Rheumatoid Arthritis

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.

Despite the improved outcomes in rheumatoid arthritis (RA) observed in clinical trials from early use of biologic disease-modifying antirheumatic drugs (bDMARD) in a treat-to-target strategy, real-world use may be limited by stopping medications for various reasons. Burkard and colleagues used the Swiss RA registry to examine potential reasons for discontinuation of bDMARD and targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) among over 2500 adults with RA who stopped these medications from 1999 through 2018. In this cohort study, patients were followed from date of discontinuation of their medication until restarting a bDMARD or tsDMARD. The most common reasons for discontinuation were nonresponse and adverse events; of these patients, over 80% restarted a bDMARD or tsDMARD. Only 8% of patients stopped due to remission; of these, nearly half restarted. The authors found a higher proportion of fibromyalgia among patients who stopped due to nonresponse and adverse events vs due to remission. Oddly, though 40%-50% of patients stopped for "unknown reasons" between 2002 and 2006, this proportion dropped to close to 0 after 2010; during the first time period, the proportions stopping medication due to adverse events and nonresponse were also low, suggesting possible misattribution of the reason for treatment cessation. As such, drawing further conclusions on association of different patient characteristics with reasons for treatment cessation is difficult.

The gap between control of inflammatory joint pain in RA and overall patient outcomes has come up frequently in recent studies. Gwinnutt and colleagues looked at patients participating in three European RA registries, comprising over 2500 patients followed over 8-10 years, and classified them as having high or low inflammation on the basis of Disease Activity Score (DAS28) and analyzed Health Assessment Questionnaire (HAQ) score trajectories as low vs high as a measure of disability. Overall, patients in the three registries had different trajectory patterns, though it appears clear, in keeping with other studies, that a subset of patients remain with high HAQ scores despite decreases in DAS28 scores. Older age; being a woman; and more pain, fatigue, and depressive symptoms were associated with higher HAQ trajectory in both the high and low inflammation pairs, suggesting that this phenomenon is not quite "excess disability" solely in patients with low inflammation.

An additional factor that increases morbidity as well as mortality in RA is frailty, which is associated with age as well as with RA (including people < 65 years old). Hanlon and colleagues examined the change in the "frailty phenotype" over time and its association with adverse clinical outcomes in people with early RA in the Scottish Early Rheumatoid Arthritis (SERA) and UK Biobank cohorts. Frailty was defined by different measures in the two cohorts, including elements of the HAQ disability index for SERA and self-reported fatigue, depression, and poor health for UK Biobank. The computed frailty index was higher in people with higher DAS28 scores and increased with age. Of note, frailty index values were higher prior to treatment initiation and improved somewhat with lower disease activity over time, though those with higher baseline frailty index values tended to have poorer physical function and disease activity over time. Understanding frailty in RA may allow us to better predict and prevent functional limitation, disease progression, and mortality in people with RA.

Of current interest is an observational study by van der Togt and colleagues on the response to COVID-19 vaccines in people with RA being treated with rituximab. Of patients who had previously been treated with 200, 500, or 1000 mg of rituximab prior to COVID-19 vaccination, those who received 200 mg  rituximab as well as those who had longer intervals between rituximab dose and vaccination had a better response to vaccination as defined by immunoglobulins (total, IgG, and IgM) against SARS-CoV-2. Although this study lacked a control arm of people being treated with other disease-modifying antirheumatic drugs and did not evaluate COVID-19 infections or outcomes, its findings do suggest that dosage and timing of rituximab in people with RA should be studied further in regard to vaccine response and infection risk.

Despite the improved outcomes in rheumatoid arthritis (RA) observed in clinical trials from early use of biologic disease-modifying antirheumatic drugs (bDMARD) in a treat-to-target strategy, real-world use may be limited by stopping medications for various reasons. Burkard and colleagues used the Swiss RA registry to examine potential reasons for discontinuation of bDMARD and targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) among over 2500 adults with RA who stopped these medications from 1999 through 2018. In this cohort study, patients were followed from date of discontinuation of their medication until restarting a bDMARD or tsDMARD. The most common reasons for discontinuation were nonresponse and adverse events; of these patients, over 80% restarted a bDMARD or tsDMARD. Only 8% of patients stopped due to remission; of these, nearly half restarted. The authors found a higher proportion of fibromyalgia among patients who stopped due to nonresponse and adverse events vs due to remission. Oddly, though 40%-50% of patients stopped for "unknown reasons" between 2002 and 2006, this proportion dropped to close to 0 after 2010; during the first time period, the proportions stopping medication due to adverse events and nonresponse were also low, suggesting possible misattribution of the reason for treatment cessation. As such, drawing further conclusions on association of different patient characteristics with reasons for treatment cessation is difficult.

