title: The Effect of Reduced or Withdrawn Etanercept-methotrexate Therapy on Patient-reported Outcomes in Patients with Early Rheumatoid Arthritis.
abstract: An analysis of a clinical trial to assess the effects of treatment reduction and withdrawal on patient-reported outcomes (PRO) in patients with early, moderate to severe rheumatoid arthritis (RA) who achieved 28-joint Disease Activity Score (DAS28) low disease activity (LDA) or remission with etanercept (ETN) plus methotrexate (MTX) therapy.
  
  
  
  During treatment induction, patients received open-label ETN 50 mg weekly plus MTX for 52 weeks. In the reduced-treatment phase, patients with DAS28-erythrocyte sedimentation rate (ESR) ≤ 3.2 at Week 39 and DAS28-ESR < 2.6 at Week 52 in the open-label phase were randomized to double-blind treatment with ETN 25 mg plus MTX, MTX, or placebo (PBO) for 39 weeks (weeks 0-39). In the third phase, patients who achieved DAS28 remission (DAS28-ESR < 2.6) or LDA (2.6 ≤ DAS28-ESR ≤ 3.2) at Week 39 in the double-blind phase had all treatment withdrawn and were observed for an additional 26 weeks (weeks 39-65).
  
  
  
  Of the 306 patients enrolled, 193 were randomized in the double-blind phase and 131 participated in the treatment-withdrawal phase. After reduction or withdrawal of ETN 50 mg/MTX, patients reduced to ETN 25 mg/MTX experienced slight, nonsignificant declines in the majority of PRO measures, whereas switching to PBO or MTX alone caused significant declines. Presenteeism and activity impairment scores were significantly better in the ETN reduced-dose group versus MTX monotherapy and PBO at Week 39 (p ≤ 0.05).
  
  
  
