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New initiative aims to test investigational OA treatments in high-risk patients after knee injury
David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.
Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.
Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.
Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.
There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
Previous clinical trials have failed
Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.
However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.
One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.
The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.
Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
Finding patients with ACL reconstruction with ‘bad outcomes’
Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.
When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.
“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.
The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.
A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.
Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.
“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
Clinical trial to test FastOA criteria
The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.
FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.
The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.
The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .
Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.
Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).
“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.
People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.
“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.
Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.
Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.
Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.
“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
‘We’re taking a leap’
PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.
Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.
Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.
Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.
“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.
Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.
The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.
PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.
“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.
“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.
Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.
While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.
“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.
The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.
Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.
Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.
Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.
Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.
There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
Previous clinical trials have failed
Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.
However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.
One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.
The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.
Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
Finding patients with ACL reconstruction with ‘bad outcomes’
Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.
When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.
“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.
The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.
A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.
Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.
“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
Clinical trial to test FastOA criteria
The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.
FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.
The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.
The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .
Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.
Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).
“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.
People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.
“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.
Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.
Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.
Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.
“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
‘We’re taking a leap’
PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.
Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.
Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.
Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.
“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.
Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.
The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.
PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.
“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.
“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.
Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.
While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.
“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.
The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.
Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
David Felson, MD, MPH, often steps out of his physician’s role to help patients with osteoarthritis (OA). “I have one now who needed me to write to her landlord to get her to a ground floor apartment because she’s unable to navigate the stairs,” said Dr. Felson, a professor of medicine and epidemiology at Boston University.
Rheumatologists don’t have a lot of options to treat patients with OA, Dr. Felson said. The most effective treatments are NSAIDs. While reasonably effective, they have a lot of side effects and are not always safe to use, he said.
Exercise also works, but people don’t adhere to it after a while. “Another useful strategy is getting cortisone injections into the affected joint, but that doesn’t last for very long, and I think we’re all reluctant to do it over and over again,” Dr. Felson said.
Some might say, “Well, why can’t they just get a knee replacement?” Many patients don’t want the surgery, and others are too frail to qualify. They’re also not 100% successful. Patients after the surgery sometimes say that they’re still in pain.
There’s an urgent need for more effective therapies, said Dr. Felson, who’s been working on a unique approach to target patients at high risk for OA by studying two specific populations who sustain knee injury.
Previous clinical trials have failed
Clinical trials to test OA treatments have run into some roadblocks. The market for this is enormous, with the potential to benefit millions of patients, Dr. Felson continued.
However, very few large pharmaceutical companies or even biotech companies are pursuing treatment development in osteoarthritis because there have been a lot of expensive failures. “It’s made them gun shy,” Dr. Felson noted.
One issue is OA has a long disease course, taking decades to progress and see changes, said Jason Kim, PhD, vice president for osteoarthritis research at the Arthritis Foundation in Atlanta.
The typical clinical trial window runs just 2-5 years, which is insufficient to see adequate results in a disease like OA. Longer trials are prohibitively costly, especially for corporations with near-term pressures, Dr. Kim said.
Many of these trials also apply disease-modifying drugs to participants with OA who are “too far gone” and beyond repair. By the time older people present with OA to the doctor, their disease is far advanced, and it may not be reversible or even stoppable, Dr. Felson said.
Finding patients with ACL reconstruction with ‘bad outcomes’
Dr. Kim and Dr. Felson have joined other researchers to test a new approach, using people with anterior cruciate ligament (ACL) reconstruction as a starting block to sleuth out OA tendencies years before it even begins.
When someone gets an ACL or meniscal tear, the knee in many cases begins the process of developing OA. However, that process can take 10-20 years, or sometimes even longer.
“We can’t do trials that last that long,” Dr. Felson said. But there are a few people who do quickly develop OA when they sustain those injuries. “If we can grab those people and get them involved in a study where we test treatments, we could probably figure out what kinds of treatments would be effective,” Dr. Felson explained.
The challenge is finding enough patients with ACL reconstruction with bad outcomes to effectively study OA prevention and treatment. While that sounds unfortunate, “it’s what we needed,” Dr. Felson said.
A longitudinal study known as the MOON trial that tracked 2,340 ACL reconstruction cases offered some initial clues, providing a foundation for future research. Dr. Felson and Dr. Kim joined lead researcher Kurt Spindler, MD, to create the “MOON” cohort for people who underwent surgery after an ACL tear, following them for a decade.
Through the MOON trial, Spindler et al. were able to assess how many people developed OA over 2, 6, and 10 years of follow-up, and how many experienced pain.
“It allowed us to guesstimate whether we were going to have enough numbers of people getting bad outcomes to see if we could get enough numbers to treat,” Dr. Felson said.
Clinical trial to test FastOA criteria
The Arthritis Foundation, which funded the MOON trial along with the National Institutes of Health and The American Orthopaedic Society for Sports Medicine, launched the FastOA initiative, based on its findings.
FastOA is defined as “the rapid development of OA in those who have sustained a major joint injury.” One criterion for FastOA is older age. Eighteen- to 25-year-olds generally don’t have high risk for injury or OA. “It’s only when you get to your late 20s and 30s where your risk really starts to increase substantially, just like the risk of osteoarthritis does,” Dr. Felson said.
The other major risk factor for FastOA is pain. Pain after ACL reconstruction usually takes a long time to surface. Many people never experience pain. However, for a subgroup of people who get ACL reconstruction, their pain never goes away. “What the MOON data told us was that those are the people who continue to have pain later and who get osteoarthritis quicker,” he added.
The MOON results also informed researchers on the types of patients they should seek out for a future trial. “We wouldn’t just take everybody with ACL reconstructions. We’d take selected people who we knew based on the MOON data were at really high likelihood of developing FastOA,” Dr. Felson said .
Armed with these risk factors, Dr. Felson and colleagues plan to apply FastOA to a new clinical trial, Post-Injury Knee Arthritis Severity Outcomes (PIKASO), that will test the use of metformin, a well-known diabetes drug, in 500 patients at high risk of developing post-traumatic OA in the knee following ACL reconstruction.
Two groups will participate in the PIKASO trial, an initiative of the Arthritis Foundation’s Osteoarthritis Clinical Trials Network (OA-CTN).
“If you have pain at the time of ACL reconstruction, we are interested in you. And if even you don’t have pain, if you’re among older people who need ACL reconstruction, we’re also interested in you,” Dr. Felson said.
People aged 25-40 are eligible for the older category and those 18-40 are eligible for the pain group. It’s important to include younger people in the study, Dr. Felson said. One of his colleagues, a physical therapist, was disabled by a sports injury in her late teens. Now in her 30s, she’s disabled by OA and will have to wait up to 15 years to qualify for a knee replacement.
“It’s a good idea for us to focus in on the younger folks who develop osteoarthritis at a very early age where there’s nothing we can do for them in terms of surgical options for a few years,” he said.
Targeting specific groups means fewer patients will need to be followed over the period of the study, which will lower costs, Dr. Kim said.
Metformin, a popular diabetes drug with a good safety profile, is an ideal treatment for this trial, Dr. Felson said. It’s been tested in multiple animal models and has been shown to protect against OA in all those models.
Researchers will employ imaging and biomechanics measurements to assess changes in joint structure. Eight institutions will participate, including Mass General Brigham, the trial’s clinical coordinating center, and the Cleveland Clinic and University of North Carolina at Chapel Hill, which will coordinate the collection and analysis of MRI data and biomechanical and function assessments, respectively.
“Positive results from this trial would have the potential to enable surgeons to immediately prescribe the drug before a patient undergoes surgery to slow the disease progression, or even fully prevent” post-traumatic OA, according to a statement from the Arthritis Foundation.
‘We’re taking a leap’
PIKASO doesn’t come without its challenges. “There’s a lot of dangers here,” Dr. Felson acknowledged.
Even with the application of the FastOA risk factors, not enough people may end up getting OA. “We could do an expensive study with 500 people and not get enough people with OA to be able to test a treatment,” he said.
Another risk is metformin might not work in these participants to prevent disease. “We’re taking a leap and we’re hoping that leap works out,” Dr. Felson added.
Physicians outside of this project are hopeful that FastOA will facilitate the development of new OA therapeutic strategies.
“We all intuitively understand that a joint injury will increase our risk of arthritis in 5, 10 years, even 20 years if we’re lucky,” said Dominik R. Haudenschild, PhD, professor and director of translational orthopaedic research at Houston Methodist Academic Institute.
Most patients with a painful joint can recall when an injury took place. Focusing on treatments closer to the time of injury before irreversible disease sets in makes sense, he added.
The MOON researchers found that pain is not uncommon in patients with ACL reconstruction, making them an excellent choice for analysis, Dr. Haudenschild continued.
PIKASO could face some limitations, specifically with respect to the effect size – how big of a difference a treatment can make the moment a measurement is taken.
“If we’re looking at earlier disease, the intensity of pain is likely lower, or pain isn’t felt as frequently, or the extent of structural damage in the joint is smaller,” he explained. Even a perfect treatment would only make a smaller difference at the moment measurements are taken, which can be harder to measure.
“But I expect that many of the limitations can likely be overcome by making sure the appropriate outcomes are chosen,” he said.
Nancy E. Lane, MD, professor of medicine and rheumatology at UC Davis Health System, is hoping the research will better inform physicians and patients about ACL tears. They should be aware “that within a few months of an ACL injury, the bone structure around the joint changes and there are cartilage changes,” Dr. Lane said.
While early changes may not necessarily lead to OA, patients who develop joint pain with activity or joint swelling would benefit from education, additional imaging, and modifying their activities to prevent progression, she said.
“Hopefully, within a few years we will have effective treatments to slow or reverse the development of knee OA,” Dr. Lane said.
The PIKASO trial is scheduled to begin enrollment at the end of this year or in early 2024.
Dr. Felson is a board member and past and current awardee of the Arthritis Foundation. Dr. Kim is a staff member of the Arthritis Foundation. Dr. Haudenschild received a grant from the Arthritis Foundation and participates in local, regional, and national activities with the Arthritis Foundation. Dr. Lane had no disclosures.
Tricyclics may raise fracture risk in type 2 diabetes
VANCOUVER – , independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.
Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.
Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.
Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.
The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m2 or higher and hemoglobin A1c levels of 11% or below.
Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.
Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).
During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.
Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.
Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.
The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER – , independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.
Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.
Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.
Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.
The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m2 or higher and hemoglobin A1c levels of 11% or below.
Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.
Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).
During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.
Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.
Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.
The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER – , independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.
Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.
Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.
Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.
