Rheumatology

Mental disorders were significantly more likely in children whose mothers had one of five common autoimmune diseases, a new study found.

Previous research has linked both maternal and paternal autoimmune diseases and specific mental disorders, such as attention-deficit/hyperactivity disorder (ADHD), but most of these studies focused on specific conditions in relatively small populations. The new study included data on more than 2 million births, making it one of the largest efforts to date to examine the association, according to the researchers, whose findings were published in JAMA Network Open.

Previous evidence of the possible association between certain maternal autoimmune diseases and mental disorders in offspring has been “scattered and limited,” which “hampered an overall understanding” of the link, Fei Li, MD, the corresponding author of the study, told this news organization.

Dr. Li, of Shanghai Jiao Tong University China, and colleagues reviewed data from a Danish registry cohort of singleton births with up to 38 years of follow-up. They explored associations between a range of maternal autoimmune diseases diagnosed before childbirth and the risks of mental disorders in children in early childhood through young adulthood.

The study population included 2,254,234 births and 38,916,359 person-years. Data on mental health were collected from the Psychiatric Central Research Register and the country’s National Patient Register. The median age of the children at the time of assessment was 16.7 years; approximately half were male.

A total of 50,863 children (2.26%) were born to mothers who had been diagnosed with autoimmune diseases before childbirth. During the follow-up period, 5,460 children of mothers with autoimmune diseases and 303,092 children of mothers without autoimmune diseases were diagnosed with a mental disorder (10.73% vs. 13.76%), according to the researchers.

The risk of being diagnosed with a mental disorder was significantly higher among children of mothers with any autoimmune disease (hazard ratio [HR,], 1.16), with an incidence of 9.38 vs. 7.91 per 1,000 person-years, the researchers reported.

The increased risk persisted when the results were classified by organ system, including connective tissue (HR, 1.11), endocrine (HR, 1.19), gastrointestinal (HR, 1.11), blood (HR, 1.10), nervous (HR, 1.17), and skin (HR, 1.19).

The five autoimmune diseases in mothers that were most commonly associated mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.

The greatest risk for children of mothers with any autoimmune disease was observed for organic conditions such as delirium, (HR, 1.54), followed by obsessive-compulsive disorder (HR, 1.42), schizophrenia (HR, 1.54), and mood problems (HR, 1.12).

Children of mothers with any autoimmune disorder also had a significantly increased risk of autism (HR, 1.21), intellectual disability (HR, 1.19), and ADHD (HR, 1.19).

The results add to evidence that activation of the maternal immune system may drive changes in the brain and behavioral problems, which has been observed in animal studies, the researchers wrote.

Potential underlying mechanisms in need of more exploration include genetic risk factors, maternal transmission of autoantibodies to the fetus during pregnancy, and the increased risk of obstetric complications, such as preterm birth, for women with autoimmune disorders that could affect mental development in children, they added.

The study findings were limited by several factors, including the lack of data on potential exacerbation of autoimmune disease activity during pregnancy and its effect on the fetus, the researchers noted. Other limitations included potential detection bias, lack of data on mental disorders in adulthood, and potential changes in diagnostic criteria over the long study period.

The results were strengthened by the use of a population-based registry, the large sample size, and ability to consider a range of confounders, the researchers said.

“This study could help acquire a comprehensive compilation of the associations between maternal autoimmune disorders diagnosed before childbirth and offspring’s mental disorders from childhood through early adulthood,” Dr. Li said in an interview.

For clinicians, Dr. Li said, the findings suggest that the offspring of mothers with autoimmune diseases may benefit from long-term surveillance for mental health disorders.

“Further studies should provide more evidence on the detailed associations of specific maternal autoimmune diseases with a full spectrum of mental disorders in offspring, and more research on underlying mechanisms is needed as well,” she said.
 

Pay early attention

M. Susan Jay, MD, an adjunct professor of pediatrics at the Medical College of Wisconsin, Milwaukee, said previous efforts to examine the association between maternal autoimmunity were hampered by study design, small samples, and self-report of disease history – problems the new research avoids.

The large patient population allowed for detailed subgroup analysis of different conditions and outcomes. Another advantage was the availability of sociodemographic and clinical information, which allowed for the elimination of confounding factors, said Dr. Jay, who was not involved in the research.

“It would be prudent to follow children of mothers with autoimmune disorders before or during pregnancy for mental health issues, and if identified clinically, to offer psychological and developmental behavioral support options,” Dr. Jay added.

The authors have reported no relevant financial relationships.

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

Mental disorders were significantly more likely in children whose mothers had one of five common autoimmune diseases, a new study found.

Previous research has linked both maternal and paternal autoimmune diseases and specific mental disorders, such as attention-deficit/hyperactivity disorder (ADHD), but most of these studies focused on specific conditions in relatively small populations. The new study included data on more than 2 million births, making it one of the largest efforts to date to examine the association, according to the researchers, whose findings were published in JAMA Network Open.

Previous evidence of the possible association between certain maternal autoimmune diseases and mental disorders in offspring has been “scattered and limited,” which “hampered an overall understanding” of the link, Fei Li, MD, the corresponding author of the study, told this news organization.

Dr. Li, of Shanghai Jiao Tong University China, and colleagues reviewed data from a Danish registry cohort of singleton births with up to 38 years of follow-up. They explored associations between a range of maternal autoimmune diseases diagnosed before childbirth and the risks of mental disorders in children in early childhood through young adulthood.

The study population included 2,254,234 births and 38,916,359 person-years. Data on mental health were collected from the Psychiatric Central Research Register and the country’s National Patient Register. The median age of the children at the time of assessment was 16.7 years; approximately half were male.

A total of 50,863 children (2.26%) were born to mothers who had been diagnosed with autoimmune diseases before childbirth. During the follow-up period, 5,460 children of mothers with autoimmune diseases and 303,092 children of mothers without autoimmune diseases were diagnosed with a mental disorder (10.73% vs. 13.76%), according to the researchers.

The risk of being diagnosed with a mental disorder was significantly higher among children of mothers with any autoimmune disease (hazard ratio [HR,], 1.16), with an incidence of 9.38 vs. 7.91 per 1,000 person-years, the researchers reported.

The increased risk persisted when the results were classified by organ system, including connective tissue (HR, 1.11), endocrine (HR, 1.19), gastrointestinal (HR, 1.11), blood (HR, 1.10), nervous (HR, 1.17), and skin (HR, 1.19).

The five autoimmune diseases in mothers that were most commonly associated mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.

The greatest risk for children of mothers with any autoimmune disease was observed for organic conditions such as delirium, (HR, 1.54), followed by obsessive-compulsive disorder (HR, 1.42), schizophrenia (HR, 1.54), and mood problems (HR, 1.12).

Children of mothers with any autoimmune disorder also had a significantly increased risk of autism (HR, 1.21), intellectual disability (HR, 1.19), and ADHD (HR, 1.19).

The results add to evidence that activation of the maternal immune system may drive changes in the brain and behavioral problems, which has been observed in animal studies, the researchers wrote.

Potential underlying mechanisms in need of more exploration include genetic risk factors, maternal transmission of autoantibodies to the fetus during pregnancy, and the increased risk of obstetric complications, such as preterm birth, for women with autoimmune disorders that could affect mental development in children, they added.

The study findings were limited by several factors, including the lack of data on potential exacerbation of autoimmune disease activity during pregnancy and its effect on the fetus, the researchers noted. Other limitations included potential detection bias, lack of data on mental disorders in adulthood, and potential changes in diagnostic criteria over the long study period.

The results were strengthened by the use of a population-based registry, the large sample size, and ability to consider a range of confounders, the researchers said.

“This study could help acquire a comprehensive compilation of the associations between maternal autoimmune disorders diagnosed before childbirth and offspring’s mental disorders from childhood through early adulthood,” Dr. Li said in an interview.

For clinicians, Dr. Li said, the findings suggest that the offspring of mothers with autoimmune diseases may benefit from long-term surveillance for mental health disorders.

“Further studies should provide more evidence on the detailed associations of specific maternal autoimmune diseases with a full spectrum of mental disorders in offspring, and more research on underlying mechanisms is needed as well,” she said.
 

Pay early attention

M. Susan Jay, MD, an adjunct professor of pediatrics at the Medical College of Wisconsin, Milwaukee, said previous efforts to examine the association between maternal autoimmunity were hampered by study design, small samples, and self-report of disease history – problems the new research avoids.

The large patient population allowed for detailed subgroup analysis of different conditions and outcomes. Another advantage was the availability of sociodemographic and clinical information, which allowed for the elimination of confounding factors, said Dr. Jay, who was not involved in the research.

“It would be prudent to follow children of mothers with autoimmune disorders before or during pregnancy for mental health issues, and if identified clinically, to offer psychological and developmental behavioral support options,” Dr. Jay added.

The authors have reported no relevant financial relationships.

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

Mental disorders were significantly more likely in children whose mothers had one of five common autoimmune diseases, a new study found.

Previous research has linked both maternal and paternal autoimmune diseases and specific mental disorders, such as attention-deficit/hyperactivity disorder (ADHD), but most of these studies focused on specific conditions in relatively small populations. The new study included data on more than 2 million births, making it one of the largest efforts to date to examine the association, according to the researchers, whose findings were published in JAMA Network Open.

Previous evidence of the possible association between certain maternal autoimmune diseases and mental disorders in offspring has been “scattered and limited,” which “hampered an overall understanding” of the link, Fei Li, MD, the corresponding author of the study, told this news organization.

Dr. Li, of Shanghai Jiao Tong University China, and colleagues reviewed data from a Danish registry cohort of singleton births with up to 38 years of follow-up. They explored associations between a range of maternal autoimmune diseases diagnosed before childbirth and the risks of mental disorders in children in early childhood through young adulthood.

The study population included 2,254,234 births and 38,916,359 person-years. Data on mental health were collected from the Psychiatric Central Research Register and the country’s National Patient Register. The median age of the children at the time of assessment was 16.7 years; approximately half were male.

A total of 50,863 children (2.26%) were born to mothers who had been diagnosed with autoimmune diseases before childbirth. During the follow-up period, 5,460 children of mothers with autoimmune diseases and 303,092 children of mothers without autoimmune diseases were diagnosed with a mental disorder (10.73% vs. 13.76%), according to the researchers.

The risk of being diagnosed with a mental disorder was significantly higher among children of mothers with any autoimmune disease (hazard ratio [HR,], 1.16), with an incidence of 9.38 vs. 7.91 per 1,000 person-years, the researchers reported.

The increased risk persisted when the results were classified by organ system, including connective tissue (HR, 1.11), endocrine (HR, 1.19), gastrointestinal (HR, 1.11), blood (HR, 1.10), nervous (HR, 1.17), and skin (HR, 1.19).

The five autoimmune diseases in mothers that were most commonly associated mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.

The greatest risk for children of mothers with any autoimmune disease was observed for organic conditions such as delirium, (HR, 1.54), followed by obsessive-compulsive disorder (HR, 1.42), schizophrenia (HR, 1.54), and mood problems (HR, 1.12).

Children of mothers with any autoimmune disorder also had a significantly increased risk of autism (HR, 1.21), intellectual disability (HR, 1.19), and ADHD (HR, 1.19).

The results add to evidence that activation of the maternal immune system may drive changes in the brain and behavioral problems, which has been observed in animal studies, the researchers wrote.