The gap between control of inflammatory joint pain in RA and overall patient outcomes has come up frequently in recent studies. Gwinnutt and colleagues looked at patients participating in three European RA registries, comprising over 2500 patients followed over 8-10 years, and classified them as having high or low inflammation on the basis of Disease Activity Score (DAS28) and analyzed Health Assessment Questionnaire (HAQ) score trajectories as low vs high as a measure of disability. Overall, patients in the three registries had different trajectory patterns, though it appears clear, in keeping with other studies, that a subset of patients remain with high HAQ scores despite decreases in DAS28 scores. Older age; being a woman; and more pain, fatigue, and depressive symptoms were associated with higher HAQ trajectory in both the high and low inflammation pairs, suggesting that this phenomenon is not quite "excess disability" solely in patients with low inflammation.

An additional factor that increases morbidity as well as mortality in RA is frailty, which is associated with age as well as with RA (including people < 65 years old). Hanlon and colleagues examined the change in the "frailty phenotype" over time and its association with adverse clinical outcomes in people with early RA in the Scottish Early Rheumatoid Arthritis (SERA) and UK Biobank cohorts. Frailty was defined by different measures in the two cohorts, including elements of the HAQ disability index for SERA and self-reported fatigue, depression, and poor health for UK Biobank. The computed frailty index was higher in people with higher DAS28 scores and increased with age. Of note, frailty index values were higher prior to treatment initiation and improved somewhat with lower disease activity over time, though those with higher baseline frailty index values tended to have poorer physical function and disease activity over time. Understanding frailty in RA may allow us to better predict and prevent functional limitation, disease progression, and mortality in people with RA.

Of current interest is an observational study by van der Togt and colleagues on the response to COVID-19 vaccines in people with RA being treated with rituximab. Of patients who had previously been treated with 200, 500, or 1000 mg of rituximab prior to COVID-19 vaccination, those who received 200 mg  rituximab as well as those who had longer intervals between rituximab dose and vaccination had a better response to vaccination as defined by immunoglobulins (total, IgG, and IgM) against SARS-CoV-2. Although this study lacked a control arm of people being treated with other disease-modifying antirheumatic drugs and did not evaluate COVID-19 infections or outcomes, its findings do suggest that dosage and timing of rituximab in people with RA should be studied further in regard to vaccine response and infection risk.

Despite the improved outcomes in rheumatoid arthritis (RA) observed in clinical trials from early use of biologic disease-modifying antirheumatic drugs (bDMARD) in a treat-to-target strategy, real-world use may be limited by stopping medications for various reasons. Burkard and colleagues used the Swiss RA registry to examine potential reasons for discontinuation of bDMARD and targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) among over 2500 adults with RA who stopped these medications from 1999 through 2018. In this cohort study, patients were followed from date of discontinuation of their medication until restarting a bDMARD or tsDMARD. The most common reasons for discontinuation were nonresponse and adverse events; of these patients, over 80% restarted a bDMARD or tsDMARD. Only 8% of patients stopped due to remission; of these, nearly half restarted. The authors found a higher proportion of fibromyalgia among patients who stopped due to nonresponse and adverse events vs due to remission. Oddly, though 40%-50% of patients stopped for "unknown reasons" between 2002 and 2006, this proportion dropped to close to 0 after 2010; during the first time period, the proportions stopping medication due to adverse events and nonresponse were also low, suggesting possible misattribution of the reason for treatment cessation. As such, drawing further conclusions on association of different patient characteristics with reasons for treatment cessation is difficult.

The gap between control of inflammatory joint pain in RA and overall patient outcomes has come up frequently in recent studies. Gwinnutt and colleagues looked at patients participating in three European RA registries, comprising over 2500 patients followed over 8-10 years, and classified them as having high or low inflammation on the basis of Disease Activity Score (DAS28) and analyzed Health Assessment Questionnaire (HAQ) score trajectories as low vs high as a measure of disability. Overall, patients in the three registries had different trajectory patterns, though it appears clear, in keeping with other studies, that a subset of patients remain with high HAQ scores despite decreases in DAS28 scores. Older age; being a woman; and more pain, fatigue, and depressive symptoms were associated with higher HAQ trajectory in both the high and low inflammation pairs, suggesting that this phenomenon is not quite "excess disability" solely in patients with low inflammation.

