Rheumatology

An increase in body weight appears to have a detrimental effect on some radiographic features of knee, but not hip, osteoarthritis, researchers reported at the OARSI 2022 World Congress.

Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)

Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.

Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).

Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).

Importance of weight change in OA

“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.

“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”

He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
 

Why look at weight change effects in OA?

“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.

Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.

The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.

“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.

Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.

The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.

“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”

Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”

There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.

Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.

“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”

The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.
 

An increase in body weight appears to have a detrimental effect on some radiographic features of knee, but not hip, osteoarthritis, researchers reported at the OARSI 2022 World Congress.

Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)

Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.

Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).

Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).

Importance of weight change in OA

“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.

“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”

He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
 

Why look at weight change effects in OA?

“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.

Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.

The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.

“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.

Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.

The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.

“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”

Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”

There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.

Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.

“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”

The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.
 

An increase in body weight appears to have a detrimental effect on some radiographic features of knee, but not hip, osteoarthritis, researchers reported at the OARSI 2022 World Congress.

Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)

Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.

Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).

Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).

Importance of weight change in OA

“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.

“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”

He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
 

Why look at weight change effects in OA?

“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.

Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.

The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.

“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.

Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.

The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.

“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”

Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”

There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.

Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.

“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”

The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.
 

A 12-week hypocaloric diet provided suitable control of joint disease activity in patients with psoriatic arthritis (PsA), regardless of weight loss, Brazilian researchers found.

Earlier research has reported that weight loss improves the symptoms of PsA.

Improvement in the Brazilian DIETA study was linked to both better eating patterns and better quality of diet, and while omega-3 supplementation caused relevant body composition changes, it did not improve disease activity, according to Beatriz F. Leite of the division of rheumatology at the Federal University of São Paulo and colleagues.

“The DIETA trial, a nonpharmacologic approach, is an inexpensive, suitable, and efficient approach that could be combined with standardized drug therapy,” the investigators wrote online in Advances in Rheumatology.

Dietary counseling aimed at losing or controlling weight could therefore be part of the global protocol for PsA patients, the researchers added. They conceded, however, that nonpharmacologic interventions traditionally have a low rate of adherence.

This recommendation aligns with a systematic review by the National Psoriasis Foundation, which found evidence of benefit with dietary weight reduction via a hypocaloric diet in overweight and obese patients with psoriasis and/or PsA. 
 

The DIETA trial

The 12-week randomized, double-blind, placebo-controlled study, conducted at three hospitals in São Paulo from September 2012 to May 2014, assessed whether dietary changes, antioxidant supplementation, or weight loss of 5%-10% could improve skin and joint activity in 97 enrolled PsA patients.

Participants were randomized into the following supervised dietary groups:

• Diet-placebo (hypocaloric diet plus placebo supplementation).
• Diet-fish (hypocaloric diet plus 3 g/day of omega-3 supplementation).
• Placebo (with habitual diet).

Diets were carefully tailored to each individual patient. The regimen for overweight and obese patients included a 500-kcal restriction, while for eutrophic patients, diets were calculated to maintain weight with no caloric restriction.

In the 91 patients evaluable by multiple measures at 12 weeks, Ms. Leite and colleagues observed the following:

• The Disease Activity Score 28 (DAS28) for Rheumatoid Arthritis with C-Reactive Protein and the Bath Ankylosing Spondylitis Disease Activity Index improved, especially in the diet-placebo group (−0.6 ± 0.9, P = .004 and −1.39 ± 1.97, P = .001, respectively).
• Minimal disease activity improved in all groups.
• The diet-fish group showed significant weight loss (−1.79 ± 2.4 kg, P = .004), as well as reductions in waist circumference (−3.28 ± 3.5 cm, P < .001) and body fat (−1.2 ± 2.2 kg, P = .006).

Other findings from this study showed the following:

• No significant correlation was seen between weight loss and disease activity improvement.
• Each 1-unit increase in the Healthy Eating Index value reduced the likelihood of achieving remission by 4%.
• Each 100-calorie increase per day caused a 3.4-fold impairment on the DAS28-Erythrocyte Sedimentation Rate score.

The fact that no changes in PsA, medications, or physical activity were made during the study period reinforces the role of diet in the context of immunometabolism, the authors said. Supervised exercise, however, could contribute to weight loss, lean muscle mass, and better disease activity control.

The authors stressed that the data suggest “increased energy intake and worse diet quality may negatively affect joint activity and reduce the likelihood of achieving disease remission, regardless of weight loss or body composition changes.”

“There are other studies that have looked at the effect of weight loss from a very low-calorie diet, and they’ve suggested that PsA symptoms can improve, said rheumatologist Eric. M. Ruderman, MD, a professor of medicine at Northwestern Medicine in Chicago, in an interview. “The unique piece here is that they found that the improvement was really independent of weight loss.”

Dr. Ruderman, who was not involved in DIETA, cautioned, however, that the study is small and saw improvement in the placebo group as well, which could suggest that some of the improvement was related to the extra attention and regular communication with the nutritionist that came with participation in the study.

“Also, the absolute improvement was small, and the dietary restriction was pretty aggressive, so I’m not sure how generalizable this really is. While there are lots of benefits to maintaining a healthy diet and exercising, I don’t think that the results of this small study would justify taking an aggressive [dietary] approach as part of the clinical playbook for all PsA patients.”

This study was supported by the São Paulo Research Foundation and the Coordination for Improvement in Higher Education Foundation of the Ministry of Education, Brazil.

The authors had no competing interests to declare.

Dr. Ruderman disclosed no relevant competing interests.
 

A 12-week hypocaloric diet provided suitable control of joint disease activity in patients with psoriatic arthritis (PsA), regardless of weight loss, Brazilian researchers found.

Earlier research has reported that weight loss improves the symptoms of PsA.

Improvement in the Brazilian DIETA study was linked to both better eating patterns and better quality of diet, and while omega-3 supplementation caused relevant body composition changes, it did not improve disease activity, according to Beatriz F. Leite of the division of rheumatology at the Federal University of São Paulo and colleagues.

“The DIETA trial, a nonpharmacologic approach, is an inexpensive, suitable, and efficient approach that could be combined with standardized drug therapy,” the investigators wrote online in Advances in Rheumatology.

Dietary counseling aimed at losing or controlling weight could therefore be part of the global protocol for PsA patients, the researchers added. They conceded, however, that nonpharmacologic interventions traditionally have a low rate of adherence.

This recommendation aligns with a systematic review by the National Psoriasis Foundation, which found evidence of benefit with dietary weight reduction via a hypocaloric diet in overweight and obese patients with psoriasis and/or PsA. 
 

The DIETA trial

The 12-week randomized, double-blind, placebo-controlled study, conducted at three hospitals in São Paulo from September 2012 to May 2014, assessed whether dietary changes, antioxidant supplementation, or weight loss of 5%-10% could improve skin and joint activity in 97 enrolled PsA patients.

Participants were randomized into the following supervised dietary groups:

• Diet-placebo (hypocaloric diet plus placebo supplementation).
• Diet-fish (hypocaloric diet plus 3 g/day of omega-3 supplementation).
• Placebo (with habitual diet).

Diets were carefully tailored to each individual patient. The regimen for overweight and obese patients included a 500-kcal restriction, while for eutrophic patients, diets were calculated to maintain weight with no caloric restriction.

In the 91 patients evaluable by multiple measures at 12 weeks, Ms. Leite and colleagues observed the following:

• The Disease Activity Score 28 (DAS28) for Rheumatoid Arthritis with C-Reactive Protein and the Bath Ankylosing Spondylitis Disease Activity Index improved, especially in the diet-placebo group (−0.6 ± 0.9, P = .004 and −1.39 ± 1.97, P = .001, respectively).
• Minimal disease activity improved in all groups.
• The diet-fish group showed significant weight loss (−1.79 ± 2.4 kg, P = .004), as well as reductions in waist circumference (−3.28 ± 3.5 cm, P < .001) and body fat (−1.2 ± 2.2 kg, P = .006).

Other findings from this study showed the following:

• No significant correlation was seen between weight loss and disease activity improvement.
• Each 1-unit increase in the Healthy Eating Index value reduced the likelihood of achieving remission by 4%.
• Each 100-calorie increase per day caused a 3.4-fold impairment on the DAS28-Erythrocyte Sedimentation Rate score.

The fact that no changes in PsA, medications, or physical activity were made during the study period reinforces the role of diet in the context of immunometabolism, the authors said. Supervised exercise, however, could contribute to weight loss, lean muscle mass, and better disease activity control.

The authors stressed that the data suggest “increased energy intake and worse diet quality may negatively affect joint activity and reduce the likelihood of achieving disease remission, regardless of weight loss or body composition changes.”

“There are other studies that have looked at the effect of weight loss from a very low-calorie diet, and they’ve suggested that PsA symptoms can improve, said rheumatologist Eric. M. Ruderman, MD, a professor of medicine at Northwestern Medicine in Chicago, in an interview. “The unique piece here is that they found that the improvement was really independent of weight loss.”

Dr. Ruderman, who was not involved in DIETA, cautioned, however, that the study is small and saw improvement in the placebo group as well, which could suggest that some of the improvement was related to the extra attention and regular communication with the nutritionist that came with participation in the study.

“Also, the absolute improvement was small, and the dietary restriction was pretty aggressive, so I’m not sure how generalizable this really is. While there are lots of benefits to maintaining a healthy diet and exercising, I don’t think that the results of this small study would justify taking an aggressive [dietary] approach as part of the clinical playbook for all PsA patients.”

This study was supported by the São Paulo Research Foundation and the Coordination for Improvement in Higher Education Foundation of the Ministry of Education, Brazil.

The authors had no competing interests to declare.

Dr. Ruderman disclosed no relevant competing interests.
 

A 12-week hypocaloric diet provided suitable control of joint disease activity in patients with psoriatic arthritis (PsA), regardless of weight loss, Brazilian researchers found.

Earlier research has reported that weight loss improves the symptoms of PsA.

Improvement in the Brazilian DIETA study was linked to both better eating patterns and better quality of diet, and while omega-3 supplementation caused relevant body composition changes, it did not improve disease activity, according to Beatriz F. Leite of the division of rheumatology at the Federal University of São Paulo and colleagues.

“The DIETA trial, a nonpharmacologic approach, is an inexpensive, suitable, and efficient approach that could be combined with standardized drug therapy,” the investigators wrote online in Advances in Rheumatology.

Dietary counseling aimed at losing or controlling weight could therefore be part of the global protocol for PsA patients, the researchers added. They conceded, however, that nonpharmacologic interventions traditionally have a low rate of adherence.

This recommendation aligns with a systematic review by the National Psoriasis Foundation, which found evidence of benefit with dietary weight reduction via a hypocaloric diet in overweight and obese patients with psoriasis and/or PsA. 
 

The DIETA trial

The 12-week randomized, double-blind, placebo-controlled study, conducted at three hospitals in São Paulo from September 2012 to May 2014, assessed whether dietary changes, antioxidant supplementation, or weight loss of 5%-10% could improve skin and joint activity in 97 enrolled PsA patients.

Participants were randomized into the following supervised dietary groups:

• Diet-placebo (hypocaloric diet plus placebo supplementation).
• Diet-fish (hypocaloric diet plus 3 g/day of omega-3 supplementation).
• Placebo (with habitual diet).

Diets were carefully tailored to each individual patient. The regimen for overweight and obese patients included a 500-kcal restriction, while for eutrophic patients, diets were calculated to maintain weight with no caloric restriction.

In the 91 patients evaluable by multiple measures at 12 weeks, Ms. Leite and colleagues observed the following:

• The Disease Activity Score 28 (DAS28) for Rheumatoid Arthritis with C-Reactive Protein and the Bath Ankylosing Spondylitis Disease Activity Index improved, especially in the diet-placebo group (−0.6 ± 0.9, P = .004 and −1.39 ± 1.97, P = .001, respectively).
• Minimal disease activity improved in all groups.
• The diet-fish group showed significant weight loss (−1.79 ± 2.4 kg, P = .004), as well as reductions in waist circumference (−3.28 ± 3.5 cm, P < .001) and body fat (−1.2 ± 2.2 kg, P = .006).

