Marcia Frellick

CHICAGO – Higher weight and body mass index (BMI) in preadolescents are linked with poor brain health, new research suggests.

Poor brain health has been linked with obesity in adults, but little has been known about the link in children.

Lead author Simone Kaltenhauser, a postgraduate research fellow in radiology and biomedical imaging at the Yale School of Medicine, New Haven, Conn., presented her findings at the annual meeting of the Radiological Society of North America.

To represent the national sociodemographic makeup, the researchers used baseline information from the Adolescent Brain Cognitive Development (ABCD) study, which included 11,878 children aged 9 and 10 years from 21 centers across the United States.

This study included 5,169 children (51.9% girls). Children who had had traumatic brain injury, eating disorders, neurodevelopmental problems, and psychiatric diseases were excluded from the final analysis.

The researchers analyzed information from structural MRI and resting-state functional MRI, which allowed them to measure brain activity by detecting changes in blood flow.

“We analyzed the average fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusivity (RD), and neurite density (ND) of 35 white matter (WM) tracts; cortical thickness and surface of 68 regions; and functional connectivity of 91 predefined network correlations,” the authors explained.

They adjusted for age, sex, race/ethnicity, handedness, and socioeconomic status. They used linear models to determine associations between weight and BMI z-scores and the imaging metrics.
 

Loss of white matter integrity

Among children with obesity, there was pervasive loss of white matter integrity and neurite density, cortical gray matter thinning, and decreased connectivity within and between networks that have been associated with impulse control and reward-based decision-making.

“These changes persisted in a similar pattern also 2 years later,” she said.

A member of the audience asked whether a reverse relationship might be at work – that poor brain health might drive obesity rather than the other way around.

Ms. Kaltenhauser agreed that other factors could be driving the link and acknowledged as a limitation that they did not have access to genetic information on the children.

Information on the effects of overweight and obesity is critical, especially in the United States, where an estimated 1 in 5 children are obese.

Ms. Kaltenhauser said she hopes her study raises awareness of potential brain health consequences as well as the physical consequences of childhood obesity.

Senior author Sam Payabvash, MD, a neuroradiologist and assistant professor of radiology and biomedical imaging at the Yale School of Medicine, said in a press release that the study may help explain the findings from previous studies that show an association between higher BMI in children and poor cognitive functioning and academic performance.

“The longitudinal ABCD study gives us the opportunity to observe any changes that occur in children with higher weight and BMI z-scores,” Dr. Payabvash said. “We’ll need to watch over the next 6-10 years.”
 

Avenues for future research

Amit B. Desai, MD, a neuroradiologist with Mayo Clinic in Jacksonville, Fla., who was not part of the study, said that while the research demonstrates an association between brain structure and BMI and obesity, “there may be other lurking variables.”

“What’s happening at an earlier stage in life could be causing both,” he said.

He noted that he would like to see future studies involving children at even earlier ages, along with investigations of the role of genetics or socioeconomic factors.

Including older children would be interesting as well, he said.

“Myelination doesn’t complete until you’re in your late teens or early 20s, so there are structural changes happening in the brain much later on into adolescence and early adulthood,” Dr. Desai said.

It would be premature, he said, to conclude from these findings that if children have obesity, there must be something wrong with their brain.

He would like to see whether there are changes in this link if a child is obese early on and later has normal weight or if a child has normal weight early and then becomes obese.

“It’s definitely an eye-opening study, but [it] needs additional work to expand upon it,” he said.

Ms. Kaltenhauser and Dr. Desai report no relevant financial relationships.

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

CHICAGO – Higher weight and body mass index (BMI) in preadolescents are linked with poor brain health, new research suggests.

Poor brain health has been linked with obesity in adults, but little has been known about the link in children.

Lead author Simone Kaltenhauser, a postgraduate research fellow in radiology and biomedical imaging at the Yale School of Medicine, New Haven, Conn., presented her findings at the annual meeting of the Radiological Society of North America.

To represent the national sociodemographic makeup, the researchers used baseline information from the Adolescent Brain Cognitive Development (ABCD) study, which included 11,878 children aged 9 and 10 years from 21 centers across the United States.

This study included 5,169 children (51.9% girls). Children who had had traumatic brain injury, eating disorders, neurodevelopmental problems, and psychiatric diseases were excluded from the final analysis.

The researchers analyzed information from structural MRI and resting-state functional MRI, which allowed them to measure brain activity by detecting changes in blood flow.

“We analyzed the average fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusivity (RD), and neurite density (ND) of 35 white matter (WM) tracts; cortical thickness and surface of 68 regions; and functional connectivity of 91 predefined network correlations,” the authors explained.

They adjusted for age, sex, race/ethnicity, handedness, and socioeconomic status. They used linear models to determine associations between weight and BMI z-scores and the imaging metrics.
 

Loss of white matter integrity

Among children with obesity, there was pervasive loss of white matter integrity and neurite density, cortical gray matter thinning, and decreased connectivity within and between networks that have been associated with impulse control and reward-based decision-making.

“These changes persisted in a similar pattern also 2 years later,” she said.

A member of the audience asked whether a reverse relationship might be at work – that poor brain health might drive obesity rather than the other way around.

Ms. Kaltenhauser agreed that other factors could be driving the link and acknowledged as a limitation that they did not have access to genetic information on the children.

Information on the effects of overweight and obesity is critical, especially in the United States, where an estimated 1 in 5 children are obese.

Ms. Kaltenhauser said she hopes her study raises awareness of potential brain health consequences as well as the physical consequences of childhood obesity.

Senior author Sam Payabvash, MD, a neuroradiologist and assistant professor of radiology and biomedical imaging at the Yale School of Medicine, said in a press release that the study may help explain the findings from previous studies that show an association between higher BMI in children and poor cognitive functioning and academic performance.

“The longitudinal ABCD study gives us the opportunity to observe any changes that occur in children with higher weight and BMI z-scores,” Dr. Payabvash said. “We’ll need to watch over the next 6-10 years.”
 

Avenues for future research

Amit B. Desai, MD, a neuroradiologist with Mayo Clinic in Jacksonville, Fla., who was not part of the study, said that while the research demonstrates an association between brain structure and BMI and obesity, “there may be other lurking variables.”

“What’s happening at an earlier stage in life could be causing both,” he said.

He noted that he would like to see future studies involving children at even earlier ages, along with investigations of the role of genetics or socioeconomic factors.

Including older children would be interesting as well, he said.

“Myelination doesn’t complete until you’re in your late teens or early 20s, so there are structural changes happening in the brain much later on into adolescence and early adulthood,” Dr. Desai said.

It would be premature, he said, to conclude from these findings that if children have obesity, there must be something wrong with their brain.

He would like to see whether there are changes in this link if a child is obese early on and later has normal weight or if a child has normal weight early and then becomes obese.

“It’s definitely an eye-opening study, but [it] needs additional work to expand upon it,” he said.

Ms. Kaltenhauser and Dr. Desai report no relevant financial relationships.

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

CHICAGO – Higher weight and body mass index (BMI) in preadolescents are linked with poor brain health, new research suggests.

Poor brain health has been linked with obesity in adults, but little has been known about the link in children.

Lead author Simone Kaltenhauser, a postgraduate research fellow in radiology and biomedical imaging at the Yale School of Medicine, New Haven, Conn., presented her findings at the annual meeting of the Radiological Society of North America.

To represent the national sociodemographic makeup, the researchers used baseline information from the Adolescent Brain Cognitive Development (ABCD) study, which included 11,878 children aged 9 and 10 years from 21 centers across the United States.

This study included 5,169 children (51.9% girls). Children who had had traumatic brain injury, eating disorders, neurodevelopmental problems, and psychiatric diseases were excluded from the final analysis.

The researchers analyzed information from structural MRI and resting-state functional MRI, which allowed them to measure brain activity by detecting changes in blood flow.

“We analyzed the average fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusivity (RD), and neurite density (ND) of 35 white matter (WM) tracts; cortical thickness and surface of 68 regions; and functional connectivity of 91 predefined network correlations,” the authors explained.

They adjusted for age, sex, race/ethnicity, handedness, and socioeconomic status. They used linear models to determine associations between weight and BMI z-scores and the imaging metrics.
 

Loss of white matter integrity

Among children with obesity, there was pervasive loss of white matter integrity and neurite density, cortical gray matter thinning, and decreased connectivity within and between networks that have been associated with impulse control and reward-based decision-making.

“These changes persisted in a similar pattern also 2 years later,” she said.

A member of the audience asked whether a reverse relationship might be at work – that poor brain health might drive obesity rather than the other way around.

Ms. Kaltenhauser agreed that other factors could be driving the link and acknowledged as a limitation that they did not have access to genetic information on the children.

Information on the effects of overweight and obesity is critical, especially in the United States, where an estimated 1 in 5 children are obese.

Ms. Kaltenhauser said she hopes her study raises awareness of potential brain health consequences as well as the physical consequences of childhood obesity.

Senior author Sam Payabvash, MD, a neuroradiologist and assistant professor of radiology and biomedical imaging at the Yale School of Medicine, said in a press release that the study may help explain the findings from previous studies that show an association between higher BMI in children and poor cognitive functioning and academic performance.

“The longitudinal ABCD study gives us the opportunity to observe any changes that occur in children with higher weight and BMI z-scores,” Dr. Payabvash said. “We’ll need to watch over the next 6-10 years.”
 

Avenues for future research

Amit B. Desai, MD, a neuroradiologist with Mayo Clinic in Jacksonville, Fla., who was not part of the study, said that while the research demonstrates an association between brain structure and BMI and obesity, “there may be other lurking variables.”

“What’s happening at an earlier stage in life could be causing both,” he said.

He noted that he would like to see future studies involving children at even earlier ages, along with investigations of the role of genetics or socioeconomic factors.

Including older children would be interesting as well, he said.

“Myelination doesn’t complete until you’re in your late teens or early 20s, so there are structural changes happening in the brain much later on into adolescence and early adulthood,” Dr. Desai said.

It would be premature, he said, to conclude from these findings that if children have obesity, there must be something wrong with their brain.

He would like to see whether there are changes in this link if a child is obese early on and later has normal weight or if a child has normal weight early and then becomes obese.

“It’s definitely an eye-opening study, but [it] needs additional work to expand upon it,” he said.