Potential underlying mechanisms in need of more exploration include genetic risk factors, maternal transmission of autoantibodies to the fetus during pregnancy, and the increased risk of obstetric complications, such as preterm birth, for women with autoimmune disorders that could affect mental development in children, they added.

The study findings were limited by several factors, including the lack of data on potential exacerbation of autoimmune disease activity during pregnancy and its effect on the fetus, the researchers noted. Other limitations included potential detection bias, lack of data on mental disorders in adulthood, and potential changes in diagnostic criteria over the long study period.

The results were strengthened by the use of a population-based registry, the large sample size, and ability to consider a range of confounders, the researchers said.

“This study could help acquire a comprehensive compilation of the associations between maternal autoimmune disorders diagnosed before childbirth and offspring’s mental disorders from childhood through early adulthood,” Dr. Li said in an interview.

For clinicians, Dr. Li said, the findings suggest that the offspring of mothers with autoimmune diseases may benefit from long-term surveillance for mental health disorders.

“Further studies should provide more evidence on the detailed associations of specific maternal autoimmune diseases with a full spectrum of mental disorders in offspring, and more research on underlying mechanisms is needed as well,” she said.
 

Pay early attention

M. Susan Jay, MD, an adjunct professor of pediatrics at the Medical College of Wisconsin, Milwaukee, said previous efforts to examine the association between maternal autoimmunity were hampered by study design, small samples, and self-report of disease history – problems the new research avoids.

The large patient population allowed for detailed subgroup analysis of different conditions and outcomes. Another advantage was the availability of sociodemographic and clinical information, which allowed for the elimination of confounding factors, said Dr. Jay, who was not involved in the research.

“It would be prudent to follow children of mothers with autoimmune disorders before or during pregnancy for mental health issues, and if identified clinically, to offer psychological and developmental behavioral support options,” Dr. Jay added.

The authors have reported no relevant financial relationships.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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

The Food and Drug Administration has approved upadacitinib (Rinvoq) as an oral treatment for active ankylosing spondylitis in adults, its manufacturer AbbVie announced April 29.

Upadacitinib, a selective and reversible Janus kinase inhibitor, is the second drug in its class to be FDA approved for ankylosing spondylitis, after tofacitinib (Xeljanz) in December.

Upadacitinib is now indicated for patients with active ankylosing spondylitis (AS) who have had an insufficient response or intolerance with one or more tumor necrosis factor (TNF) blockers. Upadacitinib is already approved by the FDA for adults with active psoriatic arthritis, moderately to severely active rheumatoid arthritis, and moderately to severely active ulcerative colitis who have had an insufficient response or intolerance with one or more TNF inhibitors. It also has been approved for adults and pediatric patients 12 years of age and older with refractory, moderate to severe atopic dermatitis.

The European Medicines Agency gave marketing approval for upadacitinib in adults with active AS in January 2021.

Two main clinical studies form the basis for the FDA’s approval decision. The phase 3 SELECT-AXIS 2 clinical trial involved patients with an inadequate response or intolerance to one or two biologic disease-modifying antirheumatic drugs (bDMARDs). A total of 44.5% patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of at least 40% improvement in Assessment in Spondyloarthritis International Society response criteria (ASAS 40) at 14 weeks, compared against 18.2% with placebo.

The second study, the phase 2/3 SELECT-AXIS 1 clinical trial, tested upadacitinib in patients who had never taken bDMARDs and had an inadequate response or intolerance to at least two NSAIDs. In this study, significantly more patients randomly assigned to 15 mg upadacitinib achieved ASAS 40 at 14 weeks, compared with placebo (51% vs. 26%).

Patients randomly assigned to upadacitinib also showed significant improvements in signs and symptoms of AS, as well as improvements in physical function and disease activity, compared with placebo, after 14 weeks. The safety profile for patients with AS treated with upadacitinib was similar to that seen in studies of patients with rheumatoid arthritis or psoriatic arthritis. Potential severe side effects include increased risk for death in patients aged 50 years and older with at least one cardiovascular risk factor; increased risk of serious infections, such as tuberculosis; and increased risk of certain cancers, according to the company statement.

Read the complete prescribing information here.

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

Results of a meta-analysis carried out by a French team indicate that there is a link between a father’s or mother’s autoimmune disease and their children’s risk of developing certain neurodevelopmental disorders (autism spectrum disorder [ASD] and attention-deficit/hyperactivity disorder). This meta-analysis is the first to separately explore the link between a father’s or mother’s autoimmune disease and the onset of neurodevelopmental disorders in their children.

According to its authors, these associations may result from exposure to environmental factors that contribute to autoimmune disorders, such as exposure to pollutants or cigarette smoke, and/or genetic predisposition, including genes relating to cytokines or to the HLA system.

Research is needed to determine the pathophysiologic links between these associations. This study suggests that there could be a shared mechanism between both parents, even though the maternal route seems to constitute an additional excess risk.
 

Why is this important?

Neurodevelopmental disorders are said to occur because of a close interrelationship between a person’s genes and environment. Immune-mediated adverse reactions may play an important role in triggering such disorders, as has been shown in associated epidemiologic studies and in animal studies. Autoimmune and autoinflammatory disorders are effectively characterized by the activation of the immune system, the circulation of autoantibodies, and the secretion of cytokines that are harmful to certain tissues.

Some relevant studies suggest a link between autoimmune disorders in the family or in the mother and the onset of neurodevelopmental disorders in their children. However, none of the studies have distinguished the influence of each of the parents so as to provide data that can be used to assess whether this association is more likely to be direct, and thus established during pregnancy, or rather genetic or environmental.
 

Main findings

Overall, the meta-analysis involved 14 studies that included 845,411 mothers and 601,148 fathers with an autoimmune disease, 4,984,965 control mothers and 4,992,854 control fathers. There were 182,927 children with neurodevelopmental disorders and 14,168,474 with no such diagnosis.

Globally, autoimmune diseases in mothers (adjusted odds ratio, 1.27 [1.03-1.57]; P = .02; I2 = 65%) and in fathers (AOR, 1.18 [1.07-1.30]; P = .01; I2 = 15.5%) are associated with a diagnosis of ASD in children. Similarly, they are associated with an increased risk of ADHD in children (AOR, 1.31 [1.11-1.55]; P = .001; I2 = 93% and AOR, 1.14 [1.10-1.17]; P < .0001; I2 = 0%, respectively, for mothers and fathers).

In mothers, type 1 diabetes (AOR, 1.60 [1.18-2.18]; P = .002; I2 = 0%), psoriasis (AOR, 1.45 [1.14-1.85]; P = .002; I2 = 0%), and rheumatoid arthritis (AOR, 1.38 [1.14-1.68]; P = .001; I2 = 0.8%) were associated with a risk of ASD in children. These three conditions also predisposed children to the risk of ADHD (AOR, 1.36 [1.24-1.52]; 1.41 [1.29-1.54]; and 1.32 [1.25-1.40], respectively, all P < .0001).

In fathers, type 1 diabetes considered in isolation was associated with a risk of ASD and ADHD in children (AOR, 1.42 [1.10-1.83] and 1.19 [1.08-1.31], respectively), while psoriasis (AOR, 1.18 [1.12-1.24]; P < .0001) is associated with a risk of ADHD in children.

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

Results of a meta-analysis carried out by a French team indicate that there is a link between a father’s or mother’s autoimmune disease and their children’s risk of developing certain neurodevelopmental disorders (autism spectrum disorder [ASD] and attention-deficit/hyperactivity disorder). This meta-analysis is the first to separately explore the link between a father’s or mother’s autoimmune disease and the onset of neurodevelopmental disorders in their children.

According to its authors, these associations may result from exposure to environmental factors that contribute to autoimmune disorders, such as exposure to pollutants or cigarette smoke, and/or genetic predisposition, including genes relating to cytokines or to the HLA system.

Research is needed to determine the pathophysiologic links between these associations. This study suggests that there could be a shared mechanism between both parents, even though the maternal route seems to constitute an additional excess risk.
 

Why is this important?

Neurodevelopmental disorders are said to occur because of a close interrelationship between a person’s genes and environment. Immune-mediated adverse reactions may play an important role in triggering such disorders, as has been shown in associated epidemiologic studies and in animal studies. Autoimmune and autoinflammatory disorders are effectively characterized by the activation of the immune system, the circulation of autoantibodies, and the secretion of cytokines that are harmful to certain tissues.

Some relevant studies suggest a link between autoimmune disorders in the family or in the mother and the onset of neurodevelopmental disorders in their children. However, none of the studies have distinguished the influence of each of the parents so as to provide data that can be used to assess whether this association is more likely to be direct, and thus established during pregnancy, or rather genetic or environmental.
 

Main findings

Overall, the meta-analysis involved 14 studies that included 845,411 mothers and 601,148 fathers with an autoimmune disease, 4,984,965 control mothers and 4,992,854 control fathers. There were 182,927 children with neurodevelopmental disorders and 14,168,474 with no such diagnosis.

Globally, autoimmune diseases in mothers (adjusted odds ratio, 1.27 [1.03-1.57]; P = .02; I2 = 65%) and in fathers (AOR, 1.18 [1.07-1.30]; P = .01; I2 = 15.5%) are associated with a diagnosis of ASD in children. Similarly, they are associated with an increased risk of ADHD in children (AOR, 1.31 [1.11-1.55]; P = .001; I2 = 93% and AOR, 1.14 [1.10-1.17]; P < .0001; I2 = 0%, respectively, for mothers and fathers).

In mothers, type 1 diabetes (AOR, 1.60 [1.18-2.18]; P = .002; I2 = 0%), psoriasis (AOR, 1.45 [1.14-1.85]; P = .002; I2 = 0%), and rheumatoid arthritis (AOR, 1.38 [1.14-1.68]; P = .001; I2 = 0.8%) were associated with a risk of ASD in children. These three conditions also predisposed children to the risk of ADHD (AOR, 1.36 [1.24-1.52]; 1.41 [1.29-1.54]; and 1.32 [1.25-1.40], respectively, all P < .0001).

In fathers, type 1 diabetes considered in isolation was associated with a risk of ASD and ADHD in children (AOR, 1.42 [1.10-1.83] and 1.19 [1.08-1.31], respectively), while psoriasis (AOR, 1.18 [1.12-1.24]; P < .0001) is associated with a risk of ADHD in children.

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

Results of a meta-analysis carried out by a French team indicate that there is a link between a father’s or mother’s autoimmune disease and their children’s risk of developing certain neurodevelopmental disorders (autism spectrum disorder [ASD] and attention-deficit/hyperactivity disorder). This meta-analysis is the first to separately explore the link between a father’s or mother’s autoimmune disease and the onset of neurodevelopmental disorders in their children.

According to its authors, these associations may result from exposure to environmental factors that contribute to autoimmune disorders, such as exposure to pollutants or cigarette smoke, and/or genetic predisposition, including genes relating to cytokines or to the HLA system.

Research is needed to determine the pathophysiologic links between these associations. This study suggests that there could be a shared mechanism between both parents, even though the maternal route seems to constitute an additional excess risk.
 

Why is this important?

Neurodevelopmental disorders are said to occur because of a close interrelationship between a person’s genes and environment. Immune-mediated adverse reactions may play an important role in triggering such disorders, as has been shown in associated epidemiologic studies and in animal studies. Autoimmune and autoinflammatory disorders are effectively characterized by the activation of the immune system, the circulation of autoantibodies, and the secretion of cytokines that are harmful to certain tissues.

