Objective To formulate consensus treatment plans (CTPs) for induction therapy of newly-diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (jSLE). Methods A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) after considering the existing medical evidence and current treatment approaches. Results After an initial Delphi survey (response rate 70%), a 2-day consensus conference, and two follow-up Delphi surveys (response rates 63–79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypic patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized doses for six months. Additionally, the CTPs describe three options for standardized use of glucocorticoids; including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs. Conclusion CTPs for induction therapy of proliferative LN in jSLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in jSLE.

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OBJECTIVES To characterize the epidemiology and clinical course of children with juvenile idiopathic arthritis-associated uveitis (JIA-U) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and explore differences between African American (AA) and Non-Hispanic White (NHW) children. METHODS There were 3,967 NHW and AA children with JIA enrolled in the CARRA Registry. Demographic and disease-related data were collected from time of diagnosis to enrollment. Children with JIA alone were compared to those with JIA-U. Children with JIA-U were then compared by race. RESULTS Mean age of children with JIA-U was 11.4 years (±4.5), 76.9% were female and 2.8% were AA. Children with JIA-U were younger at arthritis onset, female, required more medications, had <5 joints involved, had oligoarticular JIA, and ANA (+), RF (−) and anti-CCP (−). AA children with JIA-U had decreased uveitis frequency, were older at arthritis onset and more frequently diagnosed with enthesitis-related JIA. Predictors of uveitis development include female gender, early age of arthritis onset, and oligoarticular persistent and extended JIA classification, whereas polyarticular RF-positive JIA was protective. CONCLUSIONS The prevalence of JIA-U in AA and NHW children is 11.6% in the CARRA registry. Known risk markers (ANA, age at arthritis onset, and oligoarticular JIA) were more frequent in our JIA-U cohort. AA children had a lower frequency of JIA-U. There were significant differences in age of arthritis onset and JIA subtype between NHW and AA children, although the ANA, RF and HLA-B27 were similar. Exploration of race as a risk factor should be considered.

BackgroundCanakinumab is a human anti-interleukin-1β (IL-1β) monoclonal antibody neutralizing IL-1β-mediated pathways. We sought to characterize the molecular response to canakinumab and evaluate potential markers of response using samples from two pivotal trials in systemic juvenile idiopathic arthritis (SJIA).MethodsGene expression was measured in patients with febrile SJIA and in matched healthy controls by Affymetrix DNA microarrays. Transcriptional response was assessed by gene expression changes from baseline to day 3 using adapted JIA American College of Rheumatology (aACR) response criteria (50 aACR JIA). Changes in pro-inflammatory cytokines IL-6 and IL-18 were assessed up to day 197.ResultsMicroarray analysis identified 984 probe sets differentially expressed (≥2-fold difference; P < 0.05) in patients versus controls. Over 50% of patients with ≥50 aACR JIA were recognizable by baseline expression values. Analysis of gene expression profiles from patients achieving ≥50 aACR JIA response at day 15 identified 102 probe sets differentially expressed upon treatment (≥2-fold difference; P < 0.05) on day 3 versus baseline, including IL-1β, IL-1 receptors (IL1-R1 and IL1-R2), IL-1 receptor accessory protein (IL1-RAP), and IL-6. The strongest clinical response was observed in patients with higher baseline expression of dysregulated genes and a strong transcriptional response on day 3. IL-6 declined by day 3 (≥8-fold decline; P < 0.0001) and remained suppressed. IL-18 declined on day 57 (≥1.5-fold decline, P ≤ 0.002).ConclusionsTreatment with canakinumab in SJIA patients resulted in downregulation of innate immune response genes and reductions in IL-6 and clinical symptoms. Additional research is needed to investigate potential differences in the disease mechanisms in patients with heterogeneous gene transcription profiles.Trial registrationClinicaltrials.gov: NCT00886769 (trial 1). Registered on 22 April 2009; NCT00889863 (trial 2). Registered on 21 April 2009.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1212-x) contains supplementary material, which is available to authorized users.