Rheumatology

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.

Once considered a luxury, hiring a nurse, nurse practitioner, or physician assistant is becoming a necessity in many rheumatology practices.

Seeing the wait lists pile up in her Florida practice, Stacy Yonker, MBA, chief executive officer of Sarasota Arthritis Center, knew she had to make some changes. “Everyone’s aging in the boomer generations. Particularly in Florida, we have a lot of people who retire here. In the more southern demographics, it is a very difficult challenge for practices to get new patients in,” she said.

Ms. Yonker is in the process of hiring several nurse practitioners (NPs) to assist in the clinics and infusion suites, lightening the load for the practice’s 11 rheumatologists.

Hiring an advanced practice provider (APP) to support the practice is just a first step. Getting these additional personnel up to speed means an investment in education and fostering good working relationships with NPs, PAs, and the staff’s physicians. Even more importantly, practices need to set realistic expectations on workload for these new hires.

“I tried to hire them, but I couldn’t keep them,” is a statement Christine A. Stamatos, DNP, ANP-C, hears all the time from rheumatologists. Oftentimes it’s because the practice saddles the new hire with 20 patients a day, said Dr. Stamatos, director of the Fibromyalgia Wellness Center within the division of rheumatology at Northwell Health in Huntington, New York. She is also an assistant professor at Hofstra Northwell School of Graduate Nursing and Physician Assistant Studies in Hempstead, New York.

“Twenty patients a day is too much,” Dr. Stamatos said. Overload someone, and they won’t stay. Offer them the support, mentoring, and tools they need to practice in their setting ­­— and they will.
 

Why the Profession Needs APPs

Rheumatology is a much smaller specialty than most, with only a set number of rheumatologists in the field that can provide care to patients. A growing shortage is also looming. Reports from the American College of Rheumatology have projected troubling shortfalls in rheumatologists over the next decade in all regions of the United States.

Many of them aging into retirement “poses a significant issue on being able to continue providing care for the population that experiences the rheumatic disease,” said Ms. Yonker, a director of the National Organization of Rheumatology Management (NORM), a forum that promotes education and advocacy for rheumatology practice managers. People are also living longer, which means more patients are developing arthritis and autoimmune diseases.

Julia M. Swafford, PA-C, a rheumatology physician assistant in Battle Creek, Michigan, sees many advantages of hiring NPs and PAs, and not just from a financial perspective.

Salaries for PAs and NPs aren’t as high and they’re also more accessible than a rheumatologist. “You could train an NP or PA a lot quicker during that same time frame it would take to find a new rheumatology provider,” she offered. And while they may not be as experienced as rheumatologists, “you can kind of mold me on how you like to practice, what medications you may like to use, how you like to treat your patients,” Ms. Swafford said.
 

Hiring Someone With Experience

Recruiting and retaining APPs is not without its challenges.

Finding individuals compatible with this specialty isn’t easy, noted Mark Box, MD, medical director of Carondelet Rheumatology in Kansas City, Missouri. Ideally, APPs should be inquisitive, compassionate, and ready to learn. “Rheumatology is a cognitive specialty where you have to fit many pieces together. You need an APP who wants to embrace that,” he said.

The profession isn’t that “sexy” either, noted Katie Taylor, Carondelet’s practice manager. Patients are often in head-to-toe pain, and miserable. Many have been to other specialists without answers to their questions. For these reasons, rheumatology can be a hard sell for some PAs and NPs.

Nurse practitioners aren’t always comfortable with administering things such as controlled medications, for example. “It’s a hard patient population, and it’s a specialty of exclusion. You’ve got to be really smart to understand our diseases and our processes and our drugs,” Ms. Taylor said. In other words, it’s a difficult environment for an NP to walk into if their previous experience has been limited to upper respiratory issues and urinary tract infections in the primary care setting.

When hiring an APP, rheumatologists should look for someone who demonstrates an interest in lifelong learning, because the field is changing every day. They should exhibit good scores in educational training and have experience working in an emergency department or another field that translates well into rheumatology such as critical care, immunology, hematology, and orthopedics, she said.

Carondelet Rheumatology was specifically looking for an NP with rheumatology experience to support Dr. Box’s solo practice.

He was facing enormous pressure to be in the office every single day of the week. The practice had to cancel patients for its infusion suite on a regular basis when he was out of the office, Ms. Taylor said. “We couldn’t see new patients, and he wasn’t able to touch as many patients as he wanted to. The doctor takes the oath of touching as many in your community as possible, and you’re limited when you’re a one-man show.”

The practice eventually found an NP who already knew how to do joint injections. “We started her with easier diagnoses for things like osteoporosis and gout. She had an orthopedic background, so she was familiar with some of those diseases,” she said.

Even so, she often leaves with questions every day. “It’s a commitment for her to understand and learn so much,” Ms. Taylor said.

New hires will need support from the practice to get comfortable with rheumatology, Dr. Stamatos said. Responsibility should come in gradual steps.

Instead of loading an NP with 20 patients a day, 2 or 3 patients in the first quarter, eventually graduating to 6-8 patients is a more realistic expectation, Dr. Stamatos advised.
 

Shadowing the Physician

Partnerships with physicians is a critical component to this onboarding process.

A nurse practitioner recently hired at Dr. Stamatos’ practice works alongside a physician to manage a panel of 25 patients. “We make sure she gets her training, the resources she needs. I personally meet with her to make sure her education is moving forward, connecting her with radiology, pulmonary, hematology,” and other areas of the practice relevant to her training, she added.

The NP also attends weekly grand rounds and case conferences with the fellows. This is the type of well-rounded support any APP needs, she stressed. “Without proper training, you lose people.”

At Sarasota Arthritis Center, NPs help cover the suites but also get assigned to specific physicians so that they can familiarize themselves with that physician’s panel of patients.

“When we start an APP, they shadow for about twice as long as a new physician would. Usually, they’re shadowing for about 6 weeks, just kind of learning the space. There’s a lot of nurse practitioners or PAs who may not have prior rheumatology experience, so we’re essentially training them from the ground up on rheumatology,” Ms. Yonker said.

Pairing them with one provider often directs what type of disease state they focus on, she continued. This dynamic relationship helps guide decisions on whether to include these NPs in the care of patients with more complex diseases.

At least in her practice, the NPs do not see any new patients. They are simply part of the larger care team. “That’s kind of how we present it to our patients, and it makes them feel more comfortable just because they know that they’re not necessarily being handed off to somebody — that the doctor is still overseeing their care,” Ms. Yonker said.

At the same time, the NPs know that they’re supported, that they too have access to tools and mentorship if they need it, she added.

The new NP at Carondelet Rheumatology piggybacked on the doctor’s schedule for 3 months, slowly taking on infusion patients so she could get familiar with their diseases and respective drugs. Eventually, she got her own schedule and was able to take on new patients.

It’s a team effort, Ms. Taylor noted. The NP does the preliminary workup and then the physician comes in and greets the new patient. Together, they develop a follow-up plan for the patient.
 

Education Resources for Practices

In the case of Dr. Box’s one-physician practice, he was looking for an NP who was willing to be independent and cover things in his absence. “The training has to be there to accomplish that,” said Dr. Box, who likened the training of APPs to a medical residency.

Encouraging them to ask questions, do continuing medical education online and outside reading, are important steps, he added.

In a recent editorial, rheumatologists Eli M. Miloslavsky, MD, and Bethany Marston, MD, offered some strategies for better prepping the APP workforce to meet the demands of rheumatology practices. “Consideration should be given to formal curricula or training programs to help APPs achieve both competence and confidence in treating rheumatologic conditions,” they offered, suggesting an online curriculum developed by the ACR for such a purpose. Fellowship training should also focus on working effectively with APPs, they added.

“Finally, incorporating APPs more effectively into rheumatology professional societies and supporting practices in hiring and training APPs will all be important steps in addressing the rheumatology workforce shortage,” Dr. Miloslavsky and Dr. Marston wrote.

Ms. Yonker said all her APPs take various courses that the ACR and other organizations provide for rheumatology-specific, midlevel positions. “We provide as much training as possible for them to feel comfortable in this space. They are set directly with a physician for a long time and then eventually go into their own space.”

In addition to ACR, the Rheumatology Nurses Society and the Association of Women in Rheumatology offer excellent online training resources for APPs, Ms. Yonker said. “Also, the Bone Health and Osteoporosis Foundation offers an osteoporosis fracture liaison certification which we put APPs through as well,” she added.

Rheumatology practices should also look into an important clinical training grant program from the Rheumatology Research Foundation, Dr. Stamatos advised.

To date, they have “funded almost everyone that applies,” she said. Each grantee receives $25,000 to support training and education involved in onboarding an APP to a rheumatology practice. The money covers attendance at a live rheumatology conference, online educational programs, textbooks, and any society memberships while defraying the cost of training this employee. To increase awareness of the program, the foundation has since expanded the number of available submission dates and the number of grant awardees per year. Currently, the application deadlines for the grants are December 1 and March 1.

For her own health system, Dr. Stamatos has been working on a rheumatology fellowship program for APPs. Through simulation labs, leadership exercises, and other activities, these APPs will learn how to transition from being a new provider to someone who can become part of a practice, she said.

