Rheumatoid Arthritis

Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.

The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.

Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.

Primary care physicians, surgeons, and researchers are trying to identify risk factors, medication regimens, and nondrug approaches to avoid these complications. Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.

At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.

“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.

The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.

Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.

The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
 

Prioritizing bone health

In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.

People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”

Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
 

Missed chances

One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.

A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.

Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.

When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.

Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”

Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.

Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”

“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.

Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
 

Lifelong effort

In some ways, to address bone health at the time of surgery may be too late.

Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.

The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.

To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.

For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.

Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.

Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.

Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.

The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.

The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.

Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
 

Treatment gaps

Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.

Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.

Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.

Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.

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

Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.

The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.

Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.

Primary care physicians, surgeons, and researchers are trying to identify risk factors, medication regimens, and nondrug approaches to avoid these complications. Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.

At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.

“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.

The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.

Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.

The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
 

Prioritizing bone health

In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.

People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”

Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
 

Missed chances

One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.

A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.

Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.

When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.

Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”

Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.

Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”

“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.

Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
 

Lifelong effort

In some ways, to address bone health at the time of surgery may be too late.

Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.

The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.

To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.

For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.

Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.

Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.

Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.

The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.

The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.

Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
 

Treatment gaps

Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.

Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.

Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.

Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.

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

Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.

The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.

Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.

Primary care physicians, surgeons, and researchers are trying to identify risk factors, medication regimens, and nondrug approaches to avoid these complications. Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.

At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.

“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.

The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.

Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.

The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
 

Prioritizing bone health

In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.

People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”

Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
 

Missed chances

One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.

A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.

Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.

When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.

Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”

Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.

Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”

“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.

Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
 

Lifelong effort

In some ways, to address bone health at the time of surgery may be too late.

Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.

The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.

To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.

For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.

Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.

Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.

Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.

The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.

The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.

Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
 

Treatment gaps

Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.

Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.

Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.

Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.

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

A newly discovered strain of bacteria could play a role in the development of rheumatoid arthritis, according to findings recently published in Science Translational Medicine.

Mice colonized with a strain of Subdoligranulum bacteria in their gut – a strain previously unidentified but now named Subdoligranulum didolesgii – developed joint swelling and inflammation as well as antibodies and T-cell responses similar to what is seen in RA, researchers reported.

“This was the first time that anyone has observed arthritis developing in a mouse that was not otherwise immunologically stimulated with an adjuvant of some kind, or genetically manipulated,” said Kristine Kuhn, MD, PhD, associate professor of rheumatology at the University of Colorado at Denver, Aurora, who led a team of researchers that also included investigators from Stanford (Calif.) University and Benaroya Research Institute in Seattle.

The findings offer the latest evidence – and perhaps the most compelling evidence – for the mucosal origins hypothesis, the idea that rheumatoid arthritis can start with an immune response somewhere in the mucosa because of environmental interactions, and then becomes systemic, resulting in symptoms in the joints. Anti-citrullinated protein antibodies (ACPA), hallmarks of RA, have been found at mucosal surfaces in the periodontium and the lungs, and there have been reports of them in the intestine and cervicovaginal mucosa as well.

The latest findings that implicate the new bacterium build on previous findings in which people at risk of RA, but without symptoms yet, had an expansion of B cells producing immunoglobulin A (IgA), an antibody found in the mucosa. A closer look at these B cells, using variable region sequencing, found that they arose from a family that includes both IgA and IgG members. Because IgG antibodies are systemic, this suggested a kind of evolution from an IgA-based, mucosal immune response to one that is systemic and could target the joints.

Researchers mixed monoclonal antibodies from these B cells with a pool of bacteria from the stool of a broad population of people, and then pulled out the bacteria bound by these antibodies, and sequenced them. They found that the antibodies had bound almost exclusively to Ruminococcaceae and Lachnospiraceae.

They then cultured the stool of an individual at risk of developing RA and ended up with five isolates within Ruminococcaceae – “all of which belonged to the Subdoligranulum genus,” Dr. Kuhn said. When they sequenced these, they found that they had a new strain, which was named by Meagan Chriswell, an MD-PhD candidate and member of the Cherokee Nation of Oklahoma, who chose a term based on the Cherokee word for rheumatism.

Researchers at Benaroya then mixed this strain with T cells of people with RA, and those of controls, and only the T cells of those with RA were stimulated by the bacterium, they found.

“When intestines of germ-free mice were colonized with the strain, we found that they were getting arthritis,” Dr. Kuhn said. Photos of the joints show a striking contrast between the swollen joints of the mice given Subdoligranulum didolesgii and those injected with Prevotella copri, another strain suspected of having a link to RA, as well as with another Subdoligranulum strain and a sterile media. Dr. Kuhn noted that the P. copri strain did not come from an RA-affected individual.

“We thought that our results closed the loop nicely to show that these immune responses truly were toward the Subdoligranulum, and also stimulating arthritis,” she said.

The researchers then assessed the prevalence of the strain in people at risk for RA or with RA, and in controls. They found it in 17% of those with or at risk for RA but didn’t see it at all in the healthy control population.

Dr. Kuhn and her research team, she said, are now looking at the prevalence of the strain in a larger population and doing more investigating into the link with RA.

“Does it really associate with the development of immune responses and the development of rheumatoid arthritis?” she said.

Potential etiologic role of P. copri

Another paper, published in Arthritis & Rheumatology by some of the same investigators a week before the study describing the Subdoligranulum findings, tried to ascertain the point at which individuals might develop antibodies to P. copri, which for about a decade has been suspected of having a link to the development of RA.

They found that those with early RA had higher median values of IgG anti–P. copri (Pc) antibodies, compared with matched controls. People with established RA also had higher values of IgA anti-Pc antibodies. Those with ACPA, but not rheumatoid factor (RF), showed a trend toward higher IgG anti-Pc antibodies. Those who were ACPA-positive and RF-positive had significantly increased levels of IgA anti-Pc antibodies and a trend toward higher levels of IgG anti-Pc antibodies, compared with matched controls.

The findings, according to the researchers, “support a potential etiologic role for this microorganism in both RA preclinical evolution and the subsequent pathogenesis of synovitis.”

Dr. Kuhn and others in the field say it’s likely that many microbes play a role in the development of RA, and that the P. copri findings only add evidence of that relationship.

“Maybe the bacteria are involved at different parts of the pathway, and maybe they’re involved in triggering different parts of the immune responses,” she said. “Those are all to be determined.”