An additional factor that increases morbidity as well as mortality in RA is frailty, which is associated with age as well as with RA (including people < 65 years old). Hanlon and colleagues examined the change in the "frailty phenotype" over time and its association with adverse clinical outcomes in people with early RA in the Scottish Early Rheumatoid Arthritis (SERA) and UK Biobank cohorts. Frailty was defined by different measures in the two cohorts, including elements of the HAQ disability index for SERA and self-reported fatigue, depression, and poor health for UK Biobank. The computed frailty index was higher in people with higher DAS28 scores and increased with age. Of note, frailty index values were higher prior to treatment initiation and improved somewhat with lower disease activity over time, though those with higher baseline frailty index values tended to have poorer physical function and disease activity over time. Understanding frailty in RA may allow us to better predict and prevent functional limitation, disease progression, and mortality in people with RA.

Of current interest is an observational study by van der Togt and colleagues on the response to COVID-19 vaccines in people with RA being treated with rituximab. Of patients who had previously been treated with 200, 500, or 1000 mg of rituximab prior to COVID-19 vaccination, those who received 200 mg  rituximab as well as those who had longer intervals between rituximab dose and vaccination had a better response to vaccination as defined by immunoglobulins (total, IgG, and IgM) against SARS-CoV-2. Although this study lacked a control arm of people being treated with other disease-modifying antirheumatic drugs and did not evaluate COVID-19 infections or outcomes, its findings do suggest that dosage and timing of rituximab in people with RA should be studied further in regard to vaccine response and infection risk.

Key clinical point: Peficitinib reduced the progression of joint damage compared with placebo in patients with rheumatoid arthritis (RA) who responded inadequately to prior methotrexate.

Major finding: At week 28/early termination, the mean change in overall erosion score and overall joint space narrowing score in patients receiving 100 mg and 150 mg peficitinib vs. placebo was 0.63 ± 2.03 and 0.18 ± 1.10 vs. 1.35 ± 3.01, and 0.99 ± 2.86 and 0.82 ± 2.39 vs. 1.90 ± 3.76, respectively.

Study details: This was a post hoc analysis of phase 3 trial, RAJ4, which included 481 patients with RA who had an inadequate response to methotrexate who were randomly assigned to receive 100 mg or 150 mg peficitinib or placebo, in combination with methotrexate, for 52 weeks.

Disclosures: This study was initiated and supported by Astellas Pharma Inc. Y Tanaka and T Takeuchi reported receiving speaking fees, honoraria, research grants, or consulting fees from various sources. Five authors reported being employees of Astellas Pharma Inc.

Source: Tanaka Y et al. Post hoc analysis of clinical characteristics of patients with radiographic progression in a Japanese phase 3 trial of peficitinib and methotrexate treatment (RAJ4). Mod Rheumatol. 2022 (Mar 10). Doi: 10.1093/mr/roac021

Key clinical point: Peficitinib reduced the progression of joint damage compared with placebo in patients with rheumatoid arthritis (RA) who responded inadequately to prior methotrexate.

Major finding: At week 28/early termination, the mean change in overall erosion score and overall joint space narrowing score in patients receiving 100 mg and 150 mg peficitinib vs. placebo was 0.63 ± 2.03 and 0.18 ± 1.10 vs. 1.35 ± 3.01, and 0.99 ± 2.86 and 0.82 ± 2.39 vs. 1.90 ± 3.76, respectively.

Study details: This was a post hoc analysis of phase 3 trial, RAJ4, which included 481 patients with RA who had an inadequate response to methotrexate who were randomly assigned to receive 100 mg or 150 mg peficitinib or placebo, in combination with methotrexate, for 52 weeks.

Disclosures: This study was initiated and supported by Astellas Pharma Inc. Y Tanaka and T Takeuchi reported receiving speaking fees, honoraria, research grants, or consulting fees from various sources. Five authors reported being employees of Astellas Pharma Inc.

Source: Tanaka Y et al. Post hoc analysis of clinical characteristics of patients with radiographic progression in a Japanese phase 3 trial of peficitinib and methotrexate treatment (RAJ4). Mod Rheumatol. 2022 (Mar 10). Doi: 10.1093/mr/roac021

Key clinical point: Peficitinib reduced the progression of joint damage compared with placebo in patients with rheumatoid arthritis (RA) who responded inadequately to prior methotrexate.

Major finding: At week 28/early termination, the mean change in overall erosion score and overall joint space narrowing score in patients receiving 100 mg and 150 mg peficitinib vs. placebo was 0.63 ± 2.03 and 0.18 ± 1.10 vs. 1.35 ± 3.01, and 0.99 ± 2.86 and 0.82 ± 2.39 vs. 1.90 ± 3.76, respectively.

Study details: This was a post hoc analysis of phase 3 trial, RAJ4, which included 481 patients with RA who had an inadequate response to methotrexate who were randomly assigned to receive 100 mg or 150 mg peficitinib or placebo, in combination with methotrexate, for 52 weeks.

Disclosures: This study was initiated and supported by Astellas Pharma Inc. Y Tanaka and T Takeuchi reported receiving speaking fees, honoraria, research grants, or consulting fees from various sources. Five authors reported being employees of Astellas Pharma Inc.

Source: Tanaka Y et al. Post hoc analysis of clinical characteristics of patients with radiographic progression in a Japanese phase 3 trial of peficitinib and methotrexate treatment (RAJ4). Mod Rheumatol. 2022 (Mar 10). Doi: 10.1093/mr/roac021

Key clinical point: Patients with seropositive rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitors (TNFi) were at higher risk of developing nontuberculous mycobacterium (NTM) infection in mycobacterium tuberculosis (MTB) endemic areas.

Major finding: Patients with seropositive RA from an MTB endemic area, who were treated with vs. without TNFi were at a significantly higher risk for NTM infection (adjusted hazard ratio [aHR] 1.751; 95% CI 1.105-2.774), with females (aHR 2.108), patients aged 50-65 years (aHR 2.018), and patients without comorbidities (aHR 1.742; all P < .001) at higher risk of developing NTM infection after TNFi treatment.

Study details: This was a retrospective, population-based longitudinal cohort study including patients with seropositive RA. Of these, 1089 patients treated with TNFI were propensity-matched with 4356 untreated patients.

Disclosures: The study was supported by the research fund of Hanyang University, Republic of Korea. The authors declared no conflicts of interest.

Source: Park DW et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from Phase 3 trials. Sci Rep. 2022;12:4003 (Mar 7). Doi: 10.1038/s41598-022-07968-w

Key clinical point: Patients with seropositive rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitors (TNFi) were at higher risk of developing nontuberculous mycobacterium (NTM) infection in mycobacterium tuberculosis (MTB) endemic areas.

Major finding: Patients with seropositive RA from an MTB endemic area, who were treated with vs. without TNFi were at a significantly higher risk for NTM infection (adjusted hazard ratio [aHR] 1.751; 95% CI 1.105-2.774), with females (aHR 2.108), patients aged 50-65 years (aHR 2.018), and patients without comorbidities (aHR 1.742; all P < .001) at higher risk of developing NTM infection after TNFi treatment.

Study details: This was a retrospective, population-based longitudinal cohort study including patients with seropositive RA. Of these, 1089 patients treated with TNFI were propensity-matched with 4356 untreated patients.

Disclosures: The study was supported by the research fund of Hanyang University, Republic of Korea. The authors declared no conflicts of interest.

Source: Park DW et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from Phase 3 trials. Sci Rep. 2022;12:4003 (Mar 7). Doi: 10.1038/s41598-022-07968-w

Key clinical point: Patients with seropositive rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitors (TNFi) were at higher risk of developing nontuberculous mycobacterium (NTM) infection in mycobacterium tuberculosis (MTB) endemic areas.

Major finding: Patients with seropositive RA from an MTB endemic area, who were treated with vs. without TNFi were at a significantly higher risk for NTM infection (adjusted hazard ratio [aHR] 1.751; 95% CI 1.105-2.774), with females (aHR 2.108), patients aged 50-65 years (aHR 2.018), and patients without comorbidities (aHR 1.742; all P < .001) at higher risk of developing NTM infection after TNFi treatment.

Study details: This was a retrospective, population-based longitudinal cohort study including patients with seropositive RA. Of these, 1089 patients treated with TNFI were propensity-matched with 4356 untreated patients.

Disclosures: The study was supported by the research fund of Hanyang University, Republic of Korea. The authors declared no conflicts of interest.

Source: Park DW et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from Phase 3 trials. Sci Rep. 2022;12:4003 (Mar 7). Doi: 10.1038/s41598-022-07968-w

Key clinical point: Patients with rheumatoid arthritis (RA) showed greater clinically meaningful improvements in fatigue, sleep, and health-related quality of life (HRQoL) with tofacitinib vs. placebo over 6 months, with improvements sustained up to 12 months.

Major finding: The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score, Medical Outcomes Study Sleep scale (MOS-SS) Sleep Problems Index I and II scores, and Short Form-36 Health Survey (Physical/Mental Component Summary) score improved significantly with both  5 mg or 10 mg tofacitinib doses vs. placebo at months 1, 3, and 6 (all P < .05). Improvement in FACIT-F and MOS-SS scores were significantly better with 10 mg tofacitinib vs. adalimumab at 6 and 12 months (all P < .05).

Study details: This was a post hoc analysis of three phase 3 trials including 2265 patients with RA who received tofacitinib, placebo, or adalimumab.

Disclosures: This study was sponsored by Pfizer Inc. C Murray, D Gruben, and DA Gold declared being employees and stockholders of Pfizer. Some authors declared being on steering committees, boards of directors, or speakers’ bureaus or receiving consulting fees or research grants from various sources, including Pfizer.

