Background/Purpose: Systemic sclerosis (SSc) is a progressive, debilitating disease with limited treatment options. IL-6 has been implicated in disease pathogenesis.^1,2 IL-6 receptor inhibition prevented and reversed skin fibrosis in a murine scleroderma model.³ Tocilizumab (TCZ), an IL-6 receptor inhibitor, is under evaluation in the ongoing 2-y faSScinate study, a randomized, double-blind, placebo-controlled trial. Wk 24 efficacy and safety data of TCZ in SSc pts are presented here.

Methods: Pts (≥18 y) with active SSc (1980 ACR criteria,⁴ ≤5-y disease duration, mRSS 15-40 units, and elevated acute-phase reactants) were randomized 1:1 to subcutaneous TCZ 162 mg or placebo (PBO) wkly for 48 wks. The primary end point was mean change in mRSS from baseline (BL) at wk 24, with patient and lung responses as secondary/exploratory measures.

Results: Eighty-seven pts (43 TCZ, 44 PBO) were enrolled. BL characteristics were similar between arms, including mean (SD) mRSS (TCZ, 26.4 [7.2]; PBO, 25.6 [5.9]). The primary end point, change in mRSS, and secondary end point, change in HAQ-DI, from BL to wk 24 are displayed in the Table. At 24 wks, a numerically favorable but not statistically significant effect of TCZ over PBO on mRSS was noted (TCZ, –3.9; PBO, –1.2; adjusted mean difference, –2.7 [95% CI, –5.85, 0.45]). In addition, a numerically greater proportion of TCZ pts achieved clinically meaningful reduction in mRSS of ≥4.7⁵ (TCZ, 43.2% [16/37]; PBO, 26.3% [10/38]; p = 0.15, Fisher exact test). Exploratory analysis of change in forced vital capacity (FVC; liters) showed more PBO than TCZ patients (81% vs 50%) with progression of FVC decline (≤0%) (Table) and 27% of PBO pts vs 3% of TCZ pts with ≥10% FVC decline (p = 0.009, Van Elteren test). Adverse events (AEs)/serious AEs were reported in 88.4%/20.9% of TCZ and 90.9%/25.0% of PBO pts. Fewer noninfectious SAEs were reported in the TCZ arm (5 pts) than the PBO arm (10 pts), whereas infection/infestation SAEs were more common in TCZ than PBO pts (6 pts vs 1 pt). By system organ class, the following SAEs, potentially indicative of SSc complications, were reported more frequently in the PBO than in the TCZ arm: cardiac SAE (TCZ, 0 pts; PBO, 3 pts), gastrointestinal SAE (TCZ, 0 pts; PBO, 2 pts), and renal SAE (TCZ, 0 pts; PBO, 2 pts). Three pts in the TCZ arm and 2 pts in the PBO arm discontinued due to AEs. One death occurred in each arm: 1 pulmonary infection in a TCZ pt on day 109 and 1 heart failure in a PBO pt 131 days after withdrawal.  

Conclusion: In this phase 2 study, favorable trends in skin score for TCZ were detected though the primary skin score end point was not met. In addition, encouraging changes in FVC were noted. The ongoing double-blind and open-label phases of this trial will provide additional information.
References: 1. J Rheumatol 1998;25:308. 2. Pathobiology 1993;61:239. 3. Am J Pathol 2012;180:165. 4. Arthritis Rheum 1980;23:581. 5. Ann Rheum Dis 2006;65:1325.