Socioeconomic Factors Are Associated With Severity of Hospitalization in Pediatric Lupus: An Analysis of the 2016 Kids' Inpatient Database.

OBJECTIVE: Health disparities in adult lupus, including higher disease severity and activity among those in poverty, have been identified. Similar associations in pediatric lupus have not been clearly established. This study was undertaken to investigate the relationship of income level and other socioeconomic factors with length of stay (LOS) in the hospital and severe lupus features using the 2016 Kids' Inpatient Database (KID). METHODS: Lupus hospitalizations were identified in children ages 2-20 years in the 2016 KID using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes (M32). Univariate and multivariate negative binomial regression analyses were used to analyze the association of income level, race and ethnicity, and insurance status with LOS in the hospital. Univariate and multivariate logistic regression analyses were used to analyze the association of the same predictors with the presence of severe lupus features, defined using ICD-10 codes associated with lupus sequelae (e.g., lupus nephritis). RESULTS: A total of 3,367 unweighted (4,650 weighted) lupus hospitalizations were identified. Income level was found to be a statistically significant predictor of increased LOS in the hospital for those in the lowest income quartile (adjusted incidence rate ratio 1.12 [95% confidence interval (95% CI) 1.02-1.23]). Black race, "other" race, and public insurance were also associated with severe lupus features (adjusted odds ratio [ORadj ] 1.51 [95% CI 1.11-2.06]; ORadj 1.61 [95% CI 1.01-2.55]; and ORadj 1.51 [95% CI 1.17-2.55], respectively). CONCLUSION: Using a nationally representative data set, income level was found to be a statistically significant predictor of LOS in the hospital among those with the lowest reported income, highlighting a potential target population for intervention. Additionally, Black race and public insurance were associated with severe lupus features.

Cumulative Social Disadvantage Associated with Childhood Arthritis: A Cross-Sectional Analysis of the National Survey of Children's Health.

OBJECTIVE: Health disparities in juvenile idiopathic arthritis (JIA) remain poorly understood. Social disadvantage may have a cumulative impact on health, with recent analyses using combined scoring systems to measure their impact on outcomes. Our aim was to investigate cumulative social disadvantage on childhood arthritis by using a cumulative score to analyze its association with arthritis among a nationally representative sample of children. METHODS: A cross-sectional analysis of the National Survey of Children's Health (2016-2019) was performed. A cumulative social disadvantage score was generated (1 point each, with a maximum score of 4): low guardian education (high school or less), low household income level (0-199% of federal poverty level), underinsured status (public or uninsured), and high adverse childhood experience (ACE) score (≥4). Univariate and multivariable (adjusting for age, sex, and race and ethnicity) logistic regression models were used to measure the association between cumulative social risk and the odds of an arthritis diagnosis and moderate-to-severe parent-reported arthritis severity. RESULTS: Of 131,774 surveys completed, a total of 365 children reported current arthritis. Cumulative social disadvantage was associated with an arthritis diagnosis, with the highest odds among those with a score of 4 (adjusted odds ratio [ORadj ] 12.4 [95% confidence interval (95% CI) 2.9-53.3]). Cumulative social disadvantage also was associated with increased odds of moderate-to-severe arthritis severity (ORadj 12.4 [95% CI 1.8-82.6]). CONCLUSION: In this nationally representative sample, accumulated social disadvantage, measured via a cumulative social disadvantage score based on income level, guardian education, insurance status, and ACE exposure, was associated with an arthritis diagnosis and moderate-to-severe arthritis severity.

Social determinants of health influence disease activity and functional disability in Polyarticular Juvenile Idiopathic Arthritis.

BACKGROUND: Social determinants of health (SDH) greatly influence outcomes during the first year of treatment in rheumatoid arthritis, a disease similar to polyarticular juvenile idiopathic arthritis (pJIA). We investigated the correlation of community poverty level and other SDH with the persistence of moderate to severe disease activity and functional disability over the first year of treatment in pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry. METHODS: In this cohort study, unadjusted and adjusted generalized linear mixed effects models analyzed the effect of community poverty and other SDH on disease activity, using the clinical Juvenile Arthritis Disease Activity Score-10, and disability, using the Child Health Assessment Questionnaire, measured at baseline, 6, and 12 months. RESULTS: One thousand six hundred eighty-four patients were identified. High community poverty (≥20% living below the federal poverty level) was associated with increased odds of functional disability (OR 1.82, 95% CI 1.28-2.60) but was not statistically significant after adjustment (aOR 1.23, 95% CI 0.81-1.86) and was not associated with increased disease activity. Non-white race/ethnicity was associated with higher disease activity (aOR 2.48, 95% CI: 1.41-4.36). Lower self-reported household income was associated with higher disease activity and persistent functional disability. Public insurance (aOR 1.56, 95% CI 1.06-2.29) and low family education (aOR 1.89, 95% CI 1.14-3.12) was associated with persistent functional disability. CONCLUSION: High community poverty level was associated with persistent functional disability in unadjusted analysis but not with persistent moderate to high disease activity. Race/ethnicity and other SDH were associated with persistent disease activity and functional disability.

Journal Club Review of "Avacopan for the Treatment of ANCA-Associated Vasculitis".