Ms. Kaltenhauser and Dr. Desai report no relevant financial relationships.

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

Using buprenorphine for opioid use disorder in pregnancy was linked with a lower risk of neonatal side effects than using methadone, but the risk of adverse maternal outcomes was similar between the two treatments, according to new research.

Elizabeth A. Suarez, PhD, MPH, with Brigham and Women’s Hospital in Boston, led the study published online in the New England Journal of Medicine.

Opioid use disorder in pregnant women has increased steadily in the United States since 2000, the authors write. As of 2017, about 8.2 per 1,000 deliveries were estimated to be affected by the disorder. The numbers were particularly high in people insured by Medicaid. In that group, an estimated 14.6 per 1,000 deliveries were affected.

Researchers studied pregnant women enrolled in public insurance programs in the United States from 2000 through 2018 in a dataset of 2,548,372 pregnancies that ended in live births. They analyzed outcomes in those who received buprenorphine as compared with those who received methadone.

They looked at different periods of exposure to the two medications: early pregnancy (through gestational week 19); late pregnancy (week 20 through the day before delivery); and the 30 days before delivery.

Highlighted differences in infants included:

• Neonatal abstinence syndrome in 52% of the infants who were exposed to buprenorphine in the 30 days before delivery as compared with 69.2% of those exposed to methadone (adjusted relative risk, 0.73).
• Preterm birth in 14.4% of infants exposed to buprenorphine in early pregnancy and in 24.9% of those exposed to methadone (ARR, 0.58).
• Small size for gestational age in 12.1% (buprenorphine) and 15.3% (methadone) (ARR, 0.72).
• Low birth weight in 8.3% (buprenorphine) and 14.9% (methadone) (ARR, 0.56).
• Delivery by cesarean section occurred in 33.6% of pregnant women exposed to buprenorphine in early pregnancy and 33.1% of those exposed to methadone (ARR, 1.02.).

Severe maternal complications developed in 3.3% of the women exposed to buprenorphine and 3.5% of those on methadone (ARR, 0.91.) Exposures in late pregnancy and early pregnancy yielded similar results, the authors say.

Michael Caucci, MD, of the department of psychiatry at Vanderbilt University Medical Center in Nashville, Tenn. who also runs the Women’s Mental Health Clinic at the university, said this paper supports preliminary findings from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study that suggested infants exposed to buprenorphine (compared with methadone) appeared to have lower rates of neonatal complications.

“It also supports buprenorphine as a relatively safe option for treatment of opioid use disorder during pregnancy,” said Dr. Caucci, who was not part of the study by Dr. Suarez and associates. “Reducing the fear of harming the fetus or neonate will help eliminate this barrier to perinatal substance use disorder treatment.”

But he cautions against concluding that, because buprenorphine has lower risks of fetal/neonatal complications, it is safer and therefore better than methadone in pregnancy. 

“Some women do not tolerate buprenorphine and do much better on methadone, Dr. Caucci said. “Current recommendations are that both buprenorphine and methadone are relatively safe options for treatment of OUD [opioid use disorder] in pregnancy.”

Among the differences between the treatments is that while methadone is administered daily during in-person visits to federally regulated opioid treatment programs, buprenorphine can be prescribed by approved providers, which allows patients to administer buprenorphine themselves.

Dr. Caucci said he was intrigued by the finding that there was no difference in pregnancy, neonatal, and maternal outcomes depending on the time of exposure to the agents.  

“I would have expected higher rates of neonatal abstinence syndrome (NAS) or poor fetal growth in those exposed later in pregnancy vs. those with early exposure,” he said. 

The work was supported by the National Institute on Drug Abuse. Dr. Caucci reports no relevant financial relationships. The authors’ disclosures are available with the full text.

Using buprenorphine for opioid use disorder in pregnancy was linked with a lower risk of neonatal side effects than using methadone, but the risk of adverse maternal outcomes was similar between the two treatments, according to new research.

Elizabeth A. Suarez, PhD, MPH, with Brigham and Women’s Hospital in Boston, led the study published online in the New England Journal of Medicine.

Opioid use disorder in pregnant women has increased steadily in the United States since 2000, the authors write. As of 2017, about 8.2 per 1,000 deliveries were estimated to be affected by the disorder. The numbers were particularly high in people insured by Medicaid. In that group, an estimated 14.6 per 1,000 deliveries were affected.

Researchers studied pregnant women enrolled in public insurance programs in the United States from 2000 through 2018 in a dataset of 2,548,372 pregnancies that ended in live births. They analyzed outcomes in those who received buprenorphine as compared with those who received methadone.

They looked at different periods of exposure to the two medications: early pregnancy (through gestational week 19); late pregnancy (week 20 through the day before delivery); and the 30 days before delivery.

Highlighted differences in infants included:

• Neonatal abstinence syndrome in 52% of the infants who were exposed to buprenorphine in the 30 days before delivery as compared with 69.2% of those exposed to methadone (adjusted relative risk, 0.73).
• Preterm birth in 14.4% of infants exposed to buprenorphine in early pregnancy and in 24.9% of those exposed to methadone (ARR, 0.58).
• Small size for gestational age in 12.1% (buprenorphine) and 15.3% (methadone) (ARR, 0.72).
• Low birth weight in 8.3% (buprenorphine) and 14.9% (methadone) (ARR, 0.56).
• Delivery by cesarean section occurred in 33.6% of pregnant women exposed to buprenorphine in early pregnancy and 33.1% of those exposed to methadone (ARR, 1.02.).

Severe maternal complications developed in 3.3% of the women exposed to buprenorphine and 3.5% of those on methadone (ARR, 0.91.) Exposures in late pregnancy and early pregnancy yielded similar results, the authors say.

Michael Caucci, MD, of the department of psychiatry at Vanderbilt University Medical Center in Nashville, Tenn. who also runs the Women’s Mental Health Clinic at the university, said this paper supports preliminary findings from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study that suggested infants exposed to buprenorphine (compared with methadone) appeared to have lower rates of neonatal complications.

“It also supports buprenorphine as a relatively safe option for treatment of opioid use disorder during pregnancy,” said Dr. Caucci, who was not part of the study by Dr. Suarez and associates. “Reducing the fear of harming the fetus or neonate will help eliminate this barrier to perinatal substance use disorder treatment.”

But he cautions against concluding that, because buprenorphine has lower risks of fetal/neonatal complications, it is safer and therefore better than methadone in pregnancy. 

“Some women do not tolerate buprenorphine and do much better on methadone, Dr. Caucci said. “Current recommendations are that both buprenorphine and methadone are relatively safe options for treatment of OUD [opioid use disorder] in pregnancy.”

Among the differences between the treatments is that while methadone is administered daily during in-person visits to federally regulated opioid treatment programs, buprenorphine can be prescribed by approved providers, which allows patients to administer buprenorphine themselves.

Dr. Caucci said he was intrigued by the finding that there was no difference in pregnancy, neonatal, and maternal outcomes depending on the time of exposure to the agents.  

“I would have expected higher rates of neonatal abstinence syndrome (NAS) or poor fetal growth in those exposed later in pregnancy vs. those with early exposure,” he said. 

The work was supported by the National Institute on Drug Abuse. Dr. Caucci reports no relevant financial relationships. The authors’ disclosures are available with the full text.

Using buprenorphine for opioid use disorder in pregnancy was linked with a lower risk of neonatal side effects than using methadone, but the risk of adverse maternal outcomes was similar between the two treatments, according to new research.

Elizabeth A. Suarez, PhD, MPH, with Brigham and Women’s Hospital in Boston, led the study published online in the New England Journal of Medicine.

Opioid use disorder in pregnant women has increased steadily in the United States since 2000, the authors write. As of 2017, about 8.2 per 1,000 deliveries were estimated to be affected by the disorder. The numbers were particularly high in people insured by Medicaid. In that group, an estimated 14.6 per 1,000 deliveries were affected.

Researchers studied pregnant women enrolled in public insurance programs in the United States from 2000 through 2018 in a dataset of 2,548,372 pregnancies that ended in live births. They analyzed outcomes in those who received buprenorphine as compared with those who received methadone.

They looked at different periods of exposure to the two medications: early pregnancy (through gestational week 19); late pregnancy (week 20 through the day before delivery); and the 30 days before delivery.

Highlighted differences in infants included:

• Neonatal abstinence syndrome in 52% of the infants who were exposed to buprenorphine in the 30 days before delivery as compared with 69.2% of those exposed to methadone (adjusted relative risk, 0.73).
• Preterm birth in 14.4% of infants exposed to buprenorphine in early pregnancy and in 24.9% of those exposed to methadone (ARR, 0.58).
• Small size for gestational age in 12.1% (buprenorphine) and 15.3% (methadone) (ARR, 0.72).
• Low birth weight in 8.3% (buprenorphine) and 14.9% (methadone) (ARR, 0.56).
• Delivery by cesarean section occurred in 33.6% of pregnant women exposed to buprenorphine in early pregnancy and 33.1% of those exposed to methadone (ARR, 1.02.).

Severe maternal complications developed in 3.3% of the women exposed to buprenorphine and 3.5% of those on methadone (ARR, 0.91.) Exposures in late pregnancy and early pregnancy yielded similar results, the authors say.

Michael Caucci, MD, of the department of psychiatry at Vanderbilt University Medical Center in Nashville, Tenn. who also runs the Women’s Mental Health Clinic at the university, said this paper supports preliminary findings from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study that suggested infants exposed to buprenorphine (compared with methadone) appeared to have lower rates of neonatal complications.

“It also supports buprenorphine as a relatively safe option for treatment of opioid use disorder during pregnancy,” said Dr. Caucci, who was not part of the study by Dr. Suarez and associates. “Reducing the fear of harming the fetus or neonate will help eliminate this barrier to perinatal substance use disorder treatment.”

But he cautions against concluding that, because buprenorphine has lower risks of fetal/neonatal complications, it is safer and therefore better than methadone in pregnancy. 

“Some women do not tolerate buprenorphine and do much better on methadone, Dr. Caucci said. “Current recommendations are that both buprenorphine and methadone are relatively safe options for treatment of OUD [opioid use disorder] in pregnancy.”