Some relevant studies suggest a link between autoimmune disorders in the family or in the mother and the onset of neurodevelopmental disorders in their children. However, none of the studies have distinguished the influence of each of the parents so as to provide data that can be used to assess whether this association is more likely to be direct, and thus established during pregnancy, or rather genetic or environmental.
 

Main findings

Overall, the meta-analysis involved 14 studies that included 845,411 mothers and 601,148 fathers with an autoimmune disease, 4,984,965 control mothers and 4,992,854 control fathers. There were 182,927 children with neurodevelopmental disorders and 14,168,474 with no such diagnosis.

Globally, autoimmune diseases in mothers (adjusted odds ratio, 1.27 [1.03-1.57]; P = .02; I2 = 65%) and in fathers (AOR, 1.18 [1.07-1.30]; P = .01; I2 = 15.5%) are associated with a diagnosis of ASD in children. Similarly, they are associated with an increased risk of ADHD in children (AOR, 1.31 [1.11-1.55]; P = .001; I2 = 93% and AOR, 1.14 [1.10-1.17]; P < .0001; I2 = 0%, respectively, for mothers and fathers).

In mothers, type 1 diabetes (AOR, 1.60 [1.18-2.18]; P = .002; I2 = 0%), psoriasis (AOR, 1.45 [1.14-1.85]; P = .002; I2 = 0%), and rheumatoid arthritis (AOR, 1.38 [1.14-1.68]; P = .001; I2 = 0.8%) were associated with a risk of ASD in children. These three conditions also predisposed children to the risk of ADHD (AOR, 1.36 [1.24-1.52]; 1.41 [1.29-1.54]; and 1.32 [1.25-1.40], respectively, all P < .0001).

In fathers, type 1 diabetes considered in isolation was associated with a risk of ASD and ADHD in children (AOR, 1.42 [1.10-1.83] and 1.19 [1.08-1.31], respectively), while psoriasis (AOR, 1.18 [1.12-1.24]; P < .0001) is associated with a risk of ADHD in children.

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

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

Women with systemic lupus erythematosus (SLE) experience worse outcomes after an acute stroke than does the general population, but men with SLE do not, according to an analysis of the U.S. National Inpatient Sample presented at the annual meeting of the British Society for Rheumatology.

In a study of more than 1.5 million cases of acute stroke recorded in the United States between 2015 and 2018, women with SLE were more likely to be hospitalized for longer and less likely to be routinely discharged into their home environment than were those without SLE. No such association was found for men with SLE.

“The findings imply that primary stroke prevention is of utmost importance, especially in females with SLE,” said Sona Jesenakova, a fourth-year medical student at the University of Aberdeen (Scotland).

“There might be a need to explore more effective and targeted treatment strategies to try and minimize these excessive adverse acute stroke outcomes, especially in females with SLE suffering from stroke,” she suggested.

“Even though males form only a minority of the SLE patient population, some studies have shown that they are prone to suffer from worse disease outcomes,” Ms. Jesenakova said.

Importantly, “male sex has been identified as a risk factor for death early in the course of SLE,” she added, highlighting that sex differences do seem to exist in SLE.

Stroke is an important outcome to look at because people with SLE are known to be at higher risk for developing atherosclerosis, which is a widely known risk factor for ischemic stroke, and with antiphospholipid antibody positivity and uncontrolled disease activity, that risk can be increased. A meta-analysis of older studies has suggested that the risk for death after a stroke is 68% higher in people with SLE than in those without.

To examine the risk for death and other in-hospital outcomes in a more contemporary population, Ms. Jesenakova and associates used data from the National Inpatient Sample, a large, publicly available database that contains inpatient health care information from across the United States. Their sample population consisted of 1,581,430 individuals who had been hospitalized for stroke. Of these, there were 6,100 women and 940 men who had SLE; the remainder served as the ‘no-SLE’ control population.

As might be expected, patients with SLE were about 10 years younger than those without SLE; the median age of women and men with SLE and those without SLE were a respective 60, 61, and 71 years.

There was no difference in the type of stroke between the SLE and no-SLE groups; most had an ischemic stroke (around 89%) rather than a hemorrhagic stroke (around 11%).

The researchers analyzed three key outcomes: mortality at discharge, hospitalization prolonged to a stay of more than 4 days, and routine home discharge, meaning that the patient was able to be discharged home versus more specialist facilities such as a nursing home.

They conducted a multivariate analysis with adjustments made for potential confounding factors such as age, ethnicity, type of stroke, and revascularization treatment. Comorbidities, including major cardiovascular disease, were also accounted for.

Although women with SLE were 21% more likely to die than patients without SLE, men with SLE were 24% less likely to die than was the no-SLE population. However, these differences were not statistically significant.

Women with SLE were 20% more likely to have a prolonged hospital stay and 28% less likely to have a routine home discharge, compared with patients who did not have SLE. The 95% confidence intervals were statistically significant, which was not seen when comparing the same outcomes in men with SLE (odds ratios of 1.06 and 1.18, respectively).

“As for males, even though we didn’t find anything of statistical significance, we have to bear in mind that the sample we had was quite small, and thus these results need to be interpreted with caution,” Ms. Jesenakova said. “We also think that we identified a gap in the current knowledge, and as such, further research is needed to help us understand the influence of male sex on acute stroke outcomes in patients with comorbid SLE.”

The researchers performed a secondary analysis looking at the use of revascularization treatments for ischemic stroke and found that there were no differences between individuals with and without SLE. This analysis considered the use of intravenous thrombolysis and endovascular thrombectomy in just over 1.4 million cases but did not look at sex-specific differences.

Ms. Jesenakova had no conflicts of interest to disclose.

Considerable uncertainty surrounds whether people with axial spondyloarthritis (axSpA) who are treated with biologic drugs have an increased risk for developing inflammatory bowel disease (IBD) that is higher than if they receive other treatments, according to data reported at the annual meeting of the British Society for Rheumatology.

“We noticed two patterns,” Gary Macfarlane, MD, PhD, Dsc, of the University of Aberdeen (Scotland) said in presenting findings from an analysis of the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) and a meta-analysis of available studies.

copyright varaphoto/Thinkstock

There was a “large excess risk in observational studies associated with biologic therapies, which was not replicated in RCTs [randomized, controlled trials],” he said, “and trials under extensions suggested a small absolute increased risk associated with etanercept and with [interleukin]-17 [inhibitors], although again with considerable uncertainty.”

While these data make it difficult to draw any firm conclusions, “we should be reassured that the patient groups receiving these specific biologics in routine clinical care have not demonstrated an excess risk of IBD,” Dr. Macfarlane told delegates at the meeting.
 

Addressing clinical questions

IBD is a known extra-articular manifestation of axSpA, with an estimated prevalence of about 7%, according to a 2015 meta-analysis of 69 studies involving more than 30,000 patients.

The idea that people being treated with biologics may be at higher risk for developing IBD than those taking other treatments was suggested by the results of a large (n = 80,326) Danish study in which patients who were treated with an anti–tumor necrosis factor (TNF)–alpha medication were found to be more likely to develop de novo ulcerative colitis or Crohn’s disease than were patients who did not receive biologics.

Notably, the risk for IBD seemed higher with etanercept than with other anti–TNF-alpha agents, such as infliximab and adalimumab.

The aim of the analyses that Dr. Macfarlane presented was therefore to see if there was a difference in IBD risk among patients treated with biologic agents versus other agents, and if etanercept really did pose a greater cause for concern.

“The reason that we are asking this question is that a clinician called us up and asked us if we had any data on it,” Dr. Macfarlane said. “I think that’s really important to say that one of the things the registers are designed for are to answer questions that clinicians may have.”
 

Looking for new-onset IBD

Although no longer recruiting patients, the BSRBR-AS provides a wealth of data on the real-life management of patients with axSpA who were or were not taking a biologic. Patients were recruited into the register between 2012 and 2017, with follow-up until 2018. Data analyses are still ongoing and expected to continue for another couple of years.

The current analysis of data from the BSRBR-AS included patients who did not already have IBD at enrollment into the register, and patients who had been treated with a biologic could have been treated only with a single agent. Of just over 1,800 eligible patients, 793 had been treated with a biologic and 1,058 had been given nonbiologic treatment.

As expected, there were some differences between the two groups of patients studied, with biologic-treated patients having a younger age than non–biologic-treated patients. Those who took a biologic also had higher disease activity, inflammatory scores, and rates of psoriasis, enthesitis, and peripheral joint involvement.

Incidence rates for new-onset IBD per 1,000 person-years of treatment were calculated as 17 (95% confidence interval, 10.7-25.8) for patients taking a biologic and 5.1 (95% CI, 2.7-8.7) for those not taking a biologic, giving an incidence rate difference of 11.9 (95% CI, 4.3-19.6).

There was some observed differences in the incidence of new-onset IBD associated with specific agents. Etanercept did not have a higher rate (13.9/1,000 patient-years; 95% CI, 5.1-30.3) than did other agents. But in comparison, the incidence of new-onset IBD for adalimumab was 20.4 (95% CI, 11.7-33.1) and zero for other anti-TNF agents such as certolizumab pegol and infliximab, although the duration of exposure to these drugs was much lower.

The IRDs for etanercept versus nonbiologic treatment and versus other anti-TNFs were 8.8 (95% CI, –2.7 to 20.3) and -6.4 (95% CI, –21.3 to 8.5), but with “considerable uncertainty” because the confidence intervals were very wide.
 

Uncertainty not helped by meta-analysis

“Given the uncertainty associated with the results from BSRBR-AS, we decided to undertake a meta-analysis to try to accumulate other data that could help us answer this question,” Dr. Macfarlane explained.

However, this didn’t really help clarify things because combining BSRBR-AS data with the results of a couple of observational studies suggested that the odds of of IBD doubled with any biologic treatment versus no biologic treatment (odds ratio, 2.19), and a 2.5-fold higher likelihood considering etanercept versus no biologic treatment, but no difference was seen comparing etanercept to other anti-TNF agents (OR, 0.93).

When the meta-analysis was restricted to RCTs, the rate of IBD per 1,000 person-years was 3.43 for placebo, 5.64 for all biologics, 8.14 for etanercept, 2.35 for other anti-TNFs, and 7.02 for IL-17 inhibitors.

For extensions of RCTs, IBD rates per 1,000 person-years of follow-up were 2.91 for etanercept, 0.83 for other anti-TNFs, 3.61 for IL-17 inhibitors, and 2.79 for all biologics.

“There was only a small difference in IBD incidence between the biologic therapy and the placebo groups” in the RCTs and associated studies, Dr. Macfarlane said, adding that “there was a small excess incidence associated with etanercept, compared to other anti-TNF agents, and [for] IL-17 therapy, compared to nonetanercept, anti–TNF-alpha therapies.”

Of course, the different study designs and durations of exposure to the various treatments raises significant methodological issues.

“Randomized, controlled trials should provide the highest quality evidence as a result of their design and randomizing patients to treatment,” Dr. Macfarlane said. “However, their relatively short follow-up, as well as their restrictive eligibility criteria, may work against finding a difference in IBD incidence if it were to exist.”

Observational studies are very valuable in the data they can provide but are also beset with problems, such as surveillance bias and confounding by indication.

The higher risk of IBD that was observed in observational studies could be an issue with study design, or perhaps, “in routine clinical practice, rheumatologists are taking on board factors that we have not measured, that are negating any slight increased risk,” Dr. Macfarlane said.