The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m2 or higher and hemoglobin A1c levels of 11% or below.
Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.
Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).
During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.
Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.
Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.
The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASBMR 2023
Psoriatic disease: Researchers seek a PsA diagnostic test, phenotype-targeted treatment
WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.
“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.
“We know that mechanistically, there is dominance of the IL [interleukin]-23 and IL-17 pathways, as well as TNF [tumor necrosis factor], but we think there are tissue-specific cellular interactions [and] other pathways and mechanisms to be defined, and the goal now is to go into the tissues to find out,” he said at the meeting.
Dr. Ritchlin is co-leading a new research team dedicated to psoriatic spectrum diseases as part of the $64.5 million Autoimmune and Immune-Mediated Diseases Program (AIM) of the Accelerating Medicine Partnership (AMP), a huge public-private partnership involving the National Institutes of Health that is collecting and analyzing troves of biological data in order to better understand the cellular and molecular compositions and interactions that lead to disease.
As part of its work, this eight-center project – coined ELLIPSS, for Elucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium – hopes to define at a molecular and single-cell level how the transition to PsA unfolds in the setting of psoriasis. Up to 30% of patients with cutaneous psoriasis also develop PsA.
The NPF, meanwhile, has invested over $3 million for research and development and validation of a diagnostic test for PsA – one that could potentially be used by dermatologists and primary care physicians to decrease the time to diagnosis. Researchers like Jose U. Scher, MD, director of the Psoriatic Arthritis Center at New York University and the NYU Colton Center for Autoimmunity, are in the thick of using multiple “-omics” tools and other sophisticated technologies to identify new targets and biomarkers.
As this work unfolds over the next several years, there is growing interest in combination therapy for PsA, Dr. Scher and Dr. Ritchlin said, and in addressing extra-articular traits, such as obesity and centralized pain, that are believed to have an impact on disease and on response to treatment.
A deep dive into the tissue
Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.
The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.
Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.
“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”
The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.
Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.
Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.
With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”
The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
Finding biomarkers, diagnostic signatures
The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”
A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.
Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.
Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.
At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)
Dr. Scher has also focused on skin microbiomics in looking for biomarkers for the transition to PsA. “There are potential biomarkers ... that need to be validated and expanded. We have clues,” he said at the meeting, noting that microbial signatures from nonlesional skin appear to differentiate psoriasis from PsA.
The microbiome of the skin and of the gut will also be investigated by the ELLIPPS team as they analyze biosamples and try to define psoriasis and PsA endotypes. The microbiome “is critical to psoriasis and PsA,” Dr. Ritchlin said at the meeting. “I think [our knowledge] will really expand dramatically in the next 5 years.”
Wilson Liao, MD, professor and associate vice-chair of research in the department of dermatology at the University of California, San Francisco, whose work has contributed to development of a diagnostic test, was among several experts who emphasized the importance of early diagnosis in the prevention of joint damage. Identifying the disease, he said, is “one of our true unmet needs” in psoriasis.
Dr. Liao’s research identified genes and proteins differentially expressed in PsA, psoriasis, and healthy subjects across 30 immune cells types and then identified potential biomarkers through machine learning classification of these genes and proteins along with previously published genetic risk factors for PsA.
Eyes on combination therapy
“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”
Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.
A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.
In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”
It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.
In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”
Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.
WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.
“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.
“We know that mechanistically, there is dominance of the IL [interleukin]-23 and IL-17 pathways, as well as TNF [tumor necrosis factor], but we think there are tissue-specific cellular interactions [and] other pathways and mechanisms to be defined, and the goal now is to go into the tissues to find out,” he said at the meeting.
Dr. Ritchlin is co-leading a new research team dedicated to psoriatic spectrum diseases as part of the $64.5 million Autoimmune and Immune-Mediated Diseases Program (AIM) of the Accelerating Medicine Partnership (AMP), a huge public-private partnership involving the National Institutes of Health that is collecting and analyzing troves of biological data in order to better understand the cellular and molecular compositions and interactions that lead to disease.
As part of its work, this eight-center project – coined ELLIPSS, for Elucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium – hopes to define at a molecular and single-cell level how the transition to PsA unfolds in the setting of psoriasis. Up to 30% of patients with cutaneous psoriasis also develop PsA.
The NPF, meanwhile, has invested over $3 million for research and development and validation of a diagnostic test for PsA – one that could potentially be used by dermatologists and primary care physicians to decrease the time to diagnosis. Researchers like Jose U. Scher, MD, director of the Psoriatic Arthritis Center at New York University and the NYU Colton Center for Autoimmunity, are in the thick of using multiple “-omics” tools and other sophisticated technologies to identify new targets and biomarkers.
As this work unfolds over the next several years, there is growing interest in combination therapy for PsA, Dr. Scher and Dr. Ritchlin said, and in addressing extra-articular traits, such as obesity and centralized pain, that are believed to have an impact on disease and on response to treatment.
A deep dive into the tissue
Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.
The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.
Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.
“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”
The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.
Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.
Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.
With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”
The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
Finding biomarkers, diagnostic signatures
The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”
A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.
Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.
Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.
At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)
Dr. Scher has also focused on skin microbiomics in looking for biomarkers for the transition to PsA. “There are potential biomarkers ... that need to be validated and expanded. We have clues,” he said at the meeting, noting that microbial signatures from nonlesional skin appear to differentiate psoriasis from PsA.
The microbiome of the skin and of the gut will also be investigated by the ELLIPPS team as they analyze biosamples and try to define psoriasis and PsA endotypes. The microbiome “is critical to psoriasis and PsA,” Dr. Ritchlin said at the meeting. “I think [our knowledge] will really expand dramatically in the next 5 years.”
Wilson Liao, MD, professor and associate vice-chair of research in the department of dermatology at the University of California, San Francisco, whose work has contributed to development of a diagnostic test, was among several experts who emphasized the importance of early diagnosis in the prevention of joint damage. Identifying the disease, he said, is “one of our true unmet needs” in psoriasis.
Dr. Liao’s research identified genes and proteins differentially expressed in PsA, psoriasis, and healthy subjects across 30 immune cells types and then identified potential biomarkers through machine learning classification of these genes and proteins along with previously published genetic risk factors for PsA.
Eyes on combination therapy
“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”
Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.
A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.
In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”
It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.
In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”
Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.
WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.
“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.
“We know that mechanistically, there is dominance of the IL [interleukin]-23 and IL-17 pathways, as well as TNF [tumor necrosis factor], but we think there are tissue-specific cellular interactions [and] other pathways and mechanisms to be defined, and the goal now is to go into the tissues to find out,” he said at the meeting.
Dr. Ritchlin is co-leading a new research team dedicated to psoriatic spectrum diseases as part of the $64.5 million Autoimmune and Immune-Mediated Diseases Program (AIM) of the Accelerating Medicine Partnership (AMP), a huge public-private partnership involving the National Institutes of Health that is collecting and analyzing troves of biological data in order to better understand the cellular and molecular compositions and interactions that lead to disease.
As part of its work, this eight-center project – coined ELLIPSS, for Elucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium – hopes to define at a molecular and single-cell level how the transition to PsA unfolds in the setting of psoriasis. Up to 30% of patients with cutaneous psoriasis also develop PsA.
The NPF, meanwhile, has invested over $3 million for research and development and validation of a diagnostic test for PsA – one that could potentially be used by dermatologists and primary care physicians to decrease the time to diagnosis. Researchers like Jose U. Scher, MD, director of the Psoriatic Arthritis Center at New York University and the NYU Colton Center for Autoimmunity, are in the thick of using multiple “-omics” tools and other sophisticated technologies to identify new targets and biomarkers.
As this work unfolds over the next several years, there is growing interest in combination therapy for PsA, Dr. Scher and Dr. Ritchlin said, and in addressing extra-articular traits, such as obesity and centralized pain, that are believed to have an impact on disease and on response to treatment.
A deep dive into the tissue
Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.
The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.
Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.
“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”
The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.
Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.
Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.
With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”
The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
Finding biomarkers, diagnostic signatures
The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”
A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.
Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.
Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.
At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)
Dr. Scher has also focused on skin microbiomics in looking for biomarkers for the transition to PsA. “There are potential biomarkers ... that need to be validated and expanded. We have clues,” he said at the meeting, noting that microbial signatures from nonlesional skin appear to differentiate psoriasis from PsA.
The microbiome of the skin and of the gut will also be investigated by the ELLIPPS team as they analyze biosamples and try to define psoriasis and PsA endotypes. The microbiome “is critical to psoriasis and PsA,” Dr. Ritchlin said at the meeting. “I think [our knowledge] will really expand dramatically in the next 5 years.”
Wilson Liao, MD, professor and associate vice-chair of research in the department of dermatology at the University of California, San Francisco, whose work has contributed to development of a diagnostic test, was among several experts who emphasized the importance of early diagnosis in the prevention of joint damage. Identifying the disease, he said, is “one of our true unmet needs” in psoriasis.
Dr. Liao’s research identified genes and proteins differentially expressed in PsA, psoriasis, and healthy subjects across 30 immune cells types and then identified potential biomarkers through machine learning classification of these genes and proteins along with previously published genetic risk factors for PsA.
Eyes on combination therapy
“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”
Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.
A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.
In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”
It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.
In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”
Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.
AT THE NPF RESEARCH SYMPOSIUM 2023
Researchers link two genes to Raynaud’s disease
Researchers have identified two genes that may contribute to Raynaud’s phenomenon, a condition where blood vessels in the extremities constrict and limit blood flow.
Raynaud’s is a relatively common condition, affecting 2%-5% of the general population. Though Raynaud’s can be an annoyance for some, it can also cause severe pain and can require medication.
These newly identified genes will hopefully lead to new therapeutic options, said Maik Pietzner, PhD, chair in health data modeling at Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and group leader in the Computational Medicine Group at the Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Germany.
Dr. Pietzner led the research along with Claudia Langenberg, MD, PhD, director of PHURI.
The study was published in Nature Communications.
Largest genomic study of Raynaud’s to date
The researchers looked through electronic medical records from the UK Biobank, a large-scale database that contains genetic and health information on half a million participants. They identified more than 5,100 individuals with Raynaud’s, of which 68% had primary Raynaud’s. These participants were compared with more than 439,000 controls who did not have Raynaud’s.
In a secondary analysis, the team also used health records from the Queen Mary University of London Genes & Health Study, which contains health information on individuals of South Asian ancestry.