Among the differences between the treatments is that while methadone is administered daily during in-person visits to federally regulated opioid treatment programs, buprenorphine can be prescribed by approved providers, which allows patients to administer buprenorphine themselves.

Dr. Caucci said he was intrigued by the finding that there was no difference in pregnancy, neonatal, and maternal outcomes depending on the time of exposure to the agents.  

“I would have expected higher rates of neonatal abstinence syndrome (NAS) or poor fetal growth in those exposed later in pregnancy vs. those with early exposure,” he said. 

The work was supported by the National Institute on Drug Abuse. Dr. Caucci reports no relevant financial relationships. The authors’ disclosures are available with the full text.

CHICAGO – Taking NSAIDs for knee osteoarthritis may worsen inflammation and pain over time, suggest new data revealed at the annual meeting of the Radiological Society of North America.

Johanna Luitjens, MD, a postdoctoral scholar in the department of radiology and biomedical Imaging at the University of California, San Francisco, told this news organization that NSAIDs are frequently used to treat OA pain because inflammation is one of the main drivers of OA, but whether they actually help outcomes has been unclear. Her study suggests that they don’t help – and may actually worsen – outcomes.

Denise Fulton/MDedge News

In particular, this study looked at the impact of NSAIDs on synovitis – the inflammation of the membrane lining the knee joint – by using MRI-based structural biomarkers.

OA, the most common form of arthritis, affects more than 32 million adults in the United States and more than 500 million people worldwide.
 

No approved therapy to reduce OA progression

Little is known of the long-term effects of NSAIDs on OA progression. Currently, there’s no approved therapy to cure OA or to reduce its advance.

Dr. Luitjens noted, however, that the synovial membrane mediates development and progression of OA and may be a good therapeutic target.

Researchers studied participants from the Osteoarthritis Initiative (OAI) cohort with moderate to severe OA who used NSAIDs regularly for at least 1 year between baseline and 4-year follow-up. All participants had high-quality 3T MRI of the knee at baseline and after 4 years. Images were scored for biomarkers of inflammation, including cartilage thickness and composition.

Dr. Luitjens and associates studied 721 participants who matched the inclusion criteria (129 with and 592 participants without regular NSAID use). The available data did not further specify amounts of NSAIDs used.

At baseline, significantly higher signal intensity in the infrapatellar fat pad (IFP) was seen in patients who used NSAID, compared with controls (adjusted difference in score, 0.26; 95% confidence interval, –0.5 to –0.129; P = .039).

In addition, at the end of the study period, there was a significantly greater increase in signal intensity of IFP (adjusted difference in score, 0.46; 95% CI, 0.2-0.72; P < .001) and higher increase in effusion synovitis (adjusted difference in score, 0.27; 95% CI, 0.06-0.47;  P = .01) in NSAID users, compared with controls.

IFP size and synovial proliferation score did not different significantly between groups at the start of the study and showed no significant change over time.

The results showed no long-term benefit of NSAID use. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs, compared with the control group, and worsened at 4-year follow-up.

Design limits strength

Amanda E. Nelson, MD, associate professor of medicine, division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill, cautioned against assuming causality, pointing out that the OAI is an observational cohort study. (Dr. Nelson was not involved in the OAI or Dr. Luitjens’ analysis.)

“[The OAI is] large and well known, but it wasn’t designed to compare these groups, and this was a small subset,” she said in an interview. Without randomization, it’s hard to judge the results.

“It may be that people on NSAIDs for the duration of the study had more pain and had more disease to begin with, or had more symptoms or had failed other treatments,” she said, adding that the effect sizes were small.

Measures such as the IFP are ranked 0-3, so “the clinical difference of a 0.26 difference on a 0-3 scale is a bit uncertain,” she said.

Dr. Luitjens said that the researchers tried to adjust for potential confounders but agreed that randomized controlled trials are needed to better advise physicians and patients on the benefits or harms of using NSAIDs for OA.

Weighing the risks in older adults

Una Makris, MD, associate professor of internal medicine in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, noted that NSAIDs are “not always the safest option.”

“We are still in desperate need of disease-modifying drugs in OA with rigorous randomized trials to show efficacy for outcomes that are most meaningful to patients,” Dr. Makris, who was not involved in the study, told this news organization.

“OA is most common in older adults, those often with multiple comorbidities, so we must always weigh the risks – including known adverse effects which can be amplified in older adults – and benefits with the goal of improved function and less pain,” Dr. Makris said.

NSAID use also should be considered in the context of body mass index, cardiovascular risk, prior trauma or injury, other medication use, and behavioral factors, including physical activity, she said.

Dr. Luitjens, Dr. Nelson, and Dr. Makris reported no relevant financial relationships.

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

CHICAGO – Taking NSAIDs for knee osteoarthritis may worsen inflammation and pain over time, suggest new data revealed at the annual meeting of the Radiological Society of North America.

Johanna Luitjens, MD, a postdoctoral scholar in the department of radiology and biomedical Imaging at the University of California, San Francisco, told this news organization that NSAIDs are frequently used to treat OA pain because inflammation is one of the main drivers of OA, but whether they actually help outcomes has been unclear. Her study suggests that they don’t help – and may actually worsen – outcomes.

Denise Fulton/MDedge News

In particular, this study looked at the impact of NSAIDs on synovitis – the inflammation of the membrane lining the knee joint – by using MRI-based structural biomarkers.

OA, the most common form of arthritis, affects more than 32 million adults in the United States and more than 500 million people worldwide.
 

No approved therapy to reduce OA progression

Little is known of the long-term effects of NSAIDs on OA progression. Currently, there’s no approved therapy to cure OA or to reduce its advance.

Dr. Luitjens noted, however, that the synovial membrane mediates development and progression of OA and may be a good therapeutic target.

Researchers studied participants from the Osteoarthritis Initiative (OAI) cohort with moderate to severe OA who used NSAIDs regularly for at least 1 year between baseline and 4-year follow-up. All participants had high-quality 3T MRI of the knee at baseline and after 4 years. Images were scored for biomarkers of inflammation, including cartilage thickness and composition.

Dr. Luitjens and associates studied 721 participants who matched the inclusion criteria (129 with and 592 participants without regular NSAID use). The available data did not further specify amounts of NSAIDs used.

At baseline, significantly higher signal intensity in the infrapatellar fat pad (IFP) was seen in patients who used NSAID, compared with controls (adjusted difference in score, 0.26; 95% confidence interval, –0.5 to –0.129; P = .039).

In addition, at the end of the study period, there was a significantly greater increase in signal intensity of IFP (adjusted difference in score, 0.46; 95% CI, 0.2-0.72; P < .001) and higher increase in effusion synovitis (adjusted difference in score, 0.27; 95% CI, 0.06-0.47;  P = .01) in NSAID users, compared with controls.

IFP size and synovial proliferation score did not different significantly between groups at the start of the study and showed no significant change over time.

The results showed no long-term benefit of NSAID use. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs, compared with the control group, and worsened at 4-year follow-up.

Design limits strength

Amanda E. Nelson, MD, associate professor of medicine, division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill, cautioned against assuming causality, pointing out that the OAI is an observational cohort study. (Dr. Nelson was not involved in the OAI or Dr. Luitjens’ analysis.)

“[The OAI is] large and well known, but it wasn’t designed to compare these groups, and this was a small subset,” she said in an interview. Without randomization, it’s hard to judge the results.

“It may be that people on NSAIDs for the duration of the study had more pain and had more disease to begin with, or had more symptoms or had failed other treatments,” she said, adding that the effect sizes were small.

Measures such as the IFP are ranked 0-3, so “the clinical difference of a 0.26 difference on a 0-3 scale is a bit uncertain,” she said.

Dr. Luitjens said that the researchers tried to adjust for potential confounders but agreed that randomized controlled trials are needed to better advise physicians and patients on the benefits or harms of using NSAIDs for OA.

Weighing the risks in older adults

Una Makris, MD, associate professor of internal medicine in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, noted that NSAIDs are “not always the safest option.”

“We are still in desperate need of disease-modifying drugs in OA with rigorous randomized trials to show efficacy for outcomes that are most meaningful to patients,” Dr. Makris, who was not involved in the study, told this news organization.

“OA is most common in older adults, those often with multiple comorbidities, so we must always weigh the risks – including known adverse effects which can be amplified in older adults – and benefits with the goal of improved function and less pain,” Dr. Makris said.

NSAID use also should be considered in the context of body mass index, cardiovascular risk, prior trauma or injury, other medication use, and behavioral factors, including physical activity, she said.

Dr. Luitjens, Dr. Nelson, and Dr. Makris reported no relevant financial relationships.

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

CHICAGO – Taking NSAIDs for knee osteoarthritis may worsen inflammation and pain over time, suggest new data revealed at the annual meeting of the Radiological Society of North America.

Johanna Luitjens, MD, a postdoctoral scholar in the department of radiology and biomedical Imaging at the University of California, San Francisco, told this news organization that NSAIDs are frequently used to treat OA pain because inflammation is one of the main drivers of OA, but whether they actually help outcomes has been unclear. Her study suggests that they don’t help – and may actually worsen – outcomes.

Denise Fulton/MDedge News

In particular, this study looked at the impact of NSAIDs on synovitis – the inflammation of the membrane lining the knee joint – by using MRI-based structural biomarkers.

OA, the most common form of arthritis, affects more than 32 million adults in the United States and more than 500 million people worldwide.
 

No approved therapy to reduce OA progression

Little is known of the long-term effects of NSAIDs on OA progression. Currently, there’s no approved therapy to cure OA or to reduce its advance.

Dr. Luitjens noted, however, that the synovial membrane mediates development and progression of OA and may be a good therapeutic target.

Researchers studied participants from the Osteoarthritis Initiative (OAI) cohort with moderate to severe OA who used NSAIDs regularly for at least 1 year between baseline and 4-year follow-up. All participants had high-quality 3T MRI of the knee at baseline and after 4 years. Images were scored for biomarkers of inflammation, including cartilage thickness and composition.

Dr. Luitjens and associates studied 721 participants who matched the inclusion criteria (129 with and 592 participants without regular NSAID use). The available data did not further specify amounts of NSAIDs used.

At baseline, significantly higher signal intensity in the infrapatellar fat pad (IFP) was seen in patients who used NSAID, compared with controls (adjusted difference in score, 0.26; 95% confidence interval, –0.5 to –0.129; P = .039).

