American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

the Paediatric Rheumatology International Trial Organisation and Pediatric Rheumatology Collaborative Study Group

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Objective: To develop a Childhood Lupus Improvement Index (CHILI) as a tool to measure response to therapy in childhood-onset systemic lupus erythematosus (cSLE), with a focus on clinically relevant improvement (CRI c SLE ). Methods: Pediatric nephrology and rheumatology subspecialists (n = 213) experienced in cSLE management were invited to define CRI c SLE and rate a total of 433 unique patient profiles for the presence/absence of CRI c SLE . Patient profiles included the following cSLE core response variables (CRVs): global assessment of patient well-being (patient-global), physician assessment of cSLE activity (MD-global), disease activity index score (here, we used the Systemic Lupus Erythematosus Disease Activity Index), urine protein-to-creatinine ratio, and Child Health Questionnaire physical summary score. Percentage and absolute changes in these cSLE-CRVs (baseline versus follow-up) were considered in order to develop candidate algorithms and validate their performance (sensitivity, specificity, area under the receiver operating characteristic curve [AUC]; range 0–1). Results: During an international consensus conference, unanimous agreement on a definition of CRI c SLE was achieved; cSLE experts (n = 13) concurred (100%) that the preferred CHILI algorithm considers absolute changes in the cSLE-CRVs. After transformation to a range of 0–100, a CHILI score of ≥54 had outstanding accuracy for identifying CRI c SLE (AUC 0.93, sensitivity 81.1%, and specificity 84.2%). CHILI scores also reflect minor, moderate, and major improvement for values exceeding 15, 68, and 92, respectively (all AUC ≥0.92, sensitivity ≥93.1%, and specificity ≥73.4%). Conclusion: The CHILI is a new, seemingly highly accurate index for measuring CRI in cSLE over time. This index is useful to categorize the degree of response to therapy in children and adolescents with cSLE.

Original languageEnglish (US)
Pages (from-to)579-590
Number of pages12
JournalArthritis Care and Research
Issue number5
StatePublished - May 2019

Bibliographical note

Funding Information:
We thank Kasha Wiley (overall study coordination), Susan Priest (consensus conference logistics), Carly Muller, Malea Rolfsen, Allen Watts, Gaurav Gulati, and Jamie Meyers-Eaton (patient profile testing) from Cincinnati Children Hospital Medical Center (CCHMC) as well as CCHMC Biomedical Informatics (web-based data management application development). We are indebted to the members of the External Scientific Advisory Committee of this study for their advice regarding study implementation, conduct, and statistical analysis: Drs. Tuhina Neogi, Ian Bruce, David Isenberg, Nicola Ruperto, and James Witter.

Funding Information:
12Marisa S? Klein-Gitelman, MD: Northwestern University Feinberg School of Medicine and Ann and Robert Lurie Children’s Hospital of Chicago, Chicago, 阀llinois13;J un Ying, PhD: University of Cincinnati, Cincinnati, Ohio? Dr? ?runner has received consulting fees from AbbVie, Ablynx, Amgen, AstraZeneca, ?axalta ?iosimilars, ?iogen 阀dec, ?oehringer 阀ngelheim, ?ristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, Gilead Sciences, Janssen, Med 阀mmune, Novartis, Pfizer, R-Pharm, Roche, Servier, Takeda (less than $10,000 each), speaking fees from Genentech and Novartis (more than $10,000 each), and Scientific grant support from Pfizer and ?ristol-Myers Squibb for research studies in adult lupus and juvenile idiopathic arthritis? Dr? ?runner is a full-time employee of Cincinnati Children’s Hospital, which has received contributions from ?ristol-Myers Squibb, Ho 贀man-La Roche, Janssen, Novartis, and Pfizer for the coordination activity of the Pediatric Rheumatology Collaborative Study Group network? Dr? Ravelli has received consulting and/or speaking fees from AbbVie, ?ristol-Myers Squibb, Pfizer, Ho 贀man-LaRoche, Novartis, Centocor, “Francesco Angelini,” and Reckitt ?enckiser (less than $10,000 each)? Dr? Avcin has received consulting and/or speaking fees from AbbVie and ?oehringer 阀ngelheim (less than

Funding Information:
Supported by the N 阀H (grants 5U01-AR-51868, P30-AR-AR47363, and 2UL1-RR-026314)? Dr? Silva’s work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 215/03756-4), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 303422/2015-7 and CNPq 304255/2015-7), and by Núcleo de Apoio à Pesquisa “Saúde da Criança e do Adolescente” da USP (NAP-CriAd)? Dr? Ardoin’s work was supported by CNPq 7/2016-9?

Publisher Copyright:
© 2019, American College of Rheumatology


Dive into the research topics of 'American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus'. Together they form a unique fingerprint.

Cite this