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.

For a primary composite target-lesion failure outcome, a biodegradable polymer sirolimus-eluting stent showed superiority at 2 years over a durable polymer everolimus-eluting stent in patients undergoing percutaneous intervention (PCI) for an ST-segment elevated acute myocardial infarction (STEMI), according to a late-breaking trial presentation at CRT 2021.

As in the previously reported 1-year results from the BIOSTEMI trial, the advantage of the biodegradable device was “driven by lower rates of target-lesion revascularization,” reported Thomas Pilgrim, MD, of the University of Bern (Switzerland).

Drug-eluting stents have already been established as superior to bare-metal stents, but the question asked in this study is whether the polymer that carries antiproliferative drugs, such as sirolimus or everolimus, improves lesion-based outcomes if it is biodegradable rather than durable, Dr. Pilgrim explained.

The composite primary outcome was target-lesion failure defined by cardiac death, target-lesion MI, or clinically indicated target-lesion revascularization.

After 2 years of follow-up, the rates of target-lesion failure were 5.1% and 8.1% for the biodegradable and durable polymer stents, respectively. This 0.58 rate ratio was statistically significant, favoring the biodegradable stent.

The investigator-initiated BIOSTEMI trial randomized 1,300 patients to one of two drug-eluting stents with ultrathin struts. One was the Orsiro stent that employs a biodegradable polymer to deliver sirolimus. The other was the Xience Prime/Xpedition that uses a durable polymer stent to deliver everolimus.

The strut thicknesses of the Orsiro stent are 60 mcm for stents of 3.0 mm in diameter or smaller and 80 mcm for those with a larger diameter. The strut thickness of the Xience stent is 81 mcm regardless of diameter.

“Patients with an acute myocardial infarction are at increased risk of stent-related events due to exacerbated inflammatory response and delayed arterial healing,” Dr. Pilgrim said. The theoretical advantages of polymer that biodegrades include “mitigation of the arterial injury, facilitation of endothelialization, and reduced intimal hyperplasia,” he explained at the meeting sponsored by MedStar Heart & Vascular Institute.

The rates of cardiac death (2.9% vs. 3.2%) and target-vessel MI (2.9% vs. 3.2%) were lower for the biodegradable polymer stent, but not significantly. However, the rates of target-vessel revascularization at 2 years were 2.5% versus 5.1%. The associated rate ratio of 0.52 favoring the biodegradable stent was significant.

Similar results favoring the biodegradable polymer stent were observed at 1 year, but those earlier results factored in historical data from the BIOSCIENCE trial, using a Bayesian analysis, to improve the power of the comparison. In this 2-year analysis, the superiority of the biodegradable polymer stent to the durable polymer stent remained statistically significant even when excluding those historical controls.

The advantage of the biodegradable polymer stent was confined to “device-oriented” outcomes, according to Dr. Pilgrim. When compared for important patient-oriented outcomes at 2 years, there were no significant differences. Rather, several were numerically more common, including death (4.2% vs. 3.8%) and MI (3.7% vs. 3.1%) in those who were randomized to the biodegradable polymer stent.

But these types of clinical outcomes are not necessarily related to stent assignment because “up to one-half of all events over the 2 years of follow-up were unrelated to the stent implanted,” Dr. Pilgrim said. He noted that high rates of events unrelated to the implanted stent have also been seen in follow-up of other comparative stent trials.

The superiority of the biodegradable stent is noteworthy. Although Dr. Pilgrim described the BIOSTEMI trial as “the first head-to-head comparison of two new-generation drug-eluting stents in patients undergoing a primary percutaneous intervention for acute myocardial infarction,” there have been several studies comparing stents for other indications. Significant differences have been uncommon.

“Over the last 10 years, we have seen a number of noninferiority stent trials, but only now are we seeing some superiority differences. This is a move in the right direction,” commented Sripal Bangalore, MD, director of the cardiovascular outcomes group, New York University.

However, he, like others, questioned whether the difference in outcomes in this trial could be fully attributed to the type of polymer. He noted that all stents could be characterized by multiple small and large differences in design and composition. Any specific characteristic, such as biodegradable polymer, might be an important contributor but not an isolated factor in the outcomes observed.