The researchers identified two genes that are likely involved with Raynaud’s. The first, ADRA2A, encodes for the alpha-2A adrenergic receptor that can cause vasoconstriction of small blood vessels in response to stress hormones. Researchers have long suspected that this type of receptor could be involved with Raynaud’s, but there was debate over which receptor subtype was responsible.
“Our finding of alpha-2A receptors is quite interesting because the focus has always been on alpha-2C receptors,” said Dr. Pietzner. “It’s only a letter, but it’s a massive difference in terms of biology and physiology,” he said, and could be why therapies targeting 2C receptors have been ineffective.
The second strongest association was for the transcription factor IRX1. Less is known about this gene, but the data we do have suggest that it is involved with regulating the dilation of blood vessels, Dr. Pietzner noted.
“There might be balance between the ADRA2A finding being responsible for constriction and the IRX1 finding indirectly linked to the dilation of those vessels following constrictions. Having both may explain why these prolonged episodes of vasoconstriction lead to a loss of oxygen to the tissues,” so they turn white and then blue, he said.
Because the Biobank cohort was European-centric, Dr. Pietzner and colleagues also identified 400 cases of Raynaud’s in British individuals of Bangladeshi and Pakistani ancestry and were able to replicate the association between IRX1 and Raynaud’s. Data on ADRA2A were unavailable.
The genes identified are associated with primary Raynaud’s. Secondary Raynaud’s is a rarer type of the condition that occurs along with autoimmune disorders, such as scleroderma, and is generally more severe.
It’s long been suspected that Raynaud’s had some genetic component, because half of patients with Raynaud’s have another family member with the same condition, said Laura Hummers, MD, who codirects the John Hopkins Scleroderma Center in Baltimore. She was not involved with the study.
This is “the largest study of this kind that’s been done,” she said, and the first to show a potential mechanism behind this genetic association.
The main gene finding, ADRA2A, “points to a receptor on the cells that regulate the tone of these blood vessels,” she continued. “It suggests maybe there’s too many of these receptors or they’re overly sensitive; something about them is different that makes patients more susceptible to these cold triggers. Knowing that is potentially really important, because it could give you a direct way to intervene, if true.”
New therapeutic avenues
The first-line treatment for primary Raynaud’s is behavioral interventions, such as maintaining body and extremity warmth and avoiding certain vasoconstricting drugs, said Kimberly Lakin, MD, a rheumatologist at the Hospital for Special Surgery in New York, who not involved in the research. These drugs could include over-the-counter decongestants and certain medications for attention-deficit/hyperactivity disorder.
If these behavioral interventions are not enough, clinicians most commonly prescribe calcium channel blockers. These medications are vasodilators but can be a concern for people with normal or already low blood pressure, Dr. Lakin said. They can also cause symptoms such as headache, leg swelling, constipation, and other gastrointestinal symptoms.
Other medications, such as fluoxetine, may also be considered as a later-line therapy, “but the effectiveness is fairly limited in Raynaud’s,” she said. “Certainly, other medication options that would be helpful and driven by the mechanisms of Raynaud’s would add to our ability to help patients.”
As it turns out, one of the genes identified in the study, ADRA2A, “is actually one of the most commonly targeted genes by drugs,” said Dr. Pietzner. Because the findings suggest that ADRA2A is overexpressed in Raynaud, a selective inhibitor like the antidepressant mirtazapine could be a promising candidate to repurpose for treating Raynaud’s, he said.
Limitations to electronic medical record analyses
Both Dr. Hummers and Dr. Lakin noted that research using diagnostic codes from medical records to identify cases has some limitations. The study may have included patients misdiagnosed with Raynaud’s when perhaps they had another condition. Patients with milder Raynaud’s who have not sought medical attention for the condition would not be represented in the study, Dr. Lakin said.
The UK Biobank includes individuals of mostly European descent, so an analysis confirming these findings in a more diverse population would be helpful, she said.
However, both Dr. Lakin and Dr. Hummers agreed that the study contributes to the understanding of the mechanisms behind Raynaud’s. Although the two identified genes were tied to primary Raynaud’s, the study’s findings could potentially apply to secondary Raynaud’s as well, Dr. Hummers said.
“Anything we learn about primary Raynaud’s may have implication for Raynaud’s more broadly,” she noted.
Dr. Hummers and Dr. Lakin disclosed no relevant financial relationships. Dr. Pietzner has received partnership funding for the MRC Clinical Pharmacology Training Scheme (cofunded by MRC and Roche, UCB, Eli Lilly, and Novartis) and a PhD studentship jointly funded by the UK Engineering and Physical Sciences Research Council and AstraZeneca. Dr. Pietzner also has unrestricted educational grant support for the UK Pharmacogenetics and Stratified Medicine Network from Bristol-Myers Squibb.
A version of this article appeared on Medscape.com.
Researchers have identified two genes that may contribute to Raynaud’s phenomenon, a condition where blood vessels in the extremities constrict and limit blood flow.
Raynaud’s is a relatively common condition, affecting 2%-5% of the general population. Though Raynaud’s can be an annoyance for some, it can also cause severe pain and can require medication.
These newly identified genes will hopefully lead to new therapeutic options, said Maik Pietzner, PhD, chair in health data modeling at Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and group leader in the Computational Medicine Group at the Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Germany.
Dr. Pietzner led the research along with Claudia Langenberg, MD, PhD, director of PHURI.
The study was published in Nature Communications.
Largest genomic study of Raynaud’s to date
The researchers looked through electronic medical records from the UK Biobank, a large-scale database that contains genetic and health information on half a million participants. They identified more than 5,100 individuals with Raynaud’s, of which 68% had primary Raynaud’s. These participants were compared with more than 439,000 controls who did not have Raynaud’s.
In a secondary analysis, the team also used health records from the Queen Mary University of London Genes & Health Study, which contains health information on individuals of South Asian ancestry.
The researchers identified two genes that are likely involved with Raynaud’s. The first, ADRA2A, encodes for the alpha-2A adrenergic receptor that can cause vasoconstriction of small blood vessels in response to stress hormones. Researchers have long suspected that this type of receptor could be involved with Raynaud’s, but there was debate over which receptor subtype was responsible.
“Our finding of alpha-2A receptors is quite interesting because the focus has always been on alpha-2C receptors,” said Dr. Pietzner. “It’s only a letter, but it’s a massive difference in terms of biology and physiology,” he said, and could be why therapies targeting 2C receptors have been ineffective.
The second strongest association was for the transcription factor IRX1. Less is known about this gene, but the data we do have suggest that it is involved with regulating the dilation of blood vessels, Dr. Pietzner noted.
“There might be balance between the ADRA2A finding being responsible for constriction and the IRX1 finding indirectly linked to the dilation of those vessels following constrictions. Having both may explain why these prolonged episodes of vasoconstriction lead to a loss of oxygen to the tissues,” so they turn white and then blue, he said.
Because the Biobank cohort was European-centric, Dr. Pietzner and colleagues also identified 400 cases of Raynaud’s in British individuals of Bangladeshi and Pakistani ancestry and were able to replicate the association between IRX1 and Raynaud’s. Data on ADRA2A were unavailable.
The genes identified are associated with primary Raynaud’s. Secondary Raynaud’s is a rarer type of the condition that occurs along with autoimmune disorders, such as scleroderma, and is generally more severe.
It’s long been suspected that Raynaud’s had some genetic component, because half of patients with Raynaud’s have another family member with the same condition, said Laura Hummers, MD, who codirects the John Hopkins Scleroderma Center in Baltimore. She was not involved with the study.
This is “the largest study of this kind that’s been done,” she said, and the first to show a potential mechanism behind this genetic association.
The main gene finding, ADRA2A, “points to a receptor on the cells that regulate the tone of these blood vessels,” she continued. “It suggests maybe there’s too many of these receptors or they’re overly sensitive; something about them is different that makes patients more susceptible to these cold triggers. Knowing that is potentially really important, because it could give you a direct way to intervene, if true.”
New therapeutic avenues
The first-line treatment for primary Raynaud’s is behavioral interventions, such as maintaining body and extremity warmth and avoiding certain vasoconstricting drugs, said Kimberly Lakin, MD, a rheumatologist at the Hospital for Special Surgery in New York, who not involved in the research. These drugs could include over-the-counter decongestants and certain medications for attention-deficit/hyperactivity disorder.
If these behavioral interventions are not enough, clinicians most commonly prescribe calcium channel blockers. These medications are vasodilators but can be a concern for people with normal or already low blood pressure, Dr. Lakin said. They can also cause symptoms such as headache, leg swelling, constipation, and other gastrointestinal symptoms.
Other medications, such as fluoxetine, may also be considered as a later-line therapy, “but the effectiveness is fairly limited in Raynaud’s,” she said. “Certainly, other medication options that would be helpful and driven by the mechanisms of Raynaud’s would add to our ability to help patients.”
As it turns out, one of the genes identified in the study, ADRA2A, “is actually one of the most commonly targeted genes by drugs,” said Dr. Pietzner. Because the findings suggest that ADRA2A is overexpressed in Raynaud, a selective inhibitor like the antidepressant mirtazapine could be a promising candidate to repurpose for treating Raynaud’s, he said.
Limitations to electronic medical record analyses
Both Dr. Hummers and Dr. Lakin noted that research using diagnostic codes from medical records to identify cases has some limitations. The study may have included patients misdiagnosed with Raynaud’s when perhaps they had another condition. Patients with milder Raynaud’s who have not sought medical attention for the condition would not be represented in the study, Dr. Lakin said.
The UK Biobank includes individuals of mostly European descent, so an analysis confirming these findings in a more diverse population would be helpful, she said.
However, both Dr. Lakin and Dr. Hummers agreed that the study contributes to the understanding of the mechanisms behind Raynaud’s. Although the two identified genes were tied to primary Raynaud’s, the study’s findings could potentially apply to secondary Raynaud’s as well, Dr. Hummers said.
“Anything we learn about primary Raynaud’s may have implication for Raynaud’s more broadly,” she noted.
Dr. Hummers and Dr. Lakin disclosed no relevant financial relationships. Dr. Pietzner has received partnership funding for the MRC Clinical Pharmacology Training Scheme (cofunded by MRC and Roche, UCB, Eli Lilly, and Novartis) and a PhD studentship jointly funded by the UK Engineering and Physical Sciences Research Council and AstraZeneca. Dr. Pietzner also has unrestricted educational grant support for the UK Pharmacogenetics and Stratified Medicine Network from Bristol-Myers Squibb.
A version of this article appeared on Medscape.com.