In addition, at the end of the study period, there was a significantly greater increase in signal intensity of IFP (adjusted difference in score, 0.46; 95% CI, 0.2-0.72; P < .001) and higher increase in effusion synovitis (adjusted difference in score, 0.27; 95% CI, 0.06-0.47;  P = .01) in NSAID users, compared with controls.

IFP size and synovial proliferation score did not different significantly between groups at the start of the study and showed no significant change over time.

The results showed no long-term benefit of NSAID use. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs, compared with the control group, and worsened at 4-year follow-up.

Design limits strength

Amanda E. Nelson, MD, associate professor of medicine, division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill, cautioned against assuming causality, pointing out that the OAI is an observational cohort study. (Dr. Nelson was not involved in the OAI or Dr. Luitjens’ analysis.)

“[The OAI is] large and well known, but it wasn’t designed to compare these groups, and this was a small subset,” she said in an interview. Without randomization, it’s hard to judge the results.

“It may be that people on NSAIDs for the duration of the study had more pain and had more disease to begin with, or had more symptoms or had failed other treatments,” she said, adding that the effect sizes were small.

Measures such as the IFP are ranked 0-3, so “the clinical difference of a 0.26 difference on a 0-3 scale is a bit uncertain,” she said.

Dr. Luitjens said that the researchers tried to adjust for potential confounders but agreed that randomized controlled trials are needed to better advise physicians and patients on the benefits or harms of using NSAIDs for OA.

Weighing the risks in older adults

Una Makris, MD, associate professor of internal medicine in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, noted that NSAIDs are “not always the safest option.”

“We are still in desperate need of disease-modifying drugs in OA with rigorous randomized trials to show efficacy for outcomes that are most meaningful to patients,” Dr. Makris, who was not involved in the study, told this news organization.

“OA is most common in older adults, those often with multiple comorbidities, so we must always weigh the risks – including known adverse effects which can be amplified in older adults – and benefits with the goal of improved function and less pain,” Dr. Makris said.

NSAID use also should be considered in the context of body mass index, cardiovascular risk, prior trauma or injury, other medication use, and behavioral factors, including physical activity, she said.

Dr. Luitjens, Dr. Nelson, and Dr. Makris reported no relevant financial relationships.

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

PHILADELPHIA – Treatment with the interleukin-6 receptor antagonist sarilumab (Kevzara), along with a 14-week taper of glucocorticoids, proved to have significant efficacy in patients with relapsing polymyalgia rheumatica (PMR) who were resistant to glucocorticoids in a phase 3 trial.

No new safety concerns were found with sarilumab in the multicenter, randomized, double-blind, placebo-controlled SAPHYR trial. Sarilumab is approved in the United States for the treatment of moderate to severe active rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.

The results, presented at the annual meeting of the American College of Rheumatology by Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York, included clinically meaningful improvement in quality-of-life scores.

The disease, which primarily affects people over age 65, can cause widespread aching and stiffness. It’s one of the most common inflammatory diseases among older adults.

PMR is relatively easy to treat with glucocorticoids, but relapses are common, which means long courses of glucocorticoid therapy and the side effects that come with them.
 

Need for a steroid-sparing therapy

“We recognize that a steroid-sparing drug in polymyalgia rheumatica seems to be an unmet need,” Dr. Spiera said at the meeting.

The trial, sponsored by Sanofi, included active, refractory PMR patients who flared within 3 months of study entry while on at least 7.5 mg/day of prednisone or the equivalent. They were randomly assigned (1:1) to 52 weeks of treatment with subcutaneous sarilumab 200 mg every 2 weeks plus the rapid 14-week glucocorticoid tapering regimen or were given placebo every 2 weeks plus a more traditional 52-week tapering of glucocorticoids.
 

COVID hampered recruitment

Recruitment was stopped early because of complications during the COVID-19 pandemic, so between October 2018 and July 2020, 118 of the intended 280 patients were recruited, and 117 were treated (sarilumab = 59, placebo = 58). Median age was 69 years in the treatment group and 70 among those taking placebo.

Of the 117 treated, only 78 patients (67%) completed treatment (sarilumab = 42, placebo = 36). The main reasons for stopping treatment were adverse events – including seven with sarilumab and four with placebo – and lack of efficacy (sarilumab = four, placebo = nine).

The primary outcome was the proportion of patients who reached sustained remission at 52 weeks, defined as disease remission by week 12 and no disease flare, normal C-reactive protein (CRP), and adherence to the glucocorticoid taper during weeks 12-52.

The researchers found that sustained remission was significantly higher in the sarilumab arm versus the control group (28.3% versus 10.3%; P = .0193).

IL-6 inhibitors lower CRP, but if you take CRP out of the definition, Dr. Spiera said, “we still saw this difference: 31.7% of patients treated with sarilumab and 13.8% treated with placebo and a longer taper achieved that endpoint.”
 

Forty-four percent lower risk of flare with sarilumab

Patients in the sarilumab group also had 44% lower risk of having a flare after achieving clinical remission versus the comparator group (16.7% versus 29.3%; hazard ratio, 0.56; 95% confidence interval, 0.35-0.90; P = .0153).

Patient-reported outcomes, which included physical and mental health scores and disability index results, favored sarilumab.

The incidence of treatment-emergent adverse events (TEAEs) was numerically higher in the sarilumab group, compared with the control group (94.9% versus 84.5%). TEAEs included neutropenia (15.3%) and arthralgia (15.3%) in the sarilumab group and insomnia (15.5%) in the comparator arm.

However, the frequency of serious AEs was higher in the control group, compared with the sarilumab arm (20.7% versus 13.6%). No deaths were reported, and, importantly in this age group treated with concurrent glucocorticoids and an IL-6 inhibitor, Dr. Spiera said, “there were no cases of diverticulitis requiring intervention.”

Dr. Spiera was asked about a seemingly low remission rate. He answered that the bar was very high for remission in this study.

Patients had to achieve remission by week 12 and with the rapid 14-week taper. “That means by week 12 the sarilumab arm patients were only on 2 mg of daily prednisone or its equivalent,” he said.

Patients had to maintain that for another 40 weeks, he noted, adding, “I think especially in the context of quality of life and function indices, these were important results.”

Sebastian E. Sattui, MD, director of the University of Pittsburgh Medical Center vasculitis clinic, told this news organization that prolonged use of glucocorticoids in patients with PMR remains an important concern and the need for other options is critical.

“Around 30% of patients with PMR remain on prednisone 5 years after diagnosis,” he said. “Low-dose glucocorticoids are still associated with significant morbidity. Until recently, there has been a paucity of high-quality data regarding the use of steroid-sparing agents in PMR. “

He noted that the SAPHYR trial data are promising “with sarilumab being successful in achieving remission while minimizing glucocorticoids in patients with relapsing PMR.” The clinically meaningful improvement in patient-reported outcomes was just as important, he added.

The main unanswered question is whether the disease-modifying ability of sarilumab will continue after it is stopped, Dr. Sattui said.

Dr. Spiera is a consultant for Sanofi, which funded the trial. He also disclosed financial relationships with GlaxoSmithKline, Boehringer Ingelheim, Corbus, InflaRx, AbbVie/Abbott, Novartis, Chemocentryx, Roche, and Vera. Dr. Sattui has received research support from AstraZeneca and has done unpaid consulting work for Sanofi.

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

PHILADELPHIA – Treatment with the interleukin-6 receptor antagonist sarilumab (Kevzara), along with a 14-week taper of glucocorticoids, proved to have significant efficacy in patients with relapsing polymyalgia rheumatica (PMR) who were resistant to glucocorticoids in a phase 3 trial.

No new safety concerns were found with sarilumab in the multicenter, randomized, double-blind, placebo-controlled SAPHYR trial. Sarilumab is approved in the United States for the treatment of moderate to severe active rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.

The results, presented at the annual meeting of the American College of Rheumatology by Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York, included clinically meaningful improvement in quality-of-life scores.

The disease, which primarily affects people over age 65, can cause widespread aching and stiffness. It’s one of the most common inflammatory diseases among older adults.

PMR is relatively easy to treat with glucocorticoids, but relapses are common, which means long courses of glucocorticoid therapy and the side effects that come with them.
 

Need for a steroid-sparing therapy

“We recognize that a steroid-sparing drug in polymyalgia rheumatica seems to be an unmet need,” Dr. Spiera said at the meeting.

The trial, sponsored by Sanofi, included active, refractory PMR patients who flared within 3 months of study entry while on at least 7.5 mg/day of prednisone or the equivalent. They were randomly assigned (1:1) to 52 weeks of treatment with subcutaneous sarilumab 200 mg every 2 weeks plus the rapid 14-week glucocorticoid tapering regimen or were given placebo every 2 weeks plus a more traditional 52-week tapering of glucocorticoids.
 

COVID hampered recruitment

Recruitment was stopped early because of complications during the COVID-19 pandemic, so between October 2018 and July 2020, 118 of the intended 280 patients were recruited, and 117 were treated (sarilumab = 59, placebo = 58). Median age was 69 years in the treatment group and 70 among those taking placebo.

Of the 117 treated, only 78 patients (67%) completed treatment (sarilumab = 42, placebo = 36). The main reasons for stopping treatment were adverse events – including seven with sarilumab and four with placebo – and lack of efficacy (sarilumab = four, placebo = nine).

The primary outcome was the proportion of patients who reached sustained remission at 52 weeks, defined as disease remission by week 12 and no disease flare, normal C-reactive protein (CRP), and adherence to the glucocorticoid taper during weeks 12-52.

The researchers found that sustained remission was significantly higher in the sarilumab arm versus the control group (28.3% versus 10.3%; P = .0193).

IL-6 inhibitors lower CRP, but if you take CRP out of the definition, Dr. Spiera said, “we still saw this difference: 31.7% of patients treated with sarilumab and 13.8% treated with placebo and a longer taper achieved that endpoint.”
 

Forty-four percent lower risk of flare with sarilumab

Patients in the sarilumab group also had 44% lower risk of having a flare after achieving clinical remission versus the comparator group (16.7% versus 29.3%; hazard ratio, 0.56; 95% confidence interval, 0.35-0.90; P = .0153).