Source: Bartlett SJ et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from phase 3 trials. Arthritis Res Ther. 2022;24:83 (Apr 5). Doi: 10.1186/s13075-022-02724-x

Key clinical point: Patients with rheumatoid arthritis (RA) showed greater clinically meaningful improvements in fatigue, sleep, and health-related quality of life (HRQoL) with tofacitinib vs. placebo over 6 months, with improvements sustained up to 12 months.

Major finding: The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score, Medical Outcomes Study Sleep scale (MOS-SS) Sleep Problems Index I and II scores, and Short Form-36 Health Survey (Physical/Mental Component Summary) score improved significantly with both  5 mg or 10 mg tofacitinib doses vs. placebo at months 1, 3, and 6 (all P < .05). Improvement in FACIT-F and MOS-SS scores were significantly better with 10 mg tofacitinib vs. adalimumab at 6 and 12 months (all P < .05).

Study details: This was a post hoc analysis of three phase 3 trials including 2265 patients with RA who received tofacitinib, placebo, or adalimumab.

Disclosures: This study was sponsored by Pfizer Inc. C Murray, D Gruben, and DA Gold declared being employees and stockholders of Pfizer. Some authors declared being on steering committees, boards of directors, or speakers’ bureaus or receiving consulting fees or research grants from various sources, including Pfizer.

Source: Bartlett SJ et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from phase 3 trials. Arthritis Res Ther. 2022;24:83 (Apr 5). Doi: 10.1186/s13075-022-02724-x

Key clinical point: Patients with rheumatoid arthritis (RA) showed greater clinically meaningful improvements in fatigue, sleep, and health-related quality of life (HRQoL) with tofacitinib vs. placebo over 6 months, with improvements sustained up to 12 months.

Major finding: The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score, Medical Outcomes Study Sleep scale (MOS-SS) Sleep Problems Index I and II scores, and Short Form-36 Health Survey (Physical/Mental Component Summary) score improved significantly with both  5 mg or 10 mg tofacitinib doses vs. placebo at months 1, 3, and 6 (all P < .05). Improvement in FACIT-F and MOS-SS scores were significantly better with 10 mg tofacitinib vs. adalimumab at 6 and 12 months (all P < .05).

Study details: This was a post hoc analysis of three phase 3 trials including 2265 patients with RA who received tofacitinib, placebo, or adalimumab.

Disclosures: This study was sponsored by Pfizer Inc. C Murray, D Gruben, and DA Gold declared being employees and stockholders of Pfizer. Some authors declared being on steering committees, boards of directors, or speakers’ bureaus or receiving consulting fees or research grants from various sources, including Pfizer.

Source: Bartlett SJ et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from phase 3 trials. Arthritis Res Ther. 2022;24:83 (Apr 5). Doi: 10.1186/s13075-022-02724-x

Key clinical point: Children of mothers, but not fathers, with rheumatoid arthritis (RA) were predisposed to the risk of developing multiple mental disorders.

Major finding: Children of mothers with RA had a significantly higher risk for autism spectrum disorders (odds ratio [OR] 1.49; 95% CI 1.01-2.20), bipolar disorder (OR 1.47; 95% CI 1.20-1.81), attention-deficit/hyperactivity disorder (OR 1.37; 95% CI 1.17-1.60), and major depressive disorder (OR 1.20; 95% CI 1.05-1.37), with no risk for these disorders observed in children of fathers with RA.

Study details: This was a retrospective cohort study including 23,981 RA-parent-child pairs and age-/sex-matched 239,810 non-RA-parent-child pairs.

Disclosures: This study received research grants from Taipei Veterans General Hospital, Yen

Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

Source: Chiu HJ et al. A nationwide study of the risks of major mental disorders among the offspring of parents with rheumatoid arthritis. Sci Rep. 2022;12:4962 (Mar 23). Doi: 10.1038/s41598-022-08834-5

Key clinical point: Children of mothers, but not fathers, with rheumatoid arthritis (RA) were predisposed to the risk of developing multiple mental disorders.

Major finding: Children of mothers with RA had a significantly higher risk for autism spectrum disorders (odds ratio [OR] 1.49; 95% CI 1.01-2.20), bipolar disorder (OR 1.47; 95% CI 1.20-1.81), attention-deficit/hyperactivity disorder (OR 1.37; 95% CI 1.17-1.60), and major depressive disorder (OR 1.20; 95% CI 1.05-1.37), with no risk for these disorders observed in children of fathers with RA.

Study details: This was a retrospective cohort study including 23,981 RA-parent-child pairs and age-/sex-matched 239,810 non-RA-parent-child pairs.