Dan Littman, MD, PhD, professor of rheumatology at New York University, who wrote a commentary reflecting on the findings of the Subdoligranulum study, said the results are “another piece of data” adding to the evidence base for the mucosal origins hypothesis.

“It’s by no means proven that this is the way pathogenesis in RA can occur, but it’s certainly a very solid study,” said Dr. Littman, who with colleagues published findings in 2013 linking P. copri to RA. “What makes it most compelling is that they seem to be able to show some evidence of causality in the mouse model.”

A newly discovered strain of bacteria could play a role in the development of rheumatoid arthritis, according to findings recently published in Science Translational Medicine.

Mice colonized with a strain of Subdoligranulum bacteria in their gut – a strain previously unidentified but now named Subdoligranulum didolesgii – developed joint swelling and inflammation as well as antibodies and T-cell responses similar to what is seen in RA, researchers reported.

“This was the first time that anyone has observed arthritis developing in a mouse that was not otherwise immunologically stimulated with an adjuvant of some kind, or genetically manipulated,” said Kristine Kuhn, MD, PhD, associate professor of rheumatology at the University of Colorado at Denver, Aurora, who led a team of researchers that also included investigators from Stanford (Calif.) University and Benaroya Research Institute in Seattle.

The findings offer the latest evidence – and perhaps the most compelling evidence – for the mucosal origins hypothesis, the idea that rheumatoid arthritis can start with an immune response somewhere in the mucosa because of environmental interactions, and then becomes systemic, resulting in symptoms in the joints. Anti-citrullinated protein antibodies (ACPA), hallmarks of RA, have been found at mucosal surfaces in the periodontium and the lungs, and there have been reports of them in the intestine and cervicovaginal mucosa as well.

The latest findings that implicate the new bacterium build on previous findings in which people at risk of RA, but without symptoms yet, had an expansion of B cells producing immunoglobulin A (IgA), an antibody found in the mucosa. A closer look at these B cells, using variable region sequencing, found that they arose from a family that includes both IgA and IgG members. Because IgG antibodies are systemic, this suggested a kind of evolution from an IgA-based, mucosal immune response to one that is systemic and could target the joints.

Researchers mixed monoclonal antibodies from these B cells with a pool of bacteria from the stool of a broad population of people, and then pulled out the bacteria bound by these antibodies, and sequenced them. They found that the antibodies had bound almost exclusively to Ruminococcaceae and Lachnospiraceae.

They then cultured the stool of an individual at risk of developing RA and ended up with five isolates within Ruminococcaceae – “all of which belonged to the Subdoligranulum genus,” Dr. Kuhn said. When they sequenced these, they found that they had a new strain, which was named by Meagan Chriswell, an MD-PhD candidate and member of the Cherokee Nation of Oklahoma, who chose a term based on the Cherokee word for rheumatism.

Researchers at Benaroya then mixed this strain with T cells of people with RA, and those of controls, and only the T cells of those with RA were stimulated by the bacterium, they found.

“When intestines of germ-free mice were colonized with the strain, we found that they were getting arthritis,” Dr. Kuhn said. Photos of the joints show a striking contrast between the swollen joints of the mice given Subdoligranulum didolesgii and those injected with Prevotella copri, another strain suspected of having a link to RA, as well as with another Subdoligranulum strain and a sterile media. Dr. Kuhn noted that the P. copri strain did not come from an RA-affected individual.

“We thought that our results closed the loop nicely to show that these immune responses truly were toward the Subdoligranulum, and also stimulating arthritis,” she said.

The researchers then assessed the prevalence of the strain in people at risk for RA or with RA, and in controls. They found it in 17% of those with or at risk for RA but didn’t see it at all in the healthy control population.

Dr. Kuhn and her research team, she said, are now looking at the prevalence of the strain in a larger population and doing more investigating into the link with RA.

“Does it really associate with the development of immune responses and the development of rheumatoid arthritis?” she said.

Potential etiologic role of P. copri

Another paper, published in Arthritis & Rheumatology by some of the same investigators a week before the study describing the Subdoligranulum findings, tried to ascertain the point at which individuals might develop antibodies to P. copri, which for about a decade has been suspected of having a link to the development of RA.

They found that those with early RA had higher median values of IgG anti–P. copri (Pc) antibodies, compared with matched controls. People with established RA also had higher values of IgA anti-Pc antibodies. Those with ACPA, but not rheumatoid factor (RF), showed a trend toward higher IgG anti-Pc antibodies. Those who were ACPA-positive and RF-positive had significantly increased levels of IgA anti-Pc antibodies and a trend toward higher levels of IgG anti-Pc antibodies, compared with matched controls.

The findings, according to the researchers, “support a potential etiologic role for this microorganism in both RA preclinical evolution and the subsequent pathogenesis of synovitis.”

Dr. Kuhn and others in the field say it’s likely that many microbes play a role in the development of RA, and that the P. copri findings only add evidence of that relationship.

“Maybe the bacteria are involved at different parts of the pathway, and maybe they’re involved in triggering different parts of the immune responses,” she said. “Those are all to be determined.”

Dan Littman, MD, PhD, professor of rheumatology at New York University, who wrote a commentary reflecting on the findings of the Subdoligranulum study, said the results are “another piece of data” adding to the evidence base for the mucosal origins hypothesis.

“It’s by no means proven that this is the way pathogenesis in RA can occur, but it’s certainly a very solid study,” said Dr. Littman, who with colleagues published findings in 2013 linking P. copri to RA. “What makes it most compelling is that they seem to be able to show some evidence of causality in the mouse model.”

A newly discovered strain of bacteria could play a role in the development of rheumatoid arthritis, according to findings recently published in Science Translational Medicine.

Mice colonized with a strain of Subdoligranulum bacteria in their gut – a strain previously unidentified but now named Subdoligranulum didolesgii – developed joint swelling and inflammation as well as antibodies and T-cell responses similar to what is seen in RA, researchers reported.

“This was the first time that anyone has observed arthritis developing in a mouse that was not otherwise immunologically stimulated with an adjuvant of some kind, or genetically manipulated,” said Kristine Kuhn, MD, PhD, associate professor of rheumatology at the University of Colorado at Denver, Aurora, who led a team of researchers that also included investigators from Stanford (Calif.) University and Benaroya Research Institute in Seattle.

