title: A Phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-α) in patients with systemic lupus erythematosus (ROSE).
abstract: OBJECTIVE
  To examine the safety and efficacy of rontalizumab, a humanised IgG1 anti-interferon α (anti-IFN-α) monoclonal antibody, in patients with moderate-to-severe systemic lupus erythematosus (SLE).
  
  
  METHODS
  Patients with active SLE were randomised (2:1) to 750 mg intravenous rontalizumab every 4 weeks or placebo (Part 1), and 300 mg subcutaneous rontalizumab every 2 weeks or placebo (Part 2).
  
  
  BACKGROUND
  Hydroxychloroquine and corticosteroids were allowed. Patients taking immunosuppressants at baseline were required per protocol to discontinue. Efficacy end points included reduction in disease activity by British Isles Lupus Disease Activity Group (BILAG)-2004 (primary), and SLE response index (SRI, secondary) at Week 24. Efficacy was also examined by an exploratory measure of IFN-regulated gene expression (interferon signature metric, ISM).
  
  
  RESULTS
  Patients (n=238) received rontalizumab (n=159) or placebo (n=79). At baseline, the mean Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI) score in all cohorts was ~10, and 75.6% of patients had a high ISM (ISM-High). Efficacy response rates by BILAG and SRI were similar between rontalizumab and placebo groups. However, in the exploratory subgroup of ISM-Low patients, SRI response was higher and steroid use was lower in the rontalizumab-treated patients. There was also a reduction in SELENA-SLEDAI flare index rates (HR 0.61, 0.46 to 0.81, p=0.004) in this subgroup. Adverse events were similar between placebo and rontalizumab groups.
  
  
  CONCLUSIONS
  The primary and secondary end points of this trial were not met in all patients or in patients with high ISM scores. In an exploratory analysis, rontalizumab treatment was associated with improvements in disease activity, reduced flares and decreased steroid use in patients with SLE with low ISM scores.
  
  
  BACKGROUND
  NCT00962832.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California, USA.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Kalunian
authors.affiliation: Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: Romeo
authors.initials: R
authors.lastname: Maciuca
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: McBride
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Townsend
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wei
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Davis
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D005938:Glucocorticoids; D007155:Immunologic Factors; C577244:rontalizumab
keywords: Autoimmune Diseases; DMARDs (biologic); Systemic Lupus Erythematosus