title: Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis: Results from Three Clinical Trials.
abstract: OBJECTIVE
  To investigate the safety of ofatumumab retreatment in rheumatoid arthritis.
  
  
  METHODS
  Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development on subcutaneous delivery. Due to differences in study designs and populations, data are summarised separately for each study.
  
  
  RESULTS
  483 patients (243, 148 and 92 in OFA110635, OFA110634 and OFA111752 respectively) received up to 7 treatment courses of intravenous ofatumumab; cumulative duration of exposure was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17-47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70/92), serious adverse events for 18% (44/243), 20% (30/148) and 12% (11/92) and serious infections for 3% (8/243), 5% (7/148) and 1% (1/92) of patients in OFA110635, OFA110634 and OFA111752, respectively. The most common adverse events were infusion-related reactions during the first infusion of the first course (48-79%); serious infusion-related reactions were rare (<1% [1/243], 5% [8/148], and 1% [1/92] of patients). Two deaths occurred (fulminant hepatitis B virus infection and interstitial lung disease).
  
  
  CONCLUSIONS
  Ofatumumab was generally well tolerated with no evidence of increased safety risks with multiple retreatments. Serious infections were uncommon and did not increase over time.
  
  
  BACKGROUND
  ClinicalTrials.gov 110635 ClinicalTrials.gov 110634 ClinicalTrials.gov 111752.
authors.affiliation: R&D Immunoinflammation, GlaxoSmithKline, Stockley Park, Middlesex, United Kingdom.
authors.forename: Emilia
authors.identifier: http://orcid.org/0000-0001-5868-9769
authors.initials: E
authors.lastname: Quattrocchi
authors.affiliation: Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Glostrup Hospital, Copenhagen, Denmark and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford Botnar Research Centre, Oxford, United Kingdom.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Taylor
authors.affiliation: Unit for Clinical Therapy Research, The Karolinska Institute, Stockholm, Sweden.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.affiliation: R&D Immunoinflammation, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.
authors.forename: Myron
authors.initials: M
authors.lastname: Chu
authors.affiliation: Clinical Statistics, GlaxoSmithKline, Stockley Park, Middlesex, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Mallett
authors.affiliation: Clinical Statistics, GlaxoSmithKline, Stockley Park, Middlesex, United Kingdom.
authors.forename: Hayley
authors.initials: H
authors.lastname: Perry
authors.affiliation: R&D Immunoinflammation, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.
authors.forename: Regina
authors.initials: R
authors.lastname: Kurrasch
mesh_terms: D061605:Administration, Intravenous; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D019233:Retreatment; D061665:Time-to-Treatment; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; C527517:ofatumumab