Other findings from this study showed the following:

• No significant correlation was seen between weight loss and disease activity improvement.
• Each 1-unit increase in the Healthy Eating Index value reduced the likelihood of achieving remission by 4%.
• Each 100-calorie increase per day caused a 3.4-fold impairment on the DAS28-Erythrocyte Sedimentation Rate score.

The fact that no changes in PsA, medications, or physical activity were made during the study period reinforces the role of diet in the context of immunometabolism, the authors said. Supervised exercise, however, could contribute to weight loss, lean muscle mass, and better disease activity control.

The authors stressed that the data suggest “increased energy intake and worse diet quality may negatively affect joint activity and reduce the likelihood of achieving disease remission, regardless of weight loss or body composition changes.”

“There are other studies that have looked at the effect of weight loss from a very low-calorie diet, and they’ve suggested that PsA symptoms can improve, said rheumatologist Eric. M. Ruderman, MD, a professor of medicine at Northwestern Medicine in Chicago, in an interview. “The unique piece here is that they found that the improvement was really independent of weight loss.”

Dr. Ruderman, who was not involved in DIETA, cautioned, however, that the study is small and saw improvement in the placebo group as well, which could suggest that some of the improvement was related to the extra attention and regular communication with the nutritionist that came with participation in the study.

“Also, the absolute improvement was small, and the dietary restriction was pretty aggressive, so I’m not sure how generalizable this really is. While there are lots of benefits to maintaining a healthy diet and exercising, I don’t think that the results of this small study would justify taking an aggressive [dietary] approach as part of the clinical playbook for all PsA patients.”

This study was supported by the São Paulo Research Foundation and the Coordination for Improvement in Higher Education Foundation of the Ministry of Education, Brazil.

The authors had no competing interests to declare.

Dr. Ruderman disclosed no relevant competing interests.
 

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

Bone strength and microarchitecture remained stronger at 24 months after treatment with denosumab compared to risedronate, in a study of 110 adults using glucocorticoids.

Patients using glucocorticoids are at increased risk for vertebral and nonvertebral fractures at both the start of treatment or as treatment continues, wrote Piet Geusens, MD, of Maastricht University, the Netherlands, and colleagues.

Imaging data collected via high-resolution peripheral quantitative computed tomography (HR-pQCT) allow for the assessment of bone microarchitecture and strength, but specific data comparing the impact of bone treatment in patients using glucocorticoids are lacking, they said.

In a study published in the Journal of Bone and Mineral Research, the researchers identified a subset of 56 patients randomized to denosumab and 54 to risedronate patients out of a total of 590 patients who were enrolled in a phase 3 randomized, controlled trial of denosumab vs. risedronate for bone mineral density. The main results of the larger trial – presented at EULAR 2018 – showed greater increases in bone strength with denosumab over risedronate in patients receiving glucocorticoids.

In the current study, the researchers reviewed HR-pQCT scans of the distal radius and tibia at baseline, 12 months, and 24 months. Bone strength and microarchitecture were defined in terms of failure load (FL) as a primary outcome. Patients also were divided into subpopulations of those initiating glucocorticoid treatment (GC-I) and continuing treatment (GC-C).

Baseline characteristics were mainly balanced among the treatment groups within the GC-I and GC-C categories.

Among the GC-I patients, in the denosumab group, FL increased significantly from baseline to 12 months at the radius at tibia (1.8% and 1.7%, respectively) but did not change significantly in the risedronate group, which translated to a significant treatment difference between the drugs of 3.3% for radius and 2.5% for tibia.

At 24 months, the radius measure of FL was unchanged from baseline in denosumab patients but significantly decreased in risedronate patients, with a difference of –4.1%, which translated to a significant between-treatment difference at the radius of 5.6% (P < .001). Changes at the tibia were not significantly different between the groups at 24 months.

Among the GC-C patients, FL was unchanged from baseline to 12 months for both the denosumab and risedronate groups. However, FL significantly increased with denosumab (4.3%) and remained unchanged in the risedronate group.

The researchers also found significant differences between denosumab and risedronate in percentage changes in cortical bone mineral density, and less prominent changes and differences in trabecular bone mineral density.

The study findings were limited by several factors including the use of the HR-pQCT scanner, which limits the measurement of trabecular microarchitecture, and the use of only standard HR-pQCT parameters, which do not allow insight into endosteal changes, and the inability to correct for multiplicity of data, the researchers noted.

However, the results support the superiority of denosumab over risedronate for preventing FL and total bone mineral density loss at the radius and tibia in new glucocorticoid users, and for increasing FL and total bone mineral density at the radius in long-term glucocorticoid users, they said.

Denosumab therefore could be a useful therapeutic option and could inform decision-making in patients initiating GC-therapy or on long-term GC-therapy, they concluded.

The study was supported by Amgen. Dr. Geusens disclosed grants from Amgen, Celgene, Lilly, Merck, Pfizer, Roche, UCB, Fresenius, Mylan, and Sandoz, and grants and other funding from AbbVie, outside the current study.

A small number of patient and physician-reported outcomes, as well as laboratory and clinical factors, may help to predict the response of patients with ankylosing spondylitis (AS) to treatment with tumor necrosis factor (TNF) inhibitors when they have never taken them before, according to an analysis of data from nearly 2,000 individuals in 10 clinical trials.

TNF inhibitors are recommended for patients with AS whose symptoms persist despite use of NSAIDs, Runsheng Wang, MD, adjunct assistant professor at Columbia University Medical Center, New York, and a practicing rheumatologist at Garden State Rheumatology Consultants, Union, N.J., and colleagues wrote. Randomized, controlled clinical trials have shown that TNF inhibitors are effective in treating AS, but approximately half of patients fail to achieve notable improvement, which suggests the need for a predictive model.

“In clinical practice, before starting a treatment, physicians and patients want to know how likely a patient would be to respond to the treatment, particularly when more than one treatment option is available,” Dr. Wang said in an interview. “In this study, we developed predictive models that can potentially answer this question.”

The results suggest that the models in the study can be used to personalize clinical decision-making for patients with AS, whether to promote confidence in choosing a TNF inhibitor or to terminate treatment in nonresponders who had a higher probability of nonresponse at baseline, the researchers wrote. Similar models for other biologic treatments can help prioritize treatment options.

The predictive models are practical for clinical use because the variables in the reduced models – can be collected easily during patient visits, Dr. Wang explained. However, data from clinical practice are needed to further validate the study findings.

In a retrospective cohort study published in JAMA Network Open, the researchers analyzed data from 10 randomized, controlled clinical trials of TNF inhibitor treatment in patients with active AS conducted during 2002-2016. The study population included 1,899 adults with active AS who received an originator TNF inhibitor for at least 12 weeks, and the training set included 1,207 individuals. In the training set, the mean age of the participants was 39 years, and 75% were men.

The outcomes included major response and no response based on change in AS Disease Activity Score (ASDAS) from baseline to 12 weeks, and the researchers used machine-learning algorithms to estimate the probability of major response or no response. Major response was defined as a decrease in ASDAS of 2.0 or greater; no response was defined as a decrease in ASDAS of less than 1.1.

In the training set, a total of 407 patients (33.7%) had a major response, and 414 (34.3%) had no response.

The key features in the full, 21-variable model that increased the probability of a major response were higher C-reactive protein (CRP) levels, higher patient global assessment (PGA) of disease activity, and Bath AS Disease Activity Index (BASDAI) question 2 scores. (Question 2 asks for the overall level of back, hip, or neck pain associated with AS.) The probability of a major response decreased with higher body mass index and Bath AS Functional Index (BASFI) scores.

The key features in the model that increased the probability of no response were older age and higher BASFI scores. The probability of no response decreased with higher CRP levels, higher BASDAI question 2 scores, and higher PGA scores.

Overall, the researchers found that models using smaller subsets of variables (three or five variables in total) that would be easier to gather clinically yielded similar predictive performance.

The models were externally validated in a testing set of 692 individuals. Baseline characteristics were similar in the testing and training sets. In the testing set, the full models demonstrated moderate to high accuracy of 0.71 in the random forest model for major response and 0.76 in the random forest model for no response, with similar results in the reduced models.

At a prevalence of 25% for major response, the positive predictive values (PPVs) for random forest and logistic regression models ranged from 0.49 to 0.60, and the negative predictive values (NPVs) ranged from 0.82 to 0.84. At a prevalence of 25% for no response, PPVs ranged from 0.61 to 0.77, and NPVs ranged from 0.81 to 0.83.

The study findings were limited by several factors including the lack of data on smoking, which has been linked both to shorter treatment adherence and worse response to TNF inhibitors; the inclusion of only TNF inhibitor–naive patients; and the exclusion of NSAIDs from the models, the researchers wrote.

Dr. Wang disclosed support from the Rheumatology Research Foundation. The study’s two other authors disclosed receiving support from the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The study was based on an analysis of data from AbbVie and Pfizer that were made available through Vivli.

A small number of patient and physician-reported outcomes, as well as laboratory and clinical factors, may help to predict the response of patients with ankylosing spondylitis (AS) to treatment with tumor necrosis factor (TNF) inhibitors when they have never taken them before, according to an analysis of data from nearly 2,000 individuals in 10 clinical trials.

TNF inhibitors are recommended for patients with AS whose symptoms persist despite use of NSAIDs, Runsheng Wang, MD, adjunct assistant professor at Columbia University Medical Center, New York, and a practicing rheumatologist at Garden State Rheumatology Consultants, Union, N.J., and colleagues wrote. Randomized, controlled clinical trials have shown that TNF inhibitors are effective in treating AS, but approximately half of patients fail to achieve notable improvement, which suggests the need for a predictive model.

“In clinical practice, before starting a treatment, physicians and patients want to know how likely a patient would be to respond to the treatment, particularly when more than one treatment option is available,” Dr. Wang said in an interview. “In this study, we developed predictive models that can potentially answer this question.”

The results suggest that the models in the study can be used to personalize clinical decision-making for patients with AS, whether to promote confidence in choosing a TNF inhibitor or to terminate treatment in nonresponders who had a higher probability of nonresponse at baseline, the researchers wrote. Similar models for other biologic treatments can help prioritize treatment options.

The predictive models are practical for clinical use because the variables in the reduced models – can be collected easily during patient visits, Dr. Wang explained. However, data from clinical practice are needed to further validate the study findings.

In a retrospective cohort study published in JAMA Network Open, the researchers analyzed data from 10 randomized, controlled clinical trials of TNF inhibitor treatment in patients with active AS conducted during 2002-2016. The study population included 1,899 adults with active AS who received an originator TNF inhibitor for at least 12 weeks, and the training set included 1,207 individuals. In the training set, the mean age of the participants was 39 years, and 75% were men.

The outcomes included major response and no response based on change in AS Disease Activity Score (ASDAS) from baseline to 12 weeks, and the researchers used machine-learning algorithms to estimate the probability of major response or no response. Major response was defined as a decrease in ASDAS of 2.0 or greater; no response was defined as a decrease in ASDAS of less than 1.1.

In the training set, a total of 407 patients (33.7%) had a major response, and 414 (34.3%) had no response.

The key features in the full, 21-variable model that increased the probability of a major response were higher C-reactive protein (CRP) levels, higher patient global assessment (PGA) of disease activity, and Bath AS Disease Activity Index (BASDAI) question 2 scores. (Question 2 asks for the overall level of back, hip, or neck pain associated with AS.) The probability of a major response decreased with higher body mass index and Bath AS Functional Index (BASFI) scores.

The key features in the model that increased the probability of no response were older age and higher BASFI scores. The probability of no response decreased with higher CRP levels, higher BASDAI question 2 scores, and higher PGA scores.

Overall, the researchers found that models using smaller subsets of variables (three or five variables in total) that would be easier to gather clinically yielded similar predictive performance.

The models were externally validated in a testing set of 692 individuals. Baseline characteristics were similar in the testing and training sets. In the testing set, the full models demonstrated moderate to high accuracy of 0.71 in the random forest model for major response and 0.76 in the random forest model for no response, with similar results in the reduced models.

At a prevalence of 25% for major response, the positive predictive values (PPVs) for random forest and logistic regression models ranged from 0.49 to 0.60, and the negative predictive values (NPVs) ranged from 0.82 to 0.84. At a prevalence of 25% for no response, PPVs ranged from 0.61 to 0.77, and NPVs ranged from 0.81 to 0.83.

The study findings were limited by several factors including the lack of data on smoking, which has been linked both to shorter treatment adherence and worse response to TNF inhibitors; the inclusion of only TNF inhibitor–naive patients; and the exclusion of NSAIDs from the models, the researchers wrote.

Dr. Wang disclosed support from the Rheumatology Research Foundation. The study’s two other authors disclosed receiving support from the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The study was based on an analysis of data from AbbVie and Pfizer that were made available through Vivli.

A small number of patient and physician-reported outcomes, as well as laboratory and clinical factors, may help to predict the response of patients with ankylosing spondylitis (AS) to treatment with tumor necrosis factor (TNF) inhibitors when they have never taken them before, according to an analysis of data from nearly 2,000 individuals in 10 clinical trials.

TNF inhibitors are recommended for patients with AS whose symptoms persist despite use of NSAIDs, Runsheng Wang, MD, adjunct assistant professor at Columbia University Medical Center, New York, and a practicing rheumatologist at Garden State Rheumatology Consultants, Union, N.J., and colleagues wrote. Randomized, controlled clinical trials have shown that TNF inhibitors are effective in treating AS, but approximately half of patients fail to achieve notable improvement, which suggests the need for a predictive model.

“In clinical practice, before starting a treatment, physicians and patients want to know how likely a patient would be to respond to the treatment, particularly when more than one treatment option is available,” Dr. Wang said in an interview. “In this study, we developed predictive models that can potentially answer this question.”

The results suggest that the models in the study can be used to personalize clinical decision-making for patients with AS, whether to promote confidence in choosing a TNF inhibitor or to terminate treatment in nonresponders who had a higher probability of nonresponse at baseline, the researchers wrote. Similar models for other biologic treatments can help prioritize treatment options.

The predictive models are practical for clinical use because the variables in the reduced models – can be collected easily during patient visits, Dr. Wang explained. However, data from clinical practice are needed to further validate the study findings.

In a retrospective cohort study published in JAMA Network Open, the researchers analyzed data from 10 randomized, controlled clinical trials of TNF inhibitor treatment in patients with active AS conducted during 2002-2016. The study population included 1,899 adults with active AS who received an originator TNF inhibitor for at least 12 weeks, and the training set included 1,207 individuals. In the training set, the mean age of the participants was 39 years, and 75% were men.

The outcomes included major response and no response based on change in AS Disease Activity Score (ASDAS) from baseline to 12 weeks, and the researchers used machine-learning algorithms to estimate the probability of major response or no response. Major response was defined as a decrease in ASDAS of 2.0 or greater; no response was defined as a decrease in ASDAS of less than 1.1.

In the training set, a total of 407 patients (33.7%) had a major response, and 414 (34.3%) had no response.

The key features in the full, 21-variable model that increased the probability of a major response were higher C-reactive protein (CRP) levels, higher patient global assessment (PGA) of disease activity, and Bath AS Disease Activity Index (BASDAI) question 2 scores. (Question 2 asks for the overall level of back, hip, or neck pain associated with AS.) The probability of a major response decreased with higher body mass index and Bath AS Functional Index (BASFI) scores.

The key features in the model that increased the probability of no response were older age and higher BASFI scores. The probability of no response decreased with higher CRP levels, higher BASDAI question 2 scores, and higher PGA scores.

Overall, the researchers found that models using smaller subsets of variables (three or five variables in total) that would be easier to gather clinically yielded similar predictive performance.

The models were externally validated in a testing set of 692 individuals. Baseline characteristics were similar in the testing and training sets. In the testing set, the full models demonstrated moderate to high accuracy of 0.71 in the random forest model for major response and 0.76 in the random forest model for no response, with similar results in the reduced models.

At a prevalence of 25% for major response, the positive predictive values (PPVs) for random forest and logistic regression models ranged from 0.49 to 0.60, and the negative predictive values (NPVs) ranged from 0.82 to 0.84. At a prevalence of 25% for no response, PPVs ranged from 0.61 to 0.77, and NPVs ranged from 0.81 to 0.83.

The study findings were limited by several factors including the lack of data on smoking, which has been linked both to shorter treatment adherence and worse response to TNF inhibitors; the inclusion of only TNF inhibitor–naive patients; and the exclusion of NSAIDs from the models, the researchers wrote.

Dr. Wang disclosed support from the Rheumatology Research Foundation. The study’s two other authors disclosed receiving support from the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The study was based on an analysis of data from AbbVie and Pfizer that were made available through Vivli.

For children with polyarticular juvenile idiopathic arthritis (pJIA), functional disability lasts longer and disease activity is increased among those who belong to a racial/ethnic minority or come from homes with low household income or low family education, according to a study published online in Pediatric Rheumatology. The findings also initially revealed a higher likelihood of functional disability among those living in a poorer community, but that association lost statistical significance after adjustment for confounders.

“We chose community poverty level as the primary predictor for outcomes in pJIA because the socioeconomic context of communities and neighborhoods affects the characteristics of the social, service, and physical environments to which all residents are exposed regardless of their own socioeconomic position and may have a greater negative impact on those with fewer individual resources,” the authors write. “While community poverty level was not associated with an increase in odds of moderate-to-severe disease activity, those with high community poverty level did have higher disease activity scores (0.33 points greater on average than those with low community poverty level, in adjusted analysis).”

Nayimisha Balmuri, MD, an assistant professor of pediatrics at Johns Hopkins Medicine and study coauthor, told this news organization that anecdotal experience from everyday practice has shown that “patients with myriad social determinants of health stacked against them present sicker, take longer to present, and require far more aggressive therapies and follow-up,” which wreaks havoc in terms of disease activity. “It’s really difficult, then, to play catch-up to other cohorts of patients,” Dr. Balmuri added.
 

Disparities in outcomes persist

A key clinical take-home message from these findings is that the differences in clinical outcomes are relevant throughout the entire year of therapy, Dr. Balmuri said. “Patients get better; however, they don’t get better the same,” she said, and this is because of a variety of reasons. “Getting in the door is one of [those reasons] but then continuing to follow-up care is another.” For general practitioners, it’s especially important to refer patients who complain of joint pains to a specialist and to then follow up to be sure they’re improving and they’re getting the care they need.

For pediatric rheumatologists and subspecialists, “it’s important for us to realize that the disparity doesn’t end when patients come into your door to begin with,” Dr. Balmuri said. “It continues over the short term and far past that into adulthood.”

Candace Feldman, MD, MPH, ScD, an assistant professor of medicine in the Division of Rheumatology, Inflammation, and Immunity at Brigham and Women’s Hospital, Boston, told this news organization that the research “provides an important foundation to the study of the impact of social determinants of health on disease activity and disability among children with JIA. Individuals with rheumatic conditions should be screened for social determinants of health–related needs, and infrastructure should exist within the rheumatology clinic to help address the needs uncovered.” Dr. Feldman was not involved in the study.

In addition to the results’ clinical significance, Dr. Feldman also noted the policy implications of these findings. “Physicians should advocate for efforts to dismantle structural racism, to address income inequality, and to mitigate the effects of climate change, which also disproportionately affect historically marginalized populations,” Dr. Feldman said. Although this study focused predominantly on poverty, she noted that financial insecurity, food insecurity, homelessness, or housing instability were other social determinants of health to consider in future research.

Dr. Balmuri and William Daniel Soulsby, MD, a clinical fellow in pediatric rheumatology at the University of California, San Francisco, who is the study’s lead author, said they focused on poverty in this study not only because it’s so understudied in patients with pJIA but also because research in adults with lupus has found that leaving poverty was associated with a reversal of accrued disease damage.

Interactions of social determinants

The authors analyzed retrospective data from 1,684 pediatric patients in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry covering the period of April 2015 to February 2020. All study participants had been diagnosed with pJIA. Symptom onset occurred before age 16, and at least five joints were involved. The authors excluded patients who had been diagnosed with other systemic inflammatory or autoimmune diseases.

The authors defined exposure to a high level of community poverty as living in a ZIP code where at least 20% of residents lived at or below the federal poverty level. The authors also collected data on household income, although these data were missing for more than a quarter of participants (27%) and were therefore included only in sensitivity analyses. They used the clinical Juvenile Arthritis Disease Activity Score–10 (cJADAS-10) and the Child Health Assessment Questionnaire (CHAQ) to assess disease activity and disability at baseline and 6 and 12 months later. A cutoff of 2.5 on the cJADAS-10 distinguished mild disease activity from moderate to high disease activity, and a CHAQ score of 0.25 was the cutoff for having functional disability.

Among those who reported household income, just over half the cohort had an income of at least $50,000. The study population was 74% White, and more non-White patients lived in high-poverty communities (36.4%) than did White patients (21.3%). Patients whose families had no more than a high school education (23.1% vs. 13.7%) and those with public insurance (43.0% vs. 21.5%) were also over-represented in poorer communities.

The median cJADAS-10 scores declined overall during patients’ first year of therapy. However, those with public insurance, a lower family education level, or residency in poorer communities made up the greatest proportion of patients who continued to have moderate to severe disease activity a year after diagnosis.

The unadjusted calculations showed that children living in high community poverty had 1.8 times greater odds of functional disability (odds ratio, 1.82; P < .001). However, after adjustment for age, sex, race/ethnicity, insurance status, family education, rheumatoid factor, and cyclic citrullinated peptide antibody, the association lost statistical significance (P = .3). Community poverty level was not associated with disease activity before or after adjustment.

“Race was adjusted for as a confounder; however, the association between race/ethnicity and social determinants of health is likely more complex,” Dr. Feldman said. “Interactions, for example, between individual race and area-level poverty could be investigated.”

Odds of persistent function disability were 1.5 times greater for children with public insurance (adjusted OR, 1.56; P = .023) and 1.9 times greater for those whose families had a lower education level (aOR, 1.89; P = .013). Children whose race/ethnicity was indicated as being other than White had more than double the odds of higher disease activity (aOR, 2.48; P = .002) and were nearly twice as likely to have persistent functional disability (aOR, 1.91; P = .031).

Future directions

Dr. Soulsby was struck by the difference in statistical significance between individual-level poverty, as measured by household income, and community-level poverty. “It’s interesting because it may suggest that both of these forms of poverty are different and have different impacts on disease,” he said. Dr. Balmuri elaborated on the nuances and interactions that exist with social determinants of health and how objective outcomes, such as disease activity as measured by clinical tools, can differ from subjective outcomes, such as patients’ reports of pain, daily disability, and social experiences.

“The human condition is far more complicated, unfortunately, than any dataset could have on their own collected,” Dr. Balmuri said. She said she plans to expand her pJIA research into other social determinants of health. “It’s first about getting people’s eyes and minds open to something we see every day that, for some reason, sometimes people are blinded to, [using] the data that we do have, and then our hope is to build upon that.”

Dr. Feldman noted that ZIP codes, which were used as a proxy for community poverty, may not provide the best perspective regarding a patient’s neighborhood, because significant variation may exist within a single ZIP code, which is something the authors noted as well. The investigators were limited in the data available from the registry, and Dr. Balmuri and Dr. Soulsby suggested that 9-digit ZIP codes or census tracts might better capture neighborhood deprivation.

The research was funded by the Arthritis Foundation and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Feldman has received research support from Pfizer and the Bristol-Myers Squibb Foundation. Dr. Soulsby and Dr. Balmuri have disclosed no relevant financial relationships.

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

For children with polyarticular juvenile idiopathic arthritis (pJIA), functional disability lasts longer and disease activity is increased among those who belong to a racial/ethnic minority or come from homes with low household income or low family education, according to a study published online in Pediatric Rheumatology. The findings also initially revealed a higher likelihood of functional disability among those living in a poorer community, but that association lost statistical significance after adjustment for confounders.

“We chose community poverty level as the primary predictor for outcomes in pJIA because the socioeconomic context of communities and neighborhoods affects the characteristics of the social, service, and physical environments to which all residents are exposed regardless of their own socioeconomic position and may have a greater negative impact on those with fewer individual resources,” the authors write. “While community poverty level was not associated with an increase in odds of moderate-to-severe disease activity, those with high community poverty level did have higher disease activity scores (0.33 points greater on average than those with low community poverty level, in adjusted analysis).”