The findings offer the latest evidence – and perhaps the most compelling evidence – for the mucosal origins hypothesis, the idea that rheumatoid arthritis can start with an immune response somewhere in the mucosa because of environmental interactions, and then becomes systemic, resulting in symptoms in the joints. Anti-citrullinated protein antibodies (ACPA), hallmarks of RA, have been found at mucosal surfaces in the periodontium and the lungs, and there have been reports of them in the intestine and cervicovaginal mucosa as well.

The latest findings that implicate the new bacterium build on previous findings in which people at risk of RA, but without symptoms yet, had an expansion of B cells producing immunoglobulin A (IgA), an antibody found in the mucosa. A closer look at these B cells, using variable region sequencing, found that they arose from a family that includes both IgA and IgG members. Because IgG antibodies are systemic, this suggested a kind of evolution from an IgA-based, mucosal immune response to one that is systemic and could target the joints.

Researchers mixed monoclonal antibodies from these B cells with a pool of bacteria from the stool of a broad population of people, and then pulled out the bacteria bound by these antibodies, and sequenced them. They found that the antibodies had bound almost exclusively to Ruminococcaceae and Lachnospiraceae.

They then cultured the stool of an individual at risk of developing RA and ended up with five isolates within Ruminococcaceae – “all of which belonged to the Subdoligranulum genus,” Dr. Kuhn said. When they sequenced these, they found that they had a new strain, which was named by Meagan Chriswell, an MD-PhD candidate and member of the Cherokee Nation of Oklahoma, who chose a term based on the Cherokee word for rheumatism.

Researchers at Benaroya then mixed this strain with T cells of people with RA, and those of controls, and only the T cells of those with RA were stimulated by the bacterium, they found.

“When intestines of germ-free mice were colonized with the strain, we found that they were getting arthritis,” Dr. Kuhn said. Photos of the joints show a striking contrast between the swollen joints of the mice given Subdoligranulum didolesgii and those injected with Prevotella copri, another strain suspected of having a link to RA, as well as with another Subdoligranulum strain and a sterile media. Dr. Kuhn noted that the P. copri strain did not come from an RA-affected individual.

“We thought that our results closed the loop nicely to show that these immune responses truly were toward the Subdoligranulum, and also stimulating arthritis,” she said.

The researchers then assessed the prevalence of the strain in people at risk for RA or with RA, and in controls. They found it in 17% of those with or at risk for RA but didn’t see it at all in the healthy control population.

Dr. Kuhn and her research team, she said, are now looking at the prevalence of the strain in a larger population and doing more investigating into the link with RA.

“Does it really associate with the development of immune responses and the development of rheumatoid arthritis?” she said.

Potential etiologic role of P. copri

Another paper, published in Arthritis & Rheumatology by some of the same investigators a week before the study describing the Subdoligranulum findings, tried to ascertain the point at which individuals might develop antibodies to P. copri, which for about a decade has been suspected of having a link to the development of RA.

They found that those with early RA had higher median values of IgG anti–P. copri (Pc) antibodies, compared with matched controls. People with established RA also had higher values of IgA anti-Pc antibodies. Those with ACPA, but not rheumatoid factor (RF), showed a trend toward higher IgG anti-Pc antibodies. Those who were ACPA-positive and RF-positive had significantly increased levels of IgA anti-Pc antibodies and a trend toward higher levels of IgG anti-Pc antibodies, compared with matched controls.

The findings, according to the researchers, “support a potential etiologic role for this microorganism in both RA preclinical evolution and the subsequent pathogenesis of synovitis.”

Dr. Kuhn and others in the field say it’s likely that many microbes play a role in the development of RA, and that the P. copri findings only add evidence of that relationship.

“Maybe the bacteria are involved at different parts of the pathway, and maybe they’re involved in triggering different parts of the immune responses,” she said. “Those are all to be determined.”

Dan Littman, MD, PhD, professor of rheumatology at New York University, who wrote a commentary reflecting on the findings of the Subdoligranulum study, said the results are “another piece of data” adding to the evidence base for the mucosal origins hypothesis.

“It’s by no means proven that this is the way pathogenesis in RA can occur, but it’s certainly a very solid study,” said Dr. Littman, who with colleagues published findings in 2013 linking P. copri to RA. “What makes it most compelling is that they seem to be able to show some evidence of causality in the mouse model.”

Multiple studies have emphasized the potential for severe COVID-19 outcomes in patients with rheumatic disease, including patients with rheumatoid arthritis (RA). Because these studies often group together patients with different diseases, medications, and manifestations, differences in outcomes between patients with these conditions may be difficult to tease out.

Figueroa-Parra and colleagues performed a retrospective cohort study comparing people with RA who developed COVID-19 to those who did not have RA to examine the effect of RA characteristics, such as interstitial lung disease (ILD), serostatus, and bone erosions, on COVID-19 outcomes. Patients with RA, particularly those with seropositive RA, bone erosions, and RA-associated ILD, had approximately twofold (or higher) risk for severe COVID-19 outcomes, such as mortality or mechanical ventilation, than did those without RA. However, there was no difference in outcomes seen between patients with RA who were seropositive compared with those who were seronegative, with or without bone erosions, or with or without ILD. The mechanism by which RA phenotypes and their treatment affect this risk remains unclear.

Li and colleagues also looked at COVID-19 outcomes in patients with RA according to vaccination status using a UK primary care database. Among unvaccinated patients, the risk for SARS-CoV-2 infection and hospitalization or mortality because of COVID-19 were modestly higher in people with RA. Among vaccinated patients, there was no increased risk for breakthrough infection, COVID-19 hospitalization, or mortality observed in patients with RA over 3 or 6 months of follow-up, with a slight increase over 9 months of follow-up. Overall, both studies support prior research suggesting a higher risk for more severe COVID-19 in patients with RA, as well as potential mitigation with vaccination.

Predictors of RA course and severity are of great interest in determining the optimal therapy to reduce joint damage and prevent RA progression while also minimizing the adverse effects of treatment. Early disease course has been shown to be important in several studies. Giollo and colleagues compared patients with "difficult-to-treat RA," ie, RA that is resistant to multiple biologic disease-modifying antirheumatic drugs (bDMARD) or targeted synthetic DMARD (tsDMARD), with those without in an inception cohort study and found that early difficult management as well as delay of methotrexate initiation was associated with persistent inflammatory symptoms. This finding does not show a causative relationship between methotrexate and protection from the development of refractory RA but does lend support for early aggressive treatment in patients with a high inflammatory burden.

