Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis  Xiang Guo, Brandon W. Higgs, Anne C. Bay-Jensen, Morten A. Karsdal, Yihong Yao, Lorin K. Roskos, Wendy I. White  Journal of Investigative Dermatology  Volume 135, Issue 10, Pages 2402-2409 (October 2015) DOI: 10.1038/jid.2015.188 Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Effects of anifrolumab and MEDI-551 on serum protein markers. (a and b) Soluble CXCL10 and CD40LG levels were significantly suppressed by anifrolumab in systemic sclerosis (SSc) patients enrolled in the MI-CP180 study but not by placebo or MEDI-551 administration in SSc patients enrolled in the MI-CP200 study. (c) In contrast, the serum BAFF level was significantly increased after MEDI-551 but not placebo or anifrolumab administration. (d and e) The reduction in CXCL10 and CD40LG level was significantly correlated with whole-blood IFN gene signature neutralization in 23 SSc patients who received single (0.1, 0.3, 1.0, 3.0, 10.0, or 20.0 mg kg−1) or four weekly intravenous doses (0.3, 1.0, or 5.0 mg kg−1 per week) of anifrolumab. *BH P<0.05, ** BH P<0.01, and *** BH P<0.001. Journal of Investigative Dermatology 2015 135, 2402-2409DOI: (10.1038/jid.2015.188) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Effects of anifrolumab on type III collagen turnover markers. (a) Significant suppression of amino-terminal propeptide of type III procollagen (PIIINP)/C3M by anifrolumab but not placebo or MEDI-551 administration in systemic sclerosis (SSc) patients enrolled in MI-CP180 and MI-CP200 trials, respectively. ***P<0.001. (b) Serum C3M levels were consistently upregulated by anifrolumab (P<0.001). Red X represents median of the C3M level at day 0 and day 56 after anifrolumab administration, respectively. Journal of Investigative Dermatology 2015 135, 2402-2409DOI: (10.1038/jid.2015.188) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Skin transcripts suppressed by multiple doses of anifrolumab. Significant suppression of type I IFN-inducible transcripts, tissue inhibitors of metalloproteinases (TIMPs), multiple collagens, integrins, transforming growth factor-β (TGF-β) receptors, and other TGF-β-associated transcripts was observed after anifrolumab administration (false discovery rate (FDR) <0.01). The heatmap shows log 2-fold change (FC) of each transcript at day 28 relative to pretreatment for 10 systemic sclerosis (SSc) patient who received four weekly intravenous doses (0.3, 1.0, or 5.0 mg kg−1 per week) of anifrolumab. Journal of Investigative Dermatology 2015 135, 2402-2409DOI: (10.1038/jid.2015.188) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions