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CS-10 Criteria for clinically relevant improvement in children & adolescents with childhood-onset systemic lupus erythematosus
  1. Hermine I Brunner1,
  2. Michael Holland1,
  3. Michael W Beresford2,
  4. Stacy P Ardoin3,
  5. Simone Appenzeller4,
  6. Clovis A Silva5,
  7. Francisco Flores6,
  8. Beatrice Goilav7,
  9. Pinar Ozge Avar1,
  10. Scott E Wenderfer8,
  11. Deborah M Levy9,
  12. Angelo Ravelli10,
  13. Raju Khunchandani11,
  14. Tadej Avcin12,
  15. Marisa S Klein-Gitelman13,
  16. Brian M Feldman9,
  17. Nicola Ruperto10 and
  18. Jun Ying14
  1. 1Department of Pediatrics, University of Cincinnati and Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
  2. 2Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of Paediatric Rheumatology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK
  3. 3Department of Pediatrics and Internal Medicine, Ohio State University, Division of Rheumatology, Nationwide Children’s Hospital and Wexner Medical Center, Columbus, OH
  4. 4Rheumatology Unit-Faculty of Medical Science; University of Campinas, Campinas, Brazil
  5. 5Children’s Institute, Hospital das Clinicas HCFMUSP; Faculdade de Medicina da Universidade de São Paulo, Brazil
  6. 6Department of Pediatrics, University of Cincinnati and Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
  7. 7The Children’s Hospital at Montefiore, Division of Nephrology and Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY
  8. 8Department of Pediatrics, Baylor College of Medicine; Renal Section, Texas Children’s Hospital Houston, TX
  9. 9Department of Pediatrics, University of Toronto and Division of Rheumatology, Hospital for Sick Children, Toronto, Canada
  10. 10Istituto G. Gaslini, Pediatria II, Reumatologia, Genoa, Italy
  11. 11Pediatric Rheumatology; Jaslok Hospital Mumbai, India
  12. 12Department of Allergology, Rheumatology and Clinical Immunology, University Children’s Hospital, University Medical Centre Ljubljana, Slovenia
  13. 13Department of Pediatrics, Northwestern University Feinberg School of Medicine and Division of Rheumatology, Ann and Robert Lurie Children’s Hospital of Chicago, Chicago, IL
  14. 14Department of Environmental Health Sciences, University of Cincinnati, Cincinnati, OH


Background There is international consensus around a core set of variables (cSLE-CRVs) to assess response to therapy with childhood-onset systemic lupus erythematosus (cSLE) [global assessment of patient well-being (Patient-global), physician assessment of cSLE activity (MD-global), disease activity index score, urine protein to creatinine ratio (PCR), Child Health Questionnaire physical function summary score (CHQ-Phs)]. Percentage changes of these cSLE-CRVs are used in the Provisional PRINTO-ACR- EULAR Criteria of Response to Therapy of cSLE (PCI). In a small dataset, we have previously shown that the PCI and the Systemic Lupus Responder Index only have fair accuracy in detecting cSLE improvement. The Objective of this research was to 1) validate the PCI and 2) develop for Children an Index of Lupus Improvement (CHILI) as a tool to measure response to therapy, with focus on clinically relevant improvement (CRIcSLE).

Methods Pediatric subspecialists (n=213) in treating cSLE were invited to define CRIcSLE and rate a total of 433 unique patient profiles for the presence/absence of CRIcSLE and various levels of improvement. Patient profiles included the cSLE-CRVs and routine laboratory tests at a baseline and follow-up time-point. To measure CRIcSLE we tested the PCI, and developed the candidate CHILI criteria that considered a) absolute and b) percentage changes of the cSLE-CRVs (baseline vs follow-up) in a trainings-dataset and initially validated these criteria in the validation-dataset. Criteria accuracy was assessed by kappa statistics (PCI) and the area under the ROC curve (AUC; range: 0–1)], respectively.

Results During an international consensus conference agreement on a definition of CRIcSLE was achieved. Response rate to patient profile ratings was 91% (194/214). The PIC had no more than fair accuracy (kappa <0.43). There was consensus (92.3%) that the CHILI is preferable to the PCI to measure CRIcSLE. As shown in the figure 1, considering absolute changes of the cSLE-CRVs, a CHILI score of ≥54 (range 0–100) was highly accurate for identifying CRIcSLE (AUC=0.93; sensitivity=81.1%; specificity=84.2%) in the validation-dataset. Likewise CHILI scores exceeding 15, 68 and 92 reflected minor, moderate and major improvement for values (all: AUC >0.92, sensitivity: >93.1%; specificity: >73.4%), respectively.

Abstract CS-10 Figure 1

CHILI scores were calculated from logit scores using multivariate logistic models considering either absolute differences between the baseline and follow-up time point at the time of follow-up relative of the baseline visit in the trainings-dataset. The range of the improvement score has been standardized to range from 0–100, the higher (lower) score indicates higher (lower) likelihood of improvement. The CHILI score =100 × raw score/(1+raw score). The raw score is calculated as follows: raw score =Exp (5.1+0.47xSLEDAI +0.7xMD-global +1.1xPC-ratio–0.32xpatient-global +0.002xCHQ-Phs)

Conclusions The CHILI is a new highly accurate index to capture improvement in the overall course of cSLE. This index is also useful to categorize the degree of cSLE response to therapy.

Acknowledgements For the Pediatric Rheumatology International Trial Network and the Pediatric Rheumatology Collaborative Study Group; the study is supported by NIH grants 5U01-AR51868, P30-AR AR47363 and 2UL1RR026314 and the PRCSG and PRINTO Coordinating Centers. This study is also supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2015/03756–4 to CAS), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 303422/2015–7 to CAS) and by Núcleo de Apoio à Pesquisa ‘Saúde da Criança e do Adolescente’ da USP (NAP-CriAd) to CAS.

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