Patient-reported outcomes, which included physical and mental health scores and disability index results, favored sarilumab.

The incidence of treatment-emergent adverse events (TEAEs) was numerically higher in the sarilumab group, compared with the control group (94.9% versus 84.5%). TEAEs included neutropenia (15.3%) and arthralgia (15.3%) in the sarilumab group and insomnia (15.5%) in the comparator arm.

However, the frequency of serious AEs was higher in the control group, compared with the sarilumab arm (20.7% versus 13.6%). No deaths were reported, and, importantly in this age group treated with concurrent glucocorticoids and an IL-6 inhibitor, Dr. Spiera said, “there were no cases of diverticulitis requiring intervention.”

Dr. Spiera was asked about a seemingly low remission rate. He answered that the bar was very high for remission in this study.

Patients had to achieve remission by week 12 and with the rapid 14-week taper. “That means by week 12 the sarilumab arm patients were only on 2 mg of daily prednisone or its equivalent,” he said.

Patients had to maintain that for another 40 weeks, he noted, adding, “I think especially in the context of quality of life and function indices, these were important results.”

Sebastian E. Sattui, MD, director of the University of Pittsburgh Medical Center vasculitis clinic, told this news organization that prolonged use of glucocorticoids in patients with PMR remains an important concern and the need for other options is critical.

“Around 30% of patients with PMR remain on prednisone 5 years after diagnosis,” he said. “Low-dose glucocorticoids are still associated with significant morbidity. Until recently, there has been a paucity of high-quality data regarding the use of steroid-sparing agents in PMR. “

He noted that the SAPHYR trial data are promising “with sarilumab being successful in achieving remission while minimizing glucocorticoids in patients with relapsing PMR.” The clinically meaningful improvement in patient-reported outcomes was just as important, he added.

The main unanswered question is whether the disease-modifying ability of sarilumab will continue after it is stopped, Dr. Sattui said.

Dr. Spiera is a consultant for Sanofi, which funded the trial. He also disclosed financial relationships with GlaxoSmithKline, Boehringer Ingelheim, Corbus, InflaRx, AbbVie/Abbott, Novartis, Chemocentryx, Roche, and Vera. Dr. Sattui has received research support from AstraZeneca and has done unpaid consulting work for Sanofi.

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

PHILADELPHIA – Treatment with the interleukin-6 receptor antagonist sarilumab (Kevzara), along with a 14-week taper of glucocorticoids, proved to have significant efficacy in patients with relapsing polymyalgia rheumatica (PMR) who were resistant to glucocorticoids in a phase 3 trial.

No new safety concerns were found with sarilumab in the multicenter, randomized, double-blind, placebo-controlled SAPHYR trial. Sarilumab is approved in the United States for the treatment of moderate to severe active rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.

The results, presented at the annual meeting of the American College of Rheumatology by Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York, included clinically meaningful improvement in quality-of-life scores.

The disease, which primarily affects people over age 65, can cause widespread aching and stiffness. It’s one of the most common inflammatory diseases among older adults.

PMR is relatively easy to treat with glucocorticoids, but relapses are common, which means long courses of glucocorticoid therapy and the side effects that come with them.
 

Need for a steroid-sparing therapy

“We recognize that a steroid-sparing drug in polymyalgia rheumatica seems to be an unmet need,” Dr. Spiera said at the meeting.

The trial, sponsored by Sanofi, included active, refractory PMR patients who flared within 3 months of study entry while on at least 7.5 mg/day of prednisone or the equivalent. They were randomly assigned (1:1) to 52 weeks of treatment with subcutaneous sarilumab 200 mg every 2 weeks plus the rapid 14-week glucocorticoid tapering regimen or were given placebo every 2 weeks plus a more traditional 52-week tapering of glucocorticoids.
 

COVID hampered recruitment

Recruitment was stopped early because of complications during the COVID-19 pandemic, so between October 2018 and July 2020, 118 of the intended 280 patients were recruited, and 117 were treated (sarilumab = 59, placebo = 58). Median age was 69 years in the treatment group and 70 among those taking placebo.

Of the 117 treated, only 78 patients (67%) completed treatment (sarilumab = 42, placebo = 36). The main reasons for stopping treatment were adverse events – including seven with sarilumab and four with placebo – and lack of efficacy (sarilumab = four, placebo = nine).

The primary outcome was the proportion of patients who reached sustained remission at 52 weeks, defined as disease remission by week 12 and no disease flare, normal C-reactive protein (CRP), and adherence to the glucocorticoid taper during weeks 12-52.

The researchers found that sustained remission was significantly higher in the sarilumab arm versus the control group (28.3% versus 10.3%; P = .0193).

IL-6 inhibitors lower CRP, but if you take CRP out of the definition, Dr. Spiera said, “we still saw this difference: 31.7% of patients treated with sarilumab and 13.8% treated with placebo and a longer taper achieved that endpoint.”
 

Forty-four percent lower risk of flare with sarilumab

Patients in the sarilumab group also had 44% lower risk of having a flare after achieving clinical remission versus the comparator group (16.7% versus 29.3%; hazard ratio, 0.56; 95% confidence interval, 0.35-0.90; P = .0153).

Patient-reported outcomes, which included physical and mental health scores and disability index results, favored sarilumab.

The incidence of treatment-emergent adverse events (TEAEs) was numerically higher in the sarilumab group, compared with the control group (94.9% versus 84.5%). TEAEs included neutropenia (15.3%) and arthralgia (15.3%) in the sarilumab group and insomnia (15.5%) in the comparator arm.

However, the frequency of serious AEs was higher in the control group, compared with the sarilumab arm (20.7% versus 13.6%). No deaths were reported, and, importantly in this age group treated with concurrent glucocorticoids and an IL-6 inhibitor, Dr. Spiera said, “there were no cases of diverticulitis requiring intervention.”

Dr. Spiera was asked about a seemingly low remission rate. He answered that the bar was very high for remission in this study.

Patients had to achieve remission by week 12 and with the rapid 14-week taper. “That means by week 12 the sarilumab arm patients were only on 2 mg of daily prednisone or its equivalent,” he said.

Patients had to maintain that for another 40 weeks, he noted, adding, “I think especially in the context of quality of life and function indices, these were important results.”

Sebastian E. Sattui, MD, director of the University of Pittsburgh Medical Center vasculitis clinic, told this news organization that prolonged use of glucocorticoids in patients with PMR remains an important concern and the need for other options is critical.

“Around 30% of patients with PMR remain on prednisone 5 years after diagnosis,” he said. “Low-dose glucocorticoids are still associated with significant morbidity. Until recently, there has been a paucity of high-quality data regarding the use of steroid-sparing agents in PMR. “

He noted that the SAPHYR trial data are promising “with sarilumab being successful in achieving remission while minimizing glucocorticoids in patients with relapsing PMR.” The clinically meaningful improvement in patient-reported outcomes was just as important, he added.

The main unanswered question is whether the disease-modifying ability of sarilumab will continue after it is stopped, Dr. Sattui said.

Dr. Spiera is a consultant for Sanofi, which funded the trial. He also disclosed financial relationships with GlaxoSmithKline, Boehringer Ingelheim, Corbus, InflaRx, AbbVie/Abbott, Novartis, Chemocentryx, Roche, and Vera. Dr. Sattui has received research support from AstraZeneca and has done unpaid consulting work for Sanofi.

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

PHILADELPHIA – An international group of researchers has proposed the first classification criteria for chronic nonbacterial osteomyelitis (CNO) and a severe form of it, chronic recurrent multifocal osteomyelitis (CRMO).

CNO/CRMO most frequently affect children and adolescents and can significantly affect quality of life.

Yongdong (Dan) Zhao, MD, PhD, a pediatric rheumatologist at Seattle Children’s Hospital, Seattle, Washington, and Seza Ozen, MD, MSc, medical faculty head at Hacettepe University in Ankara, Turkey – members of the expert panel for criteria development – explained the proposed criteria, developed over 6 years, at the American College of Rheumatology 2022 Annual Meeting.

They gave examples of the point system that will help researchers correctly classify CNO/CRMO if the criteria are approved by ACR and the European Alliance of Associations for Rheumatology (EULAR).

Melissa S. Oliver, MD, a pediatric rheumatologist at Riley Children’s Hospital and Indiana University, Indianapolis, told this news organization: “This proposal is important because CNO/CRMO has primarily been a diagnosis of exclusion. There are no specific tests or biomarkers for this disease. It can mimic malignancy and infectious osteomyelitis in its presentation, and these must be ruled out thoroughly first.”

However, she noted, this can be challenging and can delay diagnosis and treatment.

The classification criteria are novel, she said, because an international collaborative group used a consensus process involving physicians managing CNO and patients or caregivers of children with CNO.
 

Findings for and against CNO

Dr. Ozen summarized some examples of findings for and against a CNO/CRMO classification.

Statistically significant findings in favor of CNO/CRMO, she said, include intermittent bone pain; bone pain in upper torso; swelling of upper torso; presence of symmetric lesions; and presence of adaptive immune cell and/or fibrosis in biopsy.

Conversely, findings against CNO/CRMO include fever; signs of infection by labs; signs of cancer by biopsy; specific abnormal x-ray/CT scan; specific abnormal MRI; or pain resolved with antibiotics alone.

Dr. Zhao described a point system with a threshold of 55 points for classification of CNO/CRMO.

He gave actual examples from the registry to demonstrate high and low probability of CNO/CRMO.
 

Pro-CNO example

The first was a boy, aged 7 years 10 months, who had a year and a half of pain in his back and legs, but no fever. Pain was constant, waxing and waning. He had a personal and family history of psoriasis and was tender to palpation at multiple sites. Labs were normal and bone biopsy and vitamin C tests were not done; imaging findings showed multiple bones were affected. There was no antibiotic treatment.

That patient was scored 81, much higher than the threshold of 55, and would be classified as having CNO.
 

Non-CNO example

Conversely, the following example of a patient would score 47 – under the threshold – and would not be classified as having CNO.

That patient was an 11-year-old boy who had 2 months of pain in his right thigh with no fever. The pain was constantly waxing and waning. He was tender to palpation at only his right thigh without swelling. Labs were normal. He had no coexisting conditions. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were not measured, and no vitamin C test was performed. Imaging showed one right femur lesion on a PET-CT scan. There was no antibiotic treatment, and a bone biopsy culture showed malignancy but no inflammation or fibrosis.