Conversely, Parisi and colleagues performed a subanalysis of the STARTER study of patients with RA in clinical remission to evaluate the impact of different therapies. The STARTER study had shown an association between ultrasound detection of tenosynovitis and RA flares. Of the more than 250 patients completing the study, ultrasound evidence of tenosynovitis was better controlled in patients on combination bDMARD and conventional synthetic DMARD (csDMARD) therapy than in those on csDMARDs monotherapy, with a trend toward reduction in flares in patients on combination therapy. Given the relatively small effect, it is not clear that combination therapy is associated with deeper remission, but, as suggested in prior studies, ultrasound evidence of tenosynovitis may be worthwhile considering prior to tapering therapy.

Multiple studies have emphasized the potential for severe COVID-19 outcomes in patients with rheumatic disease, including patients with rheumatoid arthritis (RA). Because these studies often group together patients with different diseases, medications, and manifestations, differences in outcomes between patients with these conditions may be difficult to tease out.

Figueroa-Parra and colleagues performed a retrospective cohort study comparing people with RA who developed COVID-19 to those who did not have RA to examine the effect of RA characteristics, such as interstitial lung disease (ILD), serostatus, and bone erosions, on COVID-19 outcomes. Patients with RA, particularly those with seropositive RA, bone erosions, and RA-associated ILD, had approximately twofold (or higher) risk for severe COVID-19 outcomes, such as mortality or mechanical ventilation, than did those without RA. However, there was no difference in outcomes seen between patients with RA who were seropositive compared with those who were seronegative, with or without bone erosions, or with or without ILD. The mechanism by which RA phenotypes and their treatment affect this risk remains unclear.

Li and colleagues also looked at COVID-19 outcomes in patients with RA according to vaccination status using a UK primary care database. Among unvaccinated patients, the risk for SARS-CoV-2 infection and hospitalization or mortality because of COVID-19 were modestly higher in people with RA. Among vaccinated patients, there was no increased risk for breakthrough infection, COVID-19 hospitalization, or mortality observed in patients with RA over 3 or 6 months of follow-up, with a slight increase over 9 months of follow-up. Overall, both studies support prior research suggesting a higher risk for more severe COVID-19 in patients with RA, as well as potential mitigation with vaccination.

Predictors of RA course and severity are of great interest in determining the optimal therapy to reduce joint damage and prevent RA progression while also minimizing the adverse effects of treatment. Early disease course has been shown to be important in several studies. Giollo and colleagues compared patients with "difficult-to-treat RA," ie, RA that is resistant to multiple biologic disease-modifying antirheumatic drugs (bDMARD) or targeted synthetic DMARD (tsDMARD), with those without in an inception cohort study and found that early difficult management as well as delay of methotrexate initiation was associated with persistent inflammatory symptoms. This finding does not show a causative relationship between methotrexate and protection from the development of refractory RA but does lend support for early aggressive treatment in patients with a high inflammatory burden.

Conversely, Parisi and colleagues performed a subanalysis of the STARTER study of patients with RA in clinical remission to evaluate the impact of different therapies. The STARTER study had shown an association between ultrasound detection of tenosynovitis and RA flares. Of the more than 250 patients completing the study, ultrasound evidence of tenosynovitis was better controlled in patients on combination bDMARD and conventional synthetic DMARD (csDMARD) therapy than in those on csDMARDs monotherapy, with a trend toward reduction in flares in patients on combination therapy. Given the relatively small effect, it is not clear that combination therapy is associated with deeper remission, but, as suggested in prior studies, ultrasound evidence of tenosynovitis may be worthwhile considering prior to tapering therapy.

Multiple studies have emphasized the potential for severe COVID-19 outcomes in patients with rheumatic disease, including patients with rheumatoid arthritis (RA). Because these studies often group together patients with different diseases, medications, and manifestations, differences in outcomes between patients with these conditions may be difficult to tease out.

Figueroa-Parra and colleagues performed a retrospective cohort study comparing people with RA who developed COVID-19 to those who did not have RA to examine the effect of RA characteristics, such as interstitial lung disease (ILD), serostatus, and bone erosions, on COVID-19 outcomes. Patients with RA, particularly those with seropositive RA, bone erosions, and RA-associated ILD, had approximately twofold (or higher) risk for severe COVID-19 outcomes, such as mortality or mechanical ventilation, than did those without RA. However, there was no difference in outcomes seen between patients with RA who were seropositive compared with those who were seronegative, with or without bone erosions, or with or without ILD. The mechanism by which RA phenotypes and their treatment affect this risk remains unclear.

Li and colleagues also looked at COVID-19 outcomes in patients with RA according to vaccination status using a UK primary care database. Among unvaccinated patients, the risk for SARS-CoV-2 infection and hospitalization or mortality because of COVID-19 were modestly higher in people with RA. Among vaccinated patients, there was no increased risk for breakthrough infection, COVID-19 hospitalization, or mortality observed in patients with RA over 3 or 6 months of follow-up, with a slight increase over 9 months of follow-up. Overall, both studies support prior research suggesting a higher risk for more severe COVID-19 in patients with RA, as well as potential mitigation with vaccination.

Predictors of RA course and severity are of great interest in determining the optimal therapy to reduce joint damage and prevent RA progression while also minimizing the adverse effects of treatment. Early disease course has been shown to be important in several studies. Giollo and colleagues compared patients with "difficult-to-treat RA," ie, RA that is resistant to multiple biologic disease-modifying antirheumatic drugs (bDMARD) or targeted synthetic DMARD (tsDMARD), with those without in an inception cohort study and found that early difficult management as well as delay of methotrexate initiation was associated with persistent inflammatory symptoms. This finding does not show a causative relationship between methotrexate and protection from the development of refractory RA but does lend support for early aggressive treatment in patients with a high inflammatory burden.

Conversely, Parisi and colleagues performed a subanalysis of the STARTER study of patients with RA in clinical remission to evaluate the impact of different therapies. The STARTER study had shown an association between ultrasound detection of tenosynovitis and RA flares. Of the more than 250 patients completing the study, ultrasound evidence of tenosynovitis was better controlled in patients on combination bDMARD and conventional synthetic DMARD (csDMARD) therapy than in those on csDMARDs monotherapy, with a trend toward reduction in flares in patients on combination therapy. Given the relatively small effect, it is not clear that combination therapy is associated with deeper remission, but, as suggested in prior studies, ultrasound evidence of tenosynovitis may be worthwhile considering prior to tapering therapy.

