Table 1 Targeted therapies of Phase 1 and Phase 2 studies in SSc patients
| Trial drug | Target | Inclusion criteria | Treatment | IS | Endpoints | Duration | Results |
|---|---|---|---|---|---|---|---|
| Inebilizumab | B cells (CD19) | Localized mRSS ≥ 2 | Single dose 0.1–10 mg/kg | Yes |
Safety Tolerability | 12 weeks | Safe and well-tolerated |
| Dabigatran | Thrombin |
SSc-ILD HRCT ≥ 20% FVC < 70% Early (≤ 10 years) | 75 mg twice a day | Yes |
Safety Tolerability | 6 months | Safe and well-tolerated |
| C-82 | β-Catenin Signaling |
Early (median 8 months) dcSSc (mRSS ≥ 12) Localized mRSS ≥ 2 | Topical formulation | Yes |
AE Gene biomarkers | 4 weeks |
Well-tolerated Weak genes downregulation |
| Pomalidomide | Angiogenesis immunosuppression |
SSc-ILD FVC > 45 > 70 FVC > 70, recent loss of 5% HRCT > 20% Early (< 7 years) | 1 mg/day | No |
%pFVC mRSS SCTC GIT 2.0 | 52 weeks | Negative |
| Rilonacept | IL-1 |
Early (< 24 months) dcSSc (mRSS ≥ 15) |
320 mg sc loading dose 160 mg sc weekly | No |
Change in expression in 2G SSc genes mRSS | 6 weeks | Negative |
| Romilkimab | IL-4 and IL-13 | Early (≤ 36 months) dcSSc (mRSS ≥ 10) | 200 mg sc weekly | Yes |
mRSS FVC/DLCO HAQ-DI | 24 weeks | mRSS difference − 2.31 (p = 0.029) in favour of Romilkimab |
| Tocilizumab | IL-6 |
Early (< 5 years) dcSSc (mRSS ≥ 10) | 162 mg sc weekly | No |
mRSS FVC |
48 weeks (primary outcome at 24 weeks) |
mRSS change favoured TCZ (p = 0.058) Smaller decrease in FVC in TCZ |
| Tofacitinib | JAK1 and 3 |
Early (< 5 years) dcSSc (mRSS ≥ 10) | 5 mg twice a day | Yes |
Grade ≥ 3 AE mRSS HAQ-DI CRISS | 24 weeks |
No Grade 3 AE Improvement trend |
| Pirfenidone |
Myofibroblast TGF-β STAT-3 |
SSc-ILD FVC ≥ 50% DLCO ≥ 40% Early (< 7 years) |
2- or 4-week titration 801 mg daily to 2403 mg daily | Yes |
AE FVC and DLCO PRO | 16 weeks |
4-week titration better tolerated No change |
| Lenabasum | Cannabinoid receptor 2 |
Early (< 3 years or > 3 years and < 6 years with CRP > 3) dcSSc (ΔmRSS ≥ 5 last 6 months, total mRSS ≥ 12) | 5 mg/day, 20 mg/day or 20 mg twice a day for 4 weeks and then 20 mg twice a day for 8 weeks. | Yes | CRISS | 16 weeks |
Improvement (p = 0.044) in mRSS PRO PGA HAQ-DI |
| Abatacept |
B/T cells interaction (CD80/CD86) |
Early dcSSc (≤ 18 months, mRSS ≥ 10; > 18 and ≤ 36 months, mRSS ≥ 15) | 125 mg sc weekly | No |
mRSS Safety | 12 months |
Negative Good safety profile |
| Belimumab | BLys |
Early (≤ 3 years) dcSSc (mRSS > 15) recently started on MMF (2 g) | 10 mg/kg iv 2-weekly for the first three doses and then 4-weekly | Yes |
mRSS Safety Tolerability | 52 weeks |
No significant mRSS change Safe and well-tolerated |
| Riociguat | Guanylate Cyclase |
Early (≤ 18 months) dcSSc (mRSS ≥ 10) | 0.5 mg (up-titrated to a maximum dose of 2.5 mg three times a day) | No |
mRSS CRISS HAQ-DI FVC | 52 weeks | Negative Reduced mRSS progression in Riociguat |
| SAR100842 | Lysophosphatidic acid receptor 1 |
Early (≤ 36 months) dcSSc (mRSS ≥ 15) | 300 mg twice a day | Yes |
Safety Tolerability mRSS | 24 weeks |
Safe and well-tolerated No significant change in mRSS |
| Lanifibranor | PPAR |
Early (≤ 3 years) dcSSc (mRSS ≥ 10) |
400 mg twice a day 600 mg twice a day | Yes |
mRSS FVC and DLCO CRISS and PRO | 48 weeks | No significant change in mRSS |