title: Long-term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care.
abstract: OBJECTIVE
  To examine long-term organ damage and safety following treatment with belimumab plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE).
  
  
  METHODS
  Pooled data were examined from two ongoing open-label studies that enrolled patients who completed BLISS-52 or BLISS-76. Patients received belimumab every four weeks plus SoC. SLICC Damage Index (SDI) values were assessed every 48 weeks (study years) following belimumab initiation (baseline). The primary endpoint was change in SDI from baseline at study years 5-6. Incidences of adverse events (AEs) were reported for the entire study period.
  
  
  RESULTS
  The modified intent-to-treat (MITT) population comprised 998 patients. At baseline, 940 (94.2%) were female, mean (SD) age was 38.7 (11.49) years, and disease duration was 6.7 (6.24) years. The mean (SD) SELENA-SLEDAI and SDI scores were 8.2 (4.18) and 0.7 (1.19), respectively; 411 (41.2%) patients had organ damage (SDI = 1: 235 (23.5%); SDI ≥ 2: 176 (17.6%)) prior to belimumab. A total of 427 (42.8%) patients withdrew overall; the most common reasons were patient request (16.8%) and AEs (8.5%).The mean (SD) change in SDI was +0.2 (0.48) at study years 5-6 (n = 403); 343 (85.1%) patients had no change from baseline in SDI score (SDI +1: 46 (11.4%), SDI +2: 13 (3.2%), SDI +3: 1 (0.2%)). Of patients without organ damage at baseline, 211/241 (87.6%) had no change in SDI and the mean change (SD) in SDI was +0.2 (0.44). Of patients with organ damage at baseline, 132/162 (81.5%) had no change in SDI and the mean (SD) change in SDI was +0.2 (0.53). The probability of not having a worsening in SDI score was 0.88 (95% CI: 0.85, 0.91) and 0.75 (0.67, 0.81) in those without and with baseline damage, respectively (post hoc analysis).Drug-related AEs were reported for 433 (43.4%) patients; infections/infestations (282, 28.3%) and gastrointestinal disorders (139, 13.9%) were the most common.
  
  
  CONCLUSIONS
  Patients with SLE treated with long-term belimumab plus SoC had a low incidence of organ damage accrual and no unexpected AEs. High-risk patients with pre-existing organ damage also had low accrual, suggesting a favorable effect on future damage development.
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK The Kellgren Centre for Rheumatology, NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK ian.bruce@manchester.ac.uk.
authors.forename: I N
authors.initials: IN
authors.lastname: Bruce
authors.affiliation: University of Toronto and Toronto Western Hospital, Toronto, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Urowitz
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: van Vollenhoven
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Aranow
authors.affiliation: GSK, Uxbridge, Middlesex, UK.
authors.forename: J
authors.initials: J
authors.lastname: Fettiplace
authors.affiliation: GSK, Stevenage, Hertfordshire, UK.
authors.forename: M
authors.initials: M
authors.lastname: Oldham
authors.affiliation: GSK, Research Triangle Park, NC, USA.
authors.forename: B
authors.initials: B
authors.lastname: Wilson
authors.affiliation: GSK, Philadelphia, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Molta
authors.affiliation: GSK, Philadelphia, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Roth
authors.affiliation: GSK, Philadelphia, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Gordon
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D059039:Standard of Care; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; C511911:belimumab
keywords: Systemic lupus erythematosus; organ damage; safety