Nayimisha Balmuri, MD, an assistant professor of pediatrics at Johns Hopkins Medicine and study coauthor, told this news organization that anecdotal experience from everyday practice has shown that “patients with myriad social determinants of health stacked against them present sicker, take longer to present, and require far more aggressive therapies and follow-up,” which wreaks havoc in terms of disease activity. “It’s really difficult, then, to play catch-up to other cohorts of patients,” Dr. Balmuri added.
 

Disparities in outcomes persist

A key clinical take-home message from these findings is that the differences in clinical outcomes are relevant throughout the entire year of therapy, Dr. Balmuri said. “Patients get better; however, they don’t get better the same,” she said, and this is because of a variety of reasons. “Getting in the door is one of [those reasons] but then continuing to follow-up care is another.” For general practitioners, it’s especially important to refer patients who complain of joint pains to a specialist and to then follow up to be sure they’re improving and they’re getting the care they need.

For pediatric rheumatologists and subspecialists, “it’s important for us to realize that the disparity doesn’t end when patients come into your door to begin with,” Dr. Balmuri said. “It continues over the short term and far past that into adulthood.”

Candace Feldman, MD, MPH, ScD, an assistant professor of medicine in the Division of Rheumatology, Inflammation, and Immunity at Brigham and Women’s Hospital, Boston, told this news organization that the research “provides an important foundation to the study of the impact of social determinants of health on disease activity and disability among children with JIA. Individuals with rheumatic conditions should be screened for social determinants of health–related needs, and infrastructure should exist within the rheumatology clinic to help address the needs uncovered.” Dr. Feldman was not involved in the study.

In addition to the results’ clinical significance, Dr. Feldman also noted the policy implications of these findings. “Physicians should advocate for efforts to dismantle structural racism, to address income inequality, and to mitigate the effects of climate change, which also disproportionately affect historically marginalized populations,” Dr. Feldman said. Although this study focused predominantly on poverty, she noted that financial insecurity, food insecurity, homelessness, or housing instability were other social determinants of health to consider in future research.

Dr. Balmuri and William Daniel Soulsby, MD, a clinical fellow in pediatric rheumatology at the University of California, San Francisco, who is the study’s lead author, said they focused on poverty in this study not only because it’s so understudied in patients with pJIA but also because research in adults with lupus has found that leaving poverty was associated with a reversal of accrued disease damage.

Interactions of social determinants

The authors analyzed retrospective data from 1,684 pediatric patients in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry covering the period of April 2015 to February 2020. All study participants had been diagnosed with pJIA. Symptom onset occurred before age 16, and at least five joints were involved. The authors excluded patients who had been diagnosed with other systemic inflammatory or autoimmune diseases.

The authors defined exposure to a high level of community poverty as living in a ZIP code where at least 20% of residents lived at or below the federal poverty level. The authors also collected data on household income, although these data were missing for more than a quarter of participants (27%) and were therefore included only in sensitivity analyses. They used the clinical Juvenile Arthritis Disease Activity Score–10 (cJADAS-10) and the Child Health Assessment Questionnaire (CHAQ) to assess disease activity and disability at baseline and 6 and 12 months later. A cutoff of 2.5 on the cJADAS-10 distinguished mild disease activity from moderate to high disease activity, and a CHAQ score of 0.25 was the cutoff for having functional disability.

Among those who reported household income, just over half the cohort had an income of at least $50,000. The study population was 74% White, and more non-White patients lived in high-poverty communities (36.4%) than did White patients (21.3%). Patients whose families had no more than a high school education (23.1% vs. 13.7%) and those with public insurance (43.0% vs. 21.5%) were also over-represented in poorer communities.

The median cJADAS-10 scores declined overall during patients’ first year of therapy. However, those with public insurance, a lower family education level, or residency in poorer communities made up the greatest proportion of patients who continued to have moderate to severe disease activity a year after diagnosis.

The unadjusted calculations showed that children living in high community poverty had 1.8 times greater odds of functional disability (odds ratio, 1.82; P < .001). However, after adjustment for age, sex, race/ethnicity, insurance status, family education, rheumatoid factor, and cyclic citrullinated peptide antibody, the association lost statistical significance (P = .3). Community poverty level was not associated with disease activity before or after adjustment.

“Race was adjusted for as a confounder; however, the association between race/ethnicity and social determinants of health is likely more complex,” Dr. Feldman said. “Interactions, for example, between individual race and area-level poverty could be investigated.”

Odds of persistent function disability were 1.5 times greater for children with public insurance (adjusted OR, 1.56; P = .023) and 1.9 times greater for those whose families had a lower education level (aOR, 1.89; P = .013). Children whose race/ethnicity was indicated as being other than White had more than double the odds of higher disease activity (aOR, 2.48; P = .002) and were nearly twice as likely to have persistent functional disability (aOR, 1.91; P = .031).

Future directions

Dr. Soulsby was struck by the difference in statistical significance between individual-level poverty, as measured by household income, and community-level poverty. “It’s interesting because it may suggest that both of these forms of poverty are different and have different impacts on disease,” he said. Dr. Balmuri elaborated on the nuances and interactions that exist with social determinants of health and how objective outcomes, such as disease activity as measured by clinical tools, can differ from subjective outcomes, such as patients’ reports of pain, daily disability, and social experiences.

“The human condition is far more complicated, unfortunately, than any dataset could have on their own collected,” Dr. Balmuri said. She said she plans to expand her pJIA research into other social determinants of health. “It’s first about getting people’s eyes and minds open to something we see every day that, for some reason, sometimes people are blinded to, [using] the data that we do have, and then our hope is to build upon that.”

Dr. Feldman noted that ZIP codes, which were used as a proxy for community poverty, may not provide the best perspective regarding a patient’s neighborhood, because significant variation may exist within a single ZIP code, which is something the authors noted as well. The investigators were limited in the data available from the registry, and Dr. Balmuri and Dr. Soulsby suggested that 9-digit ZIP codes or census tracts might better capture neighborhood deprivation.

The research was funded by the Arthritis Foundation and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Feldman has received research support from Pfizer and the Bristol-Myers Squibb Foundation. Dr. Soulsby and Dr. Balmuri have disclosed no relevant financial relationships.

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

For children with polyarticular juvenile idiopathic arthritis (pJIA), functional disability lasts longer and disease activity is increased among those who belong to a racial/ethnic minority or come from homes with low household income or low family education, according to a study published online in Pediatric Rheumatology. The findings also initially revealed a higher likelihood of functional disability among those living in a poorer community, but that association lost statistical significance after adjustment for confounders.

“We chose community poverty level as the primary predictor for outcomes in pJIA because the socioeconomic context of communities and neighborhoods affects the characteristics of the social, service, and physical environments to which all residents are exposed regardless of their own socioeconomic position and may have a greater negative impact on those with fewer individual resources,” the authors write. “While community poverty level was not associated with an increase in odds of moderate-to-severe disease activity, those with high community poverty level did have higher disease activity scores (0.33 points greater on average than those with low community poverty level, in adjusted analysis).”

Nayimisha Balmuri, MD, an assistant professor of pediatrics at Johns Hopkins Medicine and study coauthor, told this news organization that anecdotal experience from everyday practice has shown that “patients with myriad social determinants of health stacked against them present sicker, take longer to present, and require far more aggressive therapies and follow-up,” which wreaks havoc in terms of disease activity. “It’s really difficult, then, to play catch-up to other cohorts of patients,” Dr. Balmuri added.
 

Disparities in outcomes persist

A key clinical take-home message from these findings is that the differences in clinical outcomes are relevant throughout the entire year of therapy, Dr. Balmuri said. “Patients get better; however, they don’t get better the same,” she said, and this is because of a variety of reasons. “Getting in the door is one of [those reasons] but then continuing to follow-up care is another.” For general practitioners, it’s especially important to refer patients who complain of joint pains to a specialist and to then follow up to be sure they’re improving and they’re getting the care they need.

For pediatric rheumatologists and subspecialists, “it’s important for us to realize that the disparity doesn’t end when patients come into your door to begin with,” Dr. Balmuri said. “It continues over the short term and far past that into adulthood.”

Candace Feldman, MD, MPH, ScD, an assistant professor of medicine in the Division of Rheumatology, Inflammation, and Immunity at Brigham and Women’s Hospital, Boston, told this news organization that the research “provides an important foundation to the study of the impact of social determinants of health on disease activity and disability among children with JIA. Individuals with rheumatic conditions should be screened for social determinants of health–related needs, and infrastructure should exist within the rheumatology clinic to help address the needs uncovered.” Dr. Feldman was not involved in the study.

In addition to the results’ clinical significance, Dr. Feldman also noted the policy implications of these findings. “Physicians should advocate for efforts to dismantle structural racism, to address income inequality, and to mitigate the effects of climate change, which also disproportionately affect historically marginalized populations,” Dr. Feldman said. Although this study focused predominantly on poverty, she noted that financial insecurity, food insecurity, homelessness, or housing instability were other social determinants of health to consider in future research.

Dr. Balmuri and William Daniel Soulsby, MD, a clinical fellow in pediatric rheumatology at the University of California, San Francisco, who is the study’s lead author, said they focused on poverty in this study not only because it’s so understudied in patients with pJIA but also because research in adults with lupus has found that leaving poverty was associated with a reversal of accrued disease damage.

Interactions of social determinants

The authors analyzed retrospective data from 1,684 pediatric patients in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry covering the period of April 2015 to February 2020. All study participants had been diagnosed with pJIA. Symptom onset occurred before age 16, and at least five joints were involved. The authors excluded patients who had been diagnosed with other systemic inflammatory or autoimmune diseases.

The authors defined exposure to a high level of community poverty as living in a ZIP code where at least 20% of residents lived at or below the federal poverty level. The authors also collected data on household income, although these data were missing for more than a quarter of participants (27%) and were therefore included only in sensitivity analyses. They used the clinical Juvenile Arthritis Disease Activity Score–10 (cJADAS-10) and the Child Health Assessment Questionnaire (CHAQ) to assess disease activity and disability at baseline and 6 and 12 months later. A cutoff of 2.5 on the cJADAS-10 distinguished mild disease activity from moderate to high disease activity, and a CHAQ score of 0.25 was the cutoff for having functional disability.

Among those who reported household income, just over half the cohort had an income of at least $50,000. The study population was 74% White, and more non-White patients lived in high-poverty communities (36.4%) than did White patients (21.3%). Patients whose families had no more than a high school education (23.1% vs. 13.7%) and those with public insurance (43.0% vs. 21.5%) were also over-represented in poorer communities.

The median cJADAS-10 scores declined overall during patients’ first year of therapy. However, those with public insurance, a lower family education level, or residency in poorer communities made up the greatest proportion of patients who continued to have moderate to severe disease activity a year after diagnosis.

The unadjusted calculations showed that children living in high community poverty had 1.8 times greater odds of functional disability (odds ratio, 1.82; P < .001). However, after adjustment for age, sex, race/ethnicity, insurance status, family education, rheumatoid factor, and cyclic citrullinated peptide antibody, the association lost statistical significance (P = .3). Community poverty level was not associated with disease activity before or after adjustment.

“Race was adjusted for as a confounder; however, the association between race/ethnicity and social determinants of health is likely more complex,” Dr. Feldman said. “Interactions, for example, between individual race and area-level poverty could be investigated.”

Odds of persistent function disability were 1.5 times greater for children with public insurance (adjusted OR, 1.56; P = .023) and 1.9 times greater for those whose families had a lower education level (aOR, 1.89; P = .013). Children whose race/ethnicity was indicated as being other than White had more than double the odds of higher disease activity (aOR, 2.48; P = .002) and were nearly twice as likely to have persistent functional disability (aOR, 1.91; P = .031).

Future directions

Dr. Soulsby was struck by the difference in statistical significance between individual-level poverty, as measured by household income, and community-level poverty. “It’s interesting because it may suggest that both of these forms of poverty are different and have different impacts on disease,” he said. Dr. Balmuri elaborated on the nuances and interactions that exist with social determinants of health and how objective outcomes, such as disease activity as measured by clinical tools, can differ from subjective outcomes, such as patients’ reports of pain, daily disability, and social experiences.

“The human condition is far more complicated, unfortunately, than any dataset could have on their own collected,” Dr. Balmuri said. She said she plans to expand her pJIA research into other social determinants of health. “It’s first about getting people’s eyes and minds open to something we see every day that, for some reason, sometimes people are blinded to, [using] the data that we do have, and then our hope is to build upon that.”

