Scleroderma,also known as systemic sclerosis (SSc), is a multisystem disease affecting skin
and other tissues including joints, muscles, lungs, the gastrointestinal tract and kidneys
and tissue fibrosis is widespread. SSc presents special problems for developing therapies due
to the heterogeneous clinical presentation, the variability of disease progression and the
difficulty quantifying the extent of disease. For most disease manifestations, treatment is
primarily symptomatic and generally inadequate.
This study will utilize a 4-gene biomarker of skin disease as the primary efficacy outcome in
a short duration, placebo-controlled clinical trial of rilonacept, designed to provide
preliminary data for a larger trial. These gene biomarkers should provide a strong surrogate
for such trials in the future and, if IL-1 is indeed the cytokine leading to fibrosis in this
disease, provide a highly significant start to finding a therapeutic for SSc that for the
first time might dramatically affect fibrosis. A central hypothesis of this study is that
IL-1 inhibition will downregulate the 4-gene biomarker over a relatively short period of
time, much shorter than is historically thought necessary to see changes in the MRSS, a skin
score measurement tool. Entry criteria will include the recent onset of diffuse cutaneous SSc
as this is the population most likely to show progressive skin disease and also the
population examined in previous studies showing correlations between MRSS and the 4-gene
biomarker.
Secondary outcomes will include other validated measures of SSc disease activity. MRSS and
SSc health assessment questionnaire (SHAQ), will be followed during the trial. This study
will also test the effect of rilonacept on global skin gene expression using microarray
analyses of skin biopsies. In addition, serum biomarkers of SSc disease activity (COMP, THS-1
and IFI44) and a biomarker of inflammasome activation (CRP) will be tested before and after
treatment.