health include patient-reported bleeding rates and health-related quality of life. These are practical for home management, but patients may not be able to distinguish symptoms of acute joint bleeding from chronic arthritis pain, with the potential for either under- or overtreatment, and subjective reporting is likely to miss subclinical bleeding that can occur even when patients are on prophylaxis.

Health-related quality of life tools, whether generic or specific for hemophilia, are not sensitive to small improvements, and they are not always used in routine clinical practice.

Objective measures include physical examination with scoring according to the World Federation of Hemophilia (Gilbert Scale) score or Hemophilia Joint Health Score, but these measures have limited ability to identify early or subclinical joint abnormalities.

“Therefore, joint physical examination on its own is not a sufficient measure of treatment efficacy, and it should be used in combination with other tools more objective, such as imaging,” Dr. Gualtierotti said.
 

Get the picture?

Imaging with x-rays, MRI, and, recently in some centers, point-of-care ultrasound can provide clinicians with important real-time information about the joint stability and health.

Point-of-care ultrasound in particular offers promise as a practical tool, with no ionizing radiation and high sensitivity for synovial hyperplasia subclinical joint effusion. It’s relatively inexpensive, can be used to image multiple joints, and allows for ease of follow-up, she said. The technique requires specialized training, however, and there is a lack of prospective data about its utility in hemophilia.

Various ultrasound scoring systems have been proposed, and home-based ultrasound is currently being explored in several clinical trials, Dr. Gualtierotti noted.

Other avenues for remote joint health monitoring under consideration are serum or synovial biomarkers for joint bleeding and arthropathy that could be employed at bedside or at home, smartphone apps for breakthrough bleeding and patient-reported outcomes, and sensors for detecting abnormalities in gait that may signal joint dysfunction, she said.
 

Best practice

In the question-and-answer session following the talk, Fernando Zikan, MD, from the Federal University of Rio de Janeiro noted that, “in underdeveloped countries, we still find it very difficult to guide good practices for joint health control by the patient and family members. Which strategy do you think is fundamental for the patient to feel safe to notice changes in his body?”

“It would be useful to educate patients to come to the center whenever the patient has trauma and whenever an increase in his physical activity occurs. If this is far, a bedside ultrasound evaluation by the general practitioner could help avoid joint damage. Finally, a correct rehabilitation is fundamental,” Dr. Gualtierotti replied.

Asked by several others whether she used ultrasound in her daily practice, Dr. Gualtierotti said that “we use joint ultrasound in our clinical practice in the regular annual check-up examination and whenever the patient suspects and reports hemarthrosis.”

Dr. Gualtierotti reported participation in advisory boards for Biomarin, Pfizer, Bayer, and Takeda, and in educational seminars sponsored by Pfizer, Sobi, and Roche. She has received support for congress travel and/or attendance by Bayer and Pfizer. Dr. Zikan reported no relevant disclosures.

Edward H. Livingston, MD, has resigned as deputy editor of JAMA after he and the journal faced significant backlash over a February 2021 podcast that questioned the existence of structural racism.

JAMA editor in chief Howard Bauchner, MD, apologized to JAMA staff and stakeholders and asked for and received Dr. Livingston’s resignation, according to a statement from AMA CEO James Madara.

More than 2,000 people have signed a petition on Change.org calling for an investigation at JAMA over the podcast, called “Structural Racism for Doctors: What Is It?”

It appears they are now getting their wish. Dr. Bauchner announced that the journal’s oversight committee is investigating how the podcast and a tweet promoting the episode were developed, reviewed, and ultimately posted.

“This investigation and report of its findings will be thorough and completed rapidly,” Dr. Bauchner said.

Dr. Livingston, the host of the podcast, has been heavily criticized across social media. During the podcast, Dr. Livingston, who is White, said: “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released last week, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Dr. Katz is an editor at JAMA Internal Medicine and CEO of NYC Health + Hospitals in New York.

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

The incident was met with anger and confusion in the medical community.

Herbert C. Smitherman, MD, vice dean of diversity and community affairs at Wayne State University, Detroit, noted after hearing the podcast that it was a symptom of a much larger problem.

“At its core, this podcast had racist tendencies. Those attitudes are why you don’t have as many articles by Black and Brown people in JAMA,” he said. “People’s attitudes, whether conscious or unconscious, are what drive the policies and practices which create the structural racism.”

Dr. Katz responded to the backlash last week with the following statement: “Systemic racism exists in our country. The disparate effects of the pandemic have made this painfully clear in New York City and across the country.

“As clinicians, we must understand how these structures and policies have a direct impact on the health outcomes of the patients and communities we serve. It is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it, or that we should avoid the term ‘systematic racism’ because it makes people uncomfortable. We must and can do better.”