Dr. Feldman noted that ZIP codes, which were used as a proxy for community poverty, may not provide the best perspective regarding a patient’s neighborhood, because significant variation may exist within a single ZIP code, which is something the authors noted as well. The investigators were limited in the data available from the registry, and Dr. Balmuri and Dr. Soulsby suggested that 9-digit ZIP codes or census tracts might better capture neighborhood deprivation.

The research was funded by the Arthritis Foundation and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Feldman has received research support from Pfizer and the Bristol-Myers Squibb Foundation. Dr. Soulsby and Dr. Balmuri have disclosed no relevant financial relationships.

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

The antifibrinolytic tranexamic acid (TXA) reduced serious bleeding without a significant effect on major vascular outcomes in patients undergoing noncardiac surgery at risk for these complications in the POISE-3 trial.

TXA cut the primary efficacy outcome of life-threatening, major, and critical organ bleeding at 30 days by 24% compared with placebo (9.1% vs. 11.7%; hazard ratio [HR], 0.76; P < .0001).

The primary safety outcome of myocardial injury after noncardiac surgery (MINS), nonhemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism (VTE) at 30 days occurred in 14.2% vs.. 13.9% of patients, respectively (HR, 1.023). This failed, however, to meet the study›s threshold to prove TXA noninferior to placebo (one-sided P = .044).

There was no increased risk for death or stroke with TXA, according to results published April 2 in the New England Journal of Medicine.

Principal investigator P.J. Devereaux, MD, PhD, Population Health Research Institute and McMaster University, Hamilton, Ontario, Canada, pointed out that there is only a 4.4% probability that the composite vascular outcome hazard ratio was above the noninferiority margin and that just 10 events separated the two groups (649 vs.. 639).

“Healthcare providers and patients will have to weigh a clear beneficial reduction in the composite bleeding outcome, which is an absolute difference of 2.7%, a result that was highly statistically significant, versus a low probability of a small increase in risk of the composite vascular endpoint, with an absolute difference of 0.3%,” a nonsignificant result, Dr. Devereaux said during the formal presentation of the results at the hybrid annual scientific sessions of the American College of Cardiology.

The findings, he said, should also be put in the context that 300 million adults have a major surgery each year worldwide and most don’t receive TXA. At the same time, there’s an annual global shortage of 30 million blood product units, and surgical bleeding accounts for up to 40% of all transfusions.

“POISE-3 identifies that use of TXA could avoid upwards of 8 million bleeding events resulting in transfusion on an annual basis, indicating potential for large public health and clinical benefit if TXA become standard practice in noncardiac surgery,” Dr. Devereaux said during the late-breaking trial session.

TXA is indicated for heavy menstrual bleeding and hemophilia and has been used in cardiac surgery, but it is increasingly being used in noncardiac surgeries. As previously reported, POISE showed that the beta-blocker metoprolol lowered the risk for myocardial infarction (MI) but increased the risk for severe stroke and overall death, whereas in POISE-2, perioperative low-dose aspirin lowered the risk for MI but was linked to more major bleeding.

The cumulative data have not shown an increased risk for thrombotic events in other settings, Dr. Devereaux told this news organization.

“I’m a cardiologist, and I think that we’ve been guilty at times of always only focusing on the thrombotic side of the equation and ignoring that bleeding is a very important aspect of the circulatory system,” he said. “And I think this shows for the first time clear unequivocal evidence that there’s a cheap, very encouraging, safe way to prevent this.”

“An important point is that if you can give tranexamic acid and prevent bleeding in your cardiac patients having noncardiac surgery, then you can prevent the delay of reinitiating their anticoagulants and their antiplatelets after surgery and getting them back on the medications that are important for them to prevent their cardiovascular event,” Dr. Devereaux added.

Discussant Michael J. Mack, MD, commented that TXA, widely used in cardiac surgery, is an old, inexpensive drug that “should be more widely used in noncardiac surgery.” Dr. Mack, from Baylor Scott & White Health, Dallas, added that he would limit it to major noncardiac surgery.

International trial

PeriOperative ISchemic Evaluation-3 (POISE-3) investigators at 114 hospitals in 22 countries (including countries in North and South America, Europe, and Africa; Russia; India; and Australia) randomly assigned 9,535 patients, aged 45 years or older, with or at risk for cardiovascular and bleeding complications to receive a TXA 1-g intravenous bolus or placebo at the start and end of inpatient noncardiac surgery.

Patients taking at least one long-term antihypertensive medication were also randomly assigned to a perioperative hypotension- or hypertension-avoidance strategy, which differ in the use of antihypertensives on the morning of surgery and the first 2 days after surgery, and in the target mean arterial pressure during surgery. Results from these cohorts will be presented in a separate session on April 4.

The study had planned to enroll 10,000 patients but was stopped early by the steering committee because of financial constraints resulting from slow enrollment during the pandemic. The decision was made without knowledge of the trial results but with knowledge that aggregate composite bleeding and vascular outcomes were higher than originally estimated, Dr. Devereaux noted.

Among all participants, the mean age was 70 years, 56% were male, almost a third had coronary artery disease, 15% had peripheral artery disease, and 8% had a prior stroke. About 80% were undergoing major surgery. Adherence to the study medications was 96.3% in both groups.

Secondary bleeding outcomes were lower in the TXA and placebo groups, including bleeding independently associated with mortality after surgery (8.7% vs. 11.3%), life-threatening bleeding (1.6% vs. 1.7%), major bleeding (7.6% vs. 10.4%), and critical organ bleeding (0.3% vs. 0.4%).

Importantly, the TXA group had significantly lower rates of International Society on Thrombosis and Haemostasis major bleeding (6.6% vs. 8.7%; P = .0001) and the need for transfusion of 1 or more units of packed red blood cells (9.4% vs. 12.0%; P <.0001), Dr. Devereaux noted.

In terms of secondary vascular outcomes, there were no significant differences between the TXA and placebo groups in rates of MINS (12.8% vs. 12.6%), MINS not fulfilling definition of MI (both 11.5%), MI (1.4% vs. 1.1%), and the net risk-benefit outcome (a composite of vascular death and nonfatal life-threatening, major, or critical organ bleeding, MINS, stroke, peripheral arterial thrombosis, and symptomatic proximal VTE; 20.7% vs. 21.9%).

The two groups had similar rates of all-cause (1.1% vs. 1.2%) and vascular (0.5% vs. 0.6%) mortality.

There also were no significant differences in other tertiary outcomes, such as acute kidney injury (14.1% vs. 13.7%), rehospitalization for vascular reasons (1.8% vs. 1.6%), or seizures (0.2% vs. <0.1%). The latter has been a concern, with the risk reported to increase with higher doses.

Subgroup analyses

Preplanned subgroup analyses showed a benefit for TXA over placebo for the primary efficacy outcome in orthopedic and nonorthopedic surgery and in patients with hemoglobin level below 120 g/L or 120 g/L or higher, with an estimated glomerular filtration rate less than 45 mL/min/1.73 m ²  or 45 mL/min/1.73 m ²  or higher, or with an N-terminal pro– B-type natriuretic peptide level below 200 ng/L or 200 ng/L or higher.

For the primary safety outcome, the benefit favored placebo but the interaction was not statistically significant for any of the four subgroups.

A post hoc subgroup analysis also showed similar results across the major categories of surgery, including general, vascular, urologic, and gynecologic, Dr. Devereaux told this news organization.

Although TXA is commonly used in orthopedic procedures, Dr. Devereaux noted, in other types of surgeries, “it’s not used at all.” But because TXA “is so cheap, and we can apply it to a broad population, even at an economic level it looks like it’s a winner to give to almost all patients having noncardiac surgery.”

The team also recently published a risk prediction tool that can help estimate a patient’s baseline risk for bleeding.

“So just using a model, which will bring together the patient’s type of surgery and their risk factors, you can look to see, okay, this is enough risk of bleeding, I’m just going to give tranexamic acid,” he said. “We will also be doing economic analyses because blood is also not cheap.”

The study was funded by the Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and the Research Grant Council (Hong Kong). Dr. Devereaux reports research/research grants from Abbott Diagnostics, Philips Healthcare, Roche Diagnostics, and Siemens. Dr. Mack reports receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

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

The antifibrinolytic tranexamic acid (TXA) reduced serious bleeding without a significant effect on major vascular outcomes in patients undergoing noncardiac surgery at risk for these complications in the POISE-3 trial.

TXA cut the primary efficacy outcome of life-threatening, major, and critical organ bleeding at 30 days by 24% compared with placebo (9.1% vs. 11.7%; hazard ratio [HR], 0.76; P < .0001).

The primary safety outcome of myocardial injury after noncardiac surgery (MINS), nonhemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism (VTE) at 30 days occurred in 14.2% vs.. 13.9% of patients, respectively (HR, 1.023). This failed, however, to meet the study›s threshold to prove TXA noninferior to placebo (one-sided P = .044).

There was no increased risk for death or stroke with TXA, according to results published April 2 in the New England Journal of Medicine.

Principal investigator P.J. Devereaux, MD, PhD, Population Health Research Institute and McMaster University, Hamilton, Ontario, Canada, pointed out that there is only a 4.4% probability that the composite vascular outcome hazard ratio was above the noninferiority margin and that just 10 events separated the two groups (649 vs.. 639).

“Healthcare providers and patients will have to weigh a clear beneficial reduction in the composite bleeding outcome, which is an absolute difference of 2.7%, a result that was highly statistically significant, versus a low probability of a small increase in risk of the composite vascular endpoint, with an absolute difference of 0.3%,” a nonsignificant result, Dr. Devereaux said during the formal presentation of the results at the hybrid annual scientific sessions of the American College of Cardiology.

The findings, he said, should also be put in the context that 300 million adults have a major surgery each year worldwide and most don’t receive TXA. At the same time, there’s an annual global shortage of 30 million blood product units, and surgical bleeding accounts for up to 40% of all transfusions.

“POISE-3 identifies that use of TXA could avoid upwards of 8 million bleeding events resulting in transfusion on an annual basis, indicating potential for large public health and clinical benefit if TXA become standard practice in noncardiac surgery,” Dr. Devereaux said during the late-breaking trial session.

TXA is indicated for heavy menstrual bleeding and hemophilia and has been used in cardiac surgery, but it is increasingly being used in noncardiac surgeries. As previously reported, POISE showed that the beta-blocker metoprolol lowered the risk for myocardial infarction (MI) but increased the risk for severe stroke and overall death, whereas in POISE-2, perioperative low-dose aspirin lowered the risk for MI but was linked to more major bleeding.

The cumulative data have not shown an increased risk for thrombotic events in other settings, Dr. Devereaux told this news organization.

“I’m a cardiologist, and I think that we’ve been guilty at times of always only focusing on the thrombotic side of the equation and ignoring that bleeding is a very important aspect of the circulatory system,” he said. “And I think this shows for the first time clear unequivocal evidence that there’s a cheap, very encouraging, safe way to prevent this.”

“An important point is that if you can give tranexamic acid and prevent bleeding in your cardiac patients having noncardiac surgery, then you can prevent the delay of reinitiating their anticoagulants and their antiplatelets after surgery and getting them back on the medications that are important for them to prevent their cardiovascular event,” Dr. Devereaux added.

Discussant Michael J. Mack, MD, commented that TXA, widely used in cardiac surgery, is an old, inexpensive drug that “should be more widely used in noncardiac surgery.” Dr. Mack, from Baylor Scott & White Health, Dallas, added that he would limit it to major noncardiac surgery.

International trial

PeriOperative ISchemic Evaluation-3 (POISE-3) investigators at 114 hospitals in 22 countries (including countries in North and South America, Europe, and Africa; Russia; India; and Australia) randomly assigned 9,535 patients, aged 45 years or older, with or at risk for cardiovascular and bleeding complications to receive a TXA 1-g intravenous bolus or placebo at the start and end of inpatient noncardiac surgery.

Patients taking at least one long-term antihypertensive medication were also randomly assigned to a perioperative hypotension- or hypertension-avoidance strategy, which differ in the use of antihypertensives on the morning of surgery and the first 2 days after surgery, and in the target mean arterial pressure during surgery. Results from these cohorts will be presented in a separate session on April 4.