On the day that the 2-year results of the BIOSTEMI trial were presented at the CRT 2021 meeting they were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Pilgrim reports financial relationships with several companies that make stent devices, including Biotronik and Boston Scientific. Dr. Bangalore reports no potential conflicts of interest.

For a primary composite target-lesion failure outcome, a biodegradable polymer sirolimus-eluting stent showed superiority at 2 years over a durable polymer everolimus-eluting stent in patients undergoing percutaneous intervention (PCI) for an ST-segment elevated acute myocardial infarction (STEMI), according to a late-breaking trial presentation at CRT 2021.

As in the previously reported 1-year results from the BIOSTEMI trial, the advantage of the biodegradable device was “driven by lower rates of target-lesion revascularization,” reported Thomas Pilgrim, MD, of the University of Bern (Switzerland).

Drug-eluting stents have already been established as superior to bare-metal stents, but the question asked in this study is whether the polymer that carries antiproliferative drugs, such as sirolimus or everolimus, improves lesion-based outcomes if it is biodegradable rather than durable, Dr. Pilgrim explained.

The composite primary outcome was target-lesion failure defined by cardiac death, target-lesion MI, or clinically indicated target-lesion revascularization.

After 2 years of follow-up, the rates of target-lesion failure were 5.1% and 8.1% for the biodegradable and durable polymer stents, respectively. This 0.58 rate ratio was statistically significant, favoring the biodegradable stent.

The investigator-initiated BIOSTEMI trial randomized 1,300 patients to one of two drug-eluting stents with ultrathin struts. One was the Orsiro stent that employs a biodegradable polymer to deliver sirolimus. The other was the Xience Prime/Xpedition that uses a durable polymer stent to deliver everolimus.

The strut thicknesses of the Orsiro stent are 60 mcm for stents of 3.0 mm in diameter or smaller and 80 mcm for those with a larger diameter. The strut thickness of the Xience stent is 81 mcm regardless of diameter.

“Patients with an acute myocardial infarction are at increased risk of stent-related events due to exacerbated inflammatory response and delayed arterial healing,” Dr. Pilgrim said. The theoretical advantages of polymer that biodegrades include “mitigation of the arterial injury, facilitation of endothelialization, and reduced intimal hyperplasia,” he explained at the meeting sponsored by MedStar Heart & Vascular Institute.

The rates of cardiac death (2.9% vs. 3.2%) and target-vessel MI (2.9% vs. 3.2%) were lower for the biodegradable polymer stent, but not significantly. However, the rates of target-vessel revascularization at 2 years were 2.5% versus 5.1%. The associated rate ratio of 0.52 favoring the biodegradable stent was significant.

Similar results favoring the biodegradable polymer stent were observed at 1 year, but those earlier results factored in historical data from the BIOSCIENCE trial, using a Bayesian analysis, to improve the power of the comparison. In this 2-year analysis, the superiority of the biodegradable polymer stent to the durable polymer stent remained statistically significant even when excluding those historical controls.

The advantage of the biodegradable polymer stent was confined to “device-oriented” outcomes, according to Dr. Pilgrim. When compared for important patient-oriented outcomes at 2 years, there were no significant differences. Rather, several were numerically more common, including death (4.2% vs. 3.8%) and MI (3.7% vs. 3.1%) in those who were randomized to the biodegradable polymer stent.

But these types of clinical outcomes are not necessarily related to stent assignment because “up to one-half of all events over the 2 years of follow-up were unrelated to the stent implanted,” Dr. Pilgrim said. He noted that high rates of events unrelated to the implanted stent have also been seen in follow-up of other comparative stent trials.

The superiority of the biodegradable stent is noteworthy. Although Dr. Pilgrim described the BIOSTEMI trial as “the first head-to-head comparison of two new-generation drug-eluting stents in patients undergoing a primary percutaneous intervention for acute myocardial infarction,” there have been several studies comparing stents for other indications. Significant differences have been uncommon.

“Over the last 10 years, we have seen a number of noninferiority stent trials, but only now are we seeing some superiority differences. This is a move in the right direction,” commented Sripal Bangalore, MD, director of the cardiovascular outcomes group, New York University.

However, he, like others, questioned whether the difference in outcomes in this trial could be fully attributed to the type of polymer. He noted that all stents could be characterized by multiple small and large differences in design and composition. Any specific characteristic, such as biodegradable polymer, might be an important contributor but not an isolated factor in the outcomes observed.