Key clinical point: Higher rehabilitation dose (>8 physical/occupational therapy visits) improved physical function in adults with rheumatoid arthritis (RA) who reported new rehabilitation visits after at least 1 year without rehabilitation visits.

Major finding: Worse physical function at baseline was associated with a higher rehabilitation dose (adjusted odds ratio [aOR] 1.29; 95% CI 1.04-1.60). Higher vs. lower rehabilitation dose was also associated with clinically favorable changes in physical function (aOR 1.41; 95% CI 1.03-1.92).

Study details: This prospective cohort analysis evaluated the data of 1,381 adults with RA from the FORWARD registry who reported new rehabilitation visits of low/medium/high dose over 6 months after no rehabilitation visits for past ≥1 year.

Disclosures: This study did not receive any specific funding. LM Thoma and E Wellsandt reported receiving support from the Rheumatology Research Foundation and/or National Institutes of Health.

Source: Thoma LM et al. Examining rehabilitation dose in adults with rheumatoid arthritis: Association with baseline factors and change in clinical outcomes. Arthritis Care Res (Hoboken). 2022 (Sep 12). Doi: 10.1002/acr.25019

Key clinical point: Higher rehabilitation dose (>8 physical/occupational therapy visits) improved physical function in adults with rheumatoid arthritis (RA) who reported new rehabilitation visits after at least 1 year without rehabilitation visits.

Major finding: Worse physical function at baseline was associated with a higher rehabilitation dose (adjusted odds ratio [aOR] 1.29; 95% CI 1.04-1.60). Higher vs. lower rehabilitation dose was also associated with clinically favorable changes in physical function (aOR 1.41; 95% CI 1.03-1.92).

Study details: This prospective cohort analysis evaluated the data of 1,381 adults with RA from the FORWARD registry who reported new rehabilitation visits of low/medium/high dose over 6 months after no rehabilitation visits for past ≥1 year.

Disclosures: This study did not receive any specific funding. LM Thoma and E Wellsandt reported receiving support from the Rheumatology Research Foundation and/or National Institutes of Health.

Source: Thoma LM et al. Examining rehabilitation dose in adults with rheumatoid arthritis: Association with baseline factors and change in clinical outcomes. Arthritis Care Res (Hoboken). 2022 (Sep 12). Doi: 10.1002/acr.25019

Key clinical point: Higher rehabilitation dose (>8 physical/occupational therapy visits) improved physical function in adults with rheumatoid arthritis (RA) who reported new rehabilitation visits after at least 1 year without rehabilitation visits.

Major finding: Worse physical function at baseline was associated with a higher rehabilitation dose (adjusted odds ratio [aOR] 1.29; 95% CI 1.04-1.60). Higher vs. lower rehabilitation dose was also associated with clinically favorable changes in physical function (aOR 1.41; 95% CI 1.03-1.92).

Study details: This prospective cohort analysis evaluated the data of 1,381 adults with RA from the FORWARD registry who reported new rehabilitation visits of low/medium/high dose over 6 months after no rehabilitation visits for past ≥1 year.

Disclosures: This study did not receive any specific funding. LM Thoma and E Wellsandt reported receiving support from the Rheumatology Research Foundation and/or National Institutes of Health.

Source: Thoma LM et al. Examining rehabilitation dose in adults with rheumatoid arthritis: Association with baseline factors and change in clinical outcomes. Arthritis Care Res (Hoboken). 2022 (Sep 12). Doi: 10.1002/acr.25019

Key clinical point: The prevalence for osteoporosis continues to remain high in patients with rheumatoid arthritis (RA) despite significant advances in diagnostic methods, prevention, and treatment.

Major finding: Overall, osteoporosis was highly prevalent in patients with RA (prevalence, 27.6%; 95% CI, 23.9%-31.3%), with the prevalence being the highest in studies during 2011-2015 (36.2%; 95% CI, 24.5%-47.8%), followed by 2016-2021 (27.1%; 95% CI, 20.7%-33.4%), and before 2010 (21.6%; 95% CI, 15.8%-27.4%).

Study details: Findings are from a systematic review and meta-analysis of 57 studies including 227,812 patients with RA, of which 64,290 reported osteoporosis.

Disclosures: This study was funded by Arak University of Medical Sciences. The authors declared no conflicts of interest.

Source: Moshayedi S et al. The prevalence of osteoporosis in rheumatoid arthritis patient: A systematic review and meta-analysis. Sci Rep. 2022;12(1):15844 (Sep 23). Doi: 10.1038/s41598-022-20016-x.

Key clinical point: The prevalence for osteoporosis continues to remain high in patients with rheumatoid arthritis (RA) despite significant advances in diagnostic methods, prevention, and treatment.

Major finding: Overall, osteoporosis was highly prevalent in patients with RA (prevalence, 27.6%; 95% CI, 23.9%-31.3%), with the prevalence being the highest in studies during 2011-2015 (36.2%; 95% CI, 24.5%-47.8%), followed by 2016-2021 (27.1%; 95% CI, 20.7%-33.4%), and before 2010 (21.6%; 95% CI, 15.8%-27.4%).

Study details: Findings are from a systematic review and meta-analysis of 57 studies including 227,812 patients with RA, of which 64,290 reported osteoporosis.

Disclosures: This study was funded by Arak University of Medical Sciences. The authors declared no conflicts of interest.

Source: Moshayedi S et al. The prevalence of osteoporosis in rheumatoid arthritis patient: A systematic review and meta-analysis. Sci Rep. 2022;12(1):15844 (Sep 23). Doi: 10.1038/s41598-022-20016-x.

Key clinical point: The prevalence for osteoporosis continues to remain high in patients with rheumatoid arthritis (RA) despite significant advances in diagnostic methods, prevention, and treatment.

Major finding: Overall, osteoporosis was highly prevalent in patients with RA (prevalence, 27.6%; 95% CI, 23.9%-31.3%), with the prevalence being the highest in studies during 2011-2015 (36.2%; 95% CI, 24.5%-47.8%), followed by 2016-2021 (27.1%; 95% CI, 20.7%-33.4%), and before 2010 (21.6%; 95% CI, 15.8%-27.4%).

Study details: Findings are from a systematic review and meta-analysis of 57 studies including 227,812 patients with RA, of which 64,290 reported osteoporosis.

