Table 2.

Overview of the main clinical trials that evaluate treatments against the inflammatory, fibrotic, and vascular components of SSc.

Drug name	Target	Mechanism of action	Trial ID/reference
Treatments against immune mediators
Anifrolumab   (MEDI546)	Directed against subunit 1 of type I interferon receptor	Downregulation of T-cell activation	NCT00930683
Inebilizumab (MEDI551)	Anti-CD19	Depletion of B cells through enhanced antibody-dependent cellular cytotoxicity	NCT00946699
Sifalimumab   Rontalizumab	Anti-IFNα	Specific for IFNα blocking; doesn't neutralize other type I IFNs	NCT01283139
			NCT00541749
MEDI7734	Anti-ILT7	Temporary depletion of plasmacytoid dendritic cells	NCT02780674
Rituximab	Anti-CD20	Targets CD20 expressed from pre-B cell stage to the pre-plasma cell stage	Giuggioli D et al. [10]
Basiliximab	Anti-IL-2Rα	Directed against the α chain (CD25) of the IL-2 receptor	Becker MO et al. [11]
Efalizumab	LFA1/ICAM-1	Interaction between LFA-1 and ICAM-1 is blocked, preventing T-cell's activation	Zimmerman T et al. [12]
Abatacept	CTLA4	Inhibits T-cell activation by selectively modulating costimulation (binds to CD80 or CD86 on cell surface)	Elhai M et al. [13]
AIMSPRO (®)	αMSH, IL10, CCL2	Modulates serum levels of relevant cytokines	Quillinan NP et al. [14]
Tocilizumab	IL-6R	Regulatory effect in the balance between Th17 and Tregs	NCT01532869
AM095 and SAR100842	LPA1	Targets specific G-protein-coupled receptors	NCT01651143
TAK242	TLR4	Prevents Th1 and Th17 cytokines production by inhibiting TLR4 stimulation	Bhattacharyya S et al. [15]
Treatments against Fibrosis
Imatinib	PDGF, TGF-β	Blocks both PDGF and TGF-β signalling pathways	Iwamoto N et al. [16]
Dasatinib,    Nilotinib	c-Abl, PDGF	Second-generation TKIs with higher affinity to Bcr-Abl	Akhmetshina A et al. [17]
Metelimumab (CAT-192)	TGFβ1	Specifically counteracts the TGFβ1 isoform	Denton CP et al. [18]
Fresolimumab (GC-1008)	TGFβ1,-β2,-β3	Targets all isoforms of TGFβ	NCT01284322
FG-3019	CCN2	Anti-CTGF, reduces the number of CD45-positive cells	Brenner MC et al. [19]
P144	TGFβ1	Blocks the interaction between TGFβ1 and TGFβ1 type III receptor	NCT00574613, Postlethwaite AE et al. [20]
Anti-Integrin α V β 6 (Abituzumab)	TGFβ	Inhibits binding to αv heterodimers, preventing TGF-β activation	NCT02745145, Katsumoto et al. [17], Henderson NC et al. [21]
Pirfenidone	TNFα, IL1β, TGFβ	Blocks TGF-β-stimulated collagen synthesis	Udwadia ZF et al. [22] Khanna D et al. [23]
Nintedanib   (BIBF 1120)	VEGF, PDGF, FGF	TKI-targeting FGF, PDGF, and VEGF receptors, as well as Src-family tyrosine kinases	NCT02597933, Distler et al. [24]
Treatments against vascular alterations
Bosentan,    Macitentan	ETA/ETB receptor	Blocks both ETA and ETB endothelin receptors that mediate the effects of ET-1	NCT00077584, Matucci-Cerinic M et al. [25] NCT00660179, Metha S et al. [26]
Ambrisentan	ETA receptor	Blocks the action of endothelin-1 at the ETA receptor	NCT00091598, NCT01178073, Gailè N et al. [27], Raghu G et al. [28]
Selexipag	IP receptor	Selective IP prostacyclin receptor agonist for long-term treatment of PAH	Sitbon O et al. [29], Denton CP et al. [30]
Riociguat	GMPc agonist	Soluble guanylate cyclase (sGC) modulator with both vasoactive and antifibrotic effects	NCT02283762, NCT00863681
Bardoxolone methyl	Nrf2 and NF-κB	Activation of Nrf2 and inhibition of NF-κB	NCT02036970, NCT02657356