Session chair Nicola Goodson, MBChB, PhD, of Liverpool (England) University NHS Foundation Trust, commented: “I think that could well be a very reasonable explanation, because I think as a clinician, you do tend to channel drugs away from some people and channel drugs towards others.

However, Dr. Goodson noted that there was “a glimmer” of signal coming from the RCTs.

“Methodologically, that is what you would have to take as the most robust evidence,” Dr. Macfarlane said, “but even with all the evidence available, it’s still very hard for us to quantify; that has enormous uncertainty.”

Dr. Macfarlane and Dr. Goodson had no relevant conflicts of interest to disclose. The BSRBR-AS is supported by the BSR, which receives funds to support the registry from Pfizer, AbbVie, and UCB.

Considerable uncertainty surrounds whether people with axial spondyloarthritis (axSpA) who are treated with biologic drugs have an increased risk for developing inflammatory bowel disease (IBD) that is higher than if they receive other treatments, according to data reported at the annual meeting of the British Society for Rheumatology.

“We noticed two patterns,” Gary Macfarlane, MD, PhD, Dsc, of the University of Aberdeen (Scotland) said in presenting findings from an analysis of the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) and a meta-analysis of available studies.

copyright varaphoto/Thinkstock

There was a “large excess risk in observational studies associated with biologic therapies, which was not replicated in RCTs [randomized, controlled trials],” he said, “and trials under extensions suggested a small absolute increased risk associated with etanercept and with [interleukin]-17 [inhibitors], although again with considerable uncertainty.”

While these data make it difficult to draw any firm conclusions, “we should be reassured that the patient groups receiving these specific biologics in routine clinical care have not demonstrated an excess risk of IBD,” Dr. Macfarlane told delegates at the meeting.
 

Addressing clinical questions

IBD is a known extra-articular manifestation of axSpA, with an estimated prevalence of about 7%, according to a 2015 meta-analysis of 69 studies involving more than 30,000 patients.

The idea that people being treated with biologics may be at higher risk for developing IBD than those taking other treatments was suggested by the results of a large (n = 80,326) Danish study in which patients who were treated with an anti–tumor necrosis factor (TNF)–alpha medication were found to be more likely to develop de novo ulcerative colitis or Crohn’s disease than were patients who did not receive biologics.

Notably, the risk for IBD seemed higher with etanercept than with other anti–TNF-alpha agents, such as infliximab and adalimumab.

The aim of the analyses that Dr. Macfarlane presented was therefore to see if there was a difference in IBD risk among patients treated with biologic agents versus other agents, and if etanercept really did pose a greater cause for concern.

“The reason that we are asking this question is that a clinician called us up and asked us if we had any data on it,” Dr. Macfarlane said. “I think that’s really important to say that one of the things the registers are designed for are to answer questions that clinicians may have.”
 

Looking for new-onset IBD

Although no longer recruiting patients, the BSRBR-AS provides a wealth of data on the real-life management of patients with axSpA who were or were not taking a biologic. Patients were recruited into the register between 2012 and 2017, with follow-up until 2018. Data analyses are still ongoing and expected to continue for another couple of years.

The current analysis of data from the BSRBR-AS included patients who did not already have IBD at enrollment into the register, and patients who had been treated with a biologic could have been treated only with a single agent. Of just over 1,800 eligible patients, 793 had been treated with a biologic and 1,058 had been given nonbiologic treatment.

As expected, there were some differences between the two groups of patients studied, with biologic-treated patients having a younger age than non–biologic-treated patients. Those who took a biologic also had higher disease activity, inflammatory scores, and rates of psoriasis, enthesitis, and peripheral joint involvement.

Incidence rates for new-onset IBD per 1,000 person-years of treatment were calculated as 17 (95% confidence interval, 10.7-25.8) for patients taking a biologic and 5.1 (95% CI, 2.7-8.7) for those not taking a biologic, giving an incidence rate difference of 11.9 (95% CI, 4.3-19.6).

There was some observed differences in the incidence of new-onset IBD associated with specific agents. Etanercept did not have a higher rate (13.9/1,000 patient-years; 95% CI, 5.1-30.3) than did other agents. But in comparison, the incidence of new-onset IBD for adalimumab was 20.4 (95% CI, 11.7-33.1) and zero for other anti-TNF agents such as certolizumab pegol and infliximab, although the duration of exposure to these drugs was much lower.

The IRDs for etanercept versus nonbiologic treatment and versus other anti-TNFs were 8.8 (95% CI, –2.7 to 20.3) and -6.4 (95% CI, –21.3 to 8.5), but with “considerable uncertainty” because the confidence intervals were very wide.
 

Uncertainty not helped by meta-analysis

“Given the uncertainty associated with the results from BSRBR-AS, we decided to undertake a meta-analysis to try to accumulate other data that could help us answer this question,” Dr. Macfarlane explained.

However, this didn’t really help clarify things because combining BSRBR-AS data with the results of a couple of observational studies suggested that the odds of of IBD doubled with any biologic treatment versus no biologic treatment (odds ratio, 2.19), and a 2.5-fold higher likelihood considering etanercept versus no biologic treatment, but no difference was seen comparing etanercept to other anti-TNF agents (OR, 0.93).

When the meta-analysis was restricted to RCTs, the rate of IBD per 1,000 person-years was 3.43 for placebo, 5.64 for all biologics, 8.14 for etanercept, 2.35 for other anti-TNFs, and 7.02 for IL-17 inhibitors.

For extensions of RCTs, IBD rates per 1,000 person-years of follow-up were 2.91 for etanercept, 0.83 for other anti-TNFs, 3.61 for IL-17 inhibitors, and 2.79 for all biologics.

“There was only a small difference in IBD incidence between the biologic therapy and the placebo groups” in the RCTs and associated studies, Dr. Macfarlane said, adding that “there was a small excess incidence associated with etanercept, compared to other anti-TNF agents, and [for] IL-17 therapy, compared to nonetanercept, anti–TNF-alpha therapies.”

Of course, the different study designs and durations of exposure to the various treatments raises significant methodological issues.

“Randomized, controlled trials should provide the highest quality evidence as a result of their design and randomizing patients to treatment,” Dr. Macfarlane said. “However, their relatively short follow-up, as well as their restrictive eligibility criteria, may work against finding a difference in IBD incidence if it were to exist.”

Observational studies are very valuable in the data they can provide but are also beset with problems, such as surveillance bias and confounding by indication.

The higher risk of IBD that was observed in observational studies could be an issue with study design, or perhaps, “in routine clinical practice, rheumatologists are taking on board factors that we have not measured, that are negating any slight increased risk,” Dr. Macfarlane said.

Session chair Nicola Goodson, MBChB, PhD, of Liverpool (England) University NHS Foundation Trust, commented: “I think that could well be a very reasonable explanation, because I think as a clinician, you do tend to channel drugs away from some people and channel drugs towards others.

However, Dr. Goodson noted that there was “a glimmer” of signal coming from the RCTs.

“Methodologically, that is what you would have to take as the most robust evidence,” Dr. Macfarlane said, “but even with all the evidence available, it’s still very hard for us to quantify; that has enormous uncertainty.”

Dr. Macfarlane and Dr. Goodson had no relevant conflicts of interest to disclose. The BSRBR-AS is supported by the BSR, which receives funds to support the registry from Pfizer, AbbVie, and UCB.

Considerable uncertainty surrounds whether people with axial spondyloarthritis (axSpA) who are treated with biologic drugs have an increased risk for developing inflammatory bowel disease (IBD) that is higher than if they receive other treatments, according to data reported at the annual meeting of the British Society for Rheumatology.

“We noticed two patterns,” Gary Macfarlane, MD, PhD, Dsc, of the University of Aberdeen (Scotland) said in presenting findings from an analysis of the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) and a meta-analysis of available studies.

copyright varaphoto/Thinkstock

There was a “large excess risk in observational studies associated with biologic therapies, which was not replicated in RCTs [randomized, controlled trials],” he said, “and trials under extensions suggested a small absolute increased risk associated with etanercept and with [interleukin]-17 [inhibitors], although again with considerable uncertainty.”

While these data make it difficult to draw any firm conclusions, “we should be reassured that the patient groups receiving these specific biologics in routine clinical care have not demonstrated an excess risk of IBD,” Dr. Macfarlane told delegates at the meeting.
 

Addressing clinical questions

IBD is a known extra-articular manifestation of axSpA, with an estimated prevalence of about 7%, according to a 2015 meta-analysis of 69 studies involving more than 30,000 patients.

The idea that people being treated with biologics may be at higher risk for developing IBD than those taking other treatments was suggested by the results of a large (n = 80,326) Danish study in which patients who were treated with an anti–tumor necrosis factor (TNF)–alpha medication were found to be more likely to develop de novo ulcerative colitis or Crohn’s disease than were patients who did not receive biologics.

Notably, the risk for IBD seemed higher with etanercept than with other anti–TNF-alpha agents, such as infliximab and adalimumab.

The aim of the analyses that Dr. Macfarlane presented was therefore to see if there was a difference in IBD risk among patients treated with biologic agents versus other agents, and if etanercept really did pose a greater cause for concern.

“The reason that we are asking this question is that a clinician called us up and asked us if we had any data on it,” Dr. Macfarlane said. “I think that’s really important to say that one of the things the registers are designed for are to answer questions that clinicians may have.”
 

Looking for new-onset IBD

Although no longer recruiting patients, the BSRBR-AS provides a wealth of data on the real-life management of patients with axSpA who were or were not taking a biologic. Patients were recruited into the register between 2012 and 2017, with follow-up until 2018. Data analyses are still ongoing and expected to continue for another couple of years.

The current analysis of data from the BSRBR-AS included patients who did not already have IBD at enrollment into the register, and patients who had been treated with a biologic could have been treated only with a single agent. Of just over 1,800 eligible patients, 793 had been treated with a biologic and 1,058 had been given nonbiologic treatment.

As expected, there were some differences between the two groups of patients studied, with biologic-treated patients having a younger age than non–biologic-treated patients. Those who took a biologic also had higher disease activity, inflammatory scores, and rates of psoriasis, enthesitis, and peripheral joint involvement.

Incidence rates for new-onset IBD per 1,000 person-years of treatment were calculated as 17 (95% confidence interval, 10.7-25.8) for patients taking a biologic and 5.1 (95% CI, 2.7-8.7) for those not taking a biologic, giving an incidence rate difference of 11.9 (95% CI, 4.3-19.6).

There was some observed differences in the incidence of new-onset IBD associated with specific agents. Etanercept did not have a higher rate (13.9/1,000 patient-years; 95% CI, 5.1-30.3) than did other agents. But in comparison, the incidence of new-onset IBD for adalimumab was 20.4 (95% CI, 11.7-33.1) and zero for other anti-TNF agents such as certolizumab pegol and infliximab, although the duration of exposure to these drugs was much lower.

The IRDs for etanercept versus nonbiologic treatment and versus other anti-TNFs were 8.8 (95% CI, –2.7 to 20.3) and -6.4 (95% CI, –21.3 to 8.5), but with “considerable uncertainty” because the confidence intervals were very wide.
 

Uncertainty not helped by meta-analysis

“Given the uncertainty associated with the results from BSRBR-AS, we decided to undertake a meta-analysis to try to accumulate other data that could help us answer this question,” Dr. Macfarlane explained.