On the day that the 2-year results of the BIOSTEMI trial were presented at the CRT 2021 meeting they were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Pilgrim reports financial relationships with several companies that make stent devices, including Biotronik and Boston Scientific. Dr. Bangalore reports no potential conflicts of interest.

For a primary composite target-lesion failure outcome, a biodegradable polymer sirolimus-eluting stent showed superiority at 2 years over a durable polymer everolimus-eluting stent in patients undergoing percutaneous intervention (PCI) for an ST-segment elevated acute myocardial infarction (STEMI), according to a late-breaking trial presentation at CRT 2021.

As in the previously reported 1-year results from the BIOSTEMI trial, the advantage of the biodegradable device was “driven by lower rates of target-lesion revascularization,” reported Thomas Pilgrim, MD, of the University of Bern (Switzerland).

Drug-eluting stents have already been established as superior to bare-metal stents, but the question asked in this study is whether the polymer that carries antiproliferative drugs, such as sirolimus or everolimus, improves lesion-based outcomes if it is biodegradable rather than durable, Dr. Pilgrim explained.

The composite primary outcome was target-lesion failure defined by cardiac death, target-lesion MI, or clinically indicated target-lesion revascularization.

After 2 years of follow-up, the rates of target-lesion failure were 5.1% and 8.1% for the biodegradable and durable polymer stents, respectively. This 0.58 rate ratio was statistically significant, favoring the biodegradable stent.

The investigator-initiated BIOSTEMI trial randomized 1,300 patients to one of two drug-eluting stents with ultrathin struts. One was the Orsiro stent that employs a biodegradable polymer to deliver sirolimus. The other was the Xience Prime/Xpedition that uses a durable polymer stent to deliver everolimus.

The strut thicknesses of the Orsiro stent are 60 mcm for stents of 3.0 mm in diameter or smaller and 80 mcm for those with a larger diameter. The strut thickness of the Xience stent is 81 mcm regardless of diameter.

“Patients with an acute myocardial infarction are at increased risk of stent-related events due to exacerbated inflammatory response and delayed arterial healing,” Dr. Pilgrim said. The theoretical advantages of polymer that biodegrades include “mitigation of the arterial injury, facilitation of endothelialization, and reduced intimal hyperplasia,” he explained at the meeting sponsored by MedStar Heart & Vascular Institute.

The rates of cardiac death (2.9% vs. 3.2%) and target-vessel MI (2.9% vs. 3.2%) were lower for the biodegradable polymer stent, but not significantly. However, the rates of target-vessel revascularization at 2 years were 2.5% versus 5.1%. The associated rate ratio of 0.52 favoring the biodegradable stent was significant.

Similar results favoring the biodegradable polymer stent were observed at 1 year, but those earlier results factored in historical data from the BIOSCIENCE trial, using a Bayesian analysis, to improve the power of the comparison. In this 2-year analysis, the superiority of the biodegradable polymer stent to the durable polymer stent remained statistically significant even when excluding those historical controls.

The advantage of the biodegradable polymer stent was confined to “device-oriented” outcomes, according to Dr. Pilgrim. When compared for important patient-oriented outcomes at 2 years, there were no significant differences. Rather, several were numerically more common, including death (4.2% vs. 3.8%) and MI (3.7% vs. 3.1%) in those who were randomized to the biodegradable polymer stent.

But these types of clinical outcomes are not necessarily related to stent assignment because “up to one-half of all events over the 2 years of follow-up were unrelated to the stent implanted,” Dr. Pilgrim said. He noted that high rates of events unrelated to the implanted stent have also been seen in follow-up of other comparative stent trials.

The superiority of the biodegradable stent is noteworthy. Although Dr. Pilgrim described the BIOSTEMI trial as “the first head-to-head comparison of two new-generation drug-eluting stents in patients undergoing a primary percutaneous intervention for acute myocardial infarction,” there have been several studies comparing stents for other indications. Significant differences have been uncommon.

“Over the last 10 years, we have seen a number of noninferiority stent trials, but only now are we seeing some superiority differences. This is a move in the right direction,” commented Sripal Bangalore, MD, director of the cardiovascular outcomes group, New York University.