JAMA, an independent arm of the AMA, is taking other steps to address concerns. Its executive publisher, Thomas Easley, held an employee town hall this week, and said JAMA acknowledges that “structural racism is real, pernicious, and pervasive in health care.” The journal is also starting an “end-to-end review” of all editorial processes across all JAMA publications. Finally, the journal will also create a new associate editor’s position who will provide “insight and counsel” on racism and structural racism in health care.

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

Edward H. Livingston, MD, has resigned as deputy editor of JAMA after he and the journal faced significant backlash over a February 2021 podcast that questioned the existence of structural racism.

JAMA editor in chief Howard Bauchner, MD, apologized to JAMA staff and stakeholders and asked for and received Dr. Livingston’s resignation, according to a statement from AMA CEO James Madara.

More than 2,000 people have signed a petition on Change.org calling for an investigation at JAMA over the podcast, called “Structural Racism for Doctors: What Is It?”

It appears they are now getting their wish. Dr. Bauchner announced that the journal’s oversight committee is investigating how the podcast and a tweet promoting the episode were developed, reviewed, and ultimately posted.

“This investigation and report of its findings will be thorough and completed rapidly,” Dr. Bauchner said.

Dr. Livingston, the host of the podcast, has been heavily criticized across social media. During the podcast, Dr. Livingston, who is White, said: “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released last week, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Dr. Katz is an editor at JAMA Internal Medicine and CEO of NYC Health + Hospitals in New York.

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

The incident was met with anger and confusion in the medical community.

Herbert C. Smitherman, MD, vice dean of diversity and community affairs at Wayne State University, Detroit, noted after hearing the podcast that it was a symptom of a much larger problem.

“At its core, this podcast had racist tendencies. Those attitudes are why you don’t have as many articles by Black and Brown people in JAMA,” he said. “People’s attitudes, whether conscious or unconscious, are what drive the policies and practices which create the structural racism.”

Dr. Katz responded to the backlash last week with the following statement: “Systemic racism exists in our country. The disparate effects of the pandemic have made this painfully clear in New York City and across the country.

“As clinicians, we must understand how these structures and policies have a direct impact on the health outcomes of the patients and communities we serve. It is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it, or that we should avoid the term ‘systematic racism’ because it makes people uncomfortable. We must and can do better.”

JAMA, an independent arm of the AMA, is taking other steps to address concerns. Its executive publisher, Thomas Easley, held an employee town hall this week, and said JAMA acknowledges that “structural racism is real, pernicious, and pervasive in health care.” The journal is also starting an “end-to-end review” of all editorial processes across all JAMA publications. Finally, the journal will also create a new associate editor’s position who will provide “insight and counsel” on racism and structural racism in health care.

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

Edward H. Livingston, MD, has resigned as deputy editor of JAMA after he and the journal faced significant backlash over a February 2021 podcast that questioned the existence of structural racism.

JAMA editor in chief Howard Bauchner, MD, apologized to JAMA staff and stakeholders and asked for and received Dr. Livingston’s resignation, according to a statement from AMA CEO James Madara.

More than 2,000 people have signed a petition on Change.org calling for an investigation at JAMA over the podcast, called “Structural Racism for Doctors: What Is It?”

It appears they are now getting their wish. Dr. Bauchner announced that the journal’s oversight committee is investigating how the podcast and a tweet promoting the episode were developed, reviewed, and ultimately posted.

“This investigation and report of its findings will be thorough and completed rapidly,” Dr. Bauchner said.

Dr. Livingston, the host of the podcast, has been heavily criticized across social media. During the podcast, Dr. Livingston, who is White, said: “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released last week, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Dr. Katz is an editor at JAMA Internal Medicine and CEO of NYC Health + Hospitals in New York.

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

The incident was met with anger and confusion in the medical community.

Herbert C. Smitherman, MD, vice dean of diversity and community affairs at Wayne State University, Detroit, noted after hearing the podcast that it was a symptom of a much larger problem.

“At its core, this podcast had racist tendencies. Those attitudes are why you don’t have as many articles by Black and Brown people in JAMA,” he said. “People’s attitudes, whether conscious or unconscious, are what drive the policies and practices which create the structural racism.”

Dr. Katz responded to the backlash last week with the following statement: “Systemic racism exists in our country. The disparate effects of the pandemic have made this painfully clear in New York City and across the country.

“As clinicians, we must understand how these structures and policies have a direct impact on the health outcomes of the patients and communities we serve. It is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it, or that we should avoid the term ‘systematic racism’ because it makes people uncomfortable. We must and can do better.”

JAMA, an independent arm of the AMA, is taking other steps to address concerns. Its executive publisher, Thomas Easley, held an employee town hall this week, and said JAMA acknowledges that “structural racism is real, pernicious, and pervasive in health care.” The journal is also starting an “end-to-end review” of all editorial processes across all JAMA publications. Finally, the journal will also create a new associate editor’s position who will provide “insight and counsel” on racism and structural racism in health care.

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