APPs themselves can also get proactive in this learning cycle, Ms. Swafford said. In her view, both APPs and rheumatologists should be conducting didactic lectures and organizing elective rotations with medical students to get them excited about the field. This would establish a good education base that would encourage PAs and NPs to choose rheumatology.

“That’s a huge thing that’s probably missing,” Ms. Swafford said.
 

Buy-in From the Doctor

No recruitment effort is going to work if the rheumatologists in the practice aren’t committed to the model of having an APP, Ms. Yonker said. “Everybody wants to know their purpose in their company and that they’re valued and they’re needed. And so, I think a pitfall would be if your rheumatologist is not sold on the model of expanding the care team. Because this takes work on behalf of the doctor.”

Rheumatologists are very busy, so it’s a hard sell for them to take time out of their busy clinics to train somebody to do a good job taking care of their patients, Ms. Taylor agreed. “I think that we need the physicians that have had success with this and allow them to coach the physicians that are still resistant.”

In his small practice, Dr. Box has encouraged his NP to assist with practice improvements, working with the office manager. These workers are providers and need to be treated as such, he said. “They need to feel like they contribute to the practice more than just grinding through patients.”

Peer support is another successful ingredient for these workers. Ms. Taylor’s NP finds the time to commiserate with her fellow nurse practitioners — other rheumatology nurses who are also learning the ropes. Rheumatologists are smart, and they can be very intimidating, Ms. Taylor said. In their small office, the rheumatologist is her only peer.

“She likes to get out and sort of integrate with other nurse practitioners that are learning too.”
 

When APPs Make a Difference

Practices that take on APPs are reporting positive metrics — mainly, shorter wait times for patients. Ms. Yonker’s physicians have been able to add on one to two new patients a day. Wait times have since dwindled from a 5-month to a 3-month wait with the addition of the NPs. “Three months is still long, but we’re working on getting it to that ideal 6-week wait period, which we’re hoping we can accomplish. So we’re able to get more new patients in for sure,” she said.

Prior to hiring an NP, Ms. Taylor’s practice had to defer acceptances for new patients by at least a year. Now, they’re able to accept about half of all new patient referrals. With the NP on board, “We can get them in within 30 days,” she said.

Sometimes, an APP will go beyond their scope of work to make a difference and better support patients.

Patients with rheumatic and osteopathic conditions are often underdiagnosed in the primary care space. As a result, they are not treated as often as they should be. Seeing a need for specialty care, Ms. Swafford took action.

She currently runs the only bone health clinic in southwest Michigan, coordinating with rheumatologists, NPs, urgent care, hospitalists, and interventional radiologists to attend to these patients more quickly and reduce wait times for care. Specialists will flag things such as nontraumatic hip fractures and vertebral fractures and refer them to Ms. Swafford’s clinic, which is part of Bronson Rheumatology Specialists.

The clinic gets quite a few referrals, and the practice is growing. “Usually, they don’t take as long as a rheumatology referral for a workup, so we can see them a little bit quicker,” usually within 3 weeks, she added.

APPs have an opportunity to make their mark in rheumatology at a time when the profession is experiencing significant gaps in care, Ms. Swafford continued. “Unless we find a way to fill that niche, we’re going to be in a world of trouble in the next 10, 20 years.”

None of the sources reported any disclosures or conflicts of interest.

Once considered a luxury, hiring a nurse, nurse practitioner, or physician assistant is becoming a necessity in many rheumatology practices.

Seeing the wait lists pile up in her Florida practice, Stacy Yonker, MBA, chief executive officer of Sarasota Arthritis Center, knew she had to make some changes. “Everyone’s aging in the boomer generations. Particularly in Florida, we have a lot of people who retire here. In the more southern demographics, it is a very difficult challenge for practices to get new patients in,” she said.

Ms. Yonker is in the process of hiring several nurse practitioners (NPs) to assist in the clinics and infusion suites, lightening the load for the practice’s 11 rheumatologists.

Hiring an advanced practice provider (APP) to support the practice is just a first step. Getting these additional personnel up to speed means an investment in education and fostering good working relationships with NPs, PAs, and the staff’s physicians. Even more importantly, practices need to set realistic expectations on workload for these new hires.

“I tried to hire them, but I couldn’t keep them,” is a statement Christine A. Stamatos, DNP, ANP-C, hears all the time from rheumatologists. Oftentimes it’s because the practice saddles the new hire with 20 patients a day, said Dr. Stamatos, director of the Fibromyalgia Wellness Center within the division of rheumatology at Northwell Health in Huntington, New York. She is also an assistant professor at Hofstra Northwell School of Graduate Nursing and Physician Assistant Studies in Hempstead, New York.

“Twenty patients a day is too much,” Dr. Stamatos said. Overload someone, and they won’t stay. Offer them the support, mentoring, and tools they need to practice in their setting ­­— and they will.
 

Why the Profession Needs APPs

Rheumatology is a much smaller specialty than most, with only a set number of rheumatologists in the field that can provide care to patients. A growing shortage is also looming. Reports from the American College of Rheumatology have projected troubling shortfalls in rheumatologists over the next decade in all regions of the United States.

Many of them aging into retirement “poses a significant issue on being able to continue providing care for the population that experiences the rheumatic disease,” said Ms. Yonker, a director of the National Organization of Rheumatology Management (NORM), a forum that promotes education and advocacy for rheumatology practice managers. People are also living longer, which means more patients are developing arthritis and autoimmune diseases.

Julia M. Swafford, PA-C, a rheumatology physician assistant in Battle Creek, Michigan, sees many advantages of hiring NPs and PAs, and not just from a financial perspective.

Salaries for PAs and NPs aren’t as high and they’re also more accessible than a rheumatologist. “You could train an NP or PA a lot quicker during that same time frame it would take to find a new rheumatology provider,” she offered. And while they may not be as experienced as rheumatologists, “you can kind of mold me on how you like to practice, what medications you may like to use, how you like to treat your patients,” Ms. Swafford said.
 

Hiring Someone With Experience

Recruiting and retaining APPs is not without its challenges.

Finding individuals compatible with this specialty isn’t easy, noted Mark Box, MD, medical director of Carondelet Rheumatology in Kansas City, Missouri. Ideally, APPs should be inquisitive, compassionate, and ready to learn. “Rheumatology is a cognitive specialty where you have to fit many pieces together. You need an APP who wants to embrace that,” he said.

The profession isn’t that “sexy” either, noted Katie Taylor, Carondelet’s practice manager. Patients are often in head-to-toe pain, and miserable. Many have been to other specialists without answers to their questions. For these reasons, rheumatology can be a hard sell for some PAs and NPs.

Nurse practitioners aren’t always comfortable with administering things such as controlled medications, for example. “It’s a hard patient population, and it’s a specialty of exclusion. You’ve got to be really smart to understand our diseases and our processes and our drugs,” Ms. Taylor said. In other words, it’s a difficult environment for an NP to walk into if their previous experience has been limited to upper respiratory issues and urinary tract infections in the primary care setting.

When hiring an APP, rheumatologists should look for someone who demonstrates an interest in lifelong learning, because the field is changing every day. They should exhibit good scores in educational training and have experience working in an emergency department or another field that translates well into rheumatology such as critical care, immunology, hematology, and orthopedics, she said.

Carondelet Rheumatology was specifically looking for an NP with rheumatology experience to support Dr. Box’s solo practice.

He was facing enormous pressure to be in the office every single day of the week. The practice had to cancel patients for its infusion suite on a regular basis when he was out of the office, Ms. Taylor said. “We couldn’t see new patients, and he wasn’t able to touch as many patients as he wanted to. The doctor takes the oath of touching as many in your community as possible, and you’re limited when you’re a one-man show.”

The practice eventually found an NP who already knew how to do joint injections. “We started her with easier diagnoses for things like osteoporosis and gout. She had an orthopedic background, so she was familiar with some of those diseases,” she said.

Even so, she often leaves with questions every day. “It’s a commitment for her to understand and learn so much,” Ms. Taylor said.

New hires will need support from the practice to get comfortable with rheumatology, Dr. Stamatos said. Responsibility should come in gradual steps.

Instead of loading an NP with 20 patients a day, 2 or 3 patients in the first quarter, eventually graduating to 6-8 patients is a more realistic expectation, Dr. Stamatos advised.
 

Shadowing the Physician

Partnerships with physicians is a critical component to this onboarding process.

A nurse practitioner recently hired at Dr. Stamatos’ practice works alongside a physician to manage a panel of 25 patients. “We make sure she gets her training, the resources she needs. I personally meet with her to make sure her education is moving forward, connecting her with radiology, pulmonary, hematology,” and other areas of the practice relevant to her training, she added.

The NP also attends weekly grand rounds and case conferences with the fellows. This is the type of well-rounded support any APP needs, she stressed. “Without proper training, you lose people.”

At Sarasota Arthritis Center, NPs help cover the suites but also get assigned to specific physicians so that they can familiarize themselves with that physician’s panel of patients.

“When we start an APP, they shadow for about twice as long as a new physician would. Usually, they’re shadowing for about 6 weeks, just kind of learning the space. There’s a lot of nurse practitioners or PAs who may not have prior rheumatology experience, so we’re essentially training them from the ground up on rheumatology,” Ms. Yonker said.