JOURNAL CLUB: Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med 2021;384:599-609. OBJECTIVE: The C5a receptor inhibitor avacopan is being studied for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: In this randomized, controlled trial, we assigned patients with ANCA-associated vasculitis in a 1:1 ratio to receive oral avacopan at a dose of 30 mg twice daily or oral prednisone on a tapering schedule. All the patients received either cyclophosphamide (followed by azathioprine) or rituximab. The first primary endpoint was remission, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 (on a scale from 0 to 63, with higher scores indicating greater disease activity) at week 26 and no glucocorticoid use in the previous 4 weeks. The second primary endpoint was sustained remission, defined as remission at both weeks 26 and 52. Both endpoints were tested for noninferiority (by a margin of 20 percentage points) and for superiority. RESULTS: A total of 331 patients underwent randomization; 166 were assigned to receive avacopan, and 165 were assigned to receive prednisone. The mean BVAS at baseline was 16 in both groups. Remission at week 26 (the first primary endpoint) was observed in 120 of 166 patients (72.3%) receiving avacopan and in 115 of 164 patients (70.1%) receiving prednisone (estimated common difference, 3.4 percentage points; 95% confidence interval [CI], -6.0 to 12.8; P < 0.001 for noninferiority; P = 0.24 for superiority). Sustained remission at week 52 (the second primary endpoint) was observed in 109 of 166 patients (65.7%) receiving avacopan and in 90 of 164 patients (54.9%) receiving prednisone (estimated common difference, 12.5 percentage points; 95% CI, 2.6 to 22.3; P < 0.001 for noninferiority; P = 0.007 for superiority). Serious adverse events (excluding worsening vasculitis) occurred in 37.3% of the patients receiving avacopan and in 39.0% of those receiving prednisone. CONCLUSION: In this trial involving patients with ANCA-associated vasculitis, avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52. All the patients received cyclophosphamide or rituximab. The safety and clinical effects of avacopan beyond 52 weeks were not addressed in the trial. (Funded by ChemoCentryx; ADVOCATE ClinicalTrials.gov number, NCT02994927.). https://pubmed.ncbi.nlm.nih.gov/33596356/ ANCA-associated vasculitis (AAV) is a chronic autoimmune disease characterized by progressive pauci-immune glomerulonephritis and inflammation of the respiratory tract traditionally requiring treatment with corticosteroids. The ADVOCATE trial was a phase III randomized double-blind placebo-controlled clinical trial to investigate whether avacopan, a C5a receptor inhibitor involved in blocking complement activation, could replace steroids in induction therapy for AAV in addition to standard-of-care therapy via a noninferiority trial design. The ADVOCATE trial met its primary endpoint of clinical remission at week 26 (3.4% difference between treatment and placebo; 95% CI: -6.0 to 12.8%; P < 0.001 for noninferiority) and at week 52 (12.5% difference; 95% CI: 2.6% to 22.3%; P = 0.007 for superiority). Strengths of this study include its international and multicenter involvement, rigorous study design and analysis, and minimal loss to follow-up. Potential weaknesses of this study include the lack of rituximab maintenance as part of standard-of-care treatment beyond week 4 of induction therapy and complete wean off prednisone by week 21, much faster than steroid weans in prior trials (including PEXIVAS), which may somewhat limit our interpretation of the noninferiority of avacopan to prednisone. Overall, the ADVOCATE trial yielded thought-provoking clinical implications that may revolutionize AAV treatment moving forward, including less reliance on corticosteroids to achieve clinical remission in AAV.

Community poverty level influences time to first pediatric rheumatology appointment in Polyarticular Juvenile Idiopathic Arthritis.

BACKGROUND: The impact of social determinants of health on children with polyarticular juvenile idiopathic arthritis (pJIA) is poorly understood. Prompt initiation of treatment for pJIA is important to prevent disease morbidity; however, a potential barrier to early treatment of pJIAs is delayed presentation to a pediatric rheumatologist. We examined the impact of community poverty level, a key social determinant of health, on time from patient reported symptom onset to first pediatric rheumatology visit among pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. METHODS: This is a cohort study of pJIA patients in the CARRA registry who lived in the United States from July 2015-February 2020. The primary exposure was community poverty level derived by geocoding patient addresses. The primary outcome was time to first rheumatology appointment. Kaplan-Meier analysis was performed to analyze time to first rheumatologist visit, stratified by community poverty and family income. Log-rank tests were used to identify differences between groups. Adjusted cox proportional-hazards models were used to determine the relationship between community poverty level and time from onset of disease symptoms to date first seen by rheumatologist. RESULTS: A total of 1684 patients with pJIA meeting study inclusion and exclusion criteria were identified. Median age of onset of pJIA was 7 years (IQR 3, 11), 79% were female, 17.6% identified as minority race and/or ethnicity, and 19% were from communities with ≥20% community poverty level. Kaplan-Meier analysis by community poverty level (< 20% vs ≥20%) yielded no significant differences with time to initial presentation to a pediatric rheumatologist (p = 0.6). The Cox proportional hazards model showed that patients with ≥20% community poverty level were 19% less likely (adjusted HR 0.81, 95% CI 0.67-0.99, p = 0.038) to be seen by a rheumatologist compared to patients with < 20% community poverty level, at the same time point, after adjusting for sex, race/ethnicity, insurance, education level, morning stiffness, RF status, and baseline CHAQ. CONCLUSION: In this study of pJIA patients in the CARRA registry, increased community poverty level is associated with longer time to presentation to a pediatric rheumatologist after symptom onset.