American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement
in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus
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 (CRIcSLE). Methods Pediatric nephrology and
rheumatology subspecialists (n = 213) experienced in cSLE management were invited
to define CRIcSLE and rate a total of 433 unique patient profiles for the presence/absence
of CRIcSLE. 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 CRIcSLE
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 CRIcSLE (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.