The study had planned to enroll 10,000 patients but was stopped early by the steering committee because of financial constraints resulting from slow enrollment during the pandemic. The decision was made without knowledge of the trial results but with knowledge that aggregate composite bleeding and vascular outcomes were higher than originally estimated, Dr. Devereaux noted.

Among all participants, the mean age was 70 years, 56% were male, almost a third had coronary artery disease, 15% had peripheral artery disease, and 8% had a prior stroke. About 80% were undergoing major surgery. Adherence to the study medications was 96.3% in both groups.

Secondary bleeding outcomes were lower in the TXA and placebo groups, including bleeding independently associated with mortality after surgery (8.7% vs. 11.3%), life-threatening bleeding (1.6% vs. 1.7%), major bleeding (7.6% vs. 10.4%), and critical organ bleeding (0.3% vs. 0.4%).

Importantly, the TXA group had significantly lower rates of International Society on Thrombosis and Haemostasis major bleeding (6.6% vs. 8.7%; P = .0001) and the need for transfusion of 1 or more units of packed red blood cells (9.4% vs. 12.0%; P <.0001), Dr. Devereaux noted.

In terms of secondary vascular outcomes, there were no significant differences between the TXA and placebo groups in rates of MINS (12.8% vs. 12.6%), MINS not fulfilling definition of MI (both 11.5%), MI (1.4% vs. 1.1%), and the net risk-benefit outcome (a composite of vascular death and nonfatal life-threatening, major, or critical organ bleeding, MINS, stroke, peripheral arterial thrombosis, and symptomatic proximal VTE; 20.7% vs. 21.9%).

The two groups had similar rates of all-cause (1.1% vs. 1.2%) and vascular (0.5% vs. 0.6%) mortality.

There also were no significant differences in other tertiary outcomes, such as acute kidney injury (14.1% vs. 13.7%), rehospitalization for vascular reasons (1.8% vs. 1.6%), or seizures (0.2% vs. <0.1%). The latter has been a concern, with the risk reported to increase with higher doses.

Subgroup analyses

Preplanned subgroup analyses showed a benefit for TXA over placebo for the primary efficacy outcome in orthopedic and nonorthopedic surgery and in patients with hemoglobin level below 120 g/L or 120 g/L or higher, with an estimated glomerular filtration rate less than 45 mL/min/1.73 m ²  or 45 mL/min/1.73 m ²  or higher, or with an N-terminal pro– B-type natriuretic peptide level below 200 ng/L or 200 ng/L or higher.

For the primary safety outcome, the benefit favored placebo but the interaction was not statistically significant for any of the four subgroups.

A post hoc subgroup analysis also showed similar results across the major categories of surgery, including general, vascular, urologic, and gynecologic, Dr. Devereaux told this news organization.

Although TXA is commonly used in orthopedic procedures, Dr. Devereaux noted, in other types of surgeries, “it’s not used at all.” But because TXA “is so cheap, and we can apply it to a broad population, even at an economic level it looks like it’s a winner to give to almost all patients having noncardiac surgery.”

The team also recently published a risk prediction tool that can help estimate a patient’s baseline risk for bleeding.

“So just using a model, which will bring together the patient’s type of surgery and their risk factors, you can look to see, okay, this is enough risk of bleeding, I’m just going to give tranexamic acid,” he said. “We will also be doing economic analyses because blood is also not cheap.”

The study was funded by the Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and the Research Grant Council (Hong Kong). Dr. Devereaux reports research/research grants from Abbott Diagnostics, Philips Healthcare, Roche Diagnostics, and Siemens. Dr. Mack reports receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

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

The antifibrinolytic tranexamic acid (TXA) reduced serious bleeding without a significant effect on major vascular outcomes in patients undergoing noncardiac surgery at risk for these complications in the POISE-3 trial.

TXA cut the primary efficacy outcome of life-threatening, major, and critical organ bleeding at 30 days by 24% compared with placebo (9.1% vs. 11.7%; hazard ratio [HR], 0.76; P < .0001).

The primary safety outcome of myocardial injury after noncardiac surgery (MINS), nonhemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism (VTE) at 30 days occurred in 14.2% vs.. 13.9% of patients, respectively (HR, 1.023). This failed, however, to meet the study›s threshold to prove TXA noninferior to placebo (one-sided P = .044).

There was no increased risk for death or stroke with TXA, according to results published April 2 in the New England Journal of Medicine.

Principal investigator P.J. Devereaux, MD, PhD, Population Health Research Institute and McMaster University, Hamilton, Ontario, Canada, pointed out that there is only a 4.4% probability that the composite vascular outcome hazard ratio was above the noninferiority margin and that just 10 events separated the two groups (649 vs.. 639).

“Healthcare providers and patients will have to weigh a clear beneficial reduction in the composite bleeding outcome, which is an absolute difference of 2.7%, a result that was highly statistically significant, versus a low probability of a small increase in risk of the composite vascular endpoint, with an absolute difference of 0.3%,” a nonsignificant result, Dr. Devereaux said during the formal presentation of the results at the hybrid annual scientific sessions of the American College of Cardiology.

The findings, he said, should also be put in the context that 300 million adults have a major surgery each year worldwide and most don’t receive TXA. At the same time, there’s an annual global shortage of 30 million blood product units, and surgical bleeding accounts for up to 40% of all transfusions.

“POISE-3 identifies that use of TXA could avoid upwards of 8 million bleeding events resulting in transfusion on an annual basis, indicating potential for large public health and clinical benefit if TXA become standard practice in noncardiac surgery,” Dr. Devereaux said during the late-breaking trial session.

TXA is indicated for heavy menstrual bleeding and hemophilia and has been used in cardiac surgery, but it is increasingly being used in noncardiac surgeries. As previously reported, POISE showed that the beta-blocker metoprolol lowered the risk for myocardial infarction (MI) but increased the risk for severe stroke and overall death, whereas in POISE-2, perioperative low-dose aspirin lowered the risk for MI but was linked to more major bleeding.

The cumulative data have not shown an increased risk for thrombotic events in other settings, Dr. Devereaux told this news organization.

“I’m a cardiologist, and I think that we’ve been guilty at times of always only focusing on the thrombotic side of the equation and ignoring that bleeding is a very important aspect of the circulatory system,” he said. “And I think this shows for the first time clear unequivocal evidence that there’s a cheap, very encouraging, safe way to prevent this.”

“An important point is that if you can give tranexamic acid and prevent bleeding in your cardiac patients having noncardiac surgery, then you can prevent the delay of reinitiating their anticoagulants and their antiplatelets after surgery and getting them back on the medications that are important for them to prevent their cardiovascular event,” Dr. Devereaux added.

Discussant Michael J. Mack, MD, commented that TXA, widely used in cardiac surgery, is an old, inexpensive drug that “should be more widely used in noncardiac surgery.” Dr. Mack, from Baylor Scott & White Health, Dallas, added that he would limit it to major noncardiac surgery.

International trial

PeriOperative ISchemic Evaluation-3 (POISE-3) investigators at 114 hospitals in 22 countries (including countries in North and South America, Europe, and Africa; Russia; India; and Australia) randomly assigned 9,535 patients, aged 45 years or older, with or at risk for cardiovascular and bleeding complications to receive a TXA 1-g intravenous bolus or placebo at the start and end of inpatient noncardiac surgery.

Patients taking at least one long-term antihypertensive medication were also randomly assigned to a perioperative hypotension- or hypertension-avoidance strategy, which differ in the use of antihypertensives on the morning of surgery and the first 2 days after surgery, and in the target mean arterial pressure during surgery. Results from these cohorts will be presented in a separate session on April 4.

The study had planned to enroll 10,000 patients but was stopped early by the steering committee because of financial constraints resulting from slow enrollment during the pandemic. The decision was made without knowledge of the trial results but with knowledge that aggregate composite bleeding and vascular outcomes were higher than originally estimated, Dr. Devereaux noted.

Among all participants, the mean age was 70 years, 56% were male, almost a third had coronary artery disease, 15% had peripheral artery disease, and 8% had a prior stroke. About 80% were undergoing major surgery. Adherence to the study medications was 96.3% in both groups.

Secondary bleeding outcomes were lower in the TXA and placebo groups, including bleeding independently associated with mortality after surgery (8.7% vs. 11.3%), life-threatening bleeding (1.6% vs. 1.7%), major bleeding (7.6% vs. 10.4%), and critical organ bleeding (0.3% vs. 0.4%).

Importantly, the TXA group had significantly lower rates of International Society on Thrombosis and Haemostasis major bleeding (6.6% vs. 8.7%; P = .0001) and the need for transfusion of 1 or more units of packed red blood cells (9.4% vs. 12.0%; P <.0001), Dr. Devereaux noted.

In terms of secondary vascular outcomes, there were no significant differences between the TXA and placebo groups in rates of MINS (12.8% vs. 12.6%), MINS not fulfilling definition of MI (both 11.5%), MI (1.4% vs. 1.1%), and the net risk-benefit outcome (a composite of vascular death and nonfatal life-threatening, major, or critical organ bleeding, MINS, stroke, peripheral arterial thrombosis, and symptomatic proximal VTE; 20.7% vs. 21.9%).

The two groups had similar rates of all-cause (1.1% vs. 1.2%) and vascular (0.5% vs. 0.6%) mortality.

There also were no significant differences in other tertiary outcomes, such as acute kidney injury (14.1% vs. 13.7%), rehospitalization for vascular reasons (1.8% vs. 1.6%), or seizures (0.2% vs. <0.1%). The latter has been a concern, with the risk reported to increase with higher doses.

Subgroup analyses

Preplanned subgroup analyses showed a benefit for TXA over placebo for the primary efficacy outcome in orthopedic and nonorthopedic surgery and in patients with hemoglobin level below 120 g/L or 120 g/L or higher, with an estimated glomerular filtration rate less than 45 mL/min/1.73 m ²  or 45 mL/min/1.73 m ²  or higher, or with an N-terminal pro– B-type natriuretic peptide level below 200 ng/L or 200 ng/L or higher.

For the primary safety outcome, the benefit favored placebo but the interaction was not statistically significant for any of the four subgroups.

A post hoc subgroup analysis also showed similar results across the major categories of surgery, including general, vascular, urologic, and gynecologic, Dr. Devereaux told this news organization.

Although TXA is commonly used in orthopedic procedures, Dr. Devereaux noted, in other types of surgeries, “it’s not used at all.” But because TXA “is so cheap, and we can apply it to a broad population, even at an economic level it looks like it’s a winner to give to almost all patients having noncardiac surgery.”

The team also recently published a risk prediction tool that can help estimate a patient’s baseline risk for bleeding.

“So just using a model, which will bring together the patient’s type of surgery and their risk factors, you can look to see, okay, this is enough risk of bleeding, I’m just going to give tranexamic acid,” he said. “We will also be doing economic analyses because blood is also not cheap.”

The study was funded by the Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and the Research Grant Council (Hong Kong). Dr. Devereaux reports research/research grants from Abbott Diagnostics, Philips Healthcare, Roche Diagnostics, and Siemens. Dr. Mack reports receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

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

CHICAGO – Access to medical cannabis (MC) cut opioid prescriptions for patients with chronic noncancer back pain and patients with osteoarthritis, according to preliminary data presented at the annual meeting of the American Academy of Orthopaedic Surgeons.

For those with chronic back pain, the average morphine milligram equivalents (MME) per day dropped from 15.1 to 11.0 (n = 186; P < .01). More than one-third of the patients (38.7%) stopped taking morphine after they filled prescriptions for medical cannabis.

LPETTET/Getty Images

Opioid prescriptions were filled 6 months before access to MC and then were compared with 6 months after access to MC.

In analyzing subgroups, the researchers found that patients who started at less than 15 MME/day and more than 15 MME/day showed significant decreases after filling the MC prescription.

Almost half (48.5%) of the patients in the group that started at less than 15 MME daily dropped to 0 MME/day, and 13.5% of patients who were getting more than 15 MME/day stopped using opioids.

Data on filled opioid prescriptions were gathered from a Prescription Drug Monitoring Program (PDMP) system for patients diagnosed with chronic musculoskeletal noncancer back pain who were eligible for MC access between February 2018 and July 2019.

