Table 4.

Clinical trials and other studies that evaluated the role of cytokine targeting treatment in SSc.

Drug	Target	Type of Trial(s)	Duration (Months)	Patients	Results
Tocilizumab (TCZ)	Inhibits IL-6 signaling	1. Open-label RCT (faSScinate) [162]	1. 24	1. 87 early SSc	1. Insignificant change in mRSS, but IL-6 reduction was correlated with decreased TGF-β expression
		2. EUSTAR observational study [158]	2. 5	2. 189 SSc-polyarthritis and myopathy	2. No statistically significant change in mRSS, but remarkable improvement in joint function
		3. Multicenter, double-blind RCT (focuSSed) [169]	3. 12	3. 210 dcSSc	3. Change of −1.73 in mRSS between treated and placebo groups was not statistically significant (p = 0.10), but the 4.2% improvement in predicted FVC was (p = 0.0002)
Rilonacept	Blocks IL-1b signaling	Double-blind RCT [172]	5 weeks	19 dcSSc	No changes in mRSS between treatment and placebo
Basiliximab	Anti-CD25-mediated inhibition of IL-2 inhibits T cell activation and proliferation	Small-scale, open-label study [175]	17	10 dcSSc	Median mRSS reduced from 26/51 to 11/51 at week 68 (p = 0.015) Median predicted FVC between baseline and 44 weeks after treatment increased from 82.1% to 88.4%
Fresolimumab	Blocks TGF-β signaling	Small-scale, open-label study [176]	6	15 dcSSc	Reduction of 8 units in mRSS score (p < 0.001) Reduced expression of TGF-β-regulated genes in skin biopsies (p < 0.049)
Metelimumab	Blocks TGF-β signaling	Double-blind RCT [177]	6	45 early SSc	No statistically significant change in mRSS scores
Pirfenidone	Reduces fibroblast proliferation and TGF-β-induced collagen production in primary skin fibroblasts	Open-label, phase II study (LOTUSS) [180]	4	63 SSc-ILD	No difference in the predicted FVC between baseline and post-treatment