Post Hoc Biomarker Analyses from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Repository Corticotropin Injection (Acthar (R) Gel) for Persistently Active Systemic Lupus Erythematosus

Introduction We conducted post hoc analyses of biomarker results from a multicenter, randomized, double-blind, placebo-controlled study of repository corticotropin injection (RCI; Acthar (R) Gel) in patients with persistently active systemic lupus erythematosus (SLE) despite treatment with moderate-dose glucocorticoids. Methods Adults with active SLE and moderate to severe rash and/or arthritis were enrolled in the primary study. Patients had active SLE despite treatment with stable glucocorticoids, antimalarials, and nonsteroidal anti-inflammatory drugs and/or immunosuppressants. Patients were randomly assigned to 80 U of RCI or placebo subcutaneously every other day for 4 weeks and then twice weekly through week 24. Blood samples were analyzed for serum cytokines and complement proteins using enzyme-linked immunosorbent or Luminex assays and for circulating leukocytes using flow cytometry. Biomarker levels were reported as percentages of the baseline and were further evaluated in subgroups stratified by baseline SLE Disease Activity Index-2000 (SLEDAI-2K) scores (< 10 vs. >= 10), baseline anti-double-stranded DNA levels (< 15 IU/mL vs. >= 15 IU/mL), and BILAG-based Combined Lupus Assessment (BICLA) responses at week 20 and 24. Results RCI treatment resulted in reduced levels of B cell-activating factor and interleukin-6 cytokines in all subgroups compared with placebo. RCI treatment also resulted in lower levels of CD19(+) B cells and CD19(+)IgD(-)CD27(-)CD95(+) atypical activated memory B cells than did placebo in the higher baseline disease activity subgroups and in BICLA non-responders. Furthermore, RCI treatment led to greater increases in complement component (C)3 and C4 levels than did placebo in the higher baseline disease activity subgroups and in BICLA responders. Conclusions RCI may reduce inflammation through B cell immunomodulation in patients with persistently active SLE, particularly in those with higher disease activity.