Researchers have identified two genes that may contribute to Raynaud’s phenomenon, a condition where blood vessels in the extremities constrict and limit blood flow.
Raynaud’s is a relatively common condition, affecting 2%-5% of the general population. Though Raynaud’s can be an annoyance for some, it can also cause severe pain and can require medication.
These newly identified genes will hopefully lead to new therapeutic options, said Maik Pietzner, PhD, chair in health data modeling at Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and group leader in the Computational Medicine Group at the Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Germany.
Dr. Pietzner led the research along with Claudia Langenberg, MD, PhD, director of PHURI.
The study was published in Nature Communications.
Largest genomic study of Raynaud’s to date
The researchers looked through electronic medical records from the UK Biobank, a large-scale database that contains genetic and health information on half a million participants. They identified more than 5,100 individuals with Raynaud’s, of which 68% had primary Raynaud’s. These participants were compared with more than 439,000 controls who did not have Raynaud’s.
In a secondary analysis, the team also used health records from the Queen Mary University of London Genes & Health Study, which contains health information on individuals of South Asian ancestry.
The researchers identified two genes that are likely involved with Raynaud’s. The first, ADRA2A, encodes for the alpha-2A adrenergic receptor that can cause vasoconstriction of small blood vessels in response to stress hormones. Researchers have long suspected that this type of receptor could be involved with Raynaud’s, but there was debate over which receptor subtype was responsible.
“Our finding of alpha-2A receptors is quite interesting because the focus has always been on alpha-2C receptors,” said Dr. Pietzner. “It’s only a letter, but it’s a massive difference in terms of biology and physiology,” he said, and could be why therapies targeting 2C receptors have been ineffective.
The second strongest association was for the transcription factor IRX1. Less is known about this gene, but the data we do have suggest that it is involved with regulating the dilation of blood vessels, Dr. Pietzner noted.
“There might be balance between the ADRA2A finding being responsible for constriction and the IRX1 finding indirectly linked to the dilation of those vessels following constrictions. Having both may explain why these prolonged episodes of vasoconstriction lead to a loss of oxygen to the tissues,” so they turn white and then blue, he said.
Because the Biobank cohort was European-centric, Dr. Pietzner and colleagues also identified 400 cases of Raynaud’s in British individuals of Bangladeshi and Pakistani ancestry and were able to replicate the association between IRX1 and Raynaud’s. Data on ADRA2A were unavailable.
The genes identified are associated with primary Raynaud’s. Secondary Raynaud’s is a rarer type of the condition that occurs along with autoimmune disorders, such as scleroderma, and is generally more severe.
It’s long been suspected that Raynaud’s had some genetic component, because half of patients with Raynaud’s have another family member with the same condition, said Laura Hummers, MD, who codirects the John Hopkins Scleroderma Center in Baltimore. She was not involved with the study.
This is “the largest study of this kind that’s been done,” she said, and the first to show a potential mechanism behind this genetic association.
The main gene finding, ADRA2A, “points to a receptor on the cells that regulate the tone of these blood vessels,” she continued. “It suggests maybe there’s too many of these receptors or they’re overly sensitive; something about them is different that makes patients more susceptible to these cold triggers. Knowing that is potentially really important, because it could give you a direct way to intervene, if true.”
New therapeutic avenues
The first-line treatment for primary Raynaud’s is behavioral interventions, such as maintaining body and extremity warmth and avoiding certain vasoconstricting drugs, said Kimberly Lakin, MD, a rheumatologist at the Hospital for Special Surgery in New York, who not involved in the research. These drugs could include over-the-counter decongestants and certain medications for attention-deficit/hyperactivity disorder.
If these behavioral interventions are not enough, clinicians most commonly prescribe calcium channel blockers. These medications are vasodilators but can be a concern for people with normal or already low blood pressure, Dr. Lakin said. They can also cause symptoms such as headache, leg swelling, constipation, and other gastrointestinal symptoms.
Other medications, such as fluoxetine, may also be considered as a later-line therapy, “but the effectiveness is fairly limited in Raynaud’s,” she said. “Certainly, other medication options that would be helpful and driven by the mechanisms of Raynaud’s would add to our ability to help patients.”
As it turns out, one of the genes identified in the study, ADRA2A, “is actually one of the most commonly targeted genes by drugs,” said Dr. Pietzner. Because the findings suggest that ADRA2A is overexpressed in Raynaud, a selective inhibitor like the antidepressant mirtazapine could be a promising candidate to repurpose for treating Raynaud’s, he said.
Limitations to electronic medical record analyses
Both Dr. Hummers and Dr. Lakin noted that research using diagnostic codes from medical records to identify cases has some limitations. The study may have included patients misdiagnosed with Raynaud’s when perhaps they had another condition. Patients with milder Raynaud’s who have not sought medical attention for the condition would not be represented in the study, Dr. Lakin said.
The UK Biobank includes individuals of mostly European descent, so an analysis confirming these findings in a more diverse population would be helpful, she said.
However, both Dr. Lakin and Dr. Hummers agreed that the study contributes to the understanding of the mechanisms behind Raynaud’s. Although the two identified genes were tied to primary Raynaud’s, the study’s findings could potentially apply to secondary Raynaud’s as well, Dr. Hummers said.
“Anything we learn about primary Raynaud’s may have implication for Raynaud’s more broadly,” she noted.
Dr. Hummers and Dr. Lakin disclosed no relevant financial relationships. Dr. Pietzner has received partnership funding for the MRC Clinical Pharmacology Training Scheme (cofunded by MRC and Roche, UCB, Eli Lilly, and Novartis) and a PhD studentship jointly funded by the UK Engineering and Physical Sciences Research Council and AstraZeneca. Dr. Pietzner also has unrestricted educational grant support for the UK Pharmacogenetics and Stratified Medicine Network from Bristol-Myers Squibb.
A version of this article appeared on Medscape.com.
FROM NATURE COMMUNICATIONS
Approximately 20% of U.S. adults are diagnosed with arthritis
TOPLINE:
The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.
METHODOLOGY:
- Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
- The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
- The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.
TAKEAWAY:
- Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
- Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
- When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
- The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.
IN PRACTICE:
“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.
SOURCE:
The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.
LIMITATIONS:
The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes.
DISCLOSURES:
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
TOPLINE:
The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.
METHODOLOGY:
- Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
- The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
- The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.
TAKEAWAY:
- Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
- Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
- When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
- The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.
IN PRACTICE:
“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.
SOURCE:
The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.
LIMITATIONS:
The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes.
DISCLOSURES:
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
TOPLINE:
The prevalence of reported diagnosed arthritis in the United States is highest overall in older adults with comorbid chronic conditions.
METHODOLOGY:
- Researchers reviewed data from the National Health Interview Survey (NHIS) from 2019 to 2021 to update the prevalence of self-reported arthritis in the United States.
- The sample sizes for the 2019, 2020, and 2021 NHIS were 31,997, 21,153, and 29,482, with survey response rates of 59.1%, 48.9%, and 50.9%, respectively.
- The unadjusted and age-standardized prevalence estimates were calculated for adults aged 18 years and older and based on self-reported health and demographic data.
TAKEAWAY:
- Overall, arthritis was diagnosed in 53.2 million adults aged 18 years and older in the United States; of these, 88.3% were aged 45 years and older and 48.3% were 65 years and older.
- Age-standardized prevalence of arthritis was higher in women vs men and among veterans vs nonveterans (20.9% vs 16.3% and 24.2% vs 18.5%, respectively).
- When categorized by race, age-standardized prevalence of arthritis was higher among non-Hispanic White individuals, compared with Hispanic or Latino individuals or non-Hispanic Asian individuals (20.1%, 14.7%, and 10.3%, respectively).
- The prevalence of arthritis also was higher among individuals with self-reported diagnosis of chronic conditions including dementia, chronic obstructive pulmonary disease, stroke, heart disease, diabetes, and cancer than in those without these conditions; approximately half of adults aged 65 years and older with arthritis reported at least one of these conditions.
IN PRACTICE:
“These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other community-based, arthritis-appropriate, evidence-based interventions,” the authors write.
SOURCE:
The study was led by Elizabeth A. Fallon, PhD, of the Centers for Disease Control and Prevention, Atlanta, Georgia. The data were published online in the CDC’s Morbidity and Mortality Weekly Report.
LIMITATIONS:
The cross-sectional design prevented conclusions of causality between individual characteristics and arthritis diagnosis; other limitations included the reliance on self-reports, possible response bias, and the inability to calculate prevalence of arthritis subtypes.
DISCLOSURES:
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
Fractures beget fractures at any age
VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.
The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.
As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.
“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.
Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.
The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.
Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m2. Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.
The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).
The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.
Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.
Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”
Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.
The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.
As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.
“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.
Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.
The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.
Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m2. Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.
The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).
The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.
Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.
Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”
Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER – The occurrence of a fracture predicts future fracture risk, but the increase in risk is the same no matter what the age of the patient, according to a new population-based study drawn from the Manitoba BMD Registry.
The work expands previous studies that focused mostly on fracture risk prediction after a first fracture among individuals aged 45-50 and older. Other limitations of prior studies include large age categories (such as “premenopausal”), reliance on self-reporting, and small sample sizes.
As a result, some guidelines recommend considering fracture history only for patients older than a certain age when assessing for future risk, such as with the Fracture Risk Assessment Tool (FRAX). The new study suggests a potential need to reconsider that stance.
“The [percentage] of increased risk from having had prevalent fractures in the past, no matter what your age, is about the same. I think that it’s really paradigm shifting because [when] most of us think [of] young people who fracture, we’re not thinking of osteoporosis or future fracture risk. We’re not saying, ‘Oh, I had a fracture when I was 25. When I’m 70, I should be thinking about osteoporosis.’ So, I think this study is quite eye-opening that way,” Carrie Ye, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research, said in an interview.
Participants of younger age who are referred for dual-energy x-ray absorptiometry (DXA) likely represent a population at increased risk of osteoporosis, according to Dr. Ye. “Maybe they have Crohn’s disease or maybe they’re on a bunch of steroids, and so a clinician has flagged them,” said Dr. Ye, who is an assistant professor and rheumatologist at the University of Alberta, Edmonton.
The researchers limited the analysis to nontraumatic fractures, but session moderator Nicholas Harvey, MD, PhD, wondered if a similar finding would occur with traumatic fractures. In an interview, he noted that researchers led by William Leslie, MD, at the University of Manitoba, Winnipeg, found that prior traumatic fracture also predicted future low bone-mineral density (BMD) and osteoporotic fracture. “I think that would have been one interesting question,” said Dr. Harvey, director of the Medical Research Council Lifecourse Epidemiology Centre at the University of Southampton, England.