Dr. Zhao said the mimickers most likely to be misclassified are vitamin C deficiency; hypophosphatasia; benign bone tumor, such as osteogenic osteoma; and a malignancy with normal labs and multifocal pattern of bone lesions.

The classification criteria will be “extremely helpful to diagnose patients with CNO/CRMO earlier,” said Dr. Oliver, who helped develop the criteria.

“The goal is that the proposed classification criteria will be used by all physicians to diagnose suspected CNO patients earlier and refer to a rheumatologist earlier so that appropriate therapies will not be delayed.”

The group will seek ACR and EULAR endorsement, and if granted, work toward widespread implementation. The criteria will allow researchers to have a more homogeneous study population for future clinical trials, Dr. Zhao said.

Dr. Zhao, Dr. Ozen, and Dr. Oliver declared no relevant financial relationships. Dr. Oliver helped develop the proposed guidelines.

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

PHILADELPHIA – An international group of researchers has proposed the first classification criteria for chronic nonbacterial osteomyelitis (CNO) and a severe form of it, chronic recurrent multifocal osteomyelitis (CRMO).

CNO/CRMO most frequently affect children and adolescents and can significantly affect quality of life.

Yongdong (Dan) Zhao, MD, PhD, a pediatric rheumatologist at Seattle Children’s Hospital, Seattle, Washington, and Seza Ozen, MD, MSc, medical faculty head at Hacettepe University in Ankara, Turkey – members of the expert panel for criteria development – explained the proposed criteria, developed over 6 years, at the American College of Rheumatology 2022 Annual Meeting.

They gave examples of the point system that will help researchers correctly classify CNO/CRMO if the criteria are approved by ACR and the European Alliance of Associations for Rheumatology (EULAR).

Melissa S. Oliver, MD, a pediatric rheumatologist at Riley Children’s Hospital and Indiana University, Indianapolis, told this news organization: “This proposal is important because CNO/CRMO has primarily been a diagnosis of exclusion. There are no specific tests or biomarkers for this disease. It can mimic malignancy and infectious osteomyelitis in its presentation, and these must be ruled out thoroughly first.”

However, she noted, this can be challenging and can delay diagnosis and treatment.

The classification criteria are novel, she said, because an international collaborative group used a consensus process involving physicians managing CNO and patients or caregivers of children with CNO.
 

Findings for and against CNO

Dr. Ozen summarized some examples of findings for and against a CNO/CRMO classification.

Statistically significant findings in favor of CNO/CRMO, she said, include intermittent bone pain; bone pain in upper torso; swelling of upper torso; presence of symmetric lesions; and presence of adaptive immune cell and/or fibrosis in biopsy.

Conversely, findings against CNO/CRMO include fever; signs of infection by labs; signs of cancer by biopsy; specific abnormal x-ray/CT scan; specific abnormal MRI; or pain resolved with antibiotics alone.

Dr. Zhao described a point system with a threshold of 55 points for classification of CNO/CRMO.

He gave actual examples from the registry to demonstrate high and low probability of CNO/CRMO.
 

Pro-CNO example

The first was a boy, aged 7 years 10 months, who had a year and a half of pain in his back and legs, but no fever. Pain was constant, waxing and waning. He had a personal and family history of psoriasis and was tender to palpation at multiple sites. Labs were normal and bone biopsy and vitamin C tests were not done; imaging findings showed multiple bones were affected. There was no antibiotic treatment.

That patient was scored 81, much higher than the threshold of 55, and would be classified as having CNO.
 

Non-CNO example

Conversely, the following example of a patient would score 47 – under the threshold – and would not be classified as having CNO.

That patient was an 11-year-old boy who had 2 months of pain in his right thigh with no fever. The pain was constantly waxing and waning. He was tender to palpation at only his right thigh without swelling. Labs were normal. He had no coexisting conditions. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were not measured, and no vitamin C test was performed. Imaging showed one right femur lesion on a PET-CT scan. There was no antibiotic treatment, and a bone biopsy culture showed malignancy but no inflammation or fibrosis.

Dr. Zhao said the mimickers most likely to be misclassified are vitamin C deficiency; hypophosphatasia; benign bone tumor, such as osteogenic osteoma; and a malignancy with normal labs and multifocal pattern of bone lesions.

The classification criteria will be “extremely helpful to diagnose patients with CNO/CRMO earlier,” said Dr. Oliver, who helped develop the criteria.

“The goal is that the proposed classification criteria will be used by all physicians to diagnose suspected CNO patients earlier and refer to a rheumatologist earlier so that appropriate therapies will not be delayed.”

The group will seek ACR and EULAR endorsement, and if granted, work toward widespread implementation. The criteria will allow researchers to have a more homogeneous study population for future clinical trials, Dr. Zhao said.

Dr. Zhao, Dr. Ozen, and Dr. Oliver declared no relevant financial relationships. Dr. Oliver helped develop the proposed guidelines.

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

PHILADELPHIA – An international group of researchers has proposed the first classification criteria for chronic nonbacterial osteomyelitis (CNO) and a severe form of it, chronic recurrent multifocal osteomyelitis (CRMO).

CNO/CRMO most frequently affect children and adolescents and can significantly affect quality of life.

Yongdong (Dan) Zhao, MD, PhD, a pediatric rheumatologist at Seattle Children’s Hospital, Seattle, Washington, and Seza Ozen, MD, MSc, medical faculty head at Hacettepe University in Ankara, Turkey – members of the expert panel for criteria development – explained the proposed criteria, developed over 6 years, at the American College of Rheumatology 2022 Annual Meeting.

They gave examples of the point system that will help researchers correctly classify CNO/CRMO if the criteria are approved by ACR and the European Alliance of Associations for Rheumatology (EULAR).

Melissa S. Oliver, MD, a pediatric rheumatologist at Riley Children’s Hospital and Indiana University, Indianapolis, told this news organization: “This proposal is important because CNO/CRMO has primarily been a diagnosis of exclusion. There are no specific tests or biomarkers for this disease. It can mimic malignancy and infectious osteomyelitis in its presentation, and these must be ruled out thoroughly first.”

However, she noted, this can be challenging and can delay diagnosis and treatment.

The classification criteria are novel, she said, because an international collaborative group used a consensus process involving physicians managing CNO and patients or caregivers of children with CNO.
 

Findings for and against CNO

Dr. Ozen summarized some examples of findings for and against a CNO/CRMO classification.

Statistically significant findings in favor of CNO/CRMO, she said, include intermittent bone pain; bone pain in upper torso; swelling of upper torso; presence of symmetric lesions; and presence of adaptive immune cell and/or fibrosis in biopsy.

Conversely, findings against CNO/CRMO include fever; signs of infection by labs; signs of cancer by biopsy; specific abnormal x-ray/CT scan; specific abnormal MRI; or pain resolved with antibiotics alone.

Dr. Zhao described a point system with a threshold of 55 points for classification of CNO/CRMO.

He gave actual examples from the registry to demonstrate high and low probability of CNO/CRMO.
 

Pro-CNO example

The first was a boy, aged 7 years 10 months, who had a year and a half of pain in his back and legs, but no fever. Pain was constant, waxing and waning. He had a personal and family history of psoriasis and was tender to palpation at multiple sites. Labs were normal and bone biopsy and vitamin C tests were not done; imaging findings showed multiple bones were affected. There was no antibiotic treatment.

That patient was scored 81, much higher than the threshold of 55, and would be classified as having CNO.
 

Non-CNO example

Conversely, the following example of a patient would score 47 – under the threshold – and would not be classified as having CNO.

That patient was an 11-year-old boy who had 2 months of pain in his right thigh with no fever. The pain was constantly waxing and waning. He was tender to palpation at only his right thigh without swelling. Labs were normal. He had no coexisting conditions. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were not measured, and no vitamin C test was performed. Imaging showed one right femur lesion on a PET-CT scan. There was no antibiotic treatment, and a bone biopsy culture showed malignancy but no inflammation or fibrosis.

Dr. Zhao said the mimickers most likely to be misclassified are vitamin C deficiency; hypophosphatasia; benign bone tumor, such as osteogenic osteoma; and a malignancy with normal labs and multifocal pattern of bone lesions.

The classification criteria will be “extremely helpful to diagnose patients with CNO/CRMO earlier,” said Dr. Oliver, who helped develop the criteria.

“The goal is that the proposed classification criteria will be used by all physicians to diagnose suspected CNO patients earlier and refer to a rheumatologist earlier so that appropriate therapies will not be delayed.”

The group will seek ACR and EULAR endorsement, and if granted, work toward widespread implementation. The criteria will allow researchers to have a more homogeneous study population for future clinical trials, Dr. Zhao said.

Dr. Zhao, Dr. Ozen, and Dr. Oliver declared no relevant financial relationships. Dr. Oliver helped develop the proposed guidelines.

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

Reminder messages sent through electronic health records (EHRs) to patient portals increased rates of scheduling and completion of well-child visits for those overdue for well care, as well as vaccination rates, according to data published today in JAMA Network Open.

Anne E. Berset, BA, with general and community pediatrics at Cincinnati Children’s Hospital, led a randomized clinical trial conducted at three academic primary care practices from July 30 to Oct. 4, 2021.

The practices serve a mostly non-Hispanic Black, low-income population and provide more than 60,000 visits a year to 30,000 patients.

The study population included 945 patients, 62.4% of them non-Hispanic Black and 807 (85.4%) covered by public insurance.
 

Standard message and tailored message compared

The study population was randomized to get either a standard reminder message, a tailored message, or no message (control group).

The standard messages referenced the patient’s first name and reminded parents their child was due for a well-child visit, and asked them to schedule it using the portal or by calling the number provided.

The tailored message added the date of the last well-child check-up “to address distortions of time perception experienced during the pandemic,” the authors write.

The primary outcome was whether the well-child visit was completed within 8 weeks. Other outcomes included whether a well-child visit was scheduled within 2 weeks of the first reminder message and whether the patient received a COVID-19 vaccine within 8 weeks of the reminder.
 

Reminders outperform control group

There was a significant increase in scheduling and completion of appointments after parents received the standard and tailored messages compared with controls.