However, this didn’t really help clarify things because combining BSRBR-AS data with the results of a couple of observational studies suggested that the odds of of IBD doubled with any biologic treatment versus no biologic treatment (odds ratio, 2.19), and a 2.5-fold higher likelihood considering etanercept versus no biologic treatment, but no difference was seen comparing etanercept to other anti-TNF agents (OR, 0.93).

When the meta-analysis was restricted to RCTs, the rate of IBD per 1,000 person-years was 3.43 for placebo, 5.64 for all biologics, 8.14 for etanercept, 2.35 for other anti-TNFs, and 7.02 for IL-17 inhibitors.

For extensions of RCTs, IBD rates per 1,000 person-years of follow-up were 2.91 for etanercept, 0.83 for other anti-TNFs, 3.61 for IL-17 inhibitors, and 2.79 for all biologics.

“There was only a small difference in IBD incidence between the biologic therapy and the placebo groups” in the RCTs and associated studies, Dr. Macfarlane said, adding that “there was a small excess incidence associated with etanercept, compared to other anti-TNF agents, and [for] IL-17 therapy, compared to nonetanercept, anti–TNF-alpha therapies.”

Of course, the different study designs and durations of exposure to the various treatments raises significant methodological issues.

“Randomized, controlled trials should provide the highest quality evidence as a result of their design and randomizing patients to treatment,” Dr. Macfarlane said. “However, their relatively short follow-up, as well as their restrictive eligibility criteria, may work against finding a difference in IBD incidence if it were to exist.”

Observational studies are very valuable in the data they can provide but are also beset with problems, such as surveillance bias and confounding by indication.

The higher risk of IBD that was observed in observational studies could be an issue with study design, or perhaps, “in routine clinical practice, rheumatologists are taking on board factors that we have not measured, that are negating any slight increased risk,” Dr. Macfarlane said.

Session chair Nicola Goodson, MBChB, PhD, of Liverpool (England) University NHS Foundation Trust, commented: “I think that could well be a very reasonable explanation, because I think as a clinician, you do tend to channel drugs away from some people and channel drugs towards others.

However, Dr. Goodson noted that there was “a glimmer” of signal coming from the RCTs.

“Methodologically, that is what you would have to take as the most robust evidence,” Dr. Macfarlane said, “but even with all the evidence available, it’s still very hard for us to quantify; that has enormous uncertainty.”

Dr. Macfarlane and Dr. Goodson had no relevant conflicts of interest to disclose. The BSRBR-AS is supported by the BSR, which receives funds to support the registry from Pfizer, AbbVie, and UCB.

American patients with psoriatic arthritis (PsA) and psoriasis who received the interleukin-17A inhibitor secukinumab (Cosentyx) as their first biologic treatment achieved the best response rate with a 300-mg dose regimen when compared with placebo, and those who up-titrated to 300 mg from the lower approved dose of 150 mg also saw benefits obtained at that level.

Researchers conducted a postmarketing trial of secukinumab in patients at U.S. centers, called CHOICE, after it was approved for psoriasis and PsA in 2015 and 2016 based on trials mainly conducted outside of the United States. The American patients in those studies “had a baseline clinical profile indicating harder-to-treat disease than the total study population, including higher body mass index (BMI), higher tender and swollen joint counts, increased prevalence of enthesitis and dactylitis, and more tumor necrosis factor inhibitor (TNFi) experience,” Tien Q. Nguyen, MD, a dermatologist in private practice in Irvine, Calif., and colleagues wrote in the Journal of Rheumatology.

In order to get a better sense of how secukinumab performs in U.S. patients who have not been treated with biologics, the researchers conducted the multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 4 CHOICE trial. It recruited patients for about 26 months at 67 U.S. centers during 2016-2018. The 258 patients randomized in the study to 300 mg (n = 103), 150 mg secukinumab (n = 103), or placebo (n = 52) had a mean time since PsA diagnosis of 3.0-3.9 years and all had a mean BMI of greater than 30 kg/m², with dactylitis present in 48% and enthesitis in 73%. About one-third were taking methotrexate at baseline.

At week 16, patients taking secukinumab 300 mg were about 3.5 times more likely to have 20% improvement in American College of Rheumatology response criteria than with placebo (51.5% vs. 23.1%), whereas the response rate with 150 mg was not significantly different from placebo (36.9%). Rates of achieving ACR50 were significantly greater for both 300- and 150-mg doses versus placebo (28.2% and 24.3% vs. 5.8%), but only 300 mg led to a statistically significant difference in the rate of ACR70 responses, compared with placebo (17.5% vs. 1.9%).

In general, efficacy based on ACR20/50/70 responses and either remission or low disease activity on the Disease Activity in Psoriatic Arthritis index was lower among patients with less than 10 tender joints and less than 10 swollen joints at baseline. Methotrexate use at baseline did not affect ACR20 rates at week 16 in patients taking secukinumab, but the effect of methotrexate on ACR20 rates was noticeable among placebo-treated patients (38.9% vs. 14.7%). Enthesitis appeared to resolve significantly more often among patients on secukinumab, and more patients on secukinumab also had their dactylitis resolve, but the difference was not statistically significant.

Patients with psoriasis affecting more than 3% of their body surface area experienced higher response rates on the Psoriasis Area Severity Index (PASI) for 75%, 90%, and 100% skin lesion clearance than did patients taking placebo.

Patients who switched from 150 mg to 300 mg secukinumab after week 16 in the second treatment period of the trial more often achieved ACR20/50/70 responses by week 52, going from 2.4% to 65.9% of the up-titration subset for ACR20 and from 0% to 34.1% for ACR50 and to 12.2% for ACR70. Patients on placebo who switched also experienced increases in these response rates out to week 52. However, BMI above 30 kg/m² led to numerically lower ACR50, ACR70, and PASI response rates at week 52.

The researchers noted that the response rates observed in CHOICE were lower than for the pivotal trials used for Food and Drug Administration approval for PsA, which “may have been due to patients in CHOICE having higher disease activity scores at baseline, compared with TNFi-naive patients” in the pivotal trials.

The safety profile of secukinumab appeared to be no different from what has been reported previously. The researchers said that, throughout the 52-week study, the most common adverse events in patients receiving secukinumab were upper respiratory tract infection in about 13% and diarrhea in about 7%. Most adverse events were mild or moderate, with serious adverse events occurring in 9.6% of patients taking secukinumab 300 mg and in 7.8% of patients taking secukinumab 150 mg over the 52 weeks.

“Overall, the findings from CHOICE were consistent with previous studies and demonstrated that secukinumab provides significant and sustained improvements in signs and symptoms of psoriatic arthritis. Our findings suggest that secukinumab 300 mg is safe and efficacious as a first-line biologic treatment for patients with PsA. Further studies will also help determine the optimal dose of secukinumab for treating overweight patients or those with high disease activity at treatment initiation,” the authors wrote.

The study was funded by Novartis, which manufactures secukinumab. Dr. Nguyen and some coauthors reported serving as a consultant, investigator, and/or speaker for numerous pharmaceutical companies, including Novartis.

American patients with psoriatic arthritis (PsA) and psoriasis who received the interleukin-17A inhibitor secukinumab (Cosentyx) as their first biologic treatment achieved the best response rate with a 300-mg dose regimen when compared with placebo, and those who up-titrated to 300 mg from the lower approved dose of 150 mg also saw benefits obtained at that level.

Researchers conducted a postmarketing trial of secukinumab in patients at U.S. centers, called CHOICE, after it was approved for psoriasis and PsA in 2015 and 2016 based on trials mainly conducted outside of the United States. The American patients in those studies “had a baseline clinical profile indicating harder-to-treat disease than the total study population, including higher body mass index (BMI), higher tender and swollen joint counts, increased prevalence of enthesitis and dactylitis, and more tumor necrosis factor inhibitor (TNFi) experience,” Tien Q. Nguyen, MD, a dermatologist in private practice in Irvine, Calif., and colleagues wrote in the Journal of Rheumatology.

In order to get a better sense of how secukinumab performs in U.S. patients who have not been treated with biologics, the researchers conducted the multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 4 CHOICE trial. It recruited patients for about 26 months at 67 U.S. centers during 2016-2018. The 258 patients randomized in the study to 300 mg (n = 103), 150 mg secukinumab (n = 103), or placebo (n = 52) had a mean time since PsA diagnosis of 3.0-3.9 years and all had a mean BMI of greater than 30 kg/m², with dactylitis present in 48% and enthesitis in 73%. About one-third were taking methotrexate at baseline.

At week 16, patients taking secukinumab 300 mg were about 3.5 times more likely to have 20% improvement in American College of Rheumatology response criteria than with placebo (51.5% vs. 23.1%), whereas the response rate with 150 mg was not significantly different from placebo (36.9%). Rates of achieving ACR50 were significantly greater for both 300- and 150-mg doses versus placebo (28.2% and 24.3% vs. 5.8%), but only 300 mg led to a statistically significant difference in the rate of ACR70 responses, compared with placebo (17.5% vs. 1.9%).

In general, efficacy based on ACR20/50/70 responses and either remission or low disease activity on the Disease Activity in Psoriatic Arthritis index was lower among patients with less than 10 tender joints and less than 10 swollen joints at baseline. Methotrexate use at baseline did not affect ACR20 rates at week 16 in patients taking secukinumab, but the effect of methotrexate on ACR20 rates was noticeable among placebo-treated patients (38.9% vs. 14.7%). Enthesitis appeared to resolve significantly more often among patients on secukinumab, and more patients on secukinumab also had their dactylitis resolve, but the difference was not statistically significant.

Patients with psoriasis affecting more than 3% of their body surface area experienced higher response rates on the Psoriasis Area Severity Index (PASI) for 75%, 90%, and 100% skin lesion clearance than did patients taking placebo.

Patients who switched from 150 mg to 300 mg secukinumab after week 16 in the second treatment period of the trial more often achieved ACR20/50/70 responses by week 52, going from 2.4% to 65.9% of the up-titration subset for ACR20 and from 0% to 34.1% for ACR50 and to 12.2% for ACR70. Patients on placebo who switched also experienced increases in these response rates out to week 52. However, BMI above 30 kg/m² led to numerically lower ACR50, ACR70, and PASI response rates at week 52.

The researchers noted that the response rates observed in CHOICE were lower than for the pivotal trials used for Food and Drug Administration approval for PsA, which “may have been due to patients in CHOICE having higher disease activity scores at baseline, compared with TNFi-naive patients” in the pivotal trials.

The safety profile of secukinumab appeared to be no different from what has been reported previously. The researchers said that, throughout the 52-week study, the most common adverse events in patients receiving secukinumab were upper respiratory tract infection in about 13% and diarrhea in about 7%. Most adverse events were mild or moderate, with serious adverse events occurring in 9.6% of patients taking secukinumab 300 mg and in 7.8% of patients taking secukinumab 150 mg over the 52 weeks.

“Overall, the findings from CHOICE were consistent with previous studies and demonstrated that secukinumab provides significant and sustained improvements in signs and symptoms of psoriatic arthritis. Our findings suggest that secukinumab 300 mg is safe and efficacious as a first-line biologic treatment for patients with PsA. Further studies will also help determine the optimal dose of secukinumab for treating overweight patients or those with high disease activity at treatment initiation,” the authors wrote.

The study was funded by Novartis, which manufactures secukinumab. Dr. Nguyen and some coauthors reported serving as a consultant, investigator, and/or speaker for numerous pharmaceutical companies, including Novartis.