Dr. Ye’s study included 88,696 individuals who underwent a first DXA scan between 1996 and 2018, which researchers then linked to provincial administrative health data collected between 1979 and 2018. The mean age at first DXA was 64.6 years, and 90.3% were women. Their mean body mass index was 27.4 kg/m2. Current smokers made up 10.1% of the cohort, 5.5% had a history of prolonged glucocorticoid use, 3.1% had rheumatoid arthritis, and among 14.9% of patients, there was a secondary cause of osteoporosis. Over a median 25.1 years of observation prior to DXA, clinical fracture occurred in 23.8% of participants.
The mean age of the patients at the time of their first prior fracture was 57.7 years. Over a mean 9.0 years of follow-up, 14.6% of participants experienced a fracture of any kind, 14.0% had osteoporotic fractures, 10.6% had a major osteoporotic fracture (nonankle), and 3.5% had a hip fracture. Among persons aged 20-29 years to 80 years or older, the adjusted hazard ratios for future fractures were similar, ranging from 1.51 to 2.12 (P for trend = .120).
The results were similar when age groups were analyzed with regard to all fractures, osteoporotic fractures, major osteoporotic fractures, or hip fractures.
Going forward, Dr. Ye hopes to expand the research into childhood fractures. “They can break their bones pretty easily, especially as they’re going through growth spurts and things like that,” she said.
Asked what her advice to physicians would be, Dr. Ye responded: “Don’t ignore prior fractures, even if they occurred at an early age. I think if someone’s had a fracture, they bought themselves a fracture risk assessment, and that doesn’t mean necessarily a DXA scan. It means you go through their other risk factors: What medications are they on? Do they have a family history? Are they super low BMI? Look at other reasons why you should be worried about their bones, and if you should be worried about their bones, certainly [measure their] BMD and see what’s going on.”
Dr. Ye and Dr. Harvey have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ASBMR 2023
Abatacept, certolizumab: Best biologics in early RA
TOPLINE:
In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.
METHODOLOGY:
The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.
Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:
- Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
- Certolizumab pegol.
- Abatacept.
- Tocilizumab.
In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.
TAKEAWAY:
- Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
- The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
- No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.
IN PRACTICE:
The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.
SOURCE:
The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.
LIMITATIONS:
The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.
DISCLOSURES:
The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.
METHODOLOGY:
The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.
Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:
- Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
- Certolizumab pegol.
- Abatacept.
- Tocilizumab.
In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.
TAKEAWAY:
- Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
- The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
- No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.
IN PRACTICE:
The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.
SOURCE:
The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.
LIMITATIONS:
The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.
DISCLOSURES:
The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
In combination with methotrexate, both abatacept (Orencia) and certolizumab pegol (Cimzia), but not tocilizumab (Actemra), showed superiority over different combinations of active conventional disease-modifying antirheumatic drugs (DMARDs) for promoting remission in patients with early, untreated rheumatoid arthritis.
METHODOLOGY:
The study population included 812 adults from sites in six European countries who had treatment-naive early RA (less than 24 months’ duration) and moderate to severe disease.
Participants were randomly assigned to open-label treatment with methotrexate plus one of four treatments:
- Active conventional therapy (oral , tapered quickly and discontinued after 9 months, or , hydroxychloroquine, and intra-articular glucocorticoid injections in swollen joints).
- Certolizumab pegol.
- Abatacept.
- Tocilizumab.
In all the biologic-treated groups, intra-articular glucocorticoid injections were allowed on demand up to week 12; thereafter, up to 40 mg were allowed every 12 weeks. In all groups, intra-articular glucocorticoids were prohibited in weeks 20-24 and weeks 44-48 to minimize their influence on week 24 and week 48 outcomes.
TAKEAWAY:
- Clinical remission rates at week 48 based on Clinical Disease Activity Index scores of 2.8 or less were 59.3% with abatacept and 52.3% with certolizumab, which were significantly greater than the rate of 39.2% seen with active conventional therapy. The 51.9% rate seen with tocilizumab was not superior to active conventional therapy.
- The co–primary outcome of change in van der Heijde-modified Sharp Score from baseline to week 48 was relatively low across all groups: 0.45 for active conventional therapy, and 0.62, 0.47, and 0.50 for abatacept, certolizumab pegol, and tocilizumab, respectively.
- No new safety signals appeared, nor did any significantly increased risk associated with glucocorticoid use; at least one adverse event was reported in 88.3%, 89.6%, 85.8%, and 96.7% of patients taking conventional therapy, certolizumab pegol, abatacept, and tocilizumab, respectively.
IN PRACTICE:
The results suggest that both abatacept and certolizumab pegol yield higher remission rates than optimized conventional therapy, and “should be considered when the management of patients with newly diagnosed RA is decided, both in clinical practice and in treatment recommendations,” the authors write.
SOURCE:
The lead author on the study was Mikkel Østergaard, MD, PhD, of the Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen. The study was published online in Annals of the Rheumatic Disease.
LIMITATIONS:
The open-label study design could influence some subjective outcomes, and conventional therapy included two slightly different strategies based on national recommendations for the individual countries.
DISCLOSURES:
The study was funded by multiple public sources to centers from countries participating in the study, as well as the Icelandic Society for Rheumatology, the Swedish Rheumatism Association, and the Research Fund of University Hospital, Reykjavik, Iceland. UCB and Bristol-Myers Squibb provided certolizumab pegol and abatacept, respectively, at no cost, but were not otherwise involved in the study. Many authors, including Dr. Østergaard, report financial relationships with multiple pharmaceutical companies. The full list can be found with the original article.
A version of this article first appeared on Medscape.com.
Biomarkers may help women with RA to decide on medications in pregnancy
Rheumatoid arthritis can’t be cured, but it can significantly improve naturally during pregnancy in 50%-75% of women, prior research has established. It may worsen or stay the same during pregnancy in others.
As of yet, there’s no way to tell which experience a woman with RA will have. RA occurs in 1% of adults globally and is three times more likely to occur in women.
However, a novel study of 19 women with RA suggests that blood biomarkers before pregnancy may predict who will get better or worse during pregnancy. If confirmed with larger studies, the discovery could lead to personalizing medication choices for women with RA who are seeking to become pregnant and change prepregnancy counseling for physicians.
Findings from the research, conducted by first author Matthew Wright, MS, of Children’s Hospital Oakland (Calif.) Research Institute and colleagues were published online in Arthritis Research & Therapy.
A risky choice for women
Currently, the choice is difficult because stopping medications during pregnancy could cause disease flare and continuing could risk possible harm to the baby as some of the medications have toxic side effects.
This is the first study to analyze genetic differences in women with RA who plan to get pregnant, senior author Damini Jawaheer, PhD, research associate professor of medicine in rheumatology at Northwestern University, Chicago, said in an interview.
Identifying women who have the disease and confirming they were planning to get pregnant has been extremely difficult, she noted, especially since the start of their research predated electronic health records (EHRs).
The researchers were able to develop a cohort from work they were already doing with researchers in Denmark, which has a national registry that included both women with RA and women of reproductive age. From there they could contact women about their pregnancy intentions and build the cohort for this study.
Healthy women and women with RA of Danish descent who planned to get pregnant were enrolled and were prospectively followed.
Genetic differences at prepregnancy baseline
Researchers analyzed genetic differences through RNA sequencing before pregnancy from 19 women with RA and 13 healthy women.
Of the 19 women with RA, disease activity improved during pregnancy in 14 and worsened in 5.
Before pregnancy, the researchers found, several neutrophil-related genes were significantly overexpressed in women whose RA later improved during pregnancy. Genes related to B cells were highly expressed among women who worsened. Those elevated B-cell–related gene levels were not seen in the group who improved during pregnancy, Dr. Jawaheer added.
“We don’t understand at this point why that is,” she said.
They also compared the blood samples with women in the control group who did not have RA.
“Comparisons to healthy women revealed that the B-cell signature was specific” to women with worsened RA, the authors wrote. “Thus, at the prepregnancy stage, the two groups of RA women differed significantly from each other in terms of B-cell function.”
Information could help to eliminate fear
Dr. Jawaheer said almost all the women in the cohort who have RA said they were afraid to take medications during pregnancy even if the medications they are taking are considered safe.
“If we could reliably predict who’s going to improve, those women would not have to be scared,” she said. They could stop their medications if they know they’re going to improve naturally.
“Women who are predicted to worsen could then work together with their rheumatologist so that they get treatment to prevent them from getting worse,” Dr. Jawaheer said. “Treatment could be focused on that group only.”
Arthur Kavanaugh, MD, a rheumatologist at University of California San Diego Health and director of the UCSD Center for Innovative Therapy, who was not part of the study, said his patients planning pregnancy struggle with the choices the researchers describe and that investigating potential biomarkers is important.
“Ideally, people would not want to be on anything when they’re pregnant,” he says.
He found the results “intriguing and hypothesis-generating,” but he said the small sample size makes it hard to draw conclusions about the work before it is replicated on a larger scale.
Beth L. Jonas, MD, chief of the division of rheumatology, allergy, and immunology at the University of North Carolina, Chapel Hill, also not a part of the study, said the small study size must be considered, but if the findings are validated in larger studies, the potential is “huge.”
She said doctors used to tell their patients years ago that there’s an excellent chance they will be in remission in pregnancy.
Now, she says, “We’ve tempered our advice to say there’s a good chance you’ll still have disease activity during your pregnancy.”
Rheumatologists would be very interested in a predictive biomarker, she said, as would colleagues in obstetrics/gynecology and maternal-fetal medicine physicians who manage high-risk pregnancies and do prepregnancy counseling.
She said she would also like to see these data followed over multiple pregnancies for each woman, noting that some of her patients have seen RA improve in one pregnancy and worsen in another.
A question she has is, “with a single patient with RA, could you measure this multiple times and get different results?”
Tackling the unanswered questions
Next, the researchers want to conduct the study with a larger sample in the United States and one that is more diverse than the Danish cohort, which included only White patients. Now, Dr. Jawaheer and her team will have the help of EHRs.
A big part of Dr. Jawaheer’s lab’s focus is to find out why many with RA report “never feeling better” during pregnancy – some even experience remission – and why women who improve during pregnancy report that their disease flares 3-6 months after pregnancy, she said.
Her team is also studying what happens biologically when some women worsen in pregnancy.