The results with the COVID reminders were particularly striking. While only 3.7% of the eligible patients got a vaccine when they got no message, 17.3% got the vaccine in that time frame when they got the standard message. Interestingly, only 2.7% received the shot after the tailored message.

J. Howard Smart, MD, with Sharp HealthCare in San Diego, told this publication he was not surprised that a patient portal reminder would increase the rate of scheduling overdue well-child visits. “Parents may indeed have lost track of when their children need to have check-ups” during the pandemic, he said.

Reminders without tailored information more effective

He said he was surprised, just as the investigators were, that the reminders without the tailored information seemed to be more effective for some outcomes.

The authors explained that a focus group found “that families with patient portal accounts prefer straightforward, brief, and user-friendly messages.”

That may help explain why the standard message outperformed the tailored message, the authors write.

“Families may have been distracted by the additional information related to the child’s age and date of last WCC [well-child check-up] in the tailored message,” they write.

Dr. Smart said, “Their discussion of why this might be the case sounds reasonable. Simple, short messages may be better received.”

“Evidence like this should stimulate portal software vendors to make this kind of outgoing messaging easy to set up for providers,” he said.

Simple measure, large effect

Tim Joos, MD, a pediatrician in Seattle, told this publication he “was impressed by how such a simple measure increased rates of well-child care completion.”

Minority and low-income patients have traditionally had more access challenges to completing health care visits and vaccinations on schedule, he noted, so he was glad to see positive results from the intervention in this study population.

The authors note that research on portal messages have largely looked at use in non-Hispanic Whites and the privately insured.

Dr. Joos said the intervention also offers convenience in that once patients get into the portal, they can schedule an appointment there without having to wait on the phone or leave a message.

Funding/support was received from the Center for Clinical and Translational Science and Training at the University of Cincinnati, which is funded by the National Institutes of Health. William B. Brinkman, MD, MEd, MSc, one of the study authors, holds common stock in Pfizer, Merck, Abbott Laboratories, Viatris, and Johnson & Johnson outside the submitted work. No other author disclosures were reported. Dr. Smart and Dr. Joos declared no relevant financial relationships.

Reminder messages sent through electronic health records (EHRs) to patient portals increased rates of scheduling and completion of well-child visits for those overdue for well care, as well as vaccination rates, according to data published today in JAMA Network Open.

Anne E. Berset, BA, with general and community pediatrics at Cincinnati Children’s Hospital, led a randomized clinical trial conducted at three academic primary care practices from July 30 to Oct. 4, 2021.

The practices serve a mostly non-Hispanic Black, low-income population and provide more than 60,000 visits a year to 30,000 patients.

The study population included 945 patients, 62.4% of them non-Hispanic Black and 807 (85.4%) covered by public insurance.
 

Standard message and tailored message compared

The study population was randomized to get either a standard reminder message, a tailored message, or no message (control group).

The standard messages referenced the patient’s first name and reminded parents their child was due for a well-child visit, and asked them to schedule it using the portal or by calling the number provided.

The tailored message added the date of the last well-child check-up “to address distortions of time perception experienced during the pandemic,” the authors write.

The primary outcome was whether the well-child visit was completed within 8 weeks. Other outcomes included whether a well-child visit was scheduled within 2 weeks of the first reminder message and whether the patient received a COVID-19 vaccine within 8 weeks of the reminder.
 

Reminders outperform control group

There was a significant increase in scheduling and completion of appointments after parents received the standard and tailored messages compared with controls.

The results with the COVID reminders were particularly striking. While only 3.7% of the eligible patients got a vaccine when they got no message, 17.3% got the vaccine in that time frame when they got the standard message. Interestingly, only 2.7% received the shot after the tailored message.

J. Howard Smart, MD, with Sharp HealthCare in San Diego, told this publication he was not surprised that a patient portal reminder would increase the rate of scheduling overdue well-child visits. “Parents may indeed have lost track of when their children need to have check-ups” during the pandemic, he said.

Reminders without tailored information more effective

He said he was surprised, just as the investigators were, that the reminders without the tailored information seemed to be more effective for some outcomes.

The authors explained that a focus group found “that families with patient portal accounts prefer straightforward, brief, and user-friendly messages.”

That may help explain why the standard message outperformed the tailored message, the authors write.

“Families may have been distracted by the additional information related to the child’s age and date of last WCC [well-child check-up] in the tailored message,” they write.

Dr. Smart said, “Their discussion of why this might be the case sounds reasonable. Simple, short messages may be better received.”

“Evidence like this should stimulate portal software vendors to make this kind of outgoing messaging easy to set up for providers,” he said.

Simple measure, large effect

Tim Joos, MD, a pediatrician in Seattle, told this publication he “was impressed by how such a simple measure increased rates of well-child care completion.”

Minority and low-income patients have traditionally had more access challenges to completing health care visits and vaccinations on schedule, he noted, so he was glad to see positive results from the intervention in this study population.

The authors note that research on portal messages have largely looked at use in non-Hispanic Whites and the privately insured.

Dr. Joos said the intervention also offers convenience in that once patients get into the portal, they can schedule an appointment there without having to wait on the phone or leave a message.

Funding/support was received from the Center for Clinical and Translational Science and Training at the University of Cincinnati, which is funded by the National Institutes of Health. William B. Brinkman, MD, MEd, MSc, one of the study authors, holds common stock in Pfizer, Merck, Abbott Laboratories, Viatris, and Johnson & Johnson outside the submitted work. No other author disclosures were reported. Dr. Smart and Dr. Joos declared no relevant financial relationships.

Reminder messages sent through electronic health records (EHRs) to patient portals increased rates of scheduling and completion of well-child visits for those overdue for well care, as well as vaccination rates, according to data published today in JAMA Network Open.

Anne E. Berset, BA, with general and community pediatrics at Cincinnati Children’s Hospital, led a randomized clinical trial conducted at three academic primary care practices from July 30 to Oct. 4, 2021.

The practices serve a mostly non-Hispanic Black, low-income population and provide more than 60,000 visits a year to 30,000 patients.

The study population included 945 patients, 62.4% of them non-Hispanic Black and 807 (85.4%) covered by public insurance.
 

Standard message and tailored message compared

The study population was randomized to get either a standard reminder message, a tailored message, or no message (control group).

The standard messages referenced the patient’s first name and reminded parents their child was due for a well-child visit, and asked them to schedule it using the portal or by calling the number provided.

The tailored message added the date of the last well-child check-up “to address distortions of time perception experienced during the pandemic,” the authors write.

The primary outcome was whether the well-child visit was completed within 8 weeks. Other outcomes included whether a well-child visit was scheduled within 2 weeks of the first reminder message and whether the patient received a COVID-19 vaccine within 8 weeks of the reminder.
 

Reminders outperform control group

There was a significant increase in scheduling and completion of appointments after parents received the standard and tailored messages compared with controls.

The results with the COVID reminders were particularly striking. While only 3.7% of the eligible patients got a vaccine when they got no message, 17.3% got the vaccine in that time frame when they got the standard message. Interestingly, only 2.7% received the shot after the tailored message.

J. Howard Smart, MD, with Sharp HealthCare in San Diego, told this publication he was not surprised that a patient portal reminder would increase the rate of scheduling overdue well-child visits. “Parents may indeed have lost track of when their children need to have check-ups” during the pandemic, he said.

Reminders without tailored information more effective

He said he was surprised, just as the investigators were, that the reminders without the tailored information seemed to be more effective for some outcomes.

The authors explained that a focus group found “that families with patient portal accounts prefer straightforward, brief, and user-friendly messages.”

That may help explain why the standard message outperformed the tailored message, the authors write.

“Families may have been distracted by the additional information related to the child’s age and date of last WCC [well-child check-up] in the tailored message,” they write.

Dr. Smart said, “Their discussion of why this might be the case sounds reasonable. Simple, short messages may be better received.”

“Evidence like this should stimulate portal software vendors to make this kind of outgoing messaging easy to set up for providers,” he said.

Simple measure, large effect

Tim Joos, MD, a pediatrician in Seattle, told this publication he “was impressed by how such a simple measure increased rates of well-child care completion.”

Minority and low-income patients have traditionally had more access challenges to completing health care visits and vaccinations on schedule, he noted, so he was glad to see positive results from the intervention in this study population.

The authors note that research on portal messages have largely looked at use in non-Hispanic Whites and the privately insured.

Dr. Joos said the intervention also offers convenience in that once patients get into the portal, they can schedule an appointment there without having to wait on the phone or leave a message.

Funding/support was received from the Center for Clinical and Translational Science and Training at the University of Cincinnati, which is funded by the National Institutes of Health. William B. Brinkman, MD, MEd, MSc, one of the study authors, holds common stock in Pfizer, Merck, Abbott Laboratories, Viatris, and Johnson & Johnson outside the submitted work. No other author disclosures were reported. Dr. Smart and Dr. Joos declared no relevant financial relationships.

PHILADELPHIA – Women with spondyloarthritis (SpA) who are desiring pregnancy may want to consider decreasing use or discontinuing use (with supervision) of nonsteroidal anti-inflammatory drugs before conception, new data suggest.

Researchers have found a connection between NSAID use and age and a significantly longer time to conception among women with spondyloarthritis. Sabrina Hamroun, MMed, with the rheumatology department at the University Hospital Cochin, Paris, presented the findings during a press conference at the annual meeting of the American College of Rheumatology.

Subfertility group took an average of 16 months to get pregnant

Subfertility was observed in 40 (45.4%) of the women, with an average time to conception of 16.1 months. A woman was considered subfertile if her time to conception was more than 12 months or if she did not become pregnant.

The average preconception Bath Ankylosing Spondylitis Disease Activity Index score was 2.9 (+/- 2.1), the authors noted. The average age of the participants was 32 years.

Twenty-three patients were treated with NSAIDs, eight with corticosteroids, 12 with conventional synthetic disease-modifying antirheumatic drugs, and 61 with biologics.

Researchers adjusted for factors including age, body mass index, disease duration and severity, smoking, form of SpA (axial, peripheral, or both), and medication in the preconception period.

They found significant associations between longer time to conception and age (hazard ratio, 1.22; 95% confidence interval, 1.08-1.40; P < .001), and a much higher hazard ratio with the use of NSAIDs during preconception (HR, 3.01; 95% CI, 2.15-3.85; P = .01).