Medical cannabis has shown benefit in treating chronic pain, but evidence has been limited on whether it can reduce opioid use, which can lead to substance abuse, addiction, overdose, and death, the researchers noted.

Researchers found that using MC via multiple routes of administration seemed to be important.

Patients who used only a single administration route showed a statistically insignificant decrease in MME/day from 20.0 to 15.1 (n = 68; P = .054), whereas patients who used two or more routes showed a significant decrease from 13.2 to 9.5 (n = 76; P < .01).

“We have many patients who are benefiting from a single route of delivery for chronic orthopedic pain,” Ari Greis, DO, a physical medicine and rehabilitation specialist in Bryn Mawr, Pa., and a coauthor of the MC studies for both back pain and OA, said in an interview. “However, our data shows a greater reduction in opioid consumption in patients using more than one route of delivery.”

He said delivery modes in the studies included vaporized cannabis oil or flower; sublingual tinctures; capsules or tablets; and topical lotions, creams, and salves.

Dr. Greis is the director of the medical cannabis department at Rothman Orthopaedic Institute in Bryn Mawr, and is a senior fellow in the Institute of Emerging Health Professions and the Lambert Center for the Study of Medicinal Cannabis and Hemp, both in Philadelphia.
 

Medical cannabis also reduces opioids for OA

The same team of researchers, using the data from the PDMP system, showed that medical cannabis also helped reduce opioid use for osteoarthritis.

For patients using opioids for OA, there was a significant decrease in average MME/day of prescriptions filled by patients following MC access – from 18.2 to 9.8 (n = 40; P < .05). The average drop in MME/day was 46.3%. The percentage of patients who stopped using opioids was 37.5%. Pain score on a 0-10 visual analog scale decreased significantly from 6.6 (n = 36) to 5.0 (n = 26; P < .01) at 3 months and 5.4 (n = 16; P < .05) at 6 months.

Gary Stewart, MD, an orthopedic surgeon in Morrow, Ga., who was not part of the studies, told this news organization that the studies offer good preliminary data to offer help with the opioid issue.

“I sometimes feel that we, as orthopedic surgeons and physicians in general, are working with one hand behind our back. We’re taking something that is a heroin or morphine derivative and giving it to our patients when we know it has a high risk of building tolerance and addiction. But at the same time, we have no alternative,” he said.

He said it’s important to remember the results from the relatively small study are preliminary and observational. People used different forms and amounts of MC and the data show only that prescriptions were filled, but not whether the cannabis was used. Prospective, controlled studies where opioids go head-to-head with MC are needed, he said.

“Still, this can lead us to more studies to give us an option [apart from] an opioid that we know is highly addictive,” he said.

Dr. Stewart is a member of the AAOS Opioid Task Force. Dr. Greis and several coauthors have disclosed no relevant financial relationships, and other coauthors report financial ties to companies unrelated to the research presented.

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

CHICAGO – Access to medical cannabis (MC) cut opioid prescriptions for patients with chronic noncancer back pain and patients with osteoarthritis, according to preliminary data presented at the annual meeting of the American Academy of Orthopaedic Surgeons.

For those with chronic back pain, the average morphine milligram equivalents (MME) per day dropped from 15.1 to 11.0 (n = 186; P < .01). More than one-third of the patients (38.7%) stopped taking morphine after they filled prescriptions for medical cannabis.

LPETTET/Getty Images

Opioid prescriptions were filled 6 months before access to MC and then were compared with 6 months after access to MC.

In analyzing subgroups, the researchers found that patients who started at less than 15 MME/day and more than 15 MME/day showed significant decreases after filling the MC prescription.

Almost half (48.5%) of the patients in the group that started at less than 15 MME daily dropped to 0 MME/day, and 13.5% of patients who were getting more than 15 MME/day stopped using opioids.

Data on filled opioid prescriptions were gathered from a Prescription Drug Monitoring Program (PDMP) system for patients diagnosed with chronic musculoskeletal noncancer back pain who were eligible for MC access between February 2018 and July 2019.

Medical cannabis has shown benefit in treating chronic pain, but evidence has been limited on whether it can reduce opioid use, which can lead to substance abuse, addiction, overdose, and death, the researchers noted.

Researchers found that using MC via multiple routes of administration seemed to be important.

Patients who used only a single administration route showed a statistically insignificant decrease in MME/day from 20.0 to 15.1 (n = 68; P = .054), whereas patients who used two or more routes showed a significant decrease from 13.2 to 9.5 (n = 76; P < .01).

“We have many patients who are benefiting from a single route of delivery for chronic orthopedic pain,” Ari Greis, DO, a physical medicine and rehabilitation specialist in Bryn Mawr, Pa., and a coauthor of the MC studies for both back pain and OA, said in an interview. “However, our data shows a greater reduction in opioid consumption in patients using more than one route of delivery.”

He said delivery modes in the studies included vaporized cannabis oil or flower; sublingual tinctures; capsules or tablets; and topical lotions, creams, and salves.

Dr. Greis is the director of the medical cannabis department at Rothman Orthopaedic Institute in Bryn Mawr, and is a senior fellow in the Institute of Emerging Health Professions and the Lambert Center for the Study of Medicinal Cannabis and Hemp, both in Philadelphia.
 

Medical cannabis also reduces opioids for OA

The same team of researchers, using the data from the PDMP system, showed that medical cannabis also helped reduce opioid use for osteoarthritis.

For patients using opioids for OA, there was a significant decrease in average MME/day of prescriptions filled by patients following MC access – from 18.2 to 9.8 (n = 40; P < .05). The average drop in MME/day was 46.3%. The percentage of patients who stopped using opioids was 37.5%. Pain score on a 0-10 visual analog scale decreased significantly from 6.6 (n = 36) to 5.0 (n = 26; P < .01) at 3 months and 5.4 (n = 16; P < .05) at 6 months.

Gary Stewart, MD, an orthopedic surgeon in Morrow, Ga., who was not part of the studies, told this news organization that the studies offer good preliminary data to offer help with the opioid issue.

“I sometimes feel that we, as orthopedic surgeons and physicians in general, are working with one hand behind our back. We’re taking something that is a heroin or morphine derivative and giving it to our patients when we know it has a high risk of building tolerance and addiction. But at the same time, we have no alternative,” he said.

He said it’s important to remember the results from the relatively small study are preliminary and observational. People used different forms and amounts of MC and the data show only that prescriptions were filled, but not whether the cannabis was used. Prospective, controlled studies where opioids go head-to-head with MC are needed, he said.

“Still, this can lead us to more studies to give us an option [apart from] an opioid that we know is highly addictive,” he said.

Dr. Stewart is a member of the AAOS Opioid Task Force. Dr. Greis and several coauthors have disclosed no relevant financial relationships, and other coauthors report financial ties to companies unrelated to the research presented.

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

CHICAGO – Access to medical cannabis (MC) cut opioid prescriptions for patients with chronic noncancer back pain and patients with osteoarthritis, according to preliminary data presented at the annual meeting of the American Academy of Orthopaedic Surgeons.

For those with chronic back pain, the average morphine milligram equivalents (MME) per day dropped from 15.1 to 11.0 (n = 186; P < .01). More than one-third of the patients (38.7%) stopped taking morphine after they filled prescriptions for medical cannabis.

LPETTET/Getty Images

Opioid prescriptions were filled 6 months before access to MC and then were compared with 6 months after access to MC.

In analyzing subgroups, the researchers found that patients who started at less than 15 MME/day and more than 15 MME/day showed significant decreases after filling the MC prescription.

Almost half (48.5%) of the patients in the group that started at less than 15 MME daily dropped to 0 MME/day, and 13.5% of patients who were getting more than 15 MME/day stopped using opioids.

Data on filled opioid prescriptions were gathered from a Prescription Drug Monitoring Program (PDMP) system for patients diagnosed with chronic musculoskeletal noncancer back pain who were eligible for MC access between February 2018 and July 2019.

Medical cannabis has shown benefit in treating chronic pain, but evidence has been limited on whether it can reduce opioid use, which can lead to substance abuse, addiction, overdose, and death, the researchers noted.

Researchers found that using MC via multiple routes of administration seemed to be important.

Patients who used only a single administration route showed a statistically insignificant decrease in MME/day from 20.0 to 15.1 (n = 68; P = .054), whereas patients who used two or more routes showed a significant decrease from 13.2 to 9.5 (n = 76; P < .01).

“We have many patients who are benefiting from a single route of delivery for chronic orthopedic pain,” Ari Greis, DO, a physical medicine and rehabilitation specialist in Bryn Mawr, Pa., and a coauthor of the MC studies for both back pain and OA, said in an interview. “However, our data shows a greater reduction in opioid consumption in patients using more than one route of delivery.”

He said delivery modes in the studies included vaporized cannabis oil or flower; sublingual tinctures; capsules or tablets; and topical lotions, creams, and salves.

Dr. Greis is the director of the medical cannabis department at Rothman Orthopaedic Institute in Bryn Mawr, and is a senior fellow in the Institute of Emerging Health Professions and the Lambert Center for the Study of Medicinal Cannabis and Hemp, both in Philadelphia.
 

Medical cannabis also reduces opioids for OA

The same team of researchers, using the data from the PDMP system, showed that medical cannabis also helped reduce opioid use for osteoarthritis.

For patients using opioids for OA, there was a significant decrease in average MME/day of prescriptions filled by patients following MC access – from 18.2 to 9.8 (n = 40; P < .05). The average drop in MME/day was 46.3%. The percentage of patients who stopped using opioids was 37.5%. Pain score on a 0-10 visual analog scale decreased significantly from 6.6 (n = 36) to 5.0 (n = 26; P < .01) at 3 months and 5.4 (n = 16; P < .05) at 6 months.

Gary Stewart, MD, an orthopedic surgeon in Morrow, Ga., who was not part of the studies, told this news organization that the studies offer good preliminary data to offer help with the opioid issue.

“I sometimes feel that we, as orthopedic surgeons and physicians in general, are working with one hand behind our back. We’re taking something that is a heroin or morphine derivative and giving it to our patients when we know it has a high risk of building tolerance and addiction. But at the same time, we have no alternative,” he said.

He said it’s important to remember the results from the relatively small study are preliminary and observational. People used different forms and amounts of MC and the data show only that prescriptions were filled, but not whether the cannabis was used. Prospective, controlled studies where opioids go head-to-head with MC are needed, he said.

“Still, this can lead us to more studies to give us an option [apart from] an opioid that we know is highly addictive,” he said.

Dr. Stewart is a member of the AAOS Opioid Task Force. Dr. Greis and several coauthors have disclosed no relevant financial relationships, and other coauthors report financial ties to companies unrelated to the research presented.

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

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

CHICAGO – Patients undergoing primary reverse shoulder arthroplasty (RSA) for their glenohumeral osteoarthritis had more complications of care and higher hospital costs when they also had a diagnosis of depression, new data show.

The abstract was presented at the annual meeting of the American Academy of Orthopedic Surgeons.

Researchers, led by Keith Diamond, MD, an orthopedic surgeon at Maimonides Medical Center in New York, queried a private payer database looking for patients who had primary RSA for treatment of glenohumeral OA and also had a diagnosis of depressive disorder (DD) from 2010 to 2019. Patients without DD served as the controls.

After the randomized matching with controls at a 1:5 ratio, the study consisted of 28,410 patients: 4,084 in the DD group and 24,326 in the control group.

Researchers found that patients with depression had longer hospital stays (3 vs. 2 days, P = .0007). They also had higher frequency and odds of developing side effects within the period of care (47.4% vs. 14.7%; odds ratio, 2.27; 95% CI, 2.10-2.45,  P < .0001).

Patients with depression also had significantly higher rates of medical complications surrounding the surgery and costs were higher ($19,363 vs. $17,927, P < .0001).

Pneumonia rates were much higher in patients with DD (10% vs. 1.8%; OR, 2.88; P < .0001).

Patients with depression had higher odds of cerebrovascular accident (3.1% vs. 0.7%; OR, 2.69, P < .0001); myocardial infarctions (2% vs. 0.4%; OR, 2.54; P < .0001); acute kidney injuries (11.1% vs. 2.3%; OR, 2.11, P < .0001); surgical site infections (4.4% vs. 2.4%; OR, 1.52, P < .0001); and other complications, the authors wrote.

Dr. Diamond said in an interview that there may be a few potential reasons for the associations.

In regard to the strong association with pneumonia, Dr. Diamond hypothesized, “patients with depression can be shown to have lower respiratory drive. If a patient isn’t motivated to get out of bed, that can lead to decreased inflation of the lungs.”

Acute kidney injury could be linked with depression-related lack of self-care in properly hydrating, he said. Surgical site infections could come from suboptimal hygiene related to managing the cast after surgery, which may be more difficult when patients also struggle with depression.

Asked to comment on Dr. Diamond’s study, Grant Garrigues, MD, an associate professor at Rush University Medical Center, Chicago, and director of upper extremity research, told this news organization the study helps confirm known associations between depression and arthritis.

“We know that people with depression and anxiety feel pain differently,” he said. “It might have to do with your outlook – are you catastrophizing or thinking it’s a minor inconvenience? It’s not that it’s just in your head – you physically feel it differently. That is something we’re certainly attuned to. We want to make sure the mental health part of the picture is optimized as much as possible.”

He added that there is increasing evidence of links between depression and the development of arthritis.

“I’m not saying that everyone with arthritis has depression, but with arthritis being multifactorial, there’s a relatively high incidence of symptomatic arthritis in patients with depression,” Dr. Garrigues said.

“We think it may have something to do with the fight-or-flight hormones in your body that may be revved up if you are living in a stressful environment or are living with a mental health problem. Those will actually change – on a cellular and biochemical basis – some of the things that affect arthritis.”
 

Stronger emphasis on mental health

Dr. Diamond said the field needs more emphasis on perioperative state of mind.  

“As orthopedic surgeons, we are preoccupied with the mechanical, the structural aspects of health care as we try to fix bones, ligaments, and tendons. But I think we need to recognize and explore the connection between the psychiatric and psychological health with our musculoskeletal health.”

He noted that, in the preoperative setting, providers look for hypertension, diabetes, smoking status, and other conditions that could complicate surgical outcomes and said mental health should be a factor in whether a surgery proceeds.

“If someone’s diabetes isn’t controlled you can delay an elective case until their [hemoglobin] A1c is under the recommended limit and you get clearance from their primary care doctor. I think that’s something that should be applied to patients with depressive disorders,” Dr. Diamond said.

This study did not distinguish between patients who were being treated for depression at the time of surgery and those not on treatment. More study related to whether treatment affects depression’s association with RSA outcomes is needed, Dr. Diamond added.

Dr. Garrigues said he talks candidly with patients considering surgery about how they are managing their mental health struggles.

“If they say they haven’t seen their psychiatrist or are off their medications, that’s a nonstarter,” he said.

“Anything outside of the surgery you can optimize, whether it’s mental health, medical, social situations – you want to have all your ducks in a row before you dive into surgery,” Dr. Garrigues said.

He added that patients’ mental health status may even affect the venue for the patient – whether outpatient or inpatient, where they can get more supervision and help in making transitions after surgery.

Dr. Diamond and coauthors and Dr. Garrigues disclosed no relevant financial relationships.

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

CHICAGO – Patients undergoing primary reverse shoulder arthroplasty (RSA) for their glenohumeral osteoarthritis had more complications of care and higher hospital costs when they also had a diagnosis of depression, new data show.

The abstract was presented at the annual meeting of the American Academy of Orthopedic Surgeons.

Researchers, led by Keith Diamond, MD, an orthopedic surgeon at Maimonides Medical Center in New York, queried a private payer database looking for patients who had primary RSA for treatment of glenohumeral OA and also had a diagnosis of depressive disorder (DD) from 2010 to 2019. Patients without DD served as the controls.

After the randomized matching with controls at a 1:5 ratio, the study consisted of 28,410 patients: 4,084 in the DD group and 24,326 in the control group.

Researchers found that patients with depression had longer hospital stays (3 vs. 2 days, P = .0007). They also had higher frequency and odds of developing side effects within the period of care (47.4% vs. 14.7%; odds ratio, 2.27; 95% CI, 2.10-2.45,  P < .0001).

Patients with depression also had significantly higher rates of medical complications surrounding the surgery and costs were higher ($19,363 vs. $17,927, P < .0001).

Pneumonia rates were much higher in patients with DD (10% vs. 1.8%; OR, 2.88; P < .0001).

Patients with depression had higher odds of cerebrovascular accident (3.1% vs. 0.7%; OR, 2.69, P < .0001); myocardial infarctions (2% vs. 0.4%; OR, 2.54; P < .0001); acute kidney injuries (11.1% vs. 2.3%; OR, 2.11, P < .0001); surgical site infections (4.4% vs. 2.4%; OR, 1.52, P < .0001); and other complications, the authors wrote.

Dr. Diamond said in an interview that there may be a few potential reasons for the associations.

In regard to the strong association with pneumonia, Dr. Diamond hypothesized, “patients with depression can be shown to have lower respiratory drive. If a patient isn’t motivated to get out of bed, that can lead to decreased inflation of the lungs.”

Acute kidney injury could be linked with depression-related lack of self-care in properly hydrating, he said. Surgical site infections could come from suboptimal hygiene related to managing the cast after surgery, which may be more difficult when patients also struggle with depression.

Asked to comment on Dr. Diamond’s study, Grant Garrigues, MD, an associate professor at Rush University Medical Center, Chicago, and director of upper extremity research, told this news organization the study helps confirm known associations between depression and arthritis.

“We know that people with depression and anxiety feel pain differently,” he said. “It might have to do with your outlook – are you catastrophizing or thinking it’s a minor inconvenience? It’s not that it’s just in your head – you physically feel it differently. That is something we’re certainly attuned to. We want to make sure the mental health part of the picture is optimized as much as possible.”

He added that there is increasing evidence of links between depression and the development of arthritis.

“I’m not saying that everyone with arthritis has depression, but with arthritis being multifactorial, there’s a relatively high incidence of symptomatic arthritis in patients with depression,” Dr. Garrigues said.

“We think it may have something to do with the fight-or-flight hormones in your body that may be revved up if you are living in a stressful environment or are living with a mental health problem. Those will actually change – on a cellular and biochemical basis – some of the things that affect arthritis.”
 

Stronger emphasis on mental health

Dr. Diamond said the field needs more emphasis on perioperative state of mind.  

“As orthopedic surgeons, we are preoccupied with the mechanical, the structural aspects of health care as we try to fix bones, ligaments, and tendons. But I think we need to recognize and explore the connection between the psychiatric and psychological health with our musculoskeletal health.”

He noted that, in the preoperative setting, providers look for hypertension, diabetes, smoking status, and other conditions that could complicate surgical outcomes and said mental health should be a factor in whether a surgery proceeds.

“If someone’s diabetes isn’t controlled you can delay an elective case until their [hemoglobin] A1c is under the recommended limit and you get clearance from their primary care doctor. I think that’s something that should be applied to patients with depressive disorders,” Dr. Diamond said.

This study did not distinguish between patients who were being treated for depression at the time of surgery and those not on treatment. More study related to whether treatment affects depression’s association with RSA outcomes is needed, Dr. Diamond added.

Dr. Garrigues said he talks candidly with patients considering surgery about how they are managing their mental health struggles.

“If they say they haven’t seen their psychiatrist or are off their medications, that’s a nonstarter,” he said.

“Anything outside of the surgery you can optimize, whether it’s mental health, medical, social situations – you want to have all your ducks in a row before you dive into surgery,” Dr. Garrigues said.

He added that patients’ mental health status may even affect the venue for the patient – whether outpatient or inpatient, where they can get more supervision and help in making transitions after surgery.

Dr. Diamond and coauthors and Dr. Garrigues disclosed no relevant financial relationships.

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

CHICAGO – Patients undergoing primary reverse shoulder arthroplasty (RSA) for their glenohumeral osteoarthritis had more complications of care and higher hospital costs when they also had a diagnosis of depression, new data show.

The abstract was presented at the annual meeting of the American Academy of Orthopedic Surgeons.

Researchers, led by Keith Diamond, MD, an orthopedic surgeon at Maimonides Medical Center in New York, queried a private payer database looking for patients who had primary RSA for treatment of glenohumeral OA and also had a diagnosis of depressive disorder (DD) from 2010 to 2019. Patients without DD served as the controls.

After the randomized matching with controls at a 1:5 ratio, the study consisted of 28,410 patients: 4,084 in the DD group and 24,326 in the control group.

Researchers found that patients with depression had longer hospital stays (3 vs. 2 days, P = .0007). They also had higher frequency and odds of developing side effects within the period of care (47.4% vs. 14.7%; odds ratio, 2.27; 95% CI, 2.10-2.45,  P < .0001).

Patients with depression also had significantly higher rates of medical complications surrounding the surgery and costs were higher ($19,363 vs. $17,927, P < .0001).

Pneumonia rates were much higher in patients with DD (10% vs. 1.8%; OR, 2.88; P < .0001).

Patients with depression had higher odds of cerebrovascular accident (3.1% vs. 0.7%; OR, 2.69, P < .0001); myocardial infarctions (2% vs. 0.4%; OR, 2.54; P < .0001); acute kidney injuries (11.1% vs. 2.3%; OR, 2.11, P < .0001); surgical site infections (4.4% vs. 2.4%; OR, 1.52, P < .0001); and other complications, the authors wrote.

Dr. Diamond said in an interview that there may be a few potential reasons for the associations.

In regard to the strong association with pneumonia, Dr. Diamond hypothesized, “patients with depression can be shown to have lower respiratory drive. If a patient isn’t motivated to get out of bed, that can lead to decreased inflation of the lungs.”

Acute kidney injury could be linked with depression-related lack of self-care in properly hydrating, he said. Surgical site infections could come from suboptimal hygiene related to managing the cast after surgery, which may be more difficult when patients also struggle with depression.

Asked to comment on Dr. Diamond’s study, Grant Garrigues, MD, an associate professor at Rush University Medical Center, Chicago, and director of upper extremity research, told this news organization the study helps confirm known associations between depression and arthritis.

“We know that people with depression and anxiety feel pain differently,” he said. “It might have to do with your outlook – are you catastrophizing or thinking it’s a minor inconvenience? It’s not that it’s just in your head – you physically feel it differently. That is something we’re certainly attuned to. We want to make sure the mental health part of the picture is optimized as much as possible.”

He added that there is increasing evidence of links between depression and the development of arthritis.

“I’m not saying that everyone with arthritis has depression, but with arthritis being multifactorial, there’s a relatively high incidence of symptomatic arthritis in patients with depression,” Dr. Garrigues said.

“We think it may have something to do with the fight-or-flight hormones in your body that may be revved up if you are living in a stressful environment or are living with a mental health problem. Those will actually change – on a cellular and biochemical basis – some of the things that affect arthritis.”
 

Stronger emphasis on mental health

Dr. Diamond said the field needs more emphasis on perioperative state of mind.  

“As orthopedic surgeons, we are preoccupied with the mechanical, the structural aspects of health care as we try to fix bones, ligaments, and tendons. But I think we need to recognize and explore the connection between the psychiatric and psychological health with our musculoskeletal health.”

He noted that, in the preoperative setting, providers look for hypertension, diabetes, smoking status, and other conditions that could complicate surgical outcomes and said mental health should be a factor in whether a surgery proceeds.

“If someone’s diabetes isn’t controlled you can delay an elective case until their [hemoglobin] A1c is under the recommended limit and you get clearance from their primary care doctor. I think that’s something that should be applied to patients with depressive disorders,” Dr. Diamond said.

This study did not distinguish between patients who were being treated for depression at the time of surgery and those not on treatment. More study related to whether treatment affects depression’s association with RSA outcomes is needed, Dr. Diamond added.

Dr. Garrigues said he talks candidly with patients considering surgery about how they are managing their mental health struggles.

“If they say they haven’t seen their psychiatrist or are off their medications, that’s a nonstarter,” he said.

“Anything outside of the surgery you can optimize, whether it’s mental health, medical, social situations – you want to have all your ducks in a row before you dive into surgery,” Dr. Garrigues said.

He added that patients’ mental health status may even affect the venue for the patient – whether outpatient or inpatient, where they can get more supervision and help in making transitions after surgery.

Dr. Diamond and coauthors and Dr. Garrigues disclosed no relevant financial relationships.

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