Those answers “will give us an indication of what could be a potential drug target,” she said.
The authors and Dr. Kavanaugh and Dr. Jonas reported no relevant financial relationships.
Rheumatoid arthritis can’t be cured, but it can significantly improve naturally during pregnancy in 50%-75% of women, prior research has established. It may worsen or stay the same during pregnancy in others.
As of yet, there’s no way to tell which experience a woman with RA will have. RA occurs in 1% of adults globally and is three times more likely to occur in women.
However, a novel study of 19 women with RA suggests that blood biomarkers before pregnancy may predict who will get better or worse during pregnancy. If confirmed with larger studies, the discovery could lead to personalizing medication choices for women with RA who are seeking to become pregnant and change prepregnancy counseling for physicians.
Findings from the research, conducted by first author Matthew Wright, MS, of Children’s Hospital Oakland (Calif.) Research Institute and colleagues were published online in Arthritis Research & Therapy.
A risky choice for women
Currently, the choice is difficult because stopping medications during pregnancy could cause disease flare and continuing could risk possible harm to the baby as some of the medications have toxic side effects.
This is the first study to analyze genetic differences in women with RA who plan to get pregnant, senior author Damini Jawaheer, PhD, research associate professor of medicine in rheumatology at Northwestern University, Chicago, said in an interview.
Identifying women who have the disease and confirming they were planning to get pregnant has been extremely difficult, she noted, especially since the start of their research predated electronic health records (EHRs).
The researchers were able to develop a cohort from work they were already doing with researchers in Denmark, which has a national registry that included both women with RA and women of reproductive age. From there they could contact women about their pregnancy intentions and build the cohort for this study.
Healthy women and women with RA of Danish descent who planned to get pregnant were enrolled and were prospectively followed.
Genetic differences at prepregnancy baseline
Researchers analyzed genetic differences through RNA sequencing before pregnancy from 19 women with RA and 13 healthy women.
Of the 19 women with RA, disease activity improved during pregnancy in 14 and worsened in 5.
Before pregnancy, the researchers found, several neutrophil-related genes were significantly overexpressed in women whose RA later improved during pregnancy. Genes related to B cells were highly expressed among women who worsened. Those elevated B-cell–related gene levels were not seen in the group who improved during pregnancy, Dr. Jawaheer added.
“We don’t understand at this point why that is,” she said.
They also compared the blood samples with women in the control group who did not have RA.
“Comparisons to healthy women revealed that the B-cell signature was specific” to women with worsened RA, the authors wrote. “Thus, at the prepregnancy stage, the two groups of RA women differed significantly from each other in terms of B-cell function.”
Information could help to eliminate fear
Dr. Jawaheer said almost all the women in the cohort who have RA said they were afraid to take medications during pregnancy even if the medications they are taking are considered safe.
“If we could reliably predict who’s going to improve, those women would not have to be scared,” she said. They could stop their medications if they know they’re going to improve naturally.
“Women who are predicted to worsen could then work together with their rheumatologist so that they get treatment to prevent them from getting worse,” Dr. Jawaheer said. “Treatment could be focused on that group only.”
Arthur Kavanaugh, MD, a rheumatologist at University of California San Diego Health and director of the UCSD Center for Innovative Therapy, who was not part of the study, said his patients planning pregnancy struggle with the choices the researchers describe and that investigating potential biomarkers is important.
“Ideally, people would not want to be on anything when they’re pregnant,” he says.
He found the results “intriguing and hypothesis-generating,” but he said the small sample size makes it hard to draw conclusions about the work before it is replicated on a larger scale.
Beth L. Jonas, MD, chief of the division of rheumatology, allergy, and immunology at the University of North Carolina, Chapel Hill, also not a part of the study, said the small study size must be considered, but if the findings are validated in larger studies, the potential is “huge.”
She said doctors used to tell their patients years ago that there’s an excellent chance they will be in remission in pregnancy.
Now, she says, “We’ve tempered our advice to say there’s a good chance you’ll still have disease activity during your pregnancy.”
Rheumatologists would be very interested in a predictive biomarker, she said, as would colleagues in obstetrics/gynecology and maternal-fetal medicine physicians who manage high-risk pregnancies and do prepregnancy counseling.
She said she would also like to see these data followed over multiple pregnancies for each woman, noting that some of her patients have seen RA improve in one pregnancy and worsen in another.
A question she has is, “with a single patient with RA, could you measure this multiple times and get different results?”
Tackling the unanswered questions
Next, the researchers want to conduct the study with a larger sample in the United States and one that is more diverse than the Danish cohort, which included only White patients. Now, Dr. Jawaheer and her team will have the help of EHRs.
A big part of Dr. Jawaheer’s lab’s focus is to find out why many with RA report “never feeling better” during pregnancy – some even experience remission – and why women who improve during pregnancy report that their disease flares 3-6 months after pregnancy, she said.
Her team is also studying what happens biologically when some women worsen in pregnancy.
Those answers “will give us an indication of what could be a potential drug target,” she said.
The authors and Dr. Kavanaugh and Dr. Jonas reported no relevant financial relationships.
Rheumatoid arthritis can’t be cured, but it can significantly improve naturally during pregnancy in 50%-75% of women, prior research has established. It may worsen or stay the same during pregnancy in others.
As of yet, there’s no way to tell which experience a woman with RA will have. RA occurs in 1% of adults globally and is three times more likely to occur in women.
However, a novel study of 19 women with RA suggests that blood biomarkers before pregnancy may predict who will get better or worse during pregnancy. If confirmed with larger studies, the discovery could lead to personalizing medication choices for women with RA who are seeking to become pregnant and change prepregnancy counseling for physicians.
Findings from the research, conducted by first author Matthew Wright, MS, of Children’s Hospital Oakland (Calif.) Research Institute and colleagues were published online in Arthritis Research & Therapy.
A risky choice for women
Currently, the choice is difficult because stopping medications during pregnancy could cause disease flare and continuing could risk possible harm to the baby as some of the medications have toxic side effects.
This is the first study to analyze genetic differences in women with RA who plan to get pregnant, senior author Damini Jawaheer, PhD, research associate professor of medicine in rheumatology at Northwestern University, Chicago, said in an interview.
Identifying women who have the disease and confirming they were planning to get pregnant has been extremely difficult, she noted, especially since the start of their research predated electronic health records (EHRs).
The researchers were able to develop a cohort from work they were already doing with researchers in Denmark, which has a national registry that included both women with RA and women of reproductive age. From there they could contact women about their pregnancy intentions and build the cohort for this study.
Healthy women and women with RA of Danish descent who planned to get pregnant were enrolled and were prospectively followed.
Genetic differences at prepregnancy baseline
Researchers analyzed genetic differences through RNA sequencing before pregnancy from 19 women with RA and 13 healthy women.
Of the 19 women with RA, disease activity improved during pregnancy in 14 and worsened in 5.
Before pregnancy, the researchers found, several neutrophil-related genes were significantly overexpressed in women whose RA later improved during pregnancy. Genes related to B cells were highly expressed among women who worsened. Those elevated B-cell–related gene levels were not seen in the group who improved during pregnancy, Dr. Jawaheer added.
“We don’t understand at this point why that is,” she said.
They also compared the blood samples with women in the control group who did not have RA.
“Comparisons to healthy women revealed that the B-cell signature was specific” to women with worsened RA, the authors wrote. “Thus, at the prepregnancy stage, the two groups of RA women differed significantly from each other in terms of B-cell function.”
Information could help to eliminate fear
Dr. Jawaheer said almost all the women in the cohort who have RA said they were afraid to take medications during pregnancy even if the medications they are taking are considered safe.
“If we could reliably predict who’s going to improve, those women would not have to be scared,” she said. They could stop their medications if they know they’re going to improve naturally.
“Women who are predicted to worsen could then work together with their rheumatologist so that they get treatment to prevent them from getting worse,” Dr. Jawaheer said. “Treatment could be focused on that group only.”
Arthur Kavanaugh, MD, a rheumatologist at University of California San Diego Health and director of the UCSD Center for Innovative Therapy, who was not part of the study, said his patients planning pregnancy struggle with the choices the researchers describe and that investigating potential biomarkers is important.
“Ideally, people would not want to be on anything when they’re pregnant,” he says.
He found the results “intriguing and hypothesis-generating,” but he said the small sample size makes it hard to draw conclusions about the work before it is replicated on a larger scale.
Beth L. Jonas, MD, chief of the division of rheumatology, allergy, and immunology at the University of North Carolina, Chapel Hill, also not a part of the study, said the small study size must be considered, but if the findings are validated in larger studies, the potential is “huge.”
She said doctors used to tell their patients years ago that there’s an excellent chance they will be in remission in pregnancy.
Now, she says, “We’ve tempered our advice to say there’s a good chance you’ll still have disease activity during your pregnancy.”
Rheumatologists would be very interested in a predictive biomarker, she said, as would colleagues in obstetrics/gynecology and maternal-fetal medicine physicians who manage high-risk pregnancies and do prepregnancy counseling.
She said she would also like to see these data followed over multiple pregnancies for each woman, noting that some of her patients have seen RA improve in one pregnancy and worsen in another.
A question she has is, “with a single patient with RA, could you measure this multiple times and get different results?”
Tackling the unanswered questions
Next, the researchers want to conduct the study with a larger sample in the United States and one that is more diverse than the Danish cohort, which included only White patients. Now, Dr. Jawaheer and her team will have the help of EHRs.
A big part of Dr. Jawaheer’s lab’s focus is to find out why many with RA report “never feeling better” during pregnancy – some even experience remission – and why women who improve during pregnancy report that their disease flares 3-6 months after pregnancy, she said.
Her team is also studying what happens biologically when some women worsen in pregnancy.
Those answers “will give us an indication of what could be a potential drug target,” she said.
The authors and Dr. Kavanaugh and Dr. Jonas reported no relevant financial relationships.
FROM ARTHRITIS RESEARCH & THERAPY
Tool in development aims to steer telehealth visit appropriateness in rheumatology
Researchers have created a model to suggest which rheumatology visits can be effectively carried out via telehealth and which should remain in-person visits. The model not only could help to alleviate the decision burden on providers but also help to navigate how to incorporate telehealth into daily rheumatology practice as the COVID-19 pandemic subsides, experts say.
The beginning of the pandemic quickly drove rheumatology practices to adopt telehealth – which in the past has been studied only in selective groups of relatively stable patients. In Duke University’s department of rheumatology, nearly 90% of visits were conducted via telehealth for several weeks in April and May 2020, said David L. Leverenz, MD, an assistant professor of medicine at Duke University in Durham, N.C.
