Multicenter 1-year RCTs in SSc-ILD are feasible.
FVC% predicted is responsive to change in a 1 year RCT.
Patient reported outcomes are feasible and are responsive to change.
Mahler's transition dyspnea index (TDI) is responsive to change in a 1 year RCT and minimally important difference estimate for improvement and worsening of TDI, which is 1.5 units(
21).
The Health Assessment Questionnaire Disability Index for SSc is a responsive tool in SSc-ILD over 1 year (difference of 0.16 favoring cyclophosphamide; p<=0.009), with changes greater than the minimally clinically important change for SSc(which is 0.14 for SSc(
20)).
Patients who had baseline FVC% predicted < 70% have a greater placebo-corrected improvement in their FVC% predicted (placebo corrected improvement= 4.62%, p=0.007) with CYC than other patients(22)
Change in FVC is a superior end-point to change in DLCO or the six minute walk distance and can be regarded as the preferred primary end-point for future studies.
Change in DLCO did not mirror treatment effects on FVC and other variables and is an unsatisfactory primary end-point, influenced equally by changes in interstitial and vascular disease.
Change in the six minute walk distance exhibited striking long-term variability in the BUILDS studies and is an unsatisfactory primary end-point.
Extent of fibrosis on the baseline HRCT scan is a significant predictor of worsening FVC in the placebo group and of response to CYC in the SLS(18) ••.
Extent of ground glass appearance on the baseline HRCT scan is not a significant predictor of response to CYC in the SLS •• and in the UK observational cohort.
BAL cellularity at baseline is not a predictor of response in the SLS −1(57;58)••.
Presence of placebo group may lead to a selection bias where a less severe population is enrolled in the study. In the SLS, mean (SD) decline in the FVC% predicted in the placebo group was −2.9 (8.3) over 12 months, likely leading to a small treatment effect.
