title: Safety and Efficacy of SBI-087, a Subcutaneous Agent for B Cell Depletion, in Patients with Active Rheumatoid Arthritis: Results from a Phase II Randomized, Double-blind, Placebo-controlled Study.
abstract: To evaluate subcutaneous SBI-087 to treat rheumatoid arthritis (RA).
  
  
  
  A total of 210 adult patients with active RA were randomized to receive either 200 mg SBI-087 or placebo (Pbo), according to one of these patterns: SBI/Pbo/Pbo (SBI on Day 1), SBI/SBI/Pbo (SBI days 1 and 15), SBI/Pbo/SBI (SBI days 1 and 84), SBI/SBI/SBI (SBI days 1, 15, and 84), or Pbo/Pbo/Pbo (Pbo all 3 days). All patients were seropositive and taking background methotrexate. The primary endpoint was proportion of patients achieving 20% improvement from baseline at Week 16 by American College of Rheumatology criteria (ACR20). Other outcomes included 28-joint Disease Activity Score (DAS28)-C-reactive protein (CRP), physician's and patient's global assessments of disease activity (PGA and PtGA, respectively) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Peripheral CD19+ B cells were measured by high-sensitivity flow cytometer. Statistical significance was set at 2-sided α 0.10 level.
  
  
  
  The SBI/SBI/SBI group demonstrated significant improvement in ACR20 and DAS28-CRP from Week 8 onward, sustained improvement in CRP levels from Week 12 onward, and significant improvements in PGA and PtGA in weeks 16 through 24, and in HAQ-DI at Week 24. The SBI/Pbo/Pbo and SBI/SBI/Pbo groups did not meet the primary endpoint but demonstrated improvements in several secondary endpoints. All treatment groups exhibited depletion of peripheral CD19+ B cells throughout the study. Overall, 61.5% of patients receiving SBI-087 and 55.0% of patients receiving Pbo reported adverse events.
  
  
  