Pairing them with one provider often directs what type of disease state they focus on, she continued. This dynamic relationship helps guide decisions on whether to include these NPs in the care of patients with more complex diseases.

At least in her practice, the NPs do not see any new patients. They are simply part of the larger care team. “That’s kind of how we present it to our patients, and it makes them feel more comfortable just because they know that they’re not necessarily being handed off to somebody — that the doctor is still overseeing their care,” Ms. Yonker said.

At the same time, the NPs know that they’re supported, that they too have access to tools and mentorship if they need it, she added.

The new NP at Carondelet Rheumatology piggybacked on the doctor’s schedule for 3 months, slowly taking on infusion patients so she could get familiar with their diseases and respective drugs. Eventually, she got her own schedule and was able to take on new patients.

It’s a team effort, Ms. Taylor noted. The NP does the preliminary workup and then the physician comes in and greets the new patient. Together, they develop a follow-up plan for the patient.
 

Education Resources for Practices

In the case of Dr. Box’s one-physician practice, he was looking for an NP who was willing to be independent and cover things in his absence. “The training has to be there to accomplish that,” said Dr. Box, who likened the training of APPs to a medical residency.

Encouraging them to ask questions, do continuing medical education online and outside reading, are important steps, he added.

In a recent editorial, rheumatologists Eli M. Miloslavsky, MD, and Bethany Marston, MD, offered some strategies for better prepping the APP workforce to meet the demands of rheumatology practices. “Consideration should be given to formal curricula or training programs to help APPs achieve both competence and confidence in treating rheumatologic conditions,” they offered, suggesting an online curriculum developed by the ACR for such a purpose. Fellowship training should also focus on working effectively with APPs, they added.

“Finally, incorporating APPs more effectively into rheumatology professional societies and supporting practices in hiring and training APPs will all be important steps in addressing the rheumatology workforce shortage,” Dr. Miloslavsky and Dr. Marston wrote.

Ms. Yonker said all her APPs take various courses that the ACR and other organizations provide for rheumatology-specific, midlevel positions. “We provide as much training as possible for them to feel comfortable in this space. They are set directly with a physician for a long time and then eventually go into their own space.”

In addition to ACR, the Rheumatology Nurses Society and the Association of Women in Rheumatology offer excellent online training resources for APPs, Ms. Yonker said. “Also, the Bone Health and Osteoporosis Foundation offers an osteoporosis fracture liaison certification which we put APPs through as well,” she added.

Rheumatology practices should also look into an important clinical training grant program from the Rheumatology Research Foundation, Dr. Stamatos advised.

To date, they have “funded almost everyone that applies,” she said. Each grantee receives $25,000 to support training and education involved in onboarding an APP to a rheumatology practice. The money covers attendance at a live rheumatology conference, online educational programs, textbooks, and any society memberships while defraying the cost of training this employee. To increase awareness of the program, the foundation has since expanded the number of available submission dates and the number of grant awardees per year. Currently, the application deadlines for the grants are December 1 and March 1.

For her own health system, Dr. Stamatos has been working on a rheumatology fellowship program for APPs. Through simulation labs, leadership exercises, and other activities, these APPs will learn how to transition from being a new provider to someone who can become part of a practice, she said.

APPs themselves can also get proactive in this learning cycle, Ms. Swafford said. In her view, both APPs and rheumatologists should be conducting didactic lectures and organizing elective rotations with medical students to get them excited about the field. This would establish a good education base that would encourage PAs and NPs to choose rheumatology.

“That’s a huge thing that’s probably missing,” Ms. Swafford said.
 

Buy-in From the Doctor

No recruitment effort is going to work if the rheumatologists in the practice aren’t committed to the model of having an APP, Ms. Yonker said. “Everybody wants to know their purpose in their company and that they’re valued and they’re needed. And so, I think a pitfall would be if your rheumatologist is not sold on the model of expanding the care team. Because this takes work on behalf of the doctor.”

Rheumatologists are very busy, so it’s a hard sell for them to take time out of their busy clinics to train somebody to do a good job taking care of their patients, Ms. Taylor agreed. “I think that we need the physicians that have had success with this and allow them to coach the physicians that are still resistant.”

In his small practice, Dr. Box has encouraged his NP to assist with practice improvements, working with the office manager. These workers are providers and need to be treated as such, he said. “They need to feel like they contribute to the practice more than just grinding through patients.”

Peer support is another successful ingredient for these workers. Ms. Taylor’s NP finds the time to commiserate with her fellow nurse practitioners — other rheumatology nurses who are also learning the ropes. Rheumatologists are smart, and they can be very intimidating, Ms. Taylor said. In their small office, the rheumatologist is her only peer.

“She likes to get out and sort of integrate with other nurse practitioners that are learning too.”
 

When APPs Make a Difference

Practices that take on APPs are reporting positive metrics — mainly, shorter wait times for patients. Ms. Yonker’s physicians have been able to add on one to two new patients a day. Wait times have since dwindled from a 5-month to a 3-month wait with the addition of the NPs. “Three months is still long, but we’re working on getting it to that ideal 6-week wait period, which we’re hoping we can accomplish. So we’re able to get more new patients in for sure,” she said.

Prior to hiring an NP, Ms. Taylor’s practice had to defer acceptances for new patients by at least a year. Now, they’re able to accept about half of all new patient referrals. With the NP on board, “We can get them in within 30 days,” she said.

Sometimes, an APP will go beyond their scope of work to make a difference and better support patients.

Patients with rheumatic and osteopathic conditions are often underdiagnosed in the primary care space. As a result, they are not treated as often as they should be. Seeing a need for specialty care, Ms. Swafford took action.

She currently runs the only bone health clinic in southwest Michigan, coordinating with rheumatologists, NPs, urgent care, hospitalists, and interventional radiologists to attend to these patients more quickly and reduce wait times for care. Specialists will flag things such as nontraumatic hip fractures and vertebral fractures and refer them to Ms. Swafford’s clinic, which is part of Bronson Rheumatology Specialists.

The clinic gets quite a few referrals, and the practice is growing. “Usually, they don’t take as long as a rheumatology referral for a workup, so we can see them a little bit quicker,” usually within 3 weeks, she added.

APPs have an opportunity to make their mark in rheumatology at a time when the profession is experiencing significant gaps in care, Ms. Swafford continued. “Unless we find a way to fill that niche, we’re going to be in a world of trouble in the next 10, 20 years.”

None of the sources reported any disclosures or conflicts of interest.

Once considered a luxury, hiring a nurse, nurse practitioner, or physician assistant is becoming a necessity in many rheumatology practices.

Seeing the wait lists pile up in her Florida practice, Stacy Yonker, MBA, chief executive officer of Sarasota Arthritis Center, knew she had to make some changes. “Everyone’s aging in the boomer generations. Particularly in Florida, we have a lot of people who retire here. In the more southern demographics, it is a very difficult challenge for practices to get new patients in,” she said.

Ms. Yonker is in the process of hiring several nurse practitioners (NPs) to assist in the clinics and infusion suites, lightening the load for the practice’s 11 rheumatologists.

Hiring an advanced practice provider (APP) to support the practice is just a first step. Getting these additional personnel up to speed means an investment in education and fostering good working relationships with NPs, PAs, and the staff’s physicians. Even more importantly, practices need to set realistic expectations on workload for these new hires.

“I tried to hire them, but I couldn’t keep them,” is a statement Christine A. Stamatos, DNP, ANP-C, hears all the time from rheumatologists. Oftentimes it’s because the practice saddles the new hire with 20 patients a day, said Dr. Stamatos, director of the Fibromyalgia Wellness Center within the division of rheumatology at Northwell Health in Huntington, New York. She is also an assistant professor at Hofstra Northwell School of Graduate Nursing and Physician Assistant Studies in Hempstead, New York.

“Twenty patients a day is too much,” Dr. Stamatos said. Overload someone, and they won’t stay. Offer them the support, mentoring, and tools they need to practice in their setting ­­— and they will.
 

Why the Profession Needs APPs

Rheumatology is a much smaller specialty than most, with only a set number of rheumatologists in the field that can provide care to patients. A growing shortage is also looming. Reports from the American College of Rheumatology have projected troubling shortfalls in rheumatologists over the next decade in all regions of the United States.

Many of them aging into retirement “poses a significant issue on being able to continue providing care for the population that experiences the rheumatic disease,” said Ms. Yonker, a director of the National Organization of Rheumatology Management (NORM), a forum that promotes education and advocacy for rheumatology practice managers. People are also living longer, which means more patients are developing arthritis and autoimmune diseases.

Julia M. Swafford, PA-C, a rheumatology physician assistant in Battle Creek, Michigan, sees many advantages of hiring NPs and PAs, and not just from a financial perspective.

Salaries for PAs and NPs aren’t as high and they’re also more accessible than a rheumatologist. “You could train an NP or PA a lot quicker during that same time frame it would take to find a new rheumatology provider,” she offered. And while they may not be as experienced as rheumatologists, “you can kind of mold me on how you like to practice, what medications you may like to use, how you like to treat your patients,” Ms. Swafford said.
 

Hiring Someone With Experience

Recruiting and retaining APPs is not without its challenges.