Disclosures: This study was funded by Arak University of Medical Sciences. The authors declared no conflicts of interest.

Source: Moshayedi S et al. The prevalence of osteoporosis in rheumatoid arthritis patient: A systematic review and meta-analysis. Sci Rep. 2022;12(1):15844 (Sep 23). Doi: 10.1038/s41598-022-20016-x.

Key clinical point: Serum levels of interferon beta (IFNβ) may distinguish early from late relapse after biologic disease-modifying antirheumatic drug (bDMARD) withdrawal in patients with rheumatoid arthritis (RA).

Major finding: Patients with serum IFNβ levels of 3.38 vs. <3.38 in log₂ had a significantly lower probability of sustained remission during the first 6 months of bDMARD withdrawal (log-rank test, P = .0177). Serum IFNβ levels of 3.38 in log₂ at the time of bDMARD withdrawal predicted early vs. late relapse in patients with highly probable relapses (area under the curve, 0.833) and patients with lower IFNβ levels (<3.38 in log₂) were able to safely discontinue bDMARD.

Study details: This prospective study included 40 patients with RA who maintained clinical remission with bDMARDs for >12 months, of which 26 relapsed at some point after bDMARD withdrawal.

Disclosures: This study was partially supported by unlimited research fund from Chugai Pharm, Eisai, and Mitsubishi-Tanabe provided to S Minota. The authors declared no conflicts of interest.

Source: Sakashita E et al. Serum level of IFNβ distinguishes early from late relapses after biologics withdrawal in rheumatoid arthritis. Sci Rep. 2022;12(1):16547 (Oct 3). Doi: 10.1038/s41598-022-21160-0.

Key clinical point: Serum levels of interferon beta (IFNβ) may distinguish early from late relapse after biologic disease-modifying antirheumatic drug (bDMARD) withdrawal in patients with rheumatoid arthritis (RA).

Major finding: Patients with serum IFNβ levels of 3.38 vs. <3.38 in log₂ had a significantly lower probability of sustained remission during the first 6 months of bDMARD withdrawal (log-rank test, P = .0177). Serum IFNβ levels of 3.38 in log₂ at the time of bDMARD withdrawal predicted early vs. late relapse in patients with highly probable relapses (area under the curve, 0.833) and patients with lower IFNβ levels (<3.38 in log₂) were able to safely discontinue bDMARD.

Study details: This prospective study included 40 patients with RA who maintained clinical remission with bDMARDs for >12 months, of which 26 relapsed at some point after bDMARD withdrawal.

Disclosures: This study was partially supported by unlimited research fund from Chugai Pharm, Eisai, and Mitsubishi-Tanabe provided to S Minota. The authors declared no conflicts of interest.

Source: Sakashita E et al. Serum level of IFNβ distinguishes early from late relapses after biologics withdrawal in rheumatoid arthritis. Sci Rep. 2022;12(1):16547 (Oct 3). Doi: 10.1038/s41598-022-21160-0.

Key clinical point: Serum levels of interferon beta (IFNβ) may distinguish early from late relapse after biologic disease-modifying antirheumatic drug (bDMARD) withdrawal in patients with rheumatoid arthritis (RA).

Major finding: Patients with serum IFNβ levels of 3.38 vs. <3.38 in log₂ had a significantly lower probability of sustained remission during the first 6 months of bDMARD withdrawal (log-rank test, P = .0177). Serum IFNβ levels of 3.38 in log₂ at the time of bDMARD withdrawal predicted early vs. late relapse in patients with highly probable relapses (area under the curve, 0.833) and patients with lower IFNβ levels (<3.38 in log₂) were able to safely discontinue bDMARD.

Study details: This prospective study included 40 patients with RA who maintained clinical remission with bDMARDs for >12 months, of which 26 relapsed at some point after bDMARD withdrawal.

Disclosures: This study was partially supported by unlimited research fund from Chugai Pharm, Eisai, and Mitsubishi-Tanabe provided to S Minota. The authors declared no conflicts of interest.

Source: Sakashita E et al. Serum level of IFNβ distinguishes early from late relapses after biologics withdrawal in rheumatoid arthritis. Sci Rep. 2022;12(1):16547 (Oct 3). Doi: 10.1038/s41598-022-21160-0.

Key clinical point: Patients with rheumatoid arthritis (RA) vs. general population remain at a higher risk for SARS-CoV-2 infection and its severe outcomes; although COVID-19 vaccination has reduced severe outcomes, the risk for breakthrough infections is higher among patients with RA, supporting recent recommendations for booster COVID-19 vaccination.

Major finding: Unvaccinated patients with RA vs. general population were at an increased risk for SARS-CoV-2 infection (adjusted hazard ratio [aHR] 1.11; 95% CI 1.00-1.24), COVID-19 hospitalization (aHR 1.62; 95% CI 1.34-1.96), and COVID-19 death (aHR 1.88; 95% CI 1.37-2.60). COVID-19 vaccination reduced disease severity but not the risk for breakthrough infection in patients with RA vs. general population over 9 months of follow-up (aHR1.10; 95% CI, 1.00-1.20).

Study details: Findings are from 2 cohort studies including patients with RA (unvaccinated n = 15,901; vaccinated n = 14,330) and non-RA individuals from general population (unvaccinated n = 1,558,423; vaccinated n = 1,208,659).

Disclosures: This study was supported by the National Institutes of Health and other sources. ZS Wallace declared receiving research support and consulting fees from various sources unrelated to this work.

Source: Li H et al. Risk of COVID-19 among unvaccinated and vaccinated patients with rheumatoid arthritis: A general population study. Arthritis Care Res (Hoboken). 2022 (Sep 26). Doi: 10.1002/acr.25028

Key clinical point: Patients with rheumatoid arthritis (RA) vs. general population remain at a higher risk for SARS-CoV-2 infection and its severe outcomes; although COVID-19 vaccination has reduced severe outcomes, the risk for breakthrough infections is higher among patients with RA, supporting recent recommendations for booster COVID-19 vaccination.

Major finding: Unvaccinated patients with RA vs. general population were at an increased risk for SARS-CoV-2 infection (adjusted hazard ratio [aHR] 1.11; 95% CI 1.00-1.24), COVID-19 hospitalization (aHR 1.62; 95% CI 1.34-1.96), and COVID-19 death (aHR 1.88; 95% CI 1.37-2.60). COVID-19 vaccination reduced disease severity but not the risk for breakthrough infection in patients with RA vs. general population over 9 months of follow-up (aHR1.10; 95% CI, 1.00-1.20).