  SBI-087 effectively depleted peripheral CD20 B cells and was well tolerated. Improvements were consistently observed in the SBI/SBI/SBI group for the majority of efficacy and quality-of-life outcomes.
authors.affiliation: From Belgrade University School of Medicine, Belgrade, Serbia; Wojskowy Instytut Medyczny, Warsaw, Poland; Arthritis Clinic and West Tennessee Research Institute, Jackson, Tennessee; Desert Medical Advances, Palm Desert, California; Pfizer, Collegeville, Pennsylvania; Pfizer, Cambridge, Massachusetts; Janssen, Spring House, Pennsylvania, USA. nemanjadamjanov@yahoo.com.|N. Damjanov, MD, PhD, University of Belgrade School of Medicine; M. Tlustochowicz, MD, PhD, Wojskowy Instytut Medyczny; J. Aelion, MD, Arthritis Clinic and West Tennessee Research Institute; M. Greenwald, MD, Desert Medical Advances; A. Diehl, MPH, MBA, Pfizer; I. Bhattacharya, PhD, Pfizer; E. Peeva, MD, Pfizer; S. Menon, PhD, Pfizer; I. Gourley, MD, Janssen. nemanjadamjanov@yahoo.com.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Damjanov
authors.affiliation: From Belgrade University School of Medicine, Belgrade, Serbia; Wojskowy Instytut Medyczny, Warsaw, Poland; Arthritis Clinic and West Tennessee Research Institute, Jackson, Tennessee; Desert Medical Advances, Palm Desert, California; Pfizer, Collegeville, Pennsylvania; Pfizer, Cambridge, Massachusetts; Janssen, Spring House, Pennsylvania, USA.|N. Damjanov, MD, PhD, University of Belgrade School of Medicine; M. Tlustochowicz, MD, PhD, Wojskowy Instytut Medyczny; J. Aelion, MD, Arthritis Clinic and West Tennessee Research Institute; M. Greenwald, MD, Desert Medical Advances; A. Diehl, MPH, MBA, Pfizer; I. Bhattacharya, PhD, Pfizer; E. Peeva, MD, Pfizer; S. Menon, PhD, Pfizer; I. Gourley, MD, Janssen.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Tlustochowicz
authors.affiliation: From Belgrade University School of Medicine, Belgrade, Serbia; Wojskowy Instytut Medyczny, Warsaw, Poland; Arthritis Clinic and West Tennessee Research Institute, Jackson, Tennessee; Desert Medical Advances, Palm Desert, California; Pfizer, Collegeville, Pennsylvania; Pfizer, Cambridge, Massachusetts; Janssen, Spring House, Pennsylvania, USA.|N. Damjanov, MD, PhD, University of Belgrade School of Medicine; M. Tlustochowicz, MD, PhD, Wojskowy Instytut Medyczny; J. Aelion, MD, Arthritis Clinic and West Tennessee Research Institute; M. Greenwald, MD, Desert Medical Advances; A. Diehl, MPH, MBA, Pfizer; I. Bhattacharya, PhD, Pfizer; E. Peeva, MD, Pfizer; S. Menon, PhD, Pfizer; I. Gourley, MD, Janssen.
authors.forename: Jacob
authors.initials: J
authors.lastname: Aelion
authors.affiliation: From Belgrade University School of Medicine, Belgrade, Serbia; Wojskowy Instytut Medyczny, Warsaw, Poland; Arthritis Clinic and West Tennessee Research Institute, Jackson, Tennessee; Desert Medical Advances, Palm Desert, California; Pfizer, Collegeville, Pennsylvania; Pfizer, Cambridge, Massachusetts; Janssen, Spring House, Pennsylvania, USA.|N. Damjanov, MD, PhD, University of Belgrade School of Medicine; M. Tlustochowicz, MD, PhD, Wojskowy Instytut Medyczny; J. Aelion, MD, Arthritis Clinic and West Tennessee Research Institute; M. Greenwald, MD, Desert Medical Advances; A. Diehl, MPH, MBA, Pfizer; I. Bhattacharya, PhD, Pfizer; E. Peeva, MD, Pfizer; S. Menon, PhD, Pfizer; I. Gourley, MD, Janssen.
authors.forename: Maria
authors.initials: M
authors.lastname: Greenwald
authors.affiliation: From Belgrade University School of Medicine, Belgrade, Serbia; Wojskowy Instytut Medyczny, Warsaw, Poland; Arthritis Clinic and West Tennessee Research Institute, Jackson, Tennessee; Desert Medical Advances, Palm Desert, California; Pfizer, Collegeville, Pennsylvania; Pfizer, Cambridge, Massachusetts; Janssen, Spring House, Pennsylvania, USA.|N. Damjanov, MD, PhD, University of Belgrade School of Medicine; M. Tlustochowicz, MD, PhD, Wojskowy Instytut Medyczny; J. Aelion, MD, Arthritis Clinic and West Tennessee Research Institute; M. Greenwald, MD, Desert Medical Advances; A. Diehl, MPH, MBA, Pfizer; I. Bhattacharya, PhD, Pfizer; E. Peeva, MD, Pfizer; S. Menon, PhD, Pfizer; I. Gourley, MD, Janssen.
authors.forename: Annette
authors.initials: A
authors.lastname: Diehl
authors.affiliation: From Belgrade University School of Medicine, Belgrade, Serbia; Wojskowy Instytut Medyczny, Warsaw, Poland; Arthritis Clinic and West Tennessee Research Institute, Jackson, Tennessee; Desert Medical Advances, Palm Desert, California; Pfizer, Collegeville, Pennsylvania; Pfizer, Cambridge, Massachusetts; Janssen, Spring House, Pennsylvania, USA.|N. Damjanov, MD, PhD, University of Belgrade School of Medicine; M. Tlustochowicz, MD, PhD, Wojskowy Instytut Medyczny; J. Aelion, MD, Arthritis Clinic and West Tennessee Research Institute; M. Greenwald, MD, Desert Medical Advances; A. Diehl, MPH, MBA, Pfizer; I. Bhattacharya, PhD, Pfizer; E. Peeva, MD, Pfizer; S. Menon, PhD, Pfizer; I. Gourley, MD, Janssen.
authors.forename: Indranil
authors.initials: I
authors.lastname: Bhattacharya
authors.affiliation: From Belgrade University School of Medicine, Belgrade, Serbia; Wojskowy Instytut Medyczny, Warsaw, Poland; Arthritis Clinic and West Tennessee Research Institute, Jackson, Tennessee; Desert Medical Advances, Palm Desert, California; Pfizer, Collegeville, Pennsylvania; Pfizer, Cambridge, Massachusetts; Janssen, Spring House, Pennsylvania, USA.|N. Damjanov, MD, PhD, University of Belgrade School of Medicine; M. Tlustochowicz, MD, PhD, Wojskowy Instytut Medyczny; J. Aelion, MD, Arthritis Clinic and West Tennessee Research Institute; M. Greenwald, MD, Desert Medical Advances; A. Diehl, MPH, MBA, Pfizer; I. Bhattacharya, PhD, Pfizer; E. Peeva, MD, Pfizer; S. Menon, PhD, Pfizer; I. Gourley, MD, Janssen.
authors.forename: Elena
authors.initials: E
authors.lastname: Peeva
authors.affiliation: From Belgrade University School of Medicine, Belgrade, Serbia; Wojskowy Instytut Medyczny, Warsaw, Poland; Arthritis Clinic and West Tennessee Research Institute, Jackson, Tennessee; Desert Medical Advances, Palm Desert, California; Pfizer, Collegeville, Pennsylvania; Pfizer, Cambridge, Massachusetts; Janssen, Spring House, Pennsylvania, USA.|N. Damjanov, MD, PhD, University of Belgrade School of Medicine; M. Tlustochowicz, MD, PhD, Wojskowy Instytut Medyczny; J. Aelion, MD, Arthritis Clinic and West Tennessee Research Institute; M. Greenwald, MD, Desert Medical Advances; A. Diehl, MPH, MBA, Pfizer; I. Bhattacharya, PhD, Pfizer; E. Peeva, MD, Pfizer; S. Menon, PhD, Pfizer; I. Gourley, MD, Janssen.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Menon
authors.affiliation: From Belgrade University School of Medicine, Belgrade, Serbia; Wojskowy Instytut Medyczny, Warsaw, Poland; Arthritis Clinic and West Tennessee Research Institute, Jackson, Tennessee; Desert Medical Advances, Palm Desert, California; Pfizer, Collegeville, Pennsylvania; Pfizer, Cambridge, Massachusetts; Janssen, Spring House, Pennsylvania, USA.|N. Damjanov, MD, PhD, University of Belgrade School of Medicine; M. Tlustochowicz, MD, PhD, Wojskowy Instytut Medyczny; J. Aelion, MD, Arthritis Clinic and West Tennessee Research Institute; M. Greenwald, MD, Desert Medical Advances; A. Diehl, MPH, MBA, Pfizer; I. Bhattacharya, PhD, Pfizer; E. Peeva, MD, Pfizer; S. Menon, PhD, Pfizer; I. Gourley, MD, Janssen.
authors.forename: Ian
authors.initials: I
authors.lastname: Gourley
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001402:B-Lymphocytes / Q000187:drug effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011506:Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D011506:Proteins; C000622592:SBI-087; D008727:Methotrexate
keywords: B CELL DEPLETION; DRUG SAFETY; EFFICACY; PHARMACODYNAMICS; RHEUMATOID ARTHRITIS; SBI-087