Finding individuals compatible with this specialty isn’t easy, noted Mark Box, MD, medical director of Carondelet Rheumatology in Kansas City, Missouri. Ideally, APPs should be inquisitive, compassionate, and ready to learn. “Rheumatology is a cognitive specialty where you have to fit many pieces together. You need an APP who wants to embrace that,” he said.

The profession isn’t that “sexy” either, noted Katie Taylor, Carondelet’s practice manager. Patients are often in head-to-toe pain, and miserable. Many have been to other specialists without answers to their questions. For these reasons, rheumatology can be a hard sell for some PAs and NPs.

Nurse practitioners aren’t always comfortable with administering things such as controlled medications, for example. “It’s a hard patient population, and it’s a specialty of exclusion. You’ve got to be really smart to understand our diseases and our processes and our drugs,” Ms. Taylor said. In other words, it’s a difficult environment for an NP to walk into if their previous experience has been limited to upper respiratory issues and urinary tract infections in the primary care setting.

When hiring an APP, rheumatologists should look for someone who demonstrates an interest in lifelong learning, because the field is changing every day. They should exhibit good scores in educational training and have experience working in an emergency department or another field that translates well into rheumatology such as critical care, immunology, hematology, and orthopedics, she said.

Carondelet Rheumatology was specifically looking for an NP with rheumatology experience to support Dr. Box’s solo practice.

He was facing enormous pressure to be in the office every single day of the week. The practice had to cancel patients for its infusion suite on a regular basis when he was out of the office, Ms. Taylor said. “We couldn’t see new patients, and he wasn’t able to touch as many patients as he wanted to. The doctor takes the oath of touching as many in your community as possible, and you’re limited when you’re a one-man show.”

The practice eventually found an NP who already knew how to do joint injections. “We started her with easier diagnoses for things like osteoporosis and gout. She had an orthopedic background, so she was familiar with some of those diseases,” she said.

Even so, she often leaves with questions every day. “It’s a commitment for her to understand and learn so much,” Ms. Taylor said.

New hires will need support from the practice to get comfortable with rheumatology, Dr. Stamatos said. Responsibility should come in gradual steps.

Instead of loading an NP with 20 patients a day, 2 or 3 patients in the first quarter, eventually graduating to 6-8 patients is a more realistic expectation, Dr. Stamatos advised.
 

Shadowing the Physician

Partnerships with physicians is a critical component to this onboarding process.

A nurse practitioner recently hired at Dr. Stamatos’ practice works alongside a physician to manage a panel of 25 patients. “We make sure she gets her training, the resources she needs. I personally meet with her to make sure her education is moving forward, connecting her with radiology, pulmonary, hematology,” and other areas of the practice relevant to her training, she added.

The NP also attends weekly grand rounds and case conferences with the fellows. This is the type of well-rounded support any APP needs, she stressed. “Without proper training, you lose people.”

At Sarasota Arthritis Center, NPs help cover the suites but also get assigned to specific physicians so that they can familiarize themselves with that physician’s panel of patients.

“When we start an APP, they shadow for about twice as long as a new physician would. Usually, they’re shadowing for about 6 weeks, just kind of learning the space. There’s a lot of nurse practitioners or PAs who may not have prior rheumatology experience, so we’re essentially training them from the ground up on rheumatology,” Ms. Yonker said.

Pairing them with one provider often directs what type of disease state they focus on, she continued. This dynamic relationship helps guide decisions on whether to include these NPs in the care of patients with more complex diseases.

At least in her practice, the NPs do not see any new patients. They are simply part of the larger care team. “That’s kind of how we present it to our patients, and it makes them feel more comfortable just because they know that they’re not necessarily being handed off to somebody — that the doctor is still overseeing their care,” Ms. Yonker said.

At the same time, the NPs know that they’re supported, that they too have access to tools and mentorship if they need it, she added.

The new NP at Carondelet Rheumatology piggybacked on the doctor’s schedule for 3 months, slowly taking on infusion patients so she could get familiar with their diseases and respective drugs. Eventually, she got her own schedule and was able to take on new patients.

It’s a team effort, Ms. Taylor noted. The NP does the preliminary workup and then the physician comes in and greets the new patient. Together, they develop a follow-up plan for the patient.
 

Education Resources for Practices

In the case of Dr. Box’s one-physician practice, he was looking for an NP who was willing to be independent and cover things in his absence. “The training has to be there to accomplish that,” said Dr. Box, who likened the training of APPs to a medical residency.

Encouraging them to ask questions, do continuing medical education online and outside reading, are important steps, he added.

In a recent editorial, rheumatologists Eli M. Miloslavsky, MD, and Bethany Marston, MD, offered some strategies for better prepping the APP workforce to meet the demands of rheumatology practices. “Consideration should be given to formal curricula or training programs to help APPs achieve both competence and confidence in treating rheumatologic conditions,” they offered, suggesting an online curriculum developed by the ACR for such a purpose. Fellowship training should also focus on working effectively with APPs, they added.

“Finally, incorporating APPs more effectively into rheumatology professional societies and supporting practices in hiring and training APPs will all be important steps in addressing the rheumatology workforce shortage,” Dr. Miloslavsky and Dr. Marston wrote.

Ms. Yonker said all her APPs take various courses that the ACR and other organizations provide for rheumatology-specific, midlevel positions. “We provide as much training as possible for them to feel comfortable in this space. They are set directly with a physician for a long time and then eventually go into their own space.”

In addition to ACR, the Rheumatology Nurses Society and the Association of Women in Rheumatology offer excellent online training resources for APPs, Ms. Yonker said. “Also, the Bone Health and Osteoporosis Foundation offers an osteoporosis fracture liaison certification which we put APPs through as well,” she added.

Rheumatology practices should also look into an important clinical training grant program from the Rheumatology Research Foundation, Dr. Stamatos advised.

To date, they have “funded almost everyone that applies,” she said. Each grantee receives $25,000 to support training and education involved in onboarding an APP to a rheumatology practice. The money covers attendance at a live rheumatology conference, online educational programs, textbooks, and any society memberships while defraying the cost of training this employee. To increase awareness of the program, the foundation has since expanded the number of available submission dates and the number of grant awardees per year. Currently, the application deadlines for the grants are December 1 and March 1.

For her own health system, Dr. Stamatos has been working on a rheumatology fellowship program for APPs. Through simulation labs, leadership exercises, and other activities, these APPs will learn how to transition from being a new provider to someone who can become part of a practice, she said.

APPs themselves can also get proactive in this learning cycle, Ms. Swafford said. In her view, both APPs and rheumatologists should be conducting didactic lectures and organizing elective rotations with medical students to get them excited about the field. This would establish a good education base that would encourage PAs and NPs to choose rheumatology.

“That’s a huge thing that’s probably missing,” Ms. Swafford said.
 

Buy-in From the Doctor

No recruitment effort is going to work if the rheumatologists in the practice aren’t committed to the model of having an APP, Ms. Yonker said. “Everybody wants to know their purpose in their company and that they’re valued and they’re needed. And so, I think a pitfall would be if your rheumatologist is not sold on the model of expanding the care team. Because this takes work on behalf of the doctor.”

Rheumatologists are very busy, so it’s a hard sell for them to take time out of their busy clinics to train somebody to do a good job taking care of their patients, Ms. Taylor agreed. “I think that we need the physicians that have had success with this and allow them to coach the physicians that are still resistant.”

In his small practice, Dr. Box has encouraged his NP to assist with practice improvements, working with the office manager. These workers are providers and need to be treated as such, he said. “They need to feel like they contribute to the practice more than just grinding through patients.”

Peer support is another successful ingredient for these workers. Ms. Taylor’s NP finds the time to commiserate with her fellow nurse practitioners — other rheumatology nurses who are also learning the ropes. Rheumatologists are smart, and they can be very intimidating, Ms. Taylor said. In their small office, the rheumatologist is her only peer.

“She likes to get out and sort of integrate with other nurse practitioners that are learning too.”
 

When APPs Make a Difference

Practices that take on APPs are reporting positive metrics — mainly, shorter wait times for patients. Ms. Yonker’s physicians have been able to add on one to two new patients a day. Wait times have since dwindled from a 5-month to a 3-month wait with the addition of the NPs. “Three months is still long, but we’re working on getting it to that ideal 6-week wait period, which we’re hoping we can accomplish. So we’re able to get more new patients in for sure,” she said.

Prior to hiring an NP, Ms. Taylor’s practice had to defer acceptances for new patients by at least a year. Now, they’re able to accept about half of all new patient referrals. With the NP on board, “We can get them in within 30 days,” she said.

Sometimes, an APP will go beyond their scope of work to make a difference and better support patients.

Patients with rheumatic and osteopathic conditions are often underdiagnosed in the primary care space. As a result, they are not treated as often as they should be. Seeing a need for specialty care, Ms. Swafford took action.

She currently runs the only bone health clinic in southwest Michigan, coordinating with rheumatologists, NPs, urgent care, hospitalists, and interventional radiologists to attend to these patients more quickly and reduce wait times for care. Specialists will flag things such as nontraumatic hip fractures and vertebral fractures and refer them to Ms. Swafford’s clinic, which is part of Bronson Rheumatology Specialists.

The clinic gets quite a few referrals, and the practice is growing. “Usually, they don’t take as long as a rheumatology referral for a workup, so we can see them a little bit quicker,” usually within 3 weeks, she added.

