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 |