However, he, like others, questioned whether the difference in outcomes in this trial could be fully attributed to the type of polymer. He noted that all stents could be characterized by multiple small and large differences in design and composition. Any specific characteristic, such as biodegradable polymer, might be an important contributor but not an isolated factor in the outcomes observed.

On the day that the 2-year results of the BIOSTEMI trial were presented at the CRT 2021 meeting they were simultaneously published in JACC: Cardiovascular Interventions.

Dr. Pilgrim reports financial relationships with several companies that make stent devices, including Biotronik and Boston Scientific. Dr. Bangalore reports no potential conflicts of interest.

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]

Although TFR is a reality on today's management of CML patients, it is important to emphasize a proper molecular monitoring after TKI discontinuation following the current NCCN and ELN guidelines. However, late relapses may occur after one year of therapy, although there are uncommon. In a recent letter to the editor in the journal Leukemia, investigators that participated in the EURO-SKI trial planned to follow patients beyond the 3 years scheduled in the trial and they reported the outcomes in what they called the AFTER-SKI trial. With a follow-up of 72 months, 12 out of 111 patients (10.8%) who were in TFR at 36 months, subsequently lost MMR. What is interesting is that the molecular status at 36 months appears highly predictive of later relapse, as only 1 patient out of 98 in MR4 at month 36 lost MMR in the following 3 years. Conversely, 11 of the 13 patients not in MR4 at month 36 lost MMR during follow-up.

For older CML patients not eligible for TFR or after TFR failure, long term therapy with TKI is the only option. However, we know that many patients can suffer from chronic AEs that will impact long term quality of life. A recent publication of the Italian phase III multicentric randomized OPTkIMA study aimed to evaluate if a progressive de‐escalation of TKIs was able to maintain the molecular response (MR^3.0) and improve Health Related Quality of Life (HRQoL). 166 elderly CML patients in stable MR^3.0/MR^4.0completed the first year of any TKI intermittent schedule, 1 month ON and 1 month OFF. The first-year probability of maintaining the MR^3.0 was 81%. No patients progressed to accelerated/blastic phase. All patients who lost the molecular response regained the MR^3.0 after resuming TKI continuously, and none suffered from TKI withdrawn syndrome. However, data related with quality of life was confounded by several factors and non-conclusive, for which longer follow up will be needed.
 

Although TFR is a reality on today's management of CML patients, it is important to emphasize a proper molecular monitoring after TKI discontinuation following the current NCCN and ELN guidelines. However, late relapses may occur after one year of therapy, although there are uncommon. In a recent letter to the editor in the journal Leukemia, investigators that participated in the EURO-SKI trial planned to follow patients beyond the 3 years scheduled in the trial and they reported the outcomes in what they called the AFTER-SKI trial. With a follow-up of 72 months, 12 out of 111 patients (10.8%) who were in TFR at 36 months, subsequently lost MMR. What is interesting is that the molecular status at 36 months appears highly predictive of later relapse, as only 1 patient out of 98 in MR4 at month 36 lost MMR in the following 3 years. Conversely, 11 of the 13 patients not in MR4 at month 36 lost MMR during follow-up.

For older CML patients not eligible for TFR or after TFR failure, long term therapy with TKI is the only option. However, we know that many patients can suffer from chronic AEs that will impact long term quality of life. A recent publication of the Italian phase III multicentric randomized OPTkIMA study aimed to evaluate if a progressive de‐escalation of TKIs was able to maintain the molecular response (MR^3.0) and improve Health Related Quality of Life (HRQoL). 166 elderly CML patients in stable MR^3.0/MR^4.0completed the first year of any TKI intermittent schedule, 1 month ON and 1 month OFF. The first-year probability of maintaining the MR^3.0 was 81%. No patients progressed to accelerated/blastic phase. All patients who lost the molecular response regained the MR^3.0 after resuming TKI continuously, and none suffered from TKI withdrawn syndrome. However, data related with quality of life was confounded by several factors and non-conclusive, for which longer follow up will be needed.
 