APPs have an opportunity to make their mark in rheumatology at a time when the profession is experiencing significant gaps in care, Ms. Swafford continued. “Unless we find a way to fill that niche, we’re going to be in a world of trouble in the next 10, 20 years.”

None of the sources reported any disclosures or conflicts of interest.

TOPLINE:

Adults whose rheumatoid arthritis caused them severe functional limitations showed significant improvement in measures of function and quality of life following at least 1 year of a personalized, supervised exercise program than those who received usual care.

METHODOLOGY:

• Researchers randomized 217 adults with rheumatoid arthritis and severe functional limitations to an active exercise intervention delivered by a physical therapist (PT) or usual care; the mean age of the participants was approximately 59 years, and approximately 90% were female.
• The intervention consisted of individualized goal setting, active exercises adapted to functional limitations, and education about self-management of physical activity in two sessions per week for the first 12 weeks, followed by once weekly sessions with the option for additional sessions if needed. The primary care PTs in the Netherlands who treated the patients were primarily recruited through a national network of PTs with specific expertise regarding rheumatic diseases.
• In considering each participant’s three most limited activities, the study’s primary outcome at 52 weeks measured the change from the one ranked highest at baseline on the Patient-Specific Complaints Numeric Rating Scale (PSC1 NRS); secondary outcomes included changes in the NRS for participants’ second and third most difficult activities, as well as the Patient Reported Outcome Measurement Information System Physical Function-10, the Health Assessment Questionnaire-Disability Index, the Rheumatoid Arthritis Quality of Life Questionnaire, the 36-Item Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scales (PCS and MCS), and the 6-minute walk test.

TAKEAWAY:

• At 52 weeks, the change in PSC1 NRS was significantly greater in the intervention group than in the usual care group, with a mean difference of −1.7 and a between-group effect size from baseline of 0.7.
• Improvements in secondary outcome measures at 52 weeks also were significantly greater in the intervention group than in the usual care group, with the exception of the SF-36 MCS, which showed no difference between the groups.
• A total of 89 participants in the intervention group and 45 participants in the usual care group responded to questions about muscle soreness and fatigue; 70% and 60%, and 71% and 64%, of each group reported these conditions, respectively.

IN PRACTICE:

“The completion of the trial substantiates the feasibility of recruiting and training primary care [physical therapists] to deliver a complex intervention,” although more research is needed to explore long-term outcomes and cost-effectiveness, the researchers wrote.

SOURCE:

The lead author on the study was Max M.H. Teuwen, MSc, a PhD candidate at Leiden University Medical Center, Leiden, the Netherlands. The study was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The participants were not blinded to their group, and blinded assessors became aware of the allocations, which might have impacted measurements; other limitations included lack of data on medication changes and the exclusion of physical activity amount as an outcome measure.

DISCLOSURES:

The study was supported by the Netherlands Organization for Health Research and Development; the Ministry of Health, Welfare and Sport; the Royal Dutch Society for Physical Therapy; and the Dutch Arthritis Society. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults whose rheumatoid arthritis caused them severe functional limitations showed significant improvement in measures of function and quality of life following at least 1 year of a personalized, supervised exercise program than those who received usual care.

METHODOLOGY:

• Researchers randomized 217 adults with rheumatoid arthritis and severe functional limitations to an active exercise intervention delivered by a physical therapist (PT) or usual care; the mean age of the participants was approximately 59 years, and approximately 90% were female.
• The intervention consisted of individualized goal setting, active exercises adapted to functional limitations, and education about self-management of physical activity in two sessions per week for the first 12 weeks, followed by once weekly sessions with the option for additional sessions if needed. The primary care PTs in the Netherlands who treated the patients were primarily recruited through a national network of PTs with specific expertise regarding rheumatic diseases.
• In considering each participant’s three most limited activities, the study’s primary outcome at 52 weeks measured the change from the one ranked highest at baseline on the Patient-Specific Complaints Numeric Rating Scale (PSC1 NRS); secondary outcomes included changes in the NRS for participants’ second and third most difficult activities, as well as the Patient Reported Outcome Measurement Information System Physical Function-10, the Health Assessment Questionnaire-Disability Index, the Rheumatoid Arthritis Quality of Life Questionnaire, the 36-Item Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scales (PCS and MCS), and the 6-minute walk test.

TAKEAWAY:

• At 52 weeks, the change in PSC1 NRS was significantly greater in the intervention group than in the usual care group, with a mean difference of −1.7 and a between-group effect size from baseline of 0.7.
• Improvements in secondary outcome measures at 52 weeks also were significantly greater in the intervention group than in the usual care group, with the exception of the SF-36 MCS, which showed no difference between the groups.
• A total of 89 participants in the intervention group and 45 participants in the usual care group responded to questions about muscle soreness and fatigue; 70% and 60%, and 71% and 64%, of each group reported these conditions, respectively.

IN PRACTICE:

“The completion of the trial substantiates the feasibility of recruiting and training primary care [physical therapists] to deliver a complex intervention,” although more research is needed to explore long-term outcomes and cost-effectiveness, the researchers wrote.

SOURCE:

The lead author on the study was Max M.H. Teuwen, MSc, a PhD candidate at Leiden University Medical Center, Leiden, the Netherlands. The study was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The participants were not blinded to their group, and blinded assessors became aware of the allocations, which might have impacted measurements; other limitations included lack of data on medication changes and the exclusion of physical activity amount as an outcome measure.

DISCLOSURES:

The study was supported by the Netherlands Organization for Health Research and Development; the Ministry of Health, Welfare and Sport; the Royal Dutch Society for Physical Therapy; and the Dutch Arthritis Society. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults whose rheumatoid arthritis caused them severe functional limitations showed significant improvement in measures of function and quality of life following at least 1 year of a personalized, supervised exercise program than those who received usual care.

METHODOLOGY:

• Researchers randomized 217 adults with rheumatoid arthritis and severe functional limitations to an active exercise intervention delivered by a physical therapist (PT) or usual care; the mean age of the participants was approximately 59 years, and approximately 90% were female.
• The intervention consisted of individualized goal setting, active exercises adapted to functional limitations, and education about self-management of physical activity in two sessions per week for the first 12 weeks, followed by once weekly sessions with the option for additional sessions if needed. The primary care PTs in the Netherlands who treated the patients were primarily recruited through a national network of PTs with specific expertise regarding rheumatic diseases.
• In considering each participant’s three most limited activities, the study’s primary outcome at 52 weeks measured the change from the one ranked highest at baseline on the Patient-Specific Complaints Numeric Rating Scale (PSC1 NRS); secondary outcomes included changes in the NRS for participants’ second and third most difficult activities, as well as the Patient Reported Outcome Measurement Information System Physical Function-10, the Health Assessment Questionnaire-Disability Index, the Rheumatoid Arthritis Quality of Life Questionnaire, the 36-Item Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scales (PCS and MCS), and the 6-minute walk test.

TAKEAWAY:

• At 52 weeks, the change in PSC1 NRS was significantly greater in the intervention group than in the usual care group, with a mean difference of −1.7 and a between-group effect size from baseline of 0.7.
• Improvements in secondary outcome measures at 52 weeks also were significantly greater in the intervention group than in the usual care group, with the exception of the SF-36 MCS, which showed no difference between the groups.
• A total of 89 participants in the intervention group and 45 participants in the usual care group responded to questions about muscle soreness and fatigue; 70% and 60%, and 71% and 64%, of each group reported these conditions, respectively.

IN PRACTICE:

“The completion of the trial substantiates the feasibility of recruiting and training primary care [physical therapists] to deliver a complex intervention,” although more research is needed to explore long-term outcomes and cost-effectiveness, the researchers wrote.

SOURCE:

The lead author on the study was Max M.H. Teuwen, MSc, a PhD candidate at Leiden University Medical Center, Leiden, the Netherlands. The study was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The participants were not blinded to their group, and blinded assessors became aware of the allocations, which might have impacted measurements; other limitations included lack of data on medication changes and the exclusion of physical activity amount as an outcome measure.

DISCLOSURES:

The study was supported by the Netherlands Organization for Health Research and Development; the Ministry of Health, Welfare and Sport; the Royal Dutch Society for Physical Therapy; and the Dutch Arthritis Society. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

TOPLINE:

A combination of remote, supervised aerobic training, resistance training, and a hypocaloric diet significantly improved cardiovascular risk factors in adults with rheumatoid arthritis (RA) and overweight or obesity.

METHODOLOGY:

• The researchers recruited 24 adults aged 60-80 years with RA who met criteria for overweight or obesity; participants were randomized to a Supervised Weight Loss and Exercise Training (SWET) or Counseling Health as Treatment (CHAT) program for 16 weeks.
• The SWET intervention included remote supervision of aerobic training of 150 minutes/week moderate-to-vigorous intensity, 2 days per week of resistance training, and a hypocaloric diet based on a weight loss goal of 7% of body weight. The CHAT patients served as controls and completed two lifestyle counseling sessions followed by monthly check-ins.
• The primary outcome was change in a composite measure of cardiovascular risk based on metabolic syndrome z-score (MSSc), a continuous weighted score of five metabolic syndrome components: Waist circumference, mean arterial blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol.