Study details: Findings are from 2 cohort studies including patients with RA (unvaccinated n = 15,901; vaccinated n = 14,330) and non-RA individuals from general population (unvaccinated n = 1,558,423; vaccinated n = 1,208,659).

Disclosures: This study was supported by the National Institutes of Health and other sources. ZS Wallace declared receiving research support and consulting fees from various sources unrelated to this work.

Source: Li H et al. Risk of COVID-19 among unvaccinated and vaccinated patients with rheumatoid arthritis: A general population study. Arthritis Care Res (Hoboken). 2022 (Sep 26). Doi: 10.1002/acr.25028

Key clinical point: Patients with rheumatoid arthritis (RA) vs. general population remain at a higher risk for SARS-CoV-2 infection and its severe outcomes; although COVID-19 vaccination has reduced severe outcomes, the risk for breakthrough infections is higher among patients with RA, supporting recent recommendations for booster COVID-19 vaccination.

Major finding: Unvaccinated patients with RA vs. general population were at an increased risk for SARS-CoV-2 infection (adjusted hazard ratio [aHR] 1.11; 95% CI 1.00-1.24), COVID-19 hospitalization (aHR 1.62; 95% CI 1.34-1.96), and COVID-19 death (aHR 1.88; 95% CI 1.37-2.60). COVID-19 vaccination reduced disease severity but not the risk for breakthrough infection in patients with RA vs. general population over 9 months of follow-up (aHR1.10; 95% CI, 1.00-1.20).

Study details: Findings are from 2 cohort studies including patients with RA (unvaccinated n = 15,901; vaccinated n = 14,330) and non-RA individuals from general population (unvaccinated n = 1,558,423; vaccinated n = 1,208,659).

Disclosures: This study was supported by the National Institutes of Health and other sources. ZS Wallace declared receiving research support and consulting fees from various sources unrelated to this work.

Source: Li H et al. Risk of COVID-19 among unvaccinated and vaccinated patients with rheumatoid arthritis: A general population study. Arthritis Care Res (Hoboken). 2022 (Sep 26). Doi: 10.1002/acr.25028

Key clinical point: Smoking worsened disease activity and health-related quality of life at 1 year in patients with rheumatoid arthritis (RA), with effects being persistent at 3 years and early smoking cessation vs. continued smoking being associated with improved disease activity.

Major finding: At 1 year, current smokers vs. non-smokers were at a higher risk for a swollen joint number above the median (odds ratio [OR] 1.7; P = .001) and 36-Item Short-Form Health Survey physical (OR 1.5; P = .006) and mental (OR 1.4; P = .03) scores below the median, with effects being persistent at 3 years. Patients who stopped vs. continued smoking within 1 year reported a lower swollen joint number (P = .002).

Study details: Findings are from a population-based case-control study including 1531 patients with newly diagnosed RA who were followed-up for 3 years, of which 376 patients were current smokers.

Disclosures: This study was supported by grants from the Swedish Medical Research Council and other sources. The authors declared no conflicts of interest.

Source: Alfredsson L et al. Influence of smoking on disease activity and quality of life in patients with rheumatoid arthritis: Results from a Swedish case-control study with longitudinal follow-up. Arthritis Care Res (Hoboken). 2022 (Sep 23). Doi: 10.1002/acr.25026

Key clinical point: Smoking worsened disease activity and health-related quality of life at 1 year in patients with rheumatoid arthritis (RA), with effects being persistent at 3 years and early smoking cessation vs. continued smoking being associated with improved disease activity.

Major finding: At 1 year, current smokers vs. non-smokers were at a higher risk for a swollen joint number above the median (odds ratio [OR] 1.7; P = .001) and 36-Item Short-Form Health Survey physical (OR 1.5; P = .006) and mental (OR 1.4; P = .03) scores below the median, with effects being persistent at 3 years. Patients who stopped vs. continued smoking within 1 year reported a lower swollen joint number (P = .002).

Study details: Findings are from a population-based case-control study including 1531 patients with newly diagnosed RA who were followed-up for 3 years, of which 376 patients were current smokers.

Disclosures: This study was supported by grants from the Swedish Medical Research Council and other sources. The authors declared no conflicts of interest.

Source: Alfredsson L et al. Influence of smoking on disease activity and quality of life in patients with rheumatoid arthritis: Results from a Swedish case-control study with longitudinal follow-up. Arthritis Care Res (Hoboken). 2022 (Sep 23). Doi: 10.1002/acr.25026

Key clinical point: Smoking worsened disease activity and health-related quality of life at 1 year in patients with rheumatoid arthritis (RA), with effects being persistent at 3 years and early smoking cessation vs. continued smoking being associated with improved disease activity.

Major finding: At 1 year, current smokers vs. non-smokers were at a higher risk for a swollen joint number above the median (odds ratio [OR] 1.7; P = .001) and 36-Item Short-Form Health Survey physical (OR 1.5; P = .006) and mental (OR 1.4; P = .03) scores below the median, with effects being persistent at 3 years. Patients who stopped vs. continued smoking within 1 year reported a lower swollen joint number (P = .002).

Study details: Findings are from a population-based case-control study including 1531 patients with newly diagnosed RA who were followed-up for 3 years, of which 376 patients were current smokers.

Disclosures: This study was supported by grants from the Swedish Medical Research Council and other sources. The authors declared no conflicts of interest.

Source: Alfredsson L et al. Influence of smoking on disease activity and quality of life in patients with rheumatoid arthritis: Results from a Swedish case-control study with longitudinal follow-up. Arthritis Care Res (Hoboken). 2022 (Sep 23). Doi: 10.1002/acr.25026

Key clinical point: Failure to initiate methotrexate within 3 months and discontinue glucocorticoids within 6 months during early disease management were associated with difficult-to-treat rheumatoid arthritis (D2T-RA).

Major finding: A significantly lower proportion of patients with D2T-RA had adequate methotrexate treatment duration vs. those with non-D2T-RA (70.8% v. 85.5%; P = .022). Additionally, a significantly higher proportion of patients with D2T-RA vs non-D2T-RA continued glucocorticoids beyond 6 months (70.8% vs 33.8%; P < .001), with a delay of <3 months vs >12 months in methotrexate treatment (odds ratio [OR] 0.3; P = .031) and failure to discontinue glucocorticoids (OR 4.6; P < .001) being significantly associated with D2T-RA.

