Table 2 Major randomized controlled trials investigating antifibrotic or immunosuppressive treatments in patients with non-IPF ILD
Study | Patient population (sample size) | Treatmenta | 1o endpoint | Selected 2o endpoints |
|---|---|---|---|---|
Antifibrotic medication | ||||
 SENSCIS (Phase 3) [56] NCT02597933 | SSc-ILD (576) | Nintedanib | Nintedanib 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 ILD | Nintedanib | Nintedanib 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, asbestosis | Pirfenidone (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 year | No 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 placebo | No 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) | Tocilizumab | No 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%) |