Disclosures: This study received research grants from Taipei Veterans General Hospital, Yen

Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

Source: Chiu HJ et al. A nationwide study of the risks of major mental disorders among the offspring of parents with rheumatoid arthritis. Sci Rep. 2022;12:4962 (Mar 23). Doi: 10.1038/s41598-022-08834-5

Key clinical point: Children of mothers, but not fathers, with rheumatoid arthritis (RA) were predisposed to the risk of developing multiple mental disorders.

Major finding: Children of mothers with RA had a significantly higher risk for autism spectrum disorders (odds ratio [OR] 1.49; 95% CI 1.01-2.20), bipolar disorder (OR 1.47; 95% CI 1.20-1.81), attention-deficit/hyperactivity disorder (OR 1.37; 95% CI 1.17-1.60), and major depressive disorder (OR 1.20; 95% CI 1.05-1.37), with no risk for these disorders observed in children of fathers with RA.

Study details: This was a retrospective cohort study including 23,981 RA-parent-child pairs and age-/sex-matched 239,810 non-RA-parent-child pairs.

Disclosures: This study received research grants from Taipei Veterans General Hospital, Yen

Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

Source: Chiu HJ et al. A nationwide study of the risks of major mental disorders among the offspring of parents with rheumatoid arthritis. Sci Rep. 2022;12:4962 (Mar 23). Doi: 10.1038/s41598-022-08834-5

Key clinical point: Patients with seropositive rheumatoid arthritis (RA) were at a higher risk of developing primary open-angle glaucoma (POAG) compared with matched control participants, with risk being evident within 2 years after RA diagnosis and among patients aged ≥75 years.

Major finding: Compared with matched control participants, patients with incident RA were 1.44 times more likely to develop POAG (hazard ratio [HR] 1.44; 95% CI 1.13-1.84), which was predominantly observed within 2 years of RA diagnosis (HR 1.83; 95% CI 1.28-2.61) and in patients aged ≥75 years (HR 2.12;95% CI 1.34-3.35).

Study details: This was a retrospective, nationwide cohort study including 2049 patients with seropositive RA who were propensity score-matched with 8196 control participants without RA.

Disclosures: This study was partly supported by the publication fee from the Graduate School of Public Health, Yonsei University. No conflicts of interest were declared.

Source: Kim SH et al. Development of open-angle glaucoma in adults with seropositive rheumatoid arthritis in Korea. JAMA Netw Open. 2022;5(3):e223345 (Mar 21). Doi:  10.1001/jamanetworkopen.2022.3345

Key clinical point: Patients with seropositive rheumatoid arthritis (RA) were at a higher risk of developing primary open-angle glaucoma (POAG) compared with matched control participants, with risk being evident within 2 years after RA diagnosis and among patients aged ≥75 years.

Major finding: Compared with matched control participants, patients with incident RA were 1.44 times more likely to develop POAG (hazard ratio [HR] 1.44; 95% CI 1.13-1.84), which was predominantly observed within 2 years of RA diagnosis (HR 1.83; 95% CI 1.28-2.61) and in patients aged ≥75 years (HR 2.12;95% CI 1.34-3.35).

Study details: This was a retrospective, nationwide cohort study including 2049 patients with seropositive RA who were propensity score-matched with 8196 control participants without RA.

Disclosures: This study was partly supported by the publication fee from the Graduate School of Public Health, Yonsei University. No conflicts of interest were declared.

Source: Kim SH et al. Development of open-angle glaucoma in adults with seropositive rheumatoid arthritis in Korea. JAMA Netw Open. 2022;5(3):e223345 (Mar 21). Doi:  10.1001/jamanetworkopen.2022.3345

Key clinical point: Patients with seropositive rheumatoid arthritis (RA) were at a higher risk of developing primary open-angle glaucoma (POAG) compared with matched control participants, with risk being evident within 2 years after RA diagnosis and among patients aged ≥75 years.

Major finding: Compared with matched control participants, patients with incident RA were 1.44 times more likely to develop POAG (hazard ratio [HR] 1.44; 95% CI 1.13-1.84), which was predominantly observed within 2 years of RA diagnosis (HR 1.83; 95% CI 1.28-2.61) and in patients aged ≥75 years (HR 2.12;95% CI 1.34-3.35).

Study details: This was a retrospective, nationwide cohort study including 2049 patients with seropositive RA who were propensity score-matched with 8196 control participants without RA.

Disclosures: This study was partly supported by the publication fee from the Graduate School of Public Health, Yonsei University. No conflicts of interest were declared.

Source: Kim SH et al. Development of open-angle glaucoma in adults with seropositive rheumatoid arthritis in Korea. JAMA Netw Open. 2022;5(3):e223345 (Mar 21). Doi:  10.1001/jamanetworkopen.2022.3345

Key clinical point: Some patients with rheumatoid arthritis (RA) had excess disability despite low inflammation level. This persisted over 8-10 years after onset, with age, pain, and depression being significant predictors of disability, independent of inflammation.

