Rationale for Rilonacept In This Study 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. The variability of disease progression presents particular challenges for deciding whom to treat, leading to overtreatment of patients as well as misinterpretation of open label trials. This heterogeneity of disease progression has also required recruitment of relatively large patient numbers into clinical trials, many with skin disease that is going to stabilize or improve spontaneously (Amjadi et al., 2009).