Macrophage Activation Syndrome

Macrophage activation syndrome (MAS) is a severe, potentially life-threatening condition involving a massive inflammatory response that overwhelms the whole body. It mainly affects children and symptoms include: fever, tiredness, low energy, headaches, confusion, seizures, enlarged lymph nodes, liver and spleen problems and bleeding disorders.

Current standard therapy includes high dose glucocorticoid (GC) treatment, although these have significant side effects including reduced growth rate, cataracts, mood changes and weight gain. Long term exposure to GC causes significant harm, especially in children.

The data

The data provided are based on two pooled open-label studies in children (n=39) with a diagnosis of MAS disease currently receiving GC treatment. Enrolled subjects started a new investigational drug on day 1, and one objective of the study was to reduce (taper) the GC dose to a safe level during the 8 week interventional period.

The data include daily GC doses levels for the 56 day interventional period, and also weekly average GC doses (week 1-8).

Variable Name	Variable Label
SUBJID	Subject identifier for the study
ASTDY	Analysis relative start day
AVAL1	Daily glucocorticoid dose (mg/kg/day)
AVISITN	Analysis visit (N)
AVISIT	Analysis visit
AVAL2	Weekly average glucocorticoid dose

The Challenge

• How effective was the new investigational drug in reducing GC doses over 8 weeks?
• Clinically important thresholds are 1.0, 0.5 and 0.2 mg/kg/day:
  • What proportion of subjects achieved GC doses between these levels, and how did this change over time?
  • How much variability was there in GC doses, e.g. characterise shifts between threshold levels at the individual subject level?