Major finding: Nearly 30%-45% of patients with RA persistently showed excess disability over 8-10 years of follow-up, independent of their inflammation status. Patients who were older (odds ratio [OR] 1.05; 95% CI 1.02-1.09) or had higher pain (OR 1.48; 95% CI 1.23-1.78) or depression (OR 1.40; 95% CI 1.01-1.94) were more likely to have higher vs. lower disability trajectory, irrespective of their inflammation level.

Study details: Findings are from an analysis of three cohort studies including 2500 patients with RA and <24 months symptom duration who were followed-up for 8-10 years.

Disclosures: This study was supported by the UK Medical Research Council, Versus Arthritis, UK National Institute for Health Care and Research (NIHR) Manchester Biomedical Research Centre, and NIHR Nottingham Biomedical Research Centre. The authors declared no competing interests directly relevant to this manuscript.

Source: Gwinnutt JM et al. Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Mar 11). Doi: 10.1093/rheumatology/keac137

Key clinical point: Some patients with rheumatoid arthritis (RA) had excess disability despite low inflammation level. This persisted over 8-10 years after onset, with age, pain, and depression being significant predictors of disability, independent of inflammation.

Major finding: Nearly 30%-45% of patients with RA persistently showed excess disability over 8-10 years of follow-up, independent of their inflammation status. Patients who were older (odds ratio [OR] 1.05; 95% CI 1.02-1.09) or had higher pain (OR 1.48; 95% CI 1.23-1.78) or depression (OR 1.40; 95% CI 1.01-1.94) were more likely to have higher vs. lower disability trajectory, irrespective of their inflammation level.

Study details: Findings are from an analysis of three cohort studies including 2500 patients with RA and <24 months symptom duration who were followed-up for 8-10 years.

Disclosures: This study was supported by the UK Medical Research Council, Versus Arthritis, UK National Institute for Health Care and Research (NIHR) Manchester Biomedical Research Centre, and NIHR Nottingham Biomedical Research Centre. The authors declared no competing interests directly relevant to this manuscript.

Source: Gwinnutt JM et al. Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Mar 11). Doi: 10.1093/rheumatology/keac137

Key clinical point: Some patients with rheumatoid arthritis (RA) had excess disability despite low inflammation level. This persisted over 8-10 years after onset, with age, pain, and depression being significant predictors of disability, independent of inflammation.

Major finding: Nearly 30%-45% of patients with RA persistently showed excess disability over 8-10 years of follow-up, independent of their inflammation status. Patients who were older (odds ratio [OR] 1.05; 95% CI 1.02-1.09) or had higher pain (OR 1.48; 95% CI 1.23-1.78) or depression (OR 1.40; 95% CI 1.01-1.94) were more likely to have higher vs. lower disability trajectory, irrespective of their inflammation level.

Study details: Findings are from an analysis of three cohort studies including 2500 patients with RA and <24 months symptom duration who were followed-up for 8-10 years.

Disclosures: This study was supported by the UK Medical Research Council, Versus Arthritis, UK National Institute for Health Care and Research (NIHR) Manchester Biomedical Research Centre, and NIHR Nottingham Biomedical Research Centre. The authors declared no competing interests directly relevant to this manuscript.

Source: Gwinnutt JM et al. Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Mar 11). Doi: 10.1093/rheumatology/keac137

Key clinical point: A majority of patients with rheumatoid arthritis (RA) stopped their first-time biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) because of nonresponse to the treatment. Patients who stopped because of remission vs. nonresponse had worse disease activity at treatment restart.

Major finding: Nonresponse (38%), adverse events (19%), and remission (8%) were the major reasons to stop the first-time b/tsDMARD, with the median time to restart treatment being shortest among patients with nonresponse (30 days) and longest among those with remission (1597 days). Moreover, RA disease activity was worse at b/tsDMARD restart in patients who stopped b/tsDMARD after achieving remission (P < .0001).

Study details: This was an explorative descriptive cohort study including 2526 patients with RA who stopped their first b/tsDMARD treatment.

Disclosures: The study did not declare any source of funding. No conflicts of interest were declared.

Source: Burkard T et al. Interruptions of biological and targeted synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: a descriptive cohort study assessing trends in patient characteristics in Switzerland. BMJ Open. 2022;12:e056352 (Mar 15). Doi: 10.1136/bmjopen-2021-056352

Key clinical point: A majority of patients with rheumatoid arthritis (RA) stopped their first-time biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) because of nonresponse to the treatment. Patients who stopped because of remission vs. nonresponse had worse disease activity at treatment restart.

