SLS I [31] | 12 months (double-blind) | Placebo: n=72 CYC: n=73 | 13 | >18 years of age dcSSc or lcSSc Evidence of acute alveolitis on BAL examination or ground-glass opacity on HRCT Onset of first (non-Raynaud) SSc symptom within 7 years FVC % pred 45–85% Grade 2 exertional dyspnoea on Mahler Dyspnoea Index | Change in mean±se FVC % pred: Placebo: −2.6±0.9% CYC: −1.0±0.9% | Proportion of patients with worsening of fibrosis after 12 months [32]: Placebo: 26/49 (53%) CYC: 14/49 (29%) | During randomised treatment period: Placebo: 3/79 CYC: 2/79 |
SLS II [33] | 24 months (double-blind) | CYC: n=63 MMF: n=63 | 14 | 18–75 years of age dcSSc or lcSSc FVC % pred 45–85% Any ground-glass opacity on HRCT (whether associated with reticulations or not) Onset of first (non-Raynaud) SSc symptom within 7 years Grade 2 exertional dyspnoea on Mahler Dyspnoea Index | Change in mean±se FVC % pred: CYC: +3.0±1.2% MMF: +3.3±1.1% | Change in whole lung scores: QLF score: CYC: +1.13% MMF: +2.15% QILD score: CYC: −1.84% MMF: −0.95% | During randomised treatment period: CYC: 11/73 MMF: 5/69 |
faSScinate [34] | 48 weeks (double-blind) 96 weeks (open-label extension) | Placebo: n=44 TCZ: n=43 Placebo-TCZ: n=24 Continuous TCZ: n=27 | 35 | >18 years of age Diagnosis of SSc as per 1980 ACR criteria Onset of first (non-Raynaud) SSc symptom within 5 years mRSS score 15–40 Active disease (defined by pre-specified mRSS/biomarker criteria) | Change in mean (95% CI) FVC % pred: Placebo −0.06% (−0.10– −0.03) at 48 weeks −0.03% (−0.07–0.01) at 96 weeks TCZ −0.02% (−0.04–0.00) at 48 weeks −0.01% (−0.03–0.02) at 96 weeks | Not recorded | No deaths reported |
focuSSced [35] | 48 weeks (double-blind) 96 weeks (open-label extension) | Placebo: n=106 TCZ: n=104 | 83 | Diagnosis of SSc as per ACR/EULAR criteria, meeting criteria for active disease Total disease duration ≤60 months mRSS score 10–35 | Change in median (95% CI) FVC % pred: Placebo: −3.9% (−4.8– −1.6) TCZ: −0.6% (−2.4– −0.9) | Change in whole lung scores: QLF in double-blind period (mean (95% CI)): Placebo: 0.4 (0–0.7) TCZ: −0.4 (−0.9–0.1) QILD: Placebo: 0.1 (−1.4–1.6) TCZ: −1.7 (−3.0– −0.4) | In double-blind period: Placebo: 1/106 TCZ: 1/104 |
RTX versus CYC [36] | 6 months (open-label) | RTX: n=30 CYC: n=30 | 1 | 18–60 years of age dcSSc, as per ACR classification criteria Scl-70 antibody positivity ILD confirmed by HRCT and PFTs (FVC % pred 45–85%) Onset of first (non-Raynaud) SSc symptom within 3 years Baseline dyspnoea level of NYHA class II and III | Change in mean FVC % pred: RTX: +6.2% CYC: −1.3% | Not recorded | RTX: 1/30 CYC: 1/30 |
SENSCIS [37] | 52 weeks (double-blind) | Placebo: n=288 Nintedanib: n=287 | 195 | >18 years of age SSc as per ACR/EULAR classification criteria Onset of first (non-Raynaud) SSc symptom within 7 years ILD confirmed by >10% fibrosis on HRCT within 12 months of screening FVC % pred >40% DLCO % pred 30–89% | Annual rate±se of decline in FVC % pred: Placebo: −2.6±0.4% Nintedanib: −1.4±0.4% | Data collected, to be reported | Placebo: 9/288 Nintedanib: 10/288 |
ASSET [38] | 12 months (double-blind) | Placebo: n=44 Abatacept: n=44 | | ≥18 years old SSc as per ACR/EULAR criteria, and dcSSc defined as per early SSc criteria [39] Disease duration of ≤36 months (time from the first non-Rayaud symptom) | Change in FVC % pred (LSM±se): Placebo: −4.1±1.2% Abatacept: −1.3±1.2% | Not recorded | Placebo: 1/44 Abatacept: 2/44 |
ASSIST [40] | 24 months (open-label) | CYC: n=9 HSCT: n=10 | 1 | <60 years of age dcSSc (mRSS score >14 and cutaneous involvement proximal to the elbow or knee) Internal organ involvement: DLCO % pred <80%; decline in FVC % pred >10% within past 12 months; lung fibrosis or ground-glass opacities on HRCT; ECG or GI involvement | Change in mean±sd FVC % pred: At 12 months: CYC: −6% HSCT: +12% At 24 months: HSCT: +12% | Volume of diseased lung on HRCT: At 12 months: CYC: +108 mL HSCT: −272 mL At 24 months: HSCT: −341 mL | No deaths |
ASTIS [41] | 24 months# (open-label) | CYC: n=64 HSCT: n=67 | 29 | 18–65 years of age dcSSc as per ACR criteria Maximum disease duration of 4 years mRSS score >15 Involvement of heart, lungs or kidneys Prior treatment with CYC allowed up to a cumulative dose of 5 g intravenously, or up to 2 mg·kg−1 body weight orally for 3 months | Change in mean±sd FVC % pred: HSCT: +6.3±18.3% CYC: −2.8±17.2% | Not recorded | HR for overall survival: 1 year=0.48 (95% CI 0.25–0.91; p=0.02) 2 years=0.29 (0.13–0.65; p=0.002) 4 years=0.29 (0.13–0.64; p=0.002) |
SCOT [42] | 54 months (open-label) | CYC: n=39 HSCT: n=36 | 26 | 18–69 years of age SSc as per ACR criteria Maximum disease duration of 5 years Active ILD (determined by BAL composition or chest CT) FVC or DLCO <70% pred renal involvement | Not recorded | Change from baseline in QILD score (±se) at 54 months [43]: CYC: 0±5% HSCT: −7±2% Change from baseline in QLF score (±se) at 54 months [65]: CYC: +3±3% HSCT: −1±1% | Treatment-related mortality at 54 months: CYC: 0/39 HSCT: 1/36 |