Since then, the practice has continued providing telehealth for a wider variety of patients: patients with high disease activity, those with low disease activity, people living 3 hours away or just 5 minutes from the medical center.
“Although the pandemic has really improved, and certainly we feel very safe providing in-person care, we’ve realized that it’s actually really possible to provide telehealth care to a lot of patients,” he said.
The model was then piloted with four Duke University rheumatologists for visits that took place from March through July 2022. A month prior to visits, researchers provided the rheumatologists a list of in-patient visits that the model suggested could be changed to telehealth visits. The list also included false changes, in which randomly selected visits were presented as being recommended for telehealth, although the model had not actually recommended the changes.
Dr. Leverenz and colleagues measured how frequently providers agreed with changes recommended by the model and the false changes. If a provider accepted a model-suggested change, the patient was contacted to either accept or reject the proposed switch. If a provider agreed with a false change, no additional action was taken.
Of the 201 patient encounters, there were 101 model-recommended changes and 100 artificial changes. Nearly all (99%) model-recommended changes suggested moving from in-person visits to telehealth visits. There was one recommendation to change a scheduled telehealth encounter to an in-person encounter. Of the false recommendations, 90 were for scheduled in-person visits, and 10 were for scheduled telehealth appointments.
Providers agreed with 71% of the model-recommended changes and with 21% of the false changes. Dr. Leverenz and colleagues reported “moderate agreement” between providers and model recommendations, reflected by a Cohen kappa coefficient of 0.45.
“This lined up pretty well with what providers thought was appropriate for the patient when presented with the information, and it also showed that, on top of current practice, that the model really does have the ability to expand appropriate telehealth care, which is really what we’re looking to do,” Dr. Leverenz said.
The article describing these results was published in Arthritis Care and Research.
Perhaps unsurprisingly, clinician preference for and experience with telemedicine were the biggest predictors of whether changes suggested by the model were accepted.
Focus model to specific diagnoses or many?
Currently, clinicians who are already juggling many other responsibilities throughout the day must use their own judgment to determine whether telemedicine may be appropriate. A model such as this could help alleviate that decision burden, said Kathleen Fear, PhD, the director of data and analytics at the University of Rochester Medical Center Health Lab, in New York.
“A model that can help with scheduling or prompt a provider or patient for when a visit is appropriate for telemedicine seems like a really effective way to make the most of telemedicine while reducing potential burden on providers,” she said.
Dr. Leverenz imagines that this model could be embedded into electronic health records as a “decision support tool” to aid discussions between patients and providers on whether telehealth might be appropriate for upcoming visits.
But developing a model that can generate predictions for the wide variety of conditions seen in daily rheumatology practice can be a challenge, said Christine Peoples, MD, a clinical associate professor of medicine and director of the tele-rheumatology program at the University of Pittsburgh.
“If you focus the model to certain diagnoses, at least in the beginning, that’s very helpful, because it’s too difficult to have one model for every single reason that folks see a rheumatologist,” she said.
Daniel A. Albert, MD, a professor of medicine and pediatrics at the Geisel School of Medicine at Dartmouth in Hanover, N,H., agreed. The model is “a good start,” he said, and highlights that tele-rheumatology continues to be underutilized in practice. But he argued that the moderate agreement found with the model was relatively low.
A more focused algorithm that targets a single or several more common conditions may be more accurate, he said. “You probably want to break it down,” Dr. Albert said.
But Dr. Leverenz argued that the novelty of this model is that it incorporates the many different conditions seen in daily rheumatology practice, whereas previous programs utilizing telehealth focused on specific conditions and patients with low disease activity.
In addition, the model is currently provider centric and does not take patient preference into account, Dr. Albert added. Dr. Leverenz said that that is the next step in further developing this model. He is currently conducting qualitative analyses with patients to better understand what patients think and how often their views on telehealth differ from that of their care providers.
“Hopefully, we can expand appropriate telehealth visits by teaching providers not just to do what they think is right for the patient but also meet the patient’s expectations and needs, based on what we learn,” he said.
The study was funded by a grant from Pfizer. Dr. Leverenz has received grants from Pfizer and has served as a consultant for Sanofi. None of the study’s other authors report relevant financial relationships. Dr. Peoples is an educational consultant on telehealth for Pfizer. Dr. Alberts has previously received grant funding from Pfizer. Dr. Fear has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have created a model to suggest which rheumatology visits can be effectively carried out via telehealth and which should remain in-person visits. The model not only could help to alleviate the decision burden on providers but also help to navigate how to incorporate telehealth into daily rheumatology practice as the COVID-19 pandemic subsides, experts say.
The beginning of the pandemic quickly drove rheumatology practices to adopt telehealth – which in the past has been studied only in selective groups of relatively stable patients. In Duke University’s department of rheumatology, nearly 90% of visits were conducted via telehealth for several weeks in April and May 2020, said David L. Leverenz, MD, an assistant professor of medicine at Duke University in Durham, N.C.
Since then, the practice has continued providing telehealth for a wider variety of patients: patients with high disease activity, those with low disease activity, people living 3 hours away or just 5 minutes from the medical center.
“Although the pandemic has really improved, and certainly we feel very safe providing in-person care, we’ve realized that it’s actually really possible to provide telehealth care to a lot of patients,” he said.
The model was then piloted with four Duke University rheumatologists for visits that took place from March through July 2022. A month prior to visits, researchers provided the rheumatologists a list of in-patient visits that the model suggested could be changed to telehealth visits. The list also included false changes, in which randomly selected visits were presented as being recommended for telehealth, although the model had not actually recommended the changes.
Dr. Leverenz and colleagues measured how frequently providers agreed with changes recommended by the model and the false changes. If a provider accepted a model-suggested change, the patient was contacted to either accept or reject the proposed switch. If a provider agreed with a false change, no additional action was taken.
Of the 201 patient encounters, there were 101 model-recommended changes and 100 artificial changes. Nearly all (99%) model-recommended changes suggested moving from in-person visits to telehealth visits. There was one recommendation to change a scheduled telehealth encounter to an in-person encounter. Of the false recommendations, 90 were for scheduled in-person visits, and 10 were for scheduled telehealth appointments.
Providers agreed with 71% of the model-recommended changes and with 21% of the false changes. Dr. Leverenz and colleagues reported “moderate agreement” between providers and model recommendations, reflected by a Cohen kappa coefficient of 0.45.
“This lined up pretty well with what providers thought was appropriate for the patient when presented with the information, and it also showed that, on top of current practice, that the model really does have the ability to expand appropriate telehealth care, which is really what we’re looking to do,” Dr. Leverenz said.
The article describing these results was published in Arthritis Care and Research.
Perhaps unsurprisingly, clinician preference for and experience with telemedicine were the biggest predictors of whether changes suggested by the model were accepted.
Focus model to specific diagnoses or many?
Currently, clinicians who are already juggling many other responsibilities throughout the day must use their own judgment to determine whether telemedicine may be appropriate. A model such as this could help alleviate that decision burden, said Kathleen Fear, PhD, the director of data and analytics at the University of Rochester Medical Center Health Lab, in New York.
“A model that can help with scheduling or prompt a provider or patient for when a visit is appropriate for telemedicine seems like a really effective way to make the most of telemedicine while reducing potential burden on providers,” she said.
Dr. Leverenz imagines that this model could be embedded into electronic health records as a “decision support tool” to aid discussions between patients and providers on whether telehealth might be appropriate for upcoming visits.
But developing a model that can generate predictions for the wide variety of conditions seen in daily rheumatology practice can be a challenge, said Christine Peoples, MD, a clinical associate professor of medicine and director of the tele-rheumatology program at the University of Pittsburgh.
“If you focus the model to certain diagnoses, at least in the beginning, that’s very helpful, because it’s too difficult to have one model for every single reason that folks see a rheumatologist,” she said.
Daniel A. Albert, MD, a professor of medicine and pediatrics at the Geisel School of Medicine at Dartmouth in Hanover, N,H., agreed. The model is “a good start,” he said, and highlights that tele-rheumatology continues to be underutilized in practice. But he argued that the moderate agreement found with the model was relatively low.
A more focused algorithm that targets a single or several more common conditions may be more accurate, he said. “You probably want to break it down,” Dr. Albert said.
But Dr. Leverenz argued that the novelty of this model is that it incorporates the many different conditions seen in daily rheumatology practice, whereas previous programs utilizing telehealth focused on specific conditions and patients with low disease activity.
In addition, the model is currently provider centric and does not take patient preference into account, Dr. Albert added. Dr. Leverenz said that that is the next step in further developing this model. He is currently conducting qualitative analyses with patients to better understand what patients think and how often their views on telehealth differ from that of their care providers.
“Hopefully, we can expand appropriate telehealth visits by teaching providers not just to do what they think is right for the patient but also meet the patient’s expectations and needs, based on what we learn,” he said.
The study was funded by a grant from Pfizer. Dr. Leverenz has received grants from Pfizer and has served as a consultant for Sanofi. None of the study’s other authors report relevant financial relationships. Dr. Peoples is an educational consultant on telehealth for Pfizer. Dr. Alberts has previously received grant funding from Pfizer. Dr. Fear has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers have created a model to suggest which rheumatology visits can be effectively carried out via telehealth and which should remain in-person visits. The model not only could help to alleviate the decision burden on providers but also help to navigate how to incorporate telehealth into daily rheumatology practice as the COVID-19 pandemic subsides, experts say.
The beginning of the pandemic quickly drove rheumatology practices to adopt telehealth – which in the past has been studied only in selective groups of relatively stable patients. In Duke University’s department of rheumatology, nearly 90% of visits were conducted via telehealth for several weeks in April and May 2020, said David L. Leverenz, MD, an assistant professor of medicine at Duke University in Durham, N.C.
Since then, the practice has continued providing telehealth for a wider variety of patients: patients with high disease activity, those with low disease activity, people living 3 hours away or just 5 minutes from the medical center.
“Although the pandemic has really improved, and certainly we feel very safe providing in-person care, we’ve realized that it’s actually really possible to provide telehealth care to a lot of patients,” he said.
The model was then piloted with four Duke University rheumatologists for visits that took place from March through July 2022. A month prior to visits, researchers provided the rheumatologists a list of in-patient visits that the model suggested could be changed to telehealth visits. The list also included false changes, in which randomly selected visits were presented as being recommended for telehealth, although the model had not actually recommended the changes.