TAKEAWAY:

• Both groups showed improvement in the primary outcome of MSSc, with absolute changes from baseline of −1.67 for the SWET group and −1.34 for the CHAT group (P < .01 for both).
• Participants in the SWET group showed significantly more improvement in secondary outcome measures of body weight, fat mass, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP), as well as greater improvement in patient-reported physical and mental health, physical function, and fatigue, than those in the CHAT group, but the CHAT group improved significantly compared with their baseline.
• The strongest specific effects for the different components of the intervention were those of aerobic training on physical function and fatigue, resistance training on DAS28-CRP, and weight loss on MSSc.
• Neither group experienced significant changes in lean mass, absolute peak V02, unilateral isometric knee extension, or bilateral grip strength.

IN PRACTICE:

“Findings from our study indicate, at a minimum, integrating even 2 hours of healthy lifestyle counseling may improve RA management, let alone demonstrate the substantial impact that can be provided by a comprehensive, remotely supervised lifestyle intervention,” the researchers wrote.

SOURCE:

The lead author on the study was Brian J. Andonian, MD, of Duke University, Durham, North Carolina. The study was published online in ACR Open Rheumatology.

LIMITATIONS:

The small sample size was a limitation of the study findings, as was the lack of blinding and high level of motivation in the CHAT group, who had greater improvements than expected in weight loss and increased physical activity; the study also was conducted during the COVID-19 pandemic, with potential physical and mental effects on participants who tested positive during the study period.

DISCLOSURES:

The study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Claude D. Pepper Older Americans Independence Center of the US National Institute on Aging.

A version of this article appeared on Medscape.com.

TOPLINE:

A combination of remote, supervised aerobic training, resistance training, and a hypocaloric diet significantly improved cardiovascular risk factors in adults with rheumatoid arthritis (RA) and overweight or obesity.

METHODOLOGY:

• The researchers recruited 24 adults aged 60-80 years with RA who met criteria for overweight or obesity; participants were randomized to a Supervised Weight Loss and Exercise Training (SWET) or Counseling Health as Treatment (CHAT) program for 16 weeks.
• The SWET intervention included remote supervision of aerobic training of 150 minutes/week moderate-to-vigorous intensity, 2 days per week of resistance training, and a hypocaloric diet based on a weight loss goal of 7% of body weight. The CHAT patients served as controls and completed two lifestyle counseling sessions followed by monthly check-ins.
• The primary outcome was change in a composite measure of cardiovascular risk based on metabolic syndrome z-score (MSSc), a continuous weighted score of five metabolic syndrome components: Waist circumference, mean arterial blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol.

TAKEAWAY:

• Both groups showed improvement in the primary outcome of MSSc, with absolute changes from baseline of −1.67 for the SWET group and −1.34 for the CHAT group (P < .01 for both).
• Participants in the SWET group showed significantly more improvement in secondary outcome measures of body weight, fat mass, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP), as well as greater improvement in patient-reported physical and mental health, physical function, and fatigue, than those in the CHAT group, but the CHAT group improved significantly compared with their baseline.
• The strongest specific effects for the different components of the intervention were those of aerobic training on physical function and fatigue, resistance training on DAS28-CRP, and weight loss on MSSc.
• Neither group experienced significant changes in lean mass, absolute peak V02, unilateral isometric knee extension, or bilateral grip strength.

IN PRACTICE:

“Findings from our study indicate, at a minimum, integrating even 2 hours of healthy lifestyle counseling may improve RA management, let alone demonstrate the substantial impact that can be provided by a comprehensive, remotely supervised lifestyle intervention,” the researchers wrote.

SOURCE:

The lead author on the study was Brian J. Andonian, MD, of Duke University, Durham, North Carolina. The study was published online in ACR Open Rheumatology.

LIMITATIONS:

The small sample size was a limitation of the study findings, as was the lack of blinding and high level of motivation in the CHAT group, who had greater improvements than expected in weight loss and increased physical activity; the study also was conducted during the COVID-19 pandemic, with potential physical and mental effects on participants who tested positive during the study period.

DISCLOSURES:

The study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Claude D. Pepper Older Americans Independence Center of the US National Institute on Aging.

A version of this article appeared on Medscape.com.

TOPLINE:

A combination of remote, supervised aerobic training, resistance training, and a hypocaloric diet significantly improved cardiovascular risk factors in adults with rheumatoid arthritis (RA) and overweight or obesity.

METHODOLOGY:

• The researchers recruited 24 adults aged 60-80 years with RA who met criteria for overweight or obesity; participants were randomized to a Supervised Weight Loss and Exercise Training (SWET) or Counseling Health as Treatment (CHAT) program for 16 weeks.
• The SWET intervention included remote supervision of aerobic training of 150 minutes/week moderate-to-vigorous intensity, 2 days per week of resistance training, and a hypocaloric diet based on a weight loss goal of 7% of body weight. The CHAT patients served as controls and completed two lifestyle counseling sessions followed by monthly check-ins.
• The primary outcome was change in a composite measure of cardiovascular risk based on metabolic syndrome z-score (MSSc), a continuous weighted score of five metabolic syndrome components: Waist circumference, mean arterial blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol.

TAKEAWAY:

• Both groups showed improvement in the primary outcome of MSSc, with absolute changes from baseline of −1.67 for the SWET group and −1.34 for the CHAT group (P < .01 for both).
• Participants in the SWET group showed significantly more improvement in secondary outcome measures of body weight, fat mass, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP), as well as greater improvement in patient-reported physical and mental health, physical function, and fatigue, than those in the CHAT group, but the CHAT group improved significantly compared with their baseline.
• The strongest specific effects for the different components of the intervention were those of aerobic training on physical function and fatigue, resistance training on DAS28-CRP, and weight loss on MSSc.
• Neither group experienced significant changes in lean mass, absolute peak V02, unilateral isometric knee extension, or bilateral grip strength.

IN PRACTICE:

“Findings from our study indicate, at a minimum, integrating even 2 hours of healthy lifestyle counseling may improve RA management, let alone demonstrate the substantial impact that can be provided by a comprehensive, remotely supervised lifestyle intervention,” the researchers wrote.

SOURCE:

The lead author on the study was Brian J. Andonian, MD, of Duke University, Durham, North Carolina. The study was published online in ACR Open Rheumatology.

LIMITATIONS:

The small sample size was a limitation of the study findings, as was the lack of blinding and high level of motivation in the CHAT group, who had greater improvements than expected in weight loss and increased physical activity; the study also was conducted during the COVID-19 pandemic, with potential physical and mental effects on participants who tested positive during the study period.

DISCLOSURES:

The study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Claude D. Pepper Older Americans Independence Center of the US National Institute on Aging.

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

When axial spondyloarthritis (SpA) is suspected, a “prompt referral to a rheumatologist” is in order. But with the referral possibly taking several weeks, if not months in some parts of the world, how can primary care practitioners manage patients with this type of chronic back pain in the meantime? And what is the long-term role of the primary care practitioner in managing someone diagnosed with the condition? This news organization asked rheumatologist Marina Magrey, MD, and general internal medicine physician Debra Leizman, MD, for their expert advice.

Steps to Manage Suspected Axial SpA

“As [primary care practitioners] identify patients who they suspect may have axial spondyloarthritis, the first thing they should do is a prompt referral to a rheumatologist so that there is a timely diagnosis,” said Dr. Magrey, who heads up the division of rheumatology at University Hospitals Cleveland Medical Center and is professor of medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio.

Importantly, the referral should “explicitly say that they’re suspecting axial spondyloarthritis” and not just chronic back pain, Dr. Magrey added, otherwise it may not “hit the radar” that patients need to be seen as soon as possible. Results of lab tests such as C-reactive protein, erythrocyte sedimentation rate, and human leukocyte antigen B27, along with basic pelvic imaging results, are useful to note on the referral. “If the patient comes with that information, it makes it much easier for the rheumatologist,” she said.

Additionally, primary care practitioners can carry out screening for high cholesterol and high blood pressure and check for any existing cardiovascular disorders or extraarticular manifestations before the patient gets to see the rheumatologist.

First-Line Treatment Options

“The goal is to improve the quality of life for our patients: To reduce pain, fatigue, inflammation,” Dr. Magrey noted. “So, starting a nonsteroidal anti-inflammatory drug [NSAID] with physical therapy is very useful” in primary care, she added. These remain the “cornerstone” of treatment for axial SpA even in secondary care.

Dr. Leizman agreed that her “go to” treatment for suspected axial SpA is physical therapy alongside one of the many NSAIDs available, such as naproxen or celecoxib. She may also use topical treatments such as lidocaine or diclofenac.

“I’m not going to start any biologics; I leave that for my rheumatologist,” said Dr. Leizman, who is a senior attending physician in the division of general internal medicine at University Hospitals Cleveland Medical Center and associate professor of medicine at Case Western Reserve University.

“If I think it’s a possibility that the patient will be going on to a biologic; however, I will try to check their TB status, immunizations, and vaccination titers, making sure that the patient is up to date and as healthy otherwise as possible so that they will be primed and ready, hopefully, to go on to the biologics,” she added.

Dr. Magrey cautioned that disease-modifying antirheumatic drugs, such as methotrexate and sulfasalazine, and systemic steroids such as oral prednisone “do not work in axial spondyloarthritis, so they are not recommended.”

Does the Choice of NSAID Matter?

