. 2022 Jan 29;10(2):316. doi: 10.3390/biomedicines10020316

Table 2.

Clinical trials conducted for the evaluation of broad-spectrum treatment in SSc.

Drug	Target	Type of Trial(s)	Duration (Months)	Patients	Results
Methotrexate (MTX)	Exact anti-inflammatory role is unknown	Multicenter, double-blind
		1. RCT [108]	1. 6	1. 29 early dSSc	1. Mean TSS 21.61 at baseline, 19.96 (p = 0.135) 6 months after
		2. RCT [107]	2. 12	2. 71 early dSSc	2. Mean TSS 18.3 at baseline, 14.5 (p = 0.027) 12 months post-treatment
Cyclophosphamide (CYC)	Inhibition and suppression of T helper and regulatory T cells	Double-blind, RCT (SLC) [112]	12	158 SSc-ILD	2. 53% (p < 0.03) improvement in predicted FVC and 3.02 (p = 0.08) unit improvement in mRSS in CYC’s favor
Mycophenolate mofetil (MMF)	T and B cell depletion	1. Double-blind, RCT (SLC II) [118]	1. 24	1. 69 SSc-ILD	1. Percentage of predicted FVC improved from 67 to 75, and mRSS decreased from 14.5 at baseline to 10 24 months post-treatment
Mycophenolate mofetil (MMF)	T and B cell depletion	2. Double-blind RCT [119]	2. 6	2. 41 mild SSc-ILD	2. No statistically significant improvement in mRSS and FVC scores
Autologous hematopoietic stem cell transplantation (ASCT)	Depletion of T and B cells, followed by stem cell transplantation	1. Open-label, multicenter RCT (SCOT) (NCT00860548)	1. 54	1. 75 severe SSc	1. ASCT more effective in diminishing skin fibrosis compared to CYC (−19.9 vs. −8.8, p < 0.001) and shows greater event-free survival
Autologous hematopoietic stem cell transplantation (ASCT)		2. Open-label, multicenter RCT (ASTIS) [131]	2. 24	2. 156 early dcSSc	2. Overall survival, mRSS, and FVC significantly improved with ASCT compared to CYC (67% of 1404 pairwise comparisons in favor of ASCT vs. 33% in CYC, p = 0.01)