Study details: Findings are from a retrospective cohort study including 48 patients with D2T-RA and 145 patients with non-D2T-RA.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Giollo A et al. Early characterisation of difficult-to-treat rheumatoid arthritis by suboptimal initial management A multicentre cohort study. Rheumatology (Oxford). 2022 (Oct 3). Doi: 10.1093/rheumatology/keac563

Key clinical point: Failure to initiate methotrexate within 3 months and discontinue glucocorticoids within 6 months during early disease management were associated with difficult-to-treat rheumatoid arthritis (D2T-RA).

Major finding: A significantly lower proportion of patients with D2T-RA had adequate methotrexate treatment duration vs. those with non-D2T-RA (70.8% v. 85.5%; P = .022). Additionally, a significantly higher proportion of patients with D2T-RA vs non-D2T-RA continued glucocorticoids beyond 6 months (70.8% vs 33.8%; P < .001), with a delay of <3 months vs >12 months in methotrexate treatment (odds ratio [OR] 0.3; P = .031) and failure to discontinue glucocorticoids (OR 4.6; P < .001) being significantly associated with D2T-RA.

Study details: Findings are from a retrospective cohort study including 48 patients with D2T-RA and 145 patients with non-D2T-RA.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Giollo A et al. Early characterisation of difficult-to-treat rheumatoid arthritis by suboptimal initial management A multicentre cohort study. Rheumatology (Oxford). 2022 (Oct 3). Doi: 10.1093/rheumatology/keac563

Key clinical point: Failure to initiate methotrexate within 3 months and discontinue glucocorticoids within 6 months during early disease management were associated with difficult-to-treat rheumatoid arthritis (D2T-RA).

Major finding: A significantly lower proportion of patients with D2T-RA had adequate methotrexate treatment duration vs. those with non-D2T-RA (70.8% v. 85.5%; P = .022). Additionally, a significantly higher proportion of patients with D2T-RA vs non-D2T-RA continued glucocorticoids beyond 6 months (70.8% vs 33.8%; P < .001), with a delay of <3 months vs >12 months in methotrexate treatment (odds ratio [OR] 0.3; P = .031) and failure to discontinue glucocorticoids (OR 4.6; P < .001) being significantly associated with D2T-RA.

Study details: Findings are from a retrospective cohort study including 48 patients with D2T-RA and 145 patients with non-D2T-RA.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Giollo A et al. Early characterisation of difficult-to-treat rheumatoid arthritis by suboptimal initial management A multicentre cohort study. Rheumatology (Oxford). 2022 (Oct 3). Doi: 10.1093/rheumatology/keac563

Key clinical point: Patients with rheumatoid arthritis (RA) treated with Janus kinase (JAK) vs tumor necrosis factor (TNF) inhibitors were at a higher risk for venous thromboembolism (VTE), particularly pulmonary embolism.

Major finding: Patients treated with JAK vs TNF inhibitors were at a 73% higher risk for VTE (adjusted hazard ratio [aHR] 1.73; 95% CI 1.24-2.42), with the higher risk appearing to be confined to pulmonary embolism (aHR 3.21; 95% CI 2.11-4.88) rather than deep vein thrombosis.

Study details: Findings are from a prospective, register-based, active comparator study including 85,722 patients with RA, of which 27,610 patients initiated biologic/targeted synthetic disease-modifying antirheumatic drugs and were matched with 91,207 healthy controls.

Disclosures: This study was funded by Swedish Research Council, the Swedish Heart Lung Foundation, and other sources. Karolinska Institutet has or has had research agreements with various sources for safety monitoring of biologics through ARTIS/Swedish Biologics Register.

Source: Molander V et al. Venous thromboembolism with JAK inhibitors and other immune-modulatory drugs: A Swedish comparative safety study among patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Sep 23). Doi: 10.1136/ard-2022-223050

Key clinical point: Patients with rheumatoid arthritis (RA) treated with Janus kinase (JAK) vs tumor necrosis factor (TNF) inhibitors were at a higher risk for venous thromboembolism (VTE), particularly pulmonary embolism.

Major finding: Patients treated with JAK vs TNF inhibitors were at a 73% higher risk for VTE (adjusted hazard ratio [aHR] 1.73; 95% CI 1.24-2.42), with the higher risk appearing to be confined to pulmonary embolism (aHR 3.21; 95% CI 2.11-4.88) rather than deep vein thrombosis.

Study details: Findings are from a prospective, register-based, active comparator study including 85,722 patients with RA, of which 27,610 patients initiated biologic/targeted synthetic disease-modifying antirheumatic drugs and were matched with 91,207 healthy controls.

Disclosures: This study was funded by Swedish Research Council, the Swedish Heart Lung Foundation, and other sources. Karolinska Institutet has or has had research agreements with various sources for safety monitoring of biologics through ARTIS/Swedish Biologics Register.

Source: Molander V et al. Venous thromboembolism with JAK inhibitors and other immune-modulatory drugs: A Swedish comparative safety study among patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Sep 23). Doi: 10.1136/ard-2022-223050

Key clinical point: Patients with rheumatoid arthritis (RA) treated with Janus kinase (JAK) vs tumor necrosis factor (TNF) inhibitors were at a higher risk for venous thromboembolism (VTE), particularly pulmonary embolism.

Major finding: Patients treated with JAK vs TNF inhibitors were at a 73% higher risk for VTE (adjusted hazard ratio [aHR] 1.73; 95% CI 1.24-2.42), with the higher risk appearing to be confined to pulmonary embolism (aHR 3.21; 95% CI 2.11-4.88) rather than deep vein thrombosis.

Study details: Findings are from a prospective, register-based, active comparator study including 85,722 patients with RA, of which 27,610 patients initiated biologic/targeted synthetic disease-modifying antirheumatic drugs and were matched with 91,207 healthy controls.

Disclosures: This study was funded by Swedish Research Council, the Swedish Heart Lung Foundation, and other sources. Karolinska Institutet has or has had research agreements with various sources for safety monitoring of biologics through ARTIS/Swedish Biologics Register.

Source: Molander V et al. Venous thromboembolism with JAK inhibitors and other immune-modulatory drugs: A Swedish comparative safety study among patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Sep 23). Doi: 10.1136/ard-2022-223050