The choice of NSAID is really down to the personal choice of the physician in agreement with the patient, and of course whether the medical insurance will cover it, Dr. Magrey observed. There appears to be little difference between the available NSAIDs, and it doesn’t appear to matter whether they are long-acting and taken once a day — which may be a convenient option for some patients — or short-acting and taken twice a day. The important point is that patients are taking these drugs continuously and not on demand and that they are being given at full dose.

“Start with one NSAID at the maximum strength, and then you try that for 2-4 weeks. If that doesn’t work, switch to another one,” Dr. Magrey advised.

American College of Rheumatology (ACR) guidelines for axial SpA recommend that a trial of at least two NSAIDs is undertaken before any biologic treatment is considered, but because the presentation of axial SpA is so heterogeneous, the decision to escalate treatment — usually to a tumor necrosis factor inhibitor first — is best left until after the referral and the diagnosis had been confirmed, she suggested.

What Type of Physical Therapy Works?

Physical therapy and nonpharmacologic ways to help people are integral to optimal patient management. But these still need to be prescribed and administered by a qualified physiotherapist, which means another, separate referral that can also take time, as it’s important to match the patient to the right physiotherapist, Dr. Leizman observed.

Patients need to be informed about the benefits of regular exercise, and suggesting low-impact exercises for the back can be helpful, Dr. Magrey noted.

“Supervised physical therapy is preferred over unsupervised back exercises,” Dr. Magrey said, summarizing current ACR recommendations, which also suggest that land-based activities are preferred over water-based exercises and group physical therapy rather than home-based exercises, according to the available evidence, although it is of low-to-moderate quality.

What type of physical therapy to recommend really boils down to what services are available, what facilities the patient has access to, and what they feel they are capable of doing or are willing to do.

Back pain can be frustrating for patients, said Dr. Leizman, because they hurt when they move, and there’s not a simple solution of “do this or that and you’ll get better.”

“If it’s possible for a patient to do aqua therapy, that has been a good option for many of my patients who are unable to get moving on land without pain,” she said, and “I’ve had some great success with some yoga therapists who work with my patients.”

Long-term Role of the Primary Care Practitioner

Once referred, patients with axial SpA will usually be seen by their rheumatologists at least twice a year to monitor their response to treatment. Primary care practitioners will also continue to see these people for other reasons and can help monitor for drug toxicity by performing blood and liver function tests, as well as looking for signs of associated conditions such as uveitis, psoriasis, and inflammatory bowel disease and referring patients on to other specialists as required.

Treating the inflammatory back pain may sometimes help treat the related conditions and vice versa, but not always, noted Dr. Leizman. Communication between professionals is thus very important to ensure that everyone is on the same page, and regular updates help enormously.

Dr. Leizman tries to see all her patients regularly, at least once a year, but it can be once or twice a year, depending on their age, how healthy they are, and what underlying conditions they may have that she is also managing along with the inflammatory back condition. It is a balancing act to prevent too many appointments, she said, but also helps patients manage the multiple recommendations.

At these appointments, she’ll not only check on patients’ progress and ensure that they have had all the tests that they should have, but she’ll also discuss general measures that may help with patients’ general health, such as weight control, their ability to manage disease processes with other daily activities of living, and other creative coping mechanisms.

“The weight discussion is never easy, but it is helpful to address the impact of weight if it may be contributing to their discomfort,” Dr. Leizman said. “I also think that there are diets patients can choose that are less inflammatory and that can be beneficial.”

Ultimately, “I want my patients to be on the least amount of medicine possible,” Dr. Leizman said. “If they need medications, I support my rheumatologists’ recommendations. I help my patients as they try whatever works to make them feel better, both the nonpharmaceutical options and the medications,” she said.

“Importantly, I am there for support as a resource and a partner,” Leizman added. “I’m the main quarterback for my patients.”

Key Takeaways

• Prompt referral to a rheumatologist remains key.
• The treatment goal is to improve patients’ quality of life by reducing symptoms such as pain and fatigue.
• Physical therapy and NSAIDs remain first-line treatment in primary care.
• NSAID treatment should be at the full recommended dose and given continuously, not as needed.
• The choice of NSAID does not matter; try switching the NSAID if no effects are seen.
• Physical therapy such as water-based activities and yoga may be beneficial, but exercise programs should be prescribed by a qualified therapist.
• Remember general health advice regarding diet and nutrition can be helpful.

A version of this article appeared on Medscape.com.

When axial spondyloarthritis (SpA) is suspected, a “prompt referral to a rheumatologist” is in order. But with the referral possibly taking several weeks, if not months in some parts of the world, how can primary care practitioners manage patients with this type of chronic back pain in the meantime? And what is the long-term role of the primary care practitioner in managing someone diagnosed with the condition? This news organization asked rheumatologist Marina Magrey, MD, and general internal medicine physician Debra Leizman, MD, for their expert advice.

Steps to Manage Suspected Axial SpA

“As [primary care practitioners] identify patients who they suspect may have axial spondyloarthritis, the first thing they should do is a prompt referral to a rheumatologist so that there is a timely diagnosis,” said Dr. Magrey, who heads up the division of rheumatology at University Hospitals Cleveland Medical Center and is professor of medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio.

Importantly, the referral should “explicitly say that they’re suspecting axial spondyloarthritis” and not just chronic back pain, Dr. Magrey added, otherwise it may not “hit the radar” that patients need to be seen as soon as possible. Results of lab tests such as C-reactive protein, erythrocyte sedimentation rate, and human leukocyte antigen B27, along with basic pelvic imaging results, are useful to note on the referral. “If the patient comes with that information, it makes it much easier for the rheumatologist,” she said.

Additionally, primary care practitioners can carry out screening for high cholesterol and high blood pressure and check for any existing cardiovascular disorders or extraarticular manifestations before the patient gets to see the rheumatologist.

First-Line Treatment Options

“The goal is to improve the quality of life for our patients: To reduce pain, fatigue, inflammation,” Dr. Magrey noted. “So, starting a nonsteroidal anti-inflammatory drug [NSAID] with physical therapy is very useful” in primary care, she added. These remain the “cornerstone” of treatment for axial SpA even in secondary care.

Dr. Leizman agreed that her “go to” treatment for suspected axial SpA is physical therapy alongside one of the many NSAIDs available, such as naproxen or celecoxib. She may also use topical treatments such as lidocaine or diclofenac.

“I’m not going to start any biologics; I leave that for my rheumatologist,” said Dr. Leizman, who is a senior attending physician in the division of general internal medicine at University Hospitals Cleveland Medical Center and associate professor of medicine at Case Western Reserve University.

“If I think it’s a possibility that the patient will be going on to a biologic; however, I will try to check their TB status, immunizations, and vaccination titers, making sure that the patient is up to date and as healthy otherwise as possible so that they will be primed and ready, hopefully, to go on to the biologics,” she added.

Dr. Magrey cautioned that disease-modifying antirheumatic drugs, such as methotrexate and sulfasalazine, and systemic steroids such as oral prednisone “do not work in axial spondyloarthritis, so they are not recommended.”

Does the Choice of NSAID Matter?

The choice of NSAID is really down to the personal choice of the physician in agreement with the patient, and of course whether the medical insurance will cover it, Dr. Magrey observed. There appears to be little difference between the available NSAIDs, and it doesn’t appear to matter whether they are long-acting and taken once a day — which may be a convenient option for some patients — or short-acting and taken twice a day. The important point is that patients are taking these drugs continuously and not on demand and that they are being given at full dose.

“Start with one NSAID at the maximum strength, and then you try that for 2-4 weeks. If that doesn’t work, switch to another one,” Dr. Magrey advised.

American College of Rheumatology (ACR) guidelines for axial SpA recommend that a trial of at least two NSAIDs is undertaken before any biologic treatment is considered, but because the presentation of axial SpA is so heterogeneous, the decision to escalate treatment — usually to a tumor necrosis factor inhibitor first — is best left until after the referral and the diagnosis had been confirmed, she suggested.

What Type of Physical Therapy Works?

Physical therapy and nonpharmacologic ways to help people are integral to optimal patient management. But these still need to be prescribed and administered by a qualified physiotherapist, which means another, separate referral that can also take time, as it’s important to match the patient to the right physiotherapist, Dr. Leizman observed.

Patients need to be informed about the benefits of regular exercise, and suggesting low-impact exercises for the back can be helpful, Dr. Magrey noted.

“Supervised physical therapy is preferred over unsupervised back exercises,” Dr. Magrey said, summarizing current ACR recommendations, which also suggest that land-based activities are preferred over water-based exercises and group physical therapy rather than home-based exercises, according to the available evidence, although it is of low-to-moderate quality.

What type of physical therapy to recommend really boils down to what services are available, what facilities the patient has access to, and what they feel they are capable of doing or are willing to do.

Back pain can be frustrating for patients, said Dr. Leizman, because they hurt when they move, and there’s not a simple solution of “do this or that and you’ll get better.”

“If it’s possible for a patient to do aqua therapy, that has been a good option for many of my patients who are unable to get moving on land without pain,” she said, and “I’ve had some great success with some yoga therapists who work with my patients.”