Although TFR is a reality on today's management of CML patients, it is important to emphasize a proper molecular monitoring after TKI discontinuation following the current NCCN and ELN guidelines. However, late relapses may occur after one year of therapy, although there are uncommon. In a recent letter to the editor in the journal Leukemia, investigators that participated in the EURO-SKI trial planned to follow patients beyond the 3 years scheduled in the trial and they reported the outcomes in what they called the AFTER-SKI trial. With a follow-up of 72 months, 12 out of 111 patients (10.8%) who were in TFR at 36 months, subsequently lost MMR. What is interesting is that the molecular status at 36 months appears highly predictive of later relapse, as only 1 patient out of 98 in MR4 at month 36 lost MMR in the following 3 years. Conversely, 11 of the 13 patients not in MR4 at month 36 lost MMR during follow-up.

For older CML patients not eligible for TFR or after TFR failure, long term therapy with TKI is the only option. However, we know that many patients can suffer from chronic AEs that will impact long term quality of life. A recent publication of the Italian phase III multicentric randomized OPTkIMA study aimed to evaluate if a progressive de‐escalation of TKIs was able to maintain the molecular response (MR^3.0) and improve Health Related Quality of Life (HRQoL). 166 elderly CML patients in stable MR^3.0/MR^4.0completed the first year of any TKI intermittent schedule, 1 month ON and 1 month OFF. The first-year probability of maintaining the MR^3.0 was 81%. No patients progressed to accelerated/blastic phase. All patients who lost the molecular response regained the MR^3.0 after resuming TKI continuously, and none suffered from TKI withdrawn syndrome. However, data related with quality of life was confounded by several factors and non-conclusive, for which longer follow up will be needed.
 

Key clinical point: G2677T/A and C3435T polymorphisms of multidrug resistance protein 1 (MDR1) play a role in response to imatinib mesylate (IM) in Caucasian population with chronic myeloid leukemia (CML).

Major finding: Variant T/A of G2677 marked responsiveness to IM therapy in Caucasian population under the recessive model (odds ratio [OR], 1.43; P = .01). The 3435TT genotype was significantly associated with increased resistance to IM therapy mainly in Caucasian population under dominant (OR, 1.49; P = .03) and heterozygous (OR, 1.52; P = .04) models.

Study details: Findings are from a meta-analysis of 17 studies involving 4,494 patients with CML; majority were in chronic phase.

Disclosures: The authors did not receive any financial support for research, authorship, and/or publication of this article. The authors declared no potential conflicts of interest.

Source: Louati N et al. J Oncol Pharm Pract. 2021 Feb 10. doi: 10.1177/1078155220981150.

Key clinical point: G2677T/A and C3435T polymorphisms of multidrug resistance protein 1 (MDR1) play a role in response to imatinib mesylate (IM) in Caucasian population with chronic myeloid leukemia (CML).

Major finding: Variant T/A of G2677 marked responsiveness to IM therapy in Caucasian population under the recessive model (odds ratio [OR], 1.43; P = .01). The 3435TT genotype was significantly associated with increased resistance to IM therapy mainly in Caucasian population under dominant (OR, 1.49; P = .03) and heterozygous (OR, 1.52; P = .04) models.

Study details: Findings are from a meta-analysis of 17 studies involving 4,494 patients with CML; majority were in chronic phase.

Disclosures: The authors did not receive any financial support for research, authorship, and/or publication of this article. The authors declared no potential conflicts of interest.

Source: Louati N et al. J Oncol Pharm Pract. 2021 Feb 10. doi: 10.1177/1078155220981150.

Key clinical point: G2677T/A and C3435T polymorphisms of multidrug resistance protein 1 (MDR1) play a role in response to imatinib mesylate (IM) in Caucasian population with chronic myeloid leukemia (CML).

Major finding: Variant T/A of G2677 marked responsiveness to IM therapy in Caucasian population under the recessive model (odds ratio [OR], 1.43; P = .01). The 3435TT genotype was significantly associated with increased resistance to IM therapy mainly in Caucasian population under dominant (OR, 1.49; P = .03) and heterozygous (OR, 1.52; P = .04) models.

Study details: Findings are from a meta-analysis of 17 studies involving 4,494 patients with CML; majority were in chronic phase.

Disclosures: The authors did not receive any financial support for research, authorship, and/or publication of this article. The authors declared no potential conflicts of interest.

Source: Louati N et al. J Oncol Pharm Pract. 2021 Feb 10. doi: 10.1177/1078155220981150.

Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.

Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.

Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.