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.

Objective: We compared clinical characteristics and renal response in patients with childhood‐onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen.Methods: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome.Results: One hundred forty‐five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29–1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57–3.19).Conclusion: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood‐onset proliferative LN. However, future prospective outcome studies are needed. image

Objective: Differential disease control may contribute to racial disparities in outcomes of childhood‐onset systemic lupus erythematosus (cSLE). We evaluated associations of race and individual‐ or neighborhood‐level social determinants of health (SDoH) with achievement of low lupus disease activity state (LLDAS), a clinically relevant treatment target.Methods: In this cSLE cohort study using the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, the primary exposure was self‐reported race and ethnicity, and collected SDoH included insurance status and area deprivation index (ADI). Outcomes included LLDAS, disease activity, and time‐averaged prednisone exposure. Associations among race and ethnicity, SDoH, and disease activity were estimated with multivariable regression models, adjusting for disease‐related and demographic factors.Results: Among 540 children with cSLE, 27% identified as Black, 25% identified as White, 23% identified as Latino/a, 11% identified as Asian, 9% identified as more than one race, and 5% identified as other. More Black children (41%) lived in neighborhoods of highest ADI compared to White children (16%). Black race was associated with lower LLDAS achievement (adjusted odds ratio 0.56, 95% confidence interval [CI] 0.38–0.82) and higher disease activity (adjusted β 0.94, 95% CI 0.11–1.78). The highest ADI was not associated with lower LLDAS achievement on adjustment for renal disease and insurance. However, renal disease was found to be a significant mediator (P = 0.04) of the association between ADI and prednisone exposure.Conclusions: Children with cSLE who identified as Black are less likely to achieve LLDAS and have a higher disease activity. Living in areas of higher ADI may relate to renal disease and subsequent prednisone exposure. Strategies to address root causes will be important to design interventions mitigating cSLE racial disparities.

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.