Long-term Role of the Primary Care Practitioner

Once referred, patients with axial SpA will usually be seen by their rheumatologists at least twice a year to monitor their response to treatment. Primary care practitioners will also continue to see these people for other reasons and can help monitor for drug toxicity by performing blood and liver function tests, as well as looking for signs of associated conditions such as uveitis, psoriasis, and inflammatory bowel disease and referring patients on to other specialists as required.

Treating the inflammatory back pain may sometimes help treat the related conditions and vice versa, but not always, noted Dr. Leizman. Communication between professionals is thus very important to ensure that everyone is on the same page, and regular updates help enormously.

Dr. Leizman tries to see all her patients regularly, at least once a year, but it can be once or twice a year, depending on their age, how healthy they are, and what underlying conditions they may have that she is also managing along with the inflammatory back condition. It is a balancing act to prevent too many appointments, she said, but also helps patients manage the multiple recommendations.

At these appointments, she’ll not only check on patients’ progress and ensure that they have had all the tests that they should have, but she’ll also discuss general measures that may help with patients’ general health, such as weight control, their ability to manage disease processes with other daily activities of living, and other creative coping mechanisms.

“The weight discussion is never easy, but it is helpful to address the impact of weight if it may be contributing to their discomfort,” Dr. Leizman said. “I also think that there are diets patients can choose that are less inflammatory and that can be beneficial.”

Ultimately, “I want my patients to be on the least amount of medicine possible,” Dr. Leizman said. “If they need medications, I support my rheumatologists’ recommendations. I help my patients as they try whatever works to make them feel better, both the nonpharmaceutical options and the medications,” she said.

“Importantly, I am there for support as a resource and a partner,” Leizman added. “I’m the main quarterback for my patients.”

Key Takeaways

• Prompt referral to a rheumatologist remains key.
• The treatment goal is to improve patients’ quality of life by reducing symptoms such as pain and fatigue.
• Physical therapy and NSAIDs remain first-line treatment in primary care.
• NSAID treatment should be at the full recommended dose and given continuously, not as needed.
• The choice of NSAID does not matter; try switching the NSAID if no effects are seen.
• Physical therapy such as water-based activities and yoga may be beneficial, but exercise programs should be prescribed by a qualified therapist.
• Remember general health advice regarding diet and nutrition can be helpful.

A version of this article appeared on Medscape.com.

When axial spondyloarthritis (SpA) is suspected, a “prompt referral to a rheumatologist” is in order. But with the referral possibly taking several weeks, if not months in some parts of the world, how can primary care practitioners manage patients with this type of chronic back pain in the meantime? And what is the long-term role of the primary care practitioner in managing someone diagnosed with the condition? This news organization asked rheumatologist Marina Magrey, MD, and general internal medicine physician Debra Leizman, MD, for their expert advice.

Steps to Manage Suspected Axial SpA

“As [primary care practitioners] identify patients who they suspect may have axial spondyloarthritis, the first thing they should do is a prompt referral to a rheumatologist so that there is a timely diagnosis,” said Dr. Magrey, who heads up the division of rheumatology at University Hospitals Cleveland Medical Center and is professor of medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio.

Importantly, the referral should “explicitly say that they’re suspecting axial spondyloarthritis” and not just chronic back pain, Dr. Magrey added, otherwise it may not “hit the radar” that patients need to be seen as soon as possible. Results of lab tests such as C-reactive protein, erythrocyte sedimentation rate, and human leukocyte antigen B27, along with basic pelvic imaging results, are useful to note on the referral. “If the patient comes with that information, it makes it much easier for the rheumatologist,” she said.

Additionally, primary care practitioners can carry out screening for high cholesterol and high blood pressure and check for any existing cardiovascular disorders or extraarticular manifestations before the patient gets to see the rheumatologist.

First-Line Treatment Options

“The goal is to improve the quality of life for our patients: To reduce pain, fatigue, inflammation,” Dr. Magrey noted. “So, starting a nonsteroidal anti-inflammatory drug [NSAID] with physical therapy is very useful” in primary care, she added. These remain the “cornerstone” of treatment for axial SpA even in secondary care.

Dr. Leizman agreed that her “go to” treatment for suspected axial SpA is physical therapy alongside one of the many NSAIDs available, such as naproxen or celecoxib. She may also use topical treatments such as lidocaine or diclofenac.

“I’m not going to start any biologics; I leave that for my rheumatologist,” said Dr. Leizman, who is a senior attending physician in the division of general internal medicine at University Hospitals Cleveland Medical Center and associate professor of medicine at Case Western Reserve University.

“If I think it’s a possibility that the patient will be going on to a biologic; however, I will try to check their TB status, immunizations, and vaccination titers, making sure that the patient is up to date and as healthy otherwise as possible so that they will be primed and ready, hopefully, to go on to the biologics,” she added.

Dr. Magrey cautioned that disease-modifying antirheumatic drugs, such as methotrexate and sulfasalazine, and systemic steroids such as oral prednisone “do not work in axial spondyloarthritis, so they are not recommended.”

Does the Choice of NSAID Matter?

The choice of NSAID is really down to the personal choice of the physician in agreement with the patient, and of course whether the medical insurance will cover it, Dr. Magrey observed. There appears to be little difference between the available NSAIDs, and it doesn’t appear to matter whether they are long-acting and taken once a day — which may be a convenient option for some patients — or short-acting and taken twice a day. The important point is that patients are taking these drugs continuously and not on demand and that they are being given at full dose.

“Start with one NSAID at the maximum strength, and then you try that for 2-4 weeks. If that doesn’t work, switch to another one,” Dr. Magrey advised.

American College of Rheumatology (ACR) guidelines for axial SpA recommend that a trial of at least two NSAIDs is undertaken before any biologic treatment is considered, but because the presentation of axial SpA is so heterogeneous, the decision to escalate treatment — usually to a tumor necrosis factor inhibitor first — is best left until after the referral and the diagnosis had been confirmed, she suggested.

What Type of Physical Therapy Works?

Physical therapy and nonpharmacologic ways to help people are integral to optimal patient management. But these still need to be prescribed and administered by a qualified physiotherapist, which means another, separate referral that can also take time, as it’s important to match the patient to the right physiotherapist, Dr. Leizman observed.

Patients need to be informed about the benefits of regular exercise, and suggesting low-impact exercises for the back can be helpful, Dr. Magrey noted.

“Supervised physical therapy is preferred over unsupervised back exercises,” Dr. Magrey said, summarizing current ACR recommendations, which also suggest that land-based activities are preferred over water-based exercises and group physical therapy rather than home-based exercises, according to the available evidence, although it is of low-to-moderate quality.

What type of physical therapy to recommend really boils down to what services are available, what facilities the patient has access to, and what they feel they are capable of doing or are willing to do.

Back pain can be frustrating for patients, said Dr. Leizman, because they hurt when they move, and there’s not a simple solution of “do this or that and you’ll get better.”

“If it’s possible for a patient to do aqua therapy, that has been a good option for many of my patients who are unable to get moving on land without pain,” she said, and “I’ve had some great success with some yoga therapists who work with my patients.”

Long-term Role of the Primary Care Practitioner

Once referred, patients with axial SpA will usually be seen by their rheumatologists at least twice a year to monitor their response to treatment. Primary care practitioners will also continue to see these people for other reasons and can help monitor for drug toxicity by performing blood and liver function tests, as well as looking for signs of associated conditions such as uveitis, psoriasis, and inflammatory bowel disease and referring patients on to other specialists as required.

Treating the inflammatory back pain may sometimes help treat the related conditions and vice versa, but not always, noted Dr. Leizman. Communication between professionals is thus very important to ensure that everyone is on the same page, and regular updates help enormously.

Dr. Leizman tries to see all her patients regularly, at least once a year, but it can be once or twice a year, depending on their age, how healthy they are, and what underlying conditions they may have that she is also managing along with the inflammatory back condition. It is a balancing act to prevent too many appointments, she said, but also helps patients manage the multiple recommendations.

At these appointments, she’ll not only check on patients’ progress and ensure that they have had all the tests that they should have, but she’ll also discuss general measures that may help with patients’ general health, such as weight control, their ability to manage disease processes with other daily activities of living, and other creative coping mechanisms.

“The weight discussion is never easy, but it is helpful to address the impact of weight if it may be contributing to their discomfort,” Dr. Leizman said. “I also think that there are diets patients can choose that are less inflammatory and that can be beneficial.”

Ultimately, “I want my patients to be on the least amount of medicine possible,” Dr. Leizman said. “If they need medications, I support my rheumatologists’ recommendations. I help my patients as they try whatever works to make them feel better, both the nonpharmaceutical options and the medications,” she said.

“Importantly, I am there for support as a resource and a partner,” Leizman added. “I’m the main quarterback for my patients.”

Key Takeaways

• Prompt referral to a rheumatologist remains key.
• The treatment goal is to improve patients’ quality of life by reducing symptoms such as pain and fatigue.
• Physical therapy and NSAIDs remain first-line treatment in primary care.
• NSAID treatment should be at the full recommended dose and given continuously, not as needed.
• The choice of NSAID does not matter; try switching the NSAID if no effects are seen.
• Physical therapy such as water-based activities and yoga may be beneficial, but exercise programs should be prescribed by a qualified therapist.
• Remember general health advice regarding diet and nutrition can be helpful.

A version of this article appeared on Medscape.com.