Skip to main content

Table 2 Major randomized controlled trials investigating antifibrotic or immunosuppressive treatments in patients with non-IPF ILD

From: Progression of fibrosing interstitial lung disease

StudyPatient population (sample size)Treatmenta1o endpointSelected 2o endpoints
Antifibrotic medication
 SENSCIS (Phase 3) [56]
NCT02597933
SSc-ILD (576)NintedanibNintedanib reduced the rate of FVC decline over 52 weeks (mean between-group difference 41 mL; 95%CI 2.9-79 mL, p = 0.04), with smaller absolute benefit from nintedanib compared to IPF clinical trials.No difference in mRSS and QOL.
 INBUILD (Phase 3) [14]
NCT02999178
PF-ILD (663): Fibrotic HP, CTD-ILD, iNSIP, unclassifiable ILDNintedanibNintedanib reduced the rate of FVC decline over 52 weeks (mean between-group difference 107 mL; 95%CI 65-149 mL, p < 0.001), with similar absolute benefit from nintedanib compared to IPF clinical trials.No difference in QOL and survival.
 LOTUSS (Phase 2/Open-label) [57]
NCT01933334
SSc-ILD (63)Pirfenidone
(stable background therapy with MMF allowed)
An adverse event occurred in 97% of patients over 16 weeks. Patients in the 4 week titration group had improved tolerability compared to patients in the 2 week titration group. Tolerability was similar among patients on both MMF and pirfenidone compared to patients on pirfenidone only.No difference in FVC, DLCO, patient-reported outcomes or mRSS between the titration groups.
 RELIEF (Phase 2) [23]
DRKS00009822
PF-ILD (127): CTD-ILD, fibrotic iNSIP, fibrotic HP, asbestosisPirfenidone (added to conventional therapy)Pirfenidone reduced the rate of FVC decline over 48 weeks when statistical analyses used imputed data.No difference in DLCO, 6MWD, QOL, and safety profile.
 Pirfenidone in unclassifiable ILD (Phase 2) [15]
NCT03099187
Unclassifiable PF-ILD (253)Pirfenidone (stable background therapy with MMF allowed)The prespecified analysis could not be performed due to high variability for individual daily home spirometry readings.Pirfenidone reduced the rate of FVC decline over 24 weeks using site spirometry (mean between-group difference 95.3 mL, 95%CI 36-155 mL, p = 0.002).
No differences in DLCO, 6MWD, and safety.
Immunosuppressive medication
 SLS (Phase 3) [45]
NCT00004563
SSc-ILD (158)CYC p.o.CYC reduced the rate of FVC decline over 52 weeks (mean between-group difference 2.53, 95%CI 0.28–4.79%, p < 0.03) after adjustment for baseline FVC.More adverse events in the CYC group.
 SLS II (Phase 3) [58]
NCT00883129
SSc-ILD (126)MMF for 2 years versus CYC p.o. for 1 year followed by placebo for 1 yearNo between-group difference in FVC over 24 months with a greater proportion of patients withdrawing from CYC than from MMF.No between-group difference in mRSS, change in HRCT lung fibrosis scores, or dyspnea score.
 FAST [59]SSc-ILD (45)6 months of CYC i.v. and prednisone followed by 6 months of AZA versus placeboNo between-group difference in FVC over 52 weeks in this small, potentially underpowered study.No between-group differences in HRCT fibrosis and dyspnea scores.
 FOCUSSED (Phase 3)
NCT02453256
[presented in abstract form]
SSc (210) including SSc-ILD (132)TocilizumabNo statistically significant difference in mRSS over 48 weeks (adjusted mean between-group difference − 1.73, 95%CI −3.78-0.32, p = 0.098).Tocilizumab reduced the rate of FVC decline over 48 weeks on post-hoc analysis in the subgroup of patients with SSc-ILD (mean between-group difference 6.4, 95%CI 3.3–9.4%)
  1. Abbreviations: AZA azathioprine, CI confidence interval, CTD connective tissue disease, CYC cyclophosphamide, DLCO diffusing capacity of the lungs for carbon monoxide, FVC forced vital capacity, HP hypersensitivity pneumonitis, HRCT high-resolution computed tomography, ILD interstitial lung disease, iNSIP idiopathic nonspecific interstitial pneumonia, IPF idiopathic pulmonary fibrosis, i.v. intravenous, MMF mycophenolate mofetil, mRSS modified Rodnan skin score, p.o. per os, QOL quality of life, SSc systemic sclerosis, 6MWD 6-min walk distance
  2. acompared to placebo unless otherwise stated