A new validated definition of response to therapy in juvenile systemic lupus erythematosus may help standardize the conduct and reporting of clinical trials and help physicians decide whether a child has responded adequately to therapy, authors of the definition reported.
The standard for improvement is set high: Juvenile lupus can be considered to have improved only when the symptoms have lessened by at least 50% in three of five specific outcome measures. The definition of improvement culminates a three-stage process undertaken by the Pediatric Rheumatology International Trials Organization (PRINTO) to develop and validate a set of outcome measures and a definition of clinical improvement that can be used to evaluate “global response” to therapy by a child with systemic lupus erythematosus (SLE).
The definition includes a global measure of SLE activity and measurement of 24-hour proteinuria, but it also considers a physician's subjective assessment of the level of disease activity as well as parent-reported outcomes.
“One of the reasons we don't have drugs approved, for instance, is that we haven't had good methods for assessing drugs in clinical trials,” said Dr. Edward H. Giannini of Children's Hospital Medical Center in Cincinnati, one of the authors and a facilitator of the consensus conference.
PRINTO worked on the definition in conjunction with the Pediatric Rheumatology Collaborative Study Group. The criteria were approved by the American College of Rheumatology board of directors as “provisional,” according to the report (Arthritis Rheum. 2006;55:355–63). “Now the criteria will be used in trials, in larger databases… and we'll look to see whether they continue to be valid,” Dr. Giannini said.
The new criteria define “improvement” in children with juvenile SLE as at least 50% improvement from baseline in any two of the five outcomes measures that were earlier developed and validated by PRINTO, with no more than one of the remaining measures worsening by more than 30%.
The outcomes measures include:
▸ The physician's global assessment of the patient's overall disease activity on a 10-cm visual analog scale.
▸ Global disease activity as measured using the European Consensus Lupus Activity Measurement (ECLAM) tool, the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or the Systemic Lupus Activity Measure (SLAM).
▸ Renal involvement as assessed by 24-hour proteinuria.
▸ The parent's global assessment of the child's overall well-being on a 1-cm visual analog scale.
▸ A quality of life assessment using the parent's version of the Child Health Questionnaire (physical summary score).