Dr. Leverenz and colleagues measured how frequently providers agreed with changes recommended by the model and the false changes. If a provider accepted a model-suggested change, the patient was contacted to either accept or reject the proposed switch. If a provider agreed with a false change, no additional action was taken.
Of the 201 patient encounters, there were 101 model-recommended changes and 100 artificial changes. Nearly all (99%) model-recommended changes suggested moving from in-person visits to telehealth visits. There was one recommendation to change a scheduled telehealth encounter to an in-person encounter. Of the false recommendations, 90 were for scheduled in-person visits, and 10 were for scheduled telehealth appointments.
Providers agreed with 71% of the model-recommended changes and with 21% of the false changes. Dr. Leverenz and colleagues reported “moderate agreement” between providers and model recommendations, reflected by a Cohen kappa coefficient of 0.45.
“This lined up pretty well with what providers thought was appropriate for the patient when presented with the information, and it also showed that, on top of current practice, that the model really does have the ability to expand appropriate telehealth care, which is really what we’re looking to do,” Dr. Leverenz said.
The article describing these results was published in Arthritis Care and Research.
Perhaps unsurprisingly, clinician preference for and experience with telemedicine were the biggest predictors of whether changes suggested by the model were accepted.
Focus model to specific diagnoses or many?
Currently, clinicians who are already juggling many other responsibilities throughout the day must use their own judgment to determine whether telemedicine may be appropriate. A model such as this could help alleviate that decision burden, said Kathleen Fear, PhD, the director of data and analytics at the University of Rochester Medical Center Health Lab, in New York.
“A model that can help with scheduling or prompt a provider or patient for when a visit is appropriate for telemedicine seems like a really effective way to make the most of telemedicine while reducing potential burden on providers,” she said.
Dr. Leverenz imagines that this model could be embedded into electronic health records as a “decision support tool” to aid discussions between patients and providers on whether telehealth might be appropriate for upcoming visits.
But developing a model that can generate predictions for the wide variety of conditions seen in daily rheumatology practice can be a challenge, said Christine Peoples, MD, a clinical associate professor of medicine and director of the tele-rheumatology program at the University of Pittsburgh.
“If you focus the model to certain diagnoses, at least in the beginning, that’s very helpful, because it’s too difficult to have one model for every single reason that folks see a rheumatologist,” she said.
Daniel A. Albert, MD, a professor of medicine and pediatrics at the Geisel School of Medicine at Dartmouth in Hanover, N,H., agreed. The model is “a good start,” he said, and highlights that tele-rheumatology continues to be underutilized in practice. But he argued that the moderate agreement found with the model was relatively low.
A more focused algorithm that targets a single or several more common conditions may be more accurate, he said. “You probably want to break it down,” Dr. Albert said.
But Dr. Leverenz argued that the novelty of this model is that it incorporates the many different conditions seen in daily rheumatology practice, whereas previous programs utilizing telehealth focused on specific conditions and patients with low disease activity.
In addition, the model is currently provider centric and does not take patient preference into account, Dr. Albert added. Dr. Leverenz said that that is the next step in further developing this model. He is currently conducting qualitative analyses with patients to better understand what patients think and how often their views on telehealth differ from that of their care providers.
“Hopefully, we can expand appropriate telehealth visits by teaching providers not just to do what they think is right for the patient but also meet the patient’s expectations and needs, based on what we learn,” he said.
The study was funded by a grant from Pfizer. Dr. Leverenz has received grants from Pfizer and has served as a consultant for Sanofi. None of the study’s other authors report relevant financial relationships. Dr. Peoples is an educational consultant on telehealth for Pfizer. Dr. Alberts has previously received grant funding from Pfizer. Dr. Fear has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ARTHRITIS CARE AND RESEARCH
Anemia, iron deficit common in rheumatic disease pregnancy
TOPLINE:
, according to findings from a longitudinal cohort study.
METHODOLOGY:
- Researchers analyzed data from 368 pregnancies in women with rheumatic diseases during the period 2014-2022; nearly two-thirds (62%) had a connective tissue disease, 16% had rheumatoid arthritis or juvenile idiopathic arthritis, 14% had spondyloarthritis, 3% had vasculitis, and 7% had other diseases.
- Patients were aged 17-44 years, with a median age of 32 years at the time of birth.
- Researchers examined the frequency of anemia and iron deficiency and the impact of anemia on adverse maternal and child outcomes.
TAKEAWAY:
- The prevalence of iron deficiency was 28%, 51%, and 62% in the first, second, and third trimesters, respectively.
- The prevalence of anemia was 18%, 27%, and 33% in the first, second, and third trimesters, respectively.
- There was an increased risk for fetal complications such as malformation, infections, small for gestational age, neonatal lupus, preterm birth, and abortion or stillbirth in association with maternal connective tissue disease (odds ratio, 2.14) and also with low maternal hemoglobin levels and maternal iron deficiency (ORs, 0.52 and 0.86, respectively).
- Lower maternal hemoglobin levels were associated with an increased risk for maternal complications (OR, 1.47) such as flare with adaption of rheumatic medication and pregnancy-related adverse events (preeclampsia, gestational diabetes, bleeding complications, and thromboembolism), but patients with connective tissue disease had a lower risk for maternal complications (OR, 0.51); mean serum ferritin had no significant impact on maternal complications (OR, 1.02).
IN PRACTICE:
“Patients with rheumatic diseases suffer more often and already in early pregnancy from iron deficiency,” the researchers write. Therefore, early identification of anemia and iron deficiency in this population could inform prepregnancy counseling.
SOURCE:
The lead author on the study was Ann-Christin Pecher, MD, of University Hospital Tübingen, Germany. The study was published online in Joint Bone Spine.
LIMITATIONS:
The findings were limited by the use of a single dataset that might not be representative of all pregnant patients with rheumatic diseases. Other limitations included the lack of a standardized approach to iron supplementation.
DISCLOSURES:
The study was supported by a grant from the Medical Faculty of Tübingen Clinician-Scientist to the lead author. The researchers report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
, according to findings from a longitudinal cohort study.
METHODOLOGY:
- Researchers analyzed data from 368 pregnancies in women with rheumatic diseases during the period 2014-2022; nearly two-thirds (62%) had a connective tissue disease, 16% had rheumatoid arthritis or juvenile idiopathic arthritis, 14% had spondyloarthritis, 3% had vasculitis, and 7% had other diseases.
- Patients were aged 17-44 years, with a median age of 32 years at the time of birth.
- Researchers examined the frequency of anemia and iron deficiency and the impact of anemia on adverse maternal and child outcomes.
TAKEAWAY:
- The prevalence of iron deficiency was 28%, 51%, and 62% in the first, second, and third trimesters, respectively.
- The prevalence of anemia was 18%, 27%, and 33% in the first, second, and third trimesters, respectively.
- There was an increased risk for fetal complications such as malformation, infections, small for gestational age, neonatal lupus, preterm birth, and abortion or stillbirth in association with maternal connective tissue disease (odds ratio, 2.14) and also with low maternal hemoglobin levels and maternal iron deficiency (ORs, 0.52 and 0.86, respectively).
- Lower maternal hemoglobin levels were associated with an increased risk for maternal complications (OR, 1.47) such as flare with adaption of rheumatic medication and pregnancy-related adverse events (preeclampsia, gestational diabetes, bleeding complications, and thromboembolism), but patients with connective tissue disease had a lower risk for maternal complications (OR, 0.51); mean serum ferritin had no significant impact on maternal complications (OR, 1.02).
IN PRACTICE:
“Patients with rheumatic diseases suffer more often and already in early pregnancy from iron deficiency,” the researchers write. Therefore, early identification of anemia and iron deficiency in this population could inform prepregnancy counseling.
SOURCE:
The lead author on the study was Ann-Christin Pecher, MD, of University Hospital Tübingen, Germany. The study was published online in Joint Bone Spine.
LIMITATIONS:
The findings were limited by the use of a single dataset that might not be representative of all pregnant patients with rheumatic diseases. Other limitations included the lack of a standardized approach to iron supplementation.
DISCLOSURES:
The study was supported by a grant from the Medical Faculty of Tübingen Clinician-Scientist to the lead author. The researchers report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
, according to findings from a longitudinal cohort study.
METHODOLOGY:
- Researchers analyzed data from 368 pregnancies in women with rheumatic diseases during the period 2014-2022; nearly two-thirds (62%) had a connective tissue disease, 16% had rheumatoid arthritis or juvenile idiopathic arthritis, 14% had spondyloarthritis, 3% had vasculitis, and 7% had other diseases.
- Patients were aged 17-44 years, with a median age of 32 years at the time of birth.
- Researchers examined the frequency of anemia and iron deficiency and the impact of anemia on adverse maternal and child outcomes.
TAKEAWAY:
- The prevalence of iron deficiency was 28%, 51%, and 62% in the first, second, and third trimesters, respectively.
- The prevalence of anemia was 18%, 27%, and 33% in the first, second, and third trimesters, respectively.
- There was an increased risk for fetal complications such as malformation, infections, small for gestational age, neonatal lupus, preterm birth, and abortion or stillbirth in association with maternal connective tissue disease (odds ratio, 2.14) and also with low maternal hemoglobin levels and maternal iron deficiency (ORs, 0.52 and 0.86, respectively).
- Lower maternal hemoglobin levels were associated with an increased risk for maternal complications (OR, 1.47) such as flare with adaption of rheumatic medication and pregnancy-related adverse events (preeclampsia, gestational diabetes, bleeding complications, and thromboembolism), but patients with connective tissue disease had a lower risk for maternal complications (OR, 0.51); mean serum ferritin had no significant impact on maternal complications (OR, 1.02).
IN PRACTICE:
“Patients with rheumatic diseases suffer more often and already in early pregnancy from iron deficiency,” the researchers write. Therefore, early identification of anemia and iron deficiency in this population could inform prepregnancy counseling.
SOURCE:
The lead author on the study was Ann-Christin Pecher, MD, of University Hospital Tübingen, Germany. The study was published online in Joint Bone Spine.
LIMITATIONS:
The findings were limited by the use of a single dataset that might not be representative of all pregnant patients with rheumatic diseases. Other limitations included the lack of a standardized approach to iron supplementation.
DISCLOSURES:
The study was supported by a grant from the Medical Faculty of Tübingen Clinician-Scientist to the lead author. The researchers report no relevant financial relationships.
A version of this article first appeared on Medscape.com.