The relationship between forced vital capacity (FVC), modified Rodnan skin score (mRSS) and long-term patient outcomes in systemic sclerosis (SSc) with interstitial lung disease (ILD): a literature review

<bold>Background:</bold> Identifying a strong relationship between short-term clinical trial outcomes and long-term patient/payer relevant outcomes for SSc-ILD could allow faster appraisal of orphan drugs via surrogate outcomes while clinical studies are ongoing. <bold>Aim:</bold> Investigate if a surrogate relationship exists between FVC or mRSS and long-term overall survival (OS) or health-related quality of life (HRQoL) in patients with SSc-ILD. <bold>Method:</bold> A targeted literature review (TLR) of Embase, NICE appraisals and bibliography searches investigated evidence of a relationship between FVC or mRSS and long-term OS or HRQoL. Strength of associations assessed using established criteria. A clinical systematic literature review (SLR) of MEDLINE, Embase, CCTR and clinical trial registries using PRISMA guidelines established an evidence base for surrogacy analyses. GSK Studies 219938, 222153. <bold>Results:</bold> No studies in the TLR (N=10) reported correlation coefficients or coefficients of determination to evaluate the strength of relationships between outcomes. Limited evidence suggested a clinically plausible relationship between FVC and OS in SSc/SSc-ILD (3 studies), and between mRSS and OS in SSc/diffuse cutaneous SSc (2 studies). Available evidence found no relationship between FVC or mRSS and HRQoL. In the SLR, FVC, mRSS and OS were reported in most of the 35 trials identified. <bold>Conclusions:</bold> De novo surrogacy analyses are warranted to provide more robust evidence for potential relationships between FVC or mRSS and long-term outcomes in SSc-ILD; the SLR suggests this is feasible with existing evidence. <bold>Funding:</bold> GSK