Some data unavailable

Ms. Hamroun acknowledged that no data were available on the frequency of sexual intercourse or quality of life, factors that could affect time to conception. Women were asked when they discontinued contraceptive use and actively began trying to become pregnant.

She stated that information on the dose of NSAIDs used by the patients was incomplete, noting, “We were therefore unable to adjust the results of our statistical analyses on the dose used by patients.”

Additionally, because the study participants were patients at tertiary centers in France and had more severe disease, the results may not be generalizable to all women of childbearing age. Patients with less severe SpA are often managed in outpatient settings in France, she said.

When asked about alternatives to NSAIDs, Ms. Hamroun said that anti–tumor necrosis factor agents with low placental passage may be a good alternative “if a woman with long-standing difficulties to conceive needs a regular use of NSAIDs to control disease activity, in the absence of any other cause of subfertility.”

The patient’s age must also be considered, she noted.

“A therapeutic switch may be favored in a woman over 35 years of age, for example, whose fertility is already impaired by age,” Ms. Hamroun said.

As for the mechanism that might explain the effects of NSAIDs on conception, Ms. Hamroun said that prostaglandins are essential to ovulation and embryo implantation and explained that NSAIDs may work against ovulation and result in poor implantation (miscarriage) by blocking prostaglandins.

She pointed out that her results are in line with the ACR’s recommendation to discontinue NSAID use during the preconception period in women with SpA who are having difficulty conceiving.
 

Control before conception is important

Sinead Maguire, MD, a clinical and research fellow in the Spondylitis Program at Toronto (Ont.) Western Hospital who was not part of the study, said the study highlights the importance of optimizing disease control before conception.

“There are a number of things rheumatologists can do to support our SpA patients when they are trying to conceive,” she told this news organization. “One of the most important issues to address is ensuring their SpA is in remission and continues to remain so. For that reason, if a woman is requiring regular NSAIDs for symptom control, the results of this study might encourage me to consider a biologic agent sooner to ensure remission.”

She urged women who want to become pregnant to discuss medications with their rheumatologist before trying to conceive.

“It is very exciting to see studies such as this so that rheumatologists can provide answers to our patients’ questions with evidence-based advice,” she said.

Ms. Hamroun and several coauthors had no disclosures. Other coauthors disclosed relationships with companies including Merck/MSD, Novartis, Janssen, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, Eli Lilly, Novartis, and/or UCB. Dr. Maguire reports no relevant financial relationships.

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

PHILADELPHIA – Women with spondyloarthritis (SpA) who are desiring pregnancy may want to consider decreasing use or discontinuing use (with supervision) of nonsteroidal anti-inflammatory drugs before conception, new data suggest.

Researchers have found a connection between NSAID use and age and a significantly longer time to conception among women with spondyloarthritis. Sabrina Hamroun, MMed, with the rheumatology department at the University Hospital Cochin, Paris, presented the findings during a press conference at the annual meeting of the American College of Rheumatology.

Subfertility group took an average of 16 months to get pregnant

Subfertility was observed in 40 (45.4%) of the women, with an average time to conception of 16.1 months. A woman was considered subfertile if her time to conception was more than 12 months or if she did not become pregnant.

The average preconception Bath Ankylosing Spondylitis Disease Activity Index score was 2.9 (+/- 2.1), the authors noted. The average age of the participants was 32 years.

Twenty-three patients were treated with NSAIDs, eight with corticosteroids, 12 with conventional synthetic disease-modifying antirheumatic drugs, and 61 with biologics.

Researchers adjusted for factors including age, body mass index, disease duration and severity, smoking, form of SpA (axial, peripheral, or both), and medication in the preconception period.

They found significant associations between longer time to conception and age (hazard ratio, 1.22; 95% confidence interval, 1.08-1.40; P < .001), and a much higher hazard ratio with the use of NSAIDs during preconception (HR, 3.01; 95% CI, 2.15-3.85; P = .01).

Some data unavailable

Ms. Hamroun acknowledged that no data were available on the frequency of sexual intercourse or quality of life, factors that could affect time to conception. Women were asked when they discontinued contraceptive use and actively began trying to become pregnant.

She stated that information on the dose of NSAIDs used by the patients was incomplete, noting, “We were therefore unable to adjust the results of our statistical analyses on the dose used by patients.”

Additionally, because the study participants were patients at tertiary centers in France and had more severe disease, the results may not be generalizable to all women of childbearing age. Patients with less severe SpA are often managed in outpatient settings in France, she said.

When asked about alternatives to NSAIDs, Ms. Hamroun said that anti–tumor necrosis factor agents with low placental passage may be a good alternative “if a woman with long-standing difficulties to conceive needs a regular use of NSAIDs to control disease activity, in the absence of any other cause of subfertility.”

The patient’s age must also be considered, she noted.

“A therapeutic switch may be favored in a woman over 35 years of age, for example, whose fertility is already impaired by age,” Ms. Hamroun said.

As for the mechanism that might explain the effects of NSAIDs on conception, Ms. Hamroun said that prostaglandins are essential to ovulation and embryo implantation and explained that NSAIDs may work against ovulation and result in poor implantation (miscarriage) by blocking prostaglandins.

She pointed out that her results are in line with the ACR’s recommendation to discontinue NSAID use during the preconception period in women with SpA who are having difficulty conceiving.
 

Control before conception is important

Sinead Maguire, MD, a clinical and research fellow in the Spondylitis Program at Toronto (Ont.) Western Hospital who was not part of the study, said the study highlights the importance of optimizing disease control before conception.

“There are a number of things rheumatologists can do to support our SpA patients when they are trying to conceive,” she told this news organization. “One of the most important issues to address is ensuring their SpA is in remission and continues to remain so. For that reason, if a woman is requiring regular NSAIDs for symptom control, the results of this study might encourage me to consider a biologic agent sooner to ensure remission.”

She urged women who want to become pregnant to discuss medications with their rheumatologist before trying to conceive.

“It is very exciting to see studies such as this so that rheumatologists can provide answers to our patients’ questions with evidence-based advice,” she said.

Ms. Hamroun and several coauthors had no disclosures. Other coauthors disclosed relationships with companies including Merck/MSD, Novartis, Janssen, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, Eli Lilly, Novartis, and/or UCB. Dr. Maguire reports no relevant financial relationships.

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

PHILADELPHIA – Women with spondyloarthritis (SpA) who are desiring pregnancy may want to consider decreasing use or discontinuing use (with supervision) of nonsteroidal anti-inflammatory drugs before conception, new data suggest.

Researchers have found a connection between NSAID use and age and a significantly longer time to conception among women with spondyloarthritis. Sabrina Hamroun, MMed, with the rheumatology department at the University Hospital Cochin, Paris, presented the findings during a press conference at the annual meeting of the American College of Rheumatology.

Subfertility group took an average of 16 months to get pregnant

Subfertility was observed in 40 (45.4%) of the women, with an average time to conception of 16.1 months. A woman was considered subfertile if her time to conception was more than 12 months or if she did not become pregnant.

The average preconception Bath Ankylosing Spondylitis Disease Activity Index score was 2.9 (+/- 2.1), the authors noted. The average age of the participants was 32 years.

Twenty-three patients were treated with NSAIDs, eight with corticosteroids, 12 with conventional synthetic disease-modifying antirheumatic drugs, and 61 with biologics.

Researchers adjusted for factors including age, body mass index, disease duration and severity, smoking, form of SpA (axial, peripheral, or both), and medication in the preconception period.

They found significant associations between longer time to conception and age (hazard ratio, 1.22; 95% confidence interval, 1.08-1.40; P < .001), and a much higher hazard ratio with the use of NSAIDs during preconception (HR, 3.01; 95% CI, 2.15-3.85; P = .01).

Some data unavailable

Ms. Hamroun acknowledged that no data were available on the frequency of sexual intercourse or quality of life, factors that could affect time to conception. Women were asked when they discontinued contraceptive use and actively began trying to become pregnant.

She stated that information on the dose of NSAIDs used by the patients was incomplete, noting, “We were therefore unable to adjust the results of our statistical analyses on the dose used by patients.”

Additionally, because the study participants were patients at tertiary centers in France and had more severe disease, the results may not be generalizable to all women of childbearing age. Patients with less severe SpA are often managed in outpatient settings in France, she said.

When asked about alternatives to NSAIDs, Ms. Hamroun said that anti–tumor necrosis factor agents with low placental passage may be a good alternative “if a woman with long-standing difficulties to conceive needs a regular use of NSAIDs to control disease activity, in the absence of any other cause of subfertility.”

The patient’s age must also be considered, she noted.

“A therapeutic switch may be favored in a woman over 35 years of age, for example, whose fertility is already impaired by age,” Ms. Hamroun said.

As for the mechanism that might explain the effects of NSAIDs on conception, Ms. Hamroun said that prostaglandins are essential to ovulation and embryo implantation and explained that NSAIDs may work against ovulation and result in poor implantation (miscarriage) by blocking prostaglandins.

She pointed out that her results are in line with the ACR’s recommendation to discontinue NSAID use during the preconception period in women with SpA who are having difficulty conceiving.
 

Control before conception is important

Sinead Maguire, MD, a clinical and research fellow in the Spondylitis Program at Toronto (Ont.) Western Hospital who was not part of the study, said the study highlights the importance of optimizing disease control before conception.

“There are a number of things rheumatologists can do to support our SpA patients when they are trying to conceive,” she told this news organization. “One of the most important issues to address is ensuring their SpA is in remission and continues to remain so. For that reason, if a woman is requiring regular NSAIDs for symptom control, the results of this study might encourage me to consider a biologic agent sooner to ensure remission.”

She urged women who want to become pregnant to discuss medications with their rheumatologist before trying to conceive.

“It is very exciting to see studies such as this so that rheumatologists can provide answers to our patients’ questions with evidence-based advice,” she said.

Ms. Hamroun and several coauthors had no disclosures. Other coauthors disclosed relationships with companies including Merck/MSD, Novartis, Janssen, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Galapagos, Eli Lilly, Novartis, and/or UCB. Dr. Maguire reports no relevant financial relationships.

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

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

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

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

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

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

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

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

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

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

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

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

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

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

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

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

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

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

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