Major finding: Nonresponse (38%), adverse events (19%), and remission (8%) were the major reasons to stop the first-time b/tsDMARD, with the median time to restart treatment being shortest among patients with nonresponse (30 days) and longest among those with remission (1597 days). Moreover, RA disease activity was worse at b/tsDMARD restart in patients who stopped b/tsDMARD after achieving remission (P < .0001).

Study details: This was an explorative descriptive cohort study including 2526 patients with RA who stopped their first b/tsDMARD treatment.

Disclosures: The study did not declare any source of funding. No conflicts of interest were declared.

Source: Burkard T et al. Interruptions of biological and targeted synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: a descriptive cohort study assessing trends in patient characteristics in Switzerland. BMJ Open. 2022;12:e056352 (Mar 15). Doi: 10.1136/bmjopen-2021-056352

Key clinical point: A majority of patients with rheumatoid arthritis (RA) stopped their first-time biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) because of nonresponse to the treatment. Patients who stopped because of remission vs. nonresponse had worse disease activity at treatment restart.

Major finding: Nonresponse (38%), adverse events (19%), and remission (8%) were the major reasons to stop the first-time b/tsDMARD, with the median time to restart treatment being shortest among patients with nonresponse (30 days) and longest among those with remission (1597 days). Moreover, RA disease activity was worse at b/tsDMARD restart in patients who stopped b/tsDMARD after achieving remission (P < .0001).

Study details: This was an explorative descriptive cohort study including 2526 patients with RA who stopped their first b/tsDMARD treatment.

Disclosures: The study did not declare any source of funding. No conflicts of interest were declared.

Source: Burkard T et al. Interruptions of biological and targeted synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: a descriptive cohort study assessing trends in patient characteristics in Switzerland. BMJ Open. 2022;12:e056352 (Mar 15). Doi: 10.1136/bmjopen-2021-056352

Key clinical point: Higher levels of circulating adiponectin and leptin were associated with an increased risk for all-cause and cardiovascular mortality in patients with rheumatoid arthritis (RA).

Major finding: Patients in the highest vs. lowest quartile of adiponectin were at a 46% higher risk for all-cause mortality (hazard ratio [HR] 1.46; P = .009) and an 85% higher risk for cardiovascular mortality (HR 1.85; P = .003). Patients in the highest vs. lowest quartile of both adiponectin and leptin were at a 73% higher risk for all-cause mortality (HR 1.73; P = .002).

Study details: This was a longitudinal study including 2583 patients with RA.

Disclosures: This study did not declare any source of funding. JF Baker and TR MIkuls reported receiving consulting fees and research support from various sources.

Source: Baker JF et al. Elevations in adipocytokines and mortality in rheumatoid arthritis. Rheumatology (Oxford). 2022 Mar 23. Doi: 10.1093/rheumatology/keac191

Key clinical point: Higher levels of circulating adiponectin and leptin were associated with an increased risk for all-cause and cardiovascular mortality in patients with rheumatoid arthritis (RA).

Major finding: Patients in the highest vs. lowest quartile of adiponectin were at a 46% higher risk for all-cause mortality (hazard ratio [HR] 1.46; P = .009) and an 85% higher risk for cardiovascular mortality (HR 1.85; P = .003). Patients in the highest vs. lowest quartile of both adiponectin and leptin were at a 73% higher risk for all-cause mortality (HR 1.73; P = .002).

Study details: This was a longitudinal study including 2583 patients with RA.

Disclosures: This study did not declare any source of funding. JF Baker and TR MIkuls reported receiving consulting fees and research support from various sources.

Source: Baker JF et al. Elevations in adipocytokines and mortality in rheumatoid arthritis. Rheumatology (Oxford). 2022 Mar 23. Doi: 10.1093/rheumatology/keac191

Key clinical point: Higher levels of circulating adiponectin and leptin were associated with an increased risk for all-cause and cardiovascular mortality in patients with rheumatoid arthritis (RA).

Major finding: Patients in the highest vs. lowest quartile of adiponectin were at a 46% higher risk for all-cause mortality (hazard ratio [HR] 1.46; P = .009) and an 85% higher risk for cardiovascular mortality (HR 1.85; P = .003). Patients in the highest vs. lowest quartile of both adiponectin and leptin were at a 73% higher risk for all-cause mortality (HR 1.73; P = .002).

Study details: This was a longitudinal study including 2583 patients with RA.

Disclosures: This study did not declare any source of funding. JF Baker and TR MIkuls reported receiving consulting fees and research support from various sources.

Source: Baker JF et al. Elevations in adipocytokines and mortality in rheumatoid arthritis. Rheumatology (Oxford). 2022 Mar 23. Doi: 10.1093/rheumatology/keac191