  In patients with early RA who achieved remission while receiving full-dose ETN/MTX, continuing combination therapy at a lower dose did not cause a significant worsening of PRO response, but switching to MTX alone or PBO did. ClinicalTrials.gov identifier: NCT00913458.
authors.affiliation: From the Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland; Clinic of Rheumatology, HFR Fribourg - Hôpital Cantonal, Fribourg, Switzerland; Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland; Barts Health National Health Service (NHS) Trust, London, UK; Pfizer Inc., Collegeville, Pennsylvania; Pfizer Inc., New York, New York, USA.P. Wiland, MD, PhD, Professor, Head of Department, Department of Rheumatology and Internal Medicine, Wroclaw Medical University; J. Dudler, MD, Professor, Head of Department, Department of Rheumatology, HFR Fribourg - Hôpital Cantonal; D. Veale, MD, Professor, Director of Translational Research, Dublin Academic Medical Centre; H. Tahir, MFSEM (UK), FRCP (UK), Professor, Consultant Rheumatologist, Sports Physician, Barts Health NHS Trust; R. Pedersen, MS, Director of Statistics, Pfizer; J. Bukowski, MD, PhD, Medical Director, Pfizer; B. Vlahos, MBA, BSN, RN, Medical Director, Clinical Lead, Pfizer; T. Williams, PA, MS, Study Clinician, Pfizer; S. Gaylord, BSN, RN, Assistant Director, Clinical Scientist, Pfizer; S. Kotak, MBA, MS, Director, Pfizer. pwiland1@gmail.com.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wiland
authors.affiliation: From the Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland; Clinic of Rheumatology, HFR Fribourg - Hôpital Cantonal, Fribourg, Switzerland; Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland; Barts Health National Health Service (NHS) Trust, London, UK; Pfizer Inc., Collegeville, Pennsylvania; Pfizer Inc., New York, New York, USA.P. Wiland, MD, PhD, Professor, Head of Department, Department of Rheumatology and Internal Medicine, Wroclaw Medical University; J. Dudler, MD, Professor, Head of Department, Department of Rheumatology, HFR Fribourg - Hôpital Cantonal; D. Veale, MD, Professor, Director of Translational Research, Dublin Academic Medical Centre; H. Tahir, MFSEM (UK), FRCP (UK), Professor, Consultant Rheumatologist, Sports Physician, Barts Health NHS Trust; R. Pedersen, MS, Director of Statistics, Pfizer; J. Bukowski, MD, PhD, Medical Director, Pfizer; B. Vlahos, MBA, BSN, RN, Medical Director, Clinical Lead, Pfizer; T. Williams, PA, MS, Study Clinician, Pfizer; S. Gaylord, BSN, RN, Assistant Director, Clinical Scientist, Pfizer; S. Kotak, MBA, MS, Director, Pfizer.
authors.forename: Jean
authors.initials: J
authors.lastname: Dudler
authors.affiliation: From the Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland; Clinic of Rheumatology, HFR Fribourg - Hôpital Cantonal, Fribourg, Switzerland; Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland; Barts Health National Health Service (NHS) Trust, London, UK; Pfizer Inc., Collegeville, Pennsylvania; Pfizer Inc., New York, New York, USA.P. Wiland, MD, PhD, Professor, Head of Department, Department of Rheumatology and Internal Medicine, Wroclaw Medical University; J. Dudler, MD, Professor, Head of Department, Department of Rheumatology, HFR Fribourg - Hôpital Cantonal; D. Veale, MD, Professor, Director of Translational Research, Dublin Academic Medical Centre; H. Tahir, MFSEM (UK), FRCP (UK), Professor, Consultant Rheumatologist, Sports Physician, Barts Health NHS Trust; R. Pedersen, MS, Director of Statistics, Pfizer; J. Bukowski, MD, PhD, Medical Director, Pfizer; B. Vlahos, MBA, BSN, RN, Medical Director, Clinical Lead, Pfizer; T. Williams, PA, MS, Study Clinician, Pfizer; S. Gaylord, BSN, RN, Assistant Director, Clinical Scientist, Pfizer; S. Kotak, MBA, MS, Director, Pfizer.
authors.forename: Douglas
authors.initials: D
authors.lastname: Veale
authors.affiliation: From the Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland; Clinic of Rheumatology, HFR Fribourg - Hôpital Cantonal, Fribourg, Switzerland; Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland; Barts Health National Health Service (NHS) Trust, London, UK; Pfizer Inc., Collegeville, Pennsylvania; Pfizer Inc., New York, New York, USA.P. Wiland, MD, PhD, Professor, Head of Department, Department of Rheumatology and Internal Medicine, Wroclaw Medical University; J. Dudler, MD, Professor, Head of Department, Department of Rheumatology, HFR Fribourg - Hôpital Cantonal; D. Veale, MD, Professor, Director of Translational Research, Dublin Academic Medical Centre; H. Tahir, MFSEM (UK), FRCP (UK), Professor, Consultant Rheumatologist, Sports Physician, Barts Health NHS Trust; R. Pedersen, MS, Director of Statistics, Pfizer; J. Bukowski, MD, PhD, Medical Director, Pfizer; B. Vlahos, MBA, BSN, RN, Medical Director, Clinical Lead, Pfizer; T. Williams, PA, MS, Study Clinician, Pfizer; S. Gaylord, BSN, RN, Assistant Director, Clinical Scientist, Pfizer; S. Kotak, MBA, MS, Director, Pfizer.
authors.forename: Hasan
authors.initials: H
authors.lastname: Tahir
authors.affiliation: From the Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland; Clinic of Rheumatology, HFR Fribourg - Hôpital Cantonal, Fribourg, Switzerland; Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland; Barts Health National Health Service (NHS) Trust, London, UK; Pfizer Inc., Collegeville, Pennsylvania; Pfizer Inc., New York, New York, USA.P. Wiland, MD, PhD, Professor, Head of Department, Department of Rheumatology and Internal Medicine, Wroclaw Medical University; J. Dudler, MD, Professor, Head of Department, Department of Rheumatology, HFR Fribourg - Hôpital Cantonal; D. Veale, MD, Professor, Director of Translational Research, Dublin Academic Medical Centre; H. Tahir, MFSEM (UK), FRCP (UK), Professor, Consultant Rheumatologist, Sports Physician, Barts Health NHS Trust; R. Pedersen, MS, Director of Statistics, Pfizer; J. Bukowski, MD, PhD, Medical Director, Pfizer; B. Vlahos, MBA, BSN, RN, Medical Director, Clinical Lead, Pfizer; T. Williams, PA, MS, Study Clinician, Pfizer; S. Gaylord, BSN, RN, Assistant Director, Clinical Scientist, Pfizer; S. Kotak, MBA, MS, Director, Pfizer.
authors.forename: Ron
authors.initials: R
authors.lastname: Pedersen
authors.affiliation: From the Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland; Clinic of Rheumatology, HFR Fribourg - Hôpital Cantonal, Fribourg, Switzerland; Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland; Barts Health National Health Service (NHS) Trust, London, UK; Pfizer Inc., Collegeville, Pennsylvania; Pfizer Inc., New York, New York, USA.P. Wiland, MD, PhD, Professor, Head of Department, Department of Rheumatology and Internal Medicine, Wroclaw Medical University; J. Dudler, MD, Professor, Head of Department, Department of Rheumatology, HFR Fribourg - Hôpital Cantonal; D. Veale, MD, Professor, Director of Translational Research, Dublin Academic Medical Centre; H. Tahir, MFSEM (UK), FRCP (UK), Professor, Consultant Rheumatologist, Sports Physician, Barts Health NHS Trust; R. Pedersen, MS, Director of Statistics, Pfizer; J. Bukowski, MD, PhD, Medical Director, Pfizer; B. Vlahos, MBA, BSN, RN, Medical Director, Clinical Lead, Pfizer; T. Williams, PA, MS, Study Clinician, Pfizer; S. Gaylord, BSN, RN, Assistant Director, Clinical Scientist, Pfizer; S. Kotak, MBA, MS, Director, Pfizer.
authors.forename: Jack
authors.initials: J
authors.lastname: Bukowski
authors.affiliation: From the Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland; Clinic of Rheumatology, HFR Fribourg - Hôpital Cantonal, Fribourg, Switzerland; Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland; Barts Health National Health Service (NHS) Trust, London, UK; Pfizer Inc., Collegeville, Pennsylvania; Pfizer Inc., New York, New York, USA.P. Wiland, MD, PhD, Professor, Head of Department, Department of Rheumatology and Internal Medicine, Wroclaw Medical University; J. Dudler, MD, Professor, Head of Department, Department of Rheumatology, HFR Fribourg - Hôpital Cantonal; D. Veale, MD, Professor, Director of Translational Research, Dublin Academic Medical Centre; H. Tahir, MFSEM (UK), FRCP (UK), Professor, Consultant Rheumatologist, Sports Physician, Barts Health NHS Trust; R. Pedersen, MS, Director of Statistics