American patients with psoriatic arthritis (PsA) and psoriasis who received the interleukin-17A inhibitor secukinumab (Cosentyx) as their first biologic treatment achieved the best response rate with a 300-mg dose regimen when compared with placebo, and those who up-titrated to 300 mg from the lower approved dose of 150 mg also saw benefits obtained at that level.

Researchers conducted a postmarketing trial of secukinumab in patients at U.S. centers, called CHOICE, after it was approved for psoriasis and PsA in 2015 and 2016 based on trials mainly conducted outside of the United States. The American patients in those studies “had a baseline clinical profile indicating harder-to-treat disease than the total study population, including higher body mass index (BMI), higher tender and swollen joint counts, increased prevalence of enthesitis and dactylitis, and more tumor necrosis factor inhibitor (TNFi) experience,” Tien Q. Nguyen, MD, a dermatologist in private practice in Irvine, Calif., and colleagues wrote in the Journal of Rheumatology.

In order to get a better sense of how secukinumab performs in U.S. patients who have not been treated with biologics, the researchers conducted the multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 4 CHOICE trial. It recruited patients for about 26 months at 67 U.S. centers during 2016-2018. The 258 patients randomized in the study to 300 mg (n = 103), 150 mg secukinumab (n = 103), or placebo (n = 52) had a mean time since PsA diagnosis of 3.0-3.9 years and all had a mean BMI of greater than 30 kg/m², with dactylitis present in 48% and enthesitis in 73%. About one-third were taking methotrexate at baseline.

At week 16, patients taking secukinumab 300 mg were about 3.5 times more likely to have 20% improvement in American College of Rheumatology response criteria than with placebo (51.5% vs. 23.1%), whereas the response rate with 150 mg was not significantly different from placebo (36.9%). Rates of achieving ACR50 were significantly greater for both 300- and 150-mg doses versus placebo (28.2% and 24.3% vs. 5.8%), but only 300 mg led to a statistically significant difference in the rate of ACR70 responses, compared with placebo (17.5% vs. 1.9%).

In general, efficacy based on ACR20/50/70 responses and either remission or low disease activity on the Disease Activity in Psoriatic Arthritis index was lower among patients with less than 10 tender joints and less than 10 swollen joints at baseline. Methotrexate use at baseline did not affect ACR20 rates at week 16 in patients taking secukinumab, but the effect of methotrexate on ACR20 rates was noticeable among placebo-treated patients (38.9% vs. 14.7%). Enthesitis appeared to resolve significantly more often among patients on secukinumab, and more patients on secukinumab also had their dactylitis resolve, but the difference was not statistically significant.

Patients with psoriasis affecting more than 3% of their body surface area experienced higher response rates on the Psoriasis Area Severity Index (PASI) for 75%, 90%, and 100% skin lesion clearance than did patients taking placebo.

Patients who switched from 150 mg to 300 mg secukinumab after week 16 in the second treatment period of the trial more often achieved ACR20/50/70 responses by week 52, going from 2.4% to 65.9% of the up-titration subset for ACR20 and from 0% to 34.1% for ACR50 and to 12.2% for ACR70. Patients on placebo who switched also experienced increases in these response rates out to week 52. However, BMI above 30 kg/m² led to numerically lower ACR50, ACR70, and PASI response rates at week 52.

The researchers noted that the response rates observed in CHOICE were lower than for the pivotal trials used for Food and Drug Administration approval for PsA, which “may have been due to patients in CHOICE having higher disease activity scores at baseline, compared with TNFi-naive patients” in the pivotal trials.

The safety profile of secukinumab appeared to be no different from what has been reported previously. The researchers said that, throughout the 52-week study, the most common adverse events in patients receiving secukinumab were upper respiratory tract infection in about 13% and diarrhea in about 7%. Most adverse events were mild or moderate, with serious adverse events occurring in 9.6% of patients taking secukinumab 300 mg and in 7.8% of patients taking secukinumab 150 mg over the 52 weeks.

“Overall, the findings from CHOICE were consistent with previous studies and demonstrated that secukinumab provides significant and sustained improvements in signs and symptoms of psoriatic arthritis. Our findings suggest that secukinumab 300 mg is safe and efficacious as a first-line biologic treatment for patients with PsA. Further studies will also help determine the optimal dose of secukinumab for treating overweight patients or those with high disease activity at treatment initiation,” the authors wrote.

The study was funded by Novartis, which manufactures secukinumab. Dr. Nguyen and some coauthors reported serving as a consultant, investigator, and/or speaker for numerous pharmaceutical companies, including Novartis.

An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).

“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.

Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”

Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
 

Reasoning for looking at early OA

“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”

“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.

One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.

Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”

Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
 

Why just knee OA?

The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).

The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.

“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.

“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.

Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.

“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
 

Building on previous work

The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).

Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.

“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.

A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?

Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.

“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”

It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.

“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?

“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”

It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”

Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.

An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).

“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.

Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”

Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
 

Reasoning for looking at early OA

“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”

“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.

One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.

Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”

Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
 

Why just knee OA?

The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).

The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.

“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.

“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.

Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.

“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
 

Building on previous work

The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).

Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.

“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.

A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?

Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.

“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”

It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.

“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?

“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”

It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”

Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.

An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).

“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.

Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”

Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
 

Reasoning for looking at early OA

“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”

“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.

One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.

Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”

Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
 

Why just knee OA?

The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).

The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.

“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.

“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.

Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.

“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
 

Building on previous work

The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).

Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.

“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.

A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?

Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.

“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”

It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.

“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?

“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”

It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”

Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.

A small new study of women suggests that adopting a low-fat vegan diet and then eliminating remaining trigger foods may dramatically reduce symptoms of rheumatoid arthritis (RA) within months. After 16 weeks, the mean Disease Activity Score in 28 joints (DAS28) decreased from 4.5 to 2.5 (P < .001), and the mean number of swollen joints dipped from 7.0 to 3.3 (P = .03).

The study was published in the American Journal of Lifestyle Medicine. It’s not clear whether the vegan diet or the restriction of trigger foods – or both or neither – was helpful. Significant weight loss in the diet group could have played a role in reducing symptoms.

galitskaya / iStock / Getty Images

Still, the dietary strategy is “a life-changing experience for people,” lead author Neal D. Barnard, MD, an internal medicine specialist and adjunct professor of medicine at George Washington University, Washington, D.C, and president of the Physicians Committee for Responsible Medicine, said in an interview. “Doctors should know about it, and they should try it themselves.”

The researchers launched the study to determine the feasibility of a “practical and easy-to-prescribe diet” without caloric limits, Dr. Barnard said. “People have done a variety of studies where they’ve looked at diet changes, often with fasting, and the quality has been variable.”

There’s no consensus in the medical literature on which dietary approach is best for patients with RA. A 2021 systematic review by Philippa and colleagues found positive results for the Mediterranean diet, high doses of omega-3 fatty acids, vitamin D supplementation, and sodium restriction. Fasting had significant but temporary effects, and the reviewers noted “outcomes from vegetarian, elimination, peptide, or elemental diets suggested that responses are very individualized.”

For the new randomized, crossover study, researchers assigned 44 women to one of two diet phases. After 16 weeks, they had a 4-week washout period, then began the other 16-week phase. A total of 32 patients completed the study, and they had a mean age of 57 years. Overall, 66% were White, 16% were Black, and 79% held a college degree or graduate degree.

In the 16-week intervention phase, participants went on a low-fat vegan diet. After 4 weeks, they eliminated common RA trigger foods such as grains with gluten, nuts, citrus fruits, and chocolate. After week 7, the subjects added back the trigger foods one by one, keeping them in their diet if they didn’t seem to cause pain.

In the 16-week placebo phase, the women took a supplement that they were told contained omega-3 oils and vitamin E. However, the amounts of omega-3 and vitamin E were very low and had no apparent effect.

Participants in the diet phase attended weekly 1-hour dietary support-group sessions. Thirty-two women completed the full study.

Average DAS28 scores fell in the diet phase, compared with the supplement phase (treatment effect, 1.8 [95% confidence interval [CI], 3.2 to 0.4]; P = .01), as did swollen joints (treatment effect, –4.2 [95% CI, –8.3 to –0.1], P = .047).

While the researchers reported dips in the DAS28 score and swollen joints, “the reductions in the number of painful and tender joints did not reach statistical significance (treatment effects, –4.1 [95% CI, –8.7 to +0.5]; P = .08; and –1.8 [95% CI, –5.5 to +1.9]; P = .41, respectively).”

Mean body weight fell by 6.5 kg among those in the diet group, while those in the placebo group gained 0.8 kg (treatment effect, –7.3 kg [95% CI, –9.4 to –5.1]; P < .001).

The researchers noted “the presumed mechanisms by which diets such [as this intervention strategy] reduce joint symptoms relate to the removal of inflammatory elements of an omnivorous diet, the presence of anti-inflammatory constituents in a plant-based diet, and diet-induced reductions in gut permeability that may, in turn, reduce the passage of antigens into circulation.”

Patients tolerate the diet well, Dr. Barnard said. “It’s practical for day-to-day life, and you don’t have to check into a fasting hospital.”

Elliott O’Donovan Photography

The message for physicians, he said, is to encourage patients to try changing their eating patterns before turning to medication. “It’s a good idea for anyone to have a chance to try a diet change,” he said. “You’ll know within a matter of weeks whether it will work.”

Vegan diets are also cheaper than diets with meat and dairy, he added.

The study has various limitations. It began with 44 participants, but 12 failed to complete it for various reasons. Four participants who were assigned to the diet phase first refused to resume their regular diets during the next phase. It’s not clear if the lost weight is most responsible for the diet’s benefits, Harvard Medical School rheumatologist Daniel H. Solomon, MD, MPH, said in an interview. In his review of the study findings, Dr. Solomon said that another possibility is that certain aspects of the diet – and not the full diet – were responsible.

A small new study of women suggests that adopting a low-fat vegan diet and then eliminating remaining trigger foods may dramatically reduce symptoms of rheumatoid arthritis (RA) within months. After 16 weeks, the mean Disease Activity Score in 28 joints (DAS28) decreased from 4.5 to 2.5 (P < .001), and the mean number of swollen joints dipped from 7.0 to 3.3 (P = .03).

The study was published in the American Journal of Lifestyle Medicine. It’s not clear whether the vegan diet or the restriction of trigger foods – or both or neither – was helpful. Significant weight loss in the diet group could have played a role in reducing symptoms.

galitskaya / iStock / Getty Images

Still, the dietary strategy is “a life-changing experience for people,” lead author Neal D. Barnard, MD, an internal medicine specialist and adjunct professor of medicine at George Washington University, Washington, D.C, and president of the Physicians Committee for Responsible Medicine, said in an interview. “Doctors should know about it, and they should try it themselves.”

The researchers launched the study to determine the feasibility of a “practical and easy-to-prescribe diet” without caloric limits, Dr. Barnard said. “People have done a variety of studies where they’ve looked at diet changes, often with fasting, and the quality has been variable.”

There’s no consensus in the medical literature on which dietary approach is best for patients with RA. A 2021 systematic review by Philippa and colleagues found positive results for the Mediterranean diet, high doses of omega-3 fatty acids, vitamin D supplementation, and sodium restriction. Fasting had significant but temporary effects, and the reviewers noted “outcomes from vegetarian, elimination, peptide, or elemental diets suggested that responses are very individualized.”

For the new randomized, crossover study, researchers assigned 44 women to one of two diet phases. After 16 weeks, they had a 4-week washout period, then began the other 16-week phase. A total of 32 patients completed the study, and they had a mean age of 57 years. Overall, 66% were White, 16% were Black, and 79% held a college degree or graduate degree.

In the 16-week intervention phase, participants went on a low-fat vegan diet. After 4 weeks, they eliminated common RA trigger foods such as grains with gluten, nuts, citrus fruits, and chocolate. After week 7, the subjects added back the trigger foods one by one, keeping them in their diet if they didn’t seem to cause pain.

In the 16-week placebo phase, the women took a supplement that they were told contained omega-3 oils and vitamin E. However, the amounts of omega-3 and vitamin E were very low and had no apparent effect.

Participants in the diet phase attended weekly 1-hour dietary support-group sessions. Thirty-two women completed the full study.

Average DAS28 scores fell in the diet phase, compared with the supplement phase (treatment effect, 1.8 [95% confidence interval [CI], 3.2 to 0.4]; P = .01), as did swollen joints (treatment effect, –4.2 [95% CI, –8.3 to –0.1], P = .047).

While the researchers reported dips in the DAS28 score and swollen joints, “the reductions in the number of painful and tender joints did not reach statistical significance (treatment effects, –4.1 [95% CI, –8.7 to +0.5]; P = .08; and –1.8 [95% CI, –5.5 to +1.9]; P = .41, respectively).”

Mean body weight fell by 6.5 kg among those in the diet group, while those in the placebo group gained 0.8 kg (treatment effect, –7.3 kg [95% CI, –9.4 to –5.1]; P < .001).

The researchers noted “the presumed mechanisms by which diets such [as this intervention strategy] reduce joint symptoms relate to the removal of inflammatory elements of an omnivorous diet, the presence of anti-inflammatory constituents in a plant-based diet, and diet-induced reductions in gut permeability that may, in turn, reduce the passage of antigens into circulation.”

Patients tolerate the diet well, Dr. Barnard said. “It’s practical for day-to-day life, and you don’t have to check into a fasting hospital.”

Elliott O’Donovan Photography

The message for physicians, he said, is to encourage patients to try changing their eating patterns before turning to medication. “It’s a good idea for anyone to have a chance to try a diet change,” he said. “You’ll know within a matter of weeks whether it will work.”

Vegan diets are also cheaper than diets with meat and dairy, he added.

The study has various limitations. It began with 44 participants, but 12 failed to complete it for various reasons. Four participants who were assigned to the diet phase first refused to resume their regular diets during the next phase. It’s not clear if the lost weight is most responsible for the diet’s benefits, Harvard Medical School rheumatologist Daniel H. Solomon, MD, MPH, said in an interview. In his review of the study findings, Dr. Solomon said that another possibility is that certain aspects of the diet – and not the full diet – were responsible.

A small new study of women suggests that adopting a low-fat vegan diet and then eliminating remaining trigger foods may dramatically reduce symptoms of rheumatoid arthritis (RA) within months. After 16 weeks, the mean Disease Activity Score in 28 joints (DAS28) decreased from 4.5 to 2.5 (P < .001), and the mean number of swollen joints dipped from 7.0 to 3.3 (P = .03).

The study was published in the American Journal of Lifestyle Medicine. It’s not clear whether the vegan diet or the restriction of trigger foods – or both or neither – was helpful. Significant weight loss in the diet group could have played a role in reducing symptoms.

galitskaya / iStock / Getty Images

Still, the dietary strategy is “a life-changing experience for people,” lead author Neal D. Barnard, MD, an internal medicine specialist and adjunct professor of medicine at George Washington University, Washington, D.C, and president of the Physicians Committee for Responsible Medicine, said in an interview. “Doctors should know about it, and they should try it themselves.”

The researchers launched the study to determine the feasibility of a “practical and easy-to-prescribe diet” without caloric limits, Dr. Barnard said. “People have done a variety of studies where they’ve looked at diet changes, often with fasting, and the quality has been variable.”

There’s no consensus in the medical literature on which dietary approach is best for patients with RA. A 2021 systematic review by Philippa and colleagues found positive results for the Mediterranean diet, high doses of omega-3 fatty acids, vitamin D supplementation, and sodium restriction. Fasting had significant but temporary effects, and the reviewers noted “outcomes from vegetarian, elimination, peptide, or elemental diets suggested that responses are very individualized.”

For the new randomized, crossover study, researchers assigned 44 women to one of two diet phases. After 16 weeks, they had a 4-week washout period, then began the other 16-week phase. A total of 32 patients completed the study, and they had a mean age of 57 years. Overall, 66% were White, 16% were Black, and 79% held a college degree or graduate degree.

In the 16-week intervention phase, participants went on a low-fat vegan diet. After 4 weeks, they eliminated common RA trigger foods such as grains with gluten, nuts, citrus fruits, and chocolate. After week 7, the subjects added back the trigger foods one by one, keeping them in their diet if they didn’t seem to cause pain.

In the 16-week placebo phase, the women took a supplement that they were told contained omega-3 oils and vitamin E. However, the amounts of omega-3 and vitamin E were very low and had no apparent effect.

Participants in the diet phase attended weekly 1-hour dietary support-group sessions. Thirty-two women completed the full study.

Average DAS28 scores fell in the diet phase, compared with the supplement phase (treatment effect, 1.8 [95% confidence interval [CI], 3.2 to 0.4]; P = .01), as did swollen joints (treatment effect, –4.2 [95% CI, –8.3 to –0.1], P = .047).

While the researchers reported dips in the DAS28 score and swollen joints, “the reductions in the number of painful and tender joints did not reach statistical significance (treatment effects, –4.1 [95% CI, –8.7 to +0.5]; P = .08; and –1.8 [95% CI, –5.5 to +1.9]; P = .41, respectively).”

Mean body weight fell by 6.5 kg among those in the diet group, while those in the placebo group gained 0.8 kg (treatment effect, –7.3 kg [95% CI, –9.4 to –5.1]; P < .001).

The researchers noted “the presumed mechanisms by which diets such [as this intervention strategy] reduce joint symptoms relate to the removal of inflammatory elements of an omnivorous diet, the presence of anti-inflammatory constituents in a plant-based diet, and diet-induced reductions in gut permeability that may, in turn, reduce the passage of antigens into circulation.”

Patients tolerate the diet well, Dr. Barnard said. “It’s practical for day-to-day life, and you don’t have to check into a fasting hospital.”

Elliott O’Donovan Photography

The message for physicians, he said, is to encourage patients to try changing their eating patterns before turning to medication. “It’s a good idea for anyone to have a chance to try a diet change,” he said. “You’ll know within a matter of weeks whether it will work.”

Vegan diets are also cheaper than diets with meat and dairy, he added.

The study has various limitations. It began with 44 participants, but 12 failed to complete it for various reasons. Four participants who were assigned to the diet phase first refused to resume their regular diets during the next phase. It’s not clear if the lost weight is most responsible for the diet’s benefits, Harvard Medical School rheumatologist Daniel H. Solomon, MD, MPH, said in an interview. In his review of the study findings, Dr. Solomon said that another possibility is that certain aspects of the diet – and not the full diet – were responsible.

Inadequate pain relief was recorded in 68.8% of a sample of people with hip or knee OA who participated in the population-based EpiReumaPt study, researchers reported at the OARSI 2022 World Congress.

“This can be explained by a lack of effectiveness of current management strategies, low uptake of recommended interventions by health care professionals, and also by low adherence by patients to medication and lifestyle interventions,” said Daniela Sofia Albino Costa, MSc, a PhD student at NOVA University Lisbon.

BackyardProduction/Thinkstock

In addition to looking at the prevalence of inadequate pain relief ­– defined as a score of 5 or higher on the Numeric Pain Rating Scale (NPRS) – the study she presented at the congress, which was sponsored by the Osteoarthritis Research Society International, looked at the predictors for inadequate pain control.

It was found that being female, obesity, and having multimorbidity doubled the risk of inadequate versus adequate pain control, with respective odds ratios of 2.32 (P < .001), 2.26 (P = .006), and 2.07 (P = .001). Overweight was also associated with an increased odds ratio for poor pain control (OR, 1.84; P = .0035).

“We found that patients with inadequate pain relief also have a low performance on activities of daily living and a low quality of life,” Ms. Costa said.

Nearly one-third (29%) of patients in the inadequate pain relief group (n = 765) took medication, versus 15% of patients in the adequate pain relief group (n = 270). This was mostly NSAIDs, but also included analgesics and antipyretics, and in a few cases (4.8% vs. 1.3%), simple opioids.

“We know that current care is not concordant with recommendations,” said Ms. Costa, noting that medication being used as first-line treatment and core nonpharmacologic interventions are being offered to less than half of patients who are eligible.

In addition, the rate for total joint replacement has increased globally, and pain is an important predictor for this.

“So, we need to evaluate pain control and current management offered to people with hip or knee arthritis to identify to identify areas for improvement,” Ms. Costa said.

High rates of prescription opioid use before TKA

In a separate study also presented at the congress, Daniel Rhon, DPT, DSc, director of musculoskeletal research in primary care at Brooke Army Medical Center in San Antonio, gave a worrying glimpse of high rates of opioid use in the 4 years before total knee arthroplasty (TKA).

Using data from the U.S. Military Health System, the records of all individuals who had a knee replacement procedure between January 2017 and December 2018 were studied, to identify and characterize the use of prescription opioids.

Of the 46,362 individuals, 52.9% had prior opioid use, despite the fact that “opioids are not recommended for the management of knee OA,” said Dr. Rhon.

He also reported that as many as 40% of those who had at least one prescription for opioids had received a high-potency drug, such as fentanyl or oxycodone. The mean age of participants overall was 65 years, with a higher mean for those receiving opioids than those who did not (68 vs. 61.5 years). Data on sex and ethnicity were not available in time for presentation at the congress.

“Most of these individuals are getting these opioid prescriptions probably within 6 months, which maybe aligns with escalation of pain and maybe the decision to have that knee replacement,” Dr. Rhon said. Individuals that used opioids filled their most recent prescription a median of 146 days before TKA to surgery, with a mean of 317 days.

“You can’t always link the reason for the opioid prescription, that’s not really clear in the database,” he admitted; however, an analysis was performed to check if other surgeries had been performed that may have warranted the opioid treatment. The results revealed that very few of the opioid users (4%-7%) had undergone another type of surgical procedure.

“So, we feel a little bit better, that these findings weren’t for other surgical procedures,” said Dr. Rhon. He added that future qualitative research was needed to understand why health care professionals were prescribing opioids, and why patients felt like they needed them.

“That’s bad,” Haxby Abbott, PhD, DPT, a research professor at the University of Otago, Dunedin, New Zealand, commented on Twitter.

Dr. Abbott, who was not involved in the study, added: “We’ve done a similar study of the whole NZ population [currently under review] – similar to Australia and not nearly as bad as you found. That needs urgent attention.”
 

Sharp rise in opioid use 2 years before TKA

Lower rates of opioid use before TKA were seen in two European cohorts, at 43% in England and 33% in Sweden, as reported by Clara Hellberg, PhD, MD, of Lund (Sweden) University. However, rates had increased over a 10-year study period from a respective 23% and 16%, with a sharp increase in use in the 2 years before knee replacement.

The analysis was based on 49,043 patients from the English national database Clinical Practice Research Datalink, and 5,955 patients from the Swedish Skåne Healthcare register who had undergone total knee replacement between 2015 and 2019 and were matched by age, sex and general practice to individuals not undergoing knee replacement.

The prevalence ratio for using opioids over a 10-year period increased from 1.6 to 2.7 in England, and from 1.6 to 2.6 in Sweden.

“While the overall prevalence of opioid use was higher in England, the majority of both cases and controls were using weak opioids,” Dr. Hellberg said.

“Codeine was classified as a weak opioid, whereas morphine was classified as a strong opioid,” she added.

In contrast, the proportion of people using strong opioids in Sweden was greater than in England, she said.

The high opioid use found in the study highlights “the need for better opioid stewardship, and the availability of acceptable, effective alternatives,” Dr. Hellberg and associates concluded in their abstract.

The study presented by Ms. Costa was funded by the Portuguese national funding agency for science, research and technology and by an independent research grant from Pfizer. Dr. Rhon acknowledged grant funding from the National Institutes of Health and the U.S. Department of Defense. Dr. Hellberg had no conflicts of interest to disclose.

Inadequate pain relief was recorded in 68.8% of a sample of people with hip or knee OA who participated in the population-based EpiReumaPt study, researchers reported at the OARSI 2022 World Congress.

“This can be explained by a lack of effectiveness of current management strategies, low uptake of recommended interventions by health care professionals, and also by low adherence by patients to medication and lifestyle interventions,” said Daniela Sofia Albino Costa, MSc, a PhD student at NOVA University Lisbon.

BackyardProduction/Thinkstock

In addition to looking at the prevalence of inadequate pain relief ­– defined as a score of 5 or higher on the Numeric Pain Rating Scale (NPRS) – the study she presented at the congress, which was sponsored by the Osteoarthritis Research Society International, looked at the predictors for inadequate pain control.

It was found that being female, obesity, and having multimorbidity doubled the risk of inadequate versus adequate pain control, with respective odds ratios of 2.32 (P < .001), 2.26 (P = .006), and 2.07 (P = .001). Overweight was also associated with an increased odds ratio for poor pain control (OR, 1.84; P = .0035).

“We found that patients with inadequate pain relief also have a low performance on activities of daily living and a low quality of life,” Ms. Costa said.

Nearly one-third (29%) of patients in the inadequate pain relief group (n = 765) took medication, versus 15% of patients in the adequate pain relief group (n = 270). This was mostly NSAIDs, but also included analgesics and antipyretics, and in a few cases (4.8% vs. 1.3%), simple opioids.

“We know that current care is not concordant with recommendations,” said Ms. Costa, noting that medication being used as first-line treatment and core nonpharmacologic interventions are being offered to less than half of patients who are eligible.

In addition, the rate for total joint replacement has increased globally, and pain is an important predictor for this.

“So, we need to evaluate pain control and current management offered to people with hip or knee arthritis to identify to identify areas for improvement,” Ms. Costa said.

High rates of prescription opioid use before TKA

In a separate study also presented at the congress, Daniel Rhon, DPT, DSc, director of musculoskeletal research in primary care at Brooke Army Medical Center in San Antonio, gave a worrying glimpse of high rates of opioid use in the 4 years before total knee arthroplasty (TKA).

Using data from the U.S. Military Health System, the records of all individuals who had a knee replacement procedure between January 2017 and December 2018 were studied, to identify and characterize the use of prescription opioids.

Of the 46,362 individuals, 52.9% had prior opioid use, despite the fact that “opioids are not recommended for the management of knee OA,” said Dr. Rhon.

He also reported that as many as 40% of those who had at least one prescription for opioids had received a high-potency drug, such as fentanyl or oxycodone. The mean age of participants overall was 65 years, with a higher mean for those receiving opioids than those who did not (68 vs. 61.5 years). Data on sex and ethnicity were not available in time for presentation at the congress.

“Most of these individuals are getting these opioid prescriptions probably within 6 months, which maybe aligns with escalation of pain and maybe the decision to have that knee replacement,” Dr. Rhon said. Individuals that used opioids filled their most recent prescription a median of 146 days before TKA to surgery, with a mean of 317 days.

“You can’t always link the reason for the opioid prescription, that’s not really clear in the database,” he admitted; however, an analysis was performed to check if other surgeries had been performed that may have warranted the opioid treatment. The results revealed that very few of the opioid users (4%-7%) had undergone another type of surgical procedure.

“So, we feel a little bit better, that these findings weren’t for other surgical procedures,” said Dr. Rhon. He added that future qualitative research was needed to understand why health care professionals were prescribing opioids, and why patients felt like they needed them.

“That’s bad,” Haxby Abbott, PhD, DPT, a research professor at the University of Otago, Dunedin, New Zealand, commented on Twitter.

Dr. Abbott, who was not involved in the study, added: “We’ve done a similar study of the whole NZ population [currently under review] – similar to Australia and not nearly as bad as you found. That needs urgent attention.”
 

Sharp rise in opioid use 2 years before TKA

Lower rates of opioid use before TKA were seen in two European cohorts, at 43% in England and 33% in Sweden, as reported by Clara Hellberg, PhD, MD, of Lund (Sweden) University. However, rates had increased over a 10-year study period from a respective 23% and 16%, with a sharp increase in use in the 2 years before knee replacement.

The analysis was based on 49,043 patients from the English national database Clinical Practice Research Datalink, and 5,955 patients from the Swedish Skåne Healthcare register who had undergone total knee replacement between 2015 and 2019 and were matched by age, sex and general practice to individuals not undergoing knee replacement.

The prevalence ratio for using opioids over a 10-year period increased from 1.6 to 2.7 in England, and from 1.6 to 2.6 in Sweden.

“While the overall prevalence of opioid use was higher in England, the majority of both cases and controls were using weak opioids,” Dr. Hellberg said.

“Codeine was classified as a weak opioid, whereas morphine was classified as a strong opioid,” she added.

In contrast, the proportion of people using strong opioids in Sweden was greater than in England, she said.

The high opioid use found in the study highlights “the need for better opioid stewardship, and the availability of acceptable, effective alternatives,” Dr. Hellberg and associates concluded in their abstract.

The study presented by Ms. Costa was funded by the Portuguese national funding agency for science, research and technology and by an independent research grant from Pfizer. Dr. Rhon acknowledged grant funding from the National Institutes of Health and the U.S. Department of Defense. Dr. Hellberg had no conflicts of interest to disclose.

Inadequate pain relief was recorded in 68.8% of a sample of people with hip or knee OA who participated in the population-based EpiReumaPt study, researchers reported at the OARSI 2022 World Congress.

“This can be explained by a lack of effectiveness of current management strategies, low uptake of recommended interventions by health care professionals, and also by low adherence by patients to medication and lifestyle interventions,” said Daniela Sofia Albino Costa, MSc, a PhD student at NOVA University Lisbon.

BackyardProduction/Thinkstock

In addition to looking at the prevalence of inadequate pain relief ­– defined as a score of 5 or higher on the Numeric Pain Rating Scale (NPRS) – the study she presented at the congress, which was sponsored by the Osteoarthritis Research Society International, looked at the predictors for inadequate pain control.

It was found that being female, obesity, and having multimorbidity doubled the risk of inadequate versus adequate pain control, with respective odds ratios of 2.32 (P < .001), 2.26 (P = .006), and 2.07 (P = .001). Overweight was also associated with an increased odds ratio for poor pain control (OR, 1.84; P = .0035).

“We found that patients with inadequate pain relief also have a low performance on activities of daily living and a low quality of life,” Ms. Costa said.

Nearly one-third (29%) of patients in the inadequate pain relief group (n = 765) took medication, versus 15% of patients in the adequate pain relief group (n = 270). This was mostly NSAIDs, but also included analgesics and antipyretics, and in a few cases (4.8% vs. 1.3%), simple opioids.

“We know that current care is not concordant with recommendations,” said Ms. Costa, noting that medication being used as first-line treatment and core nonpharmacologic interventions are being offered to less than half of patients who are eligible.

In addition, the rate for total joint replacement has increased globally, and pain is an important predictor for this.

“So, we need to evaluate pain control and current management offered to people with hip or knee arthritis to identify to identify areas for improvement,” Ms. Costa said.

High rates of prescription opioid use before TKA

In a separate study also presented at the congress, Daniel Rhon, DPT, DSc, director of musculoskeletal research in primary care at Brooke Army Medical Center in San Antonio, gave a worrying glimpse of high rates of opioid use in the 4 years before total knee arthroplasty (TKA).

Using data from the U.S. Military Health System, the records of all individuals who had a knee replacement procedure between January 2017 and December 2018 were studied, to identify and characterize the use of prescription opioids.

Of the 46,362 individuals, 52.9% had prior opioid use, despite the fact that “opioids are not recommended for the management of knee OA,” said Dr. Rhon.

He also reported that as many as 40% of those who had at least one prescription for opioids had received a high-potency drug, such as fentanyl or oxycodone. The mean age of participants overall was 65 years, with a higher mean for those receiving opioids than those who did not (68 vs. 61.5 years). Data on sex and ethnicity were not available in time for presentation at the congress.

“Most of these individuals are getting these opioid prescriptions probably within 6 months, which maybe aligns with escalation of pain and maybe the decision to have that knee replacement,” Dr. Rhon said. Individuals that used opioids filled their most recent prescription a median of 146 days before TKA to surgery, with a mean of 317 days.

“You can’t always link the reason for the opioid prescription, that’s not really clear in the database,” he admitted; however, an analysis was performed to check if other surgeries had been performed that may have warranted the opioid treatment. The results revealed that very few of the opioid users (4%-7%) had undergone another type of surgical procedure.

“So, we feel a little bit better, that these findings weren’t for other surgical procedures,” said Dr. Rhon. He added that future qualitative research was needed to understand why health care professionals were prescribing opioids, and why patients felt like they needed them.

“That’s bad,” Haxby Abbott, PhD, DPT, a research professor at the University of Otago, Dunedin, New Zealand, commented on Twitter.

Dr. Abbott, who was not involved in the study, added: “We’ve done a similar study of the whole NZ population [currently under review] – similar to Australia and not nearly as bad as you found. That needs urgent attention.”
 

Sharp rise in opioid use 2 years before TKA

Lower rates of opioid use before TKA were seen in two European cohorts, at 43% in England and 33% in Sweden, as reported by Clara Hellberg, PhD, MD, of Lund (Sweden) University. However, rates had increased over a 10-year study period from a respective 23% and 16%, with a sharp increase in use in the 2 years before knee replacement.

The analysis was based on 49,043 patients from the English national database Clinical Practice Research Datalink, and 5,955 patients from the Swedish Skåne Healthcare register who had undergone total knee replacement between 2015 and 2019 and were matched by age, sex and general practice to individuals not undergoing knee replacement.

The prevalence ratio for using opioids over a 10-year period increased from 1.6 to 2.7 in England, and from 1.6 to 2.6 in Sweden.

“While the overall prevalence of opioid use was higher in England, the majority of both cases and controls were using weak opioids,” Dr. Hellberg said.

“Codeine was classified as a weak opioid, whereas morphine was classified as a strong opioid,” she added.

In contrast, the proportion of people using strong opioids in Sweden was greater than in England, she said.

The high opioid use found in the study highlights “the need for better opioid stewardship, and the availability of acceptable, effective alternatives,” Dr. Hellberg and associates concluded in their abstract.

The study presented by Ms. Costa was funded by the Portuguese national funding agency for science, research and technology and by an independent research grant from Pfizer. Dr. Rhon acknowledged grant funding from the National Institutes of Health and the U.S. Department of Defense. Dr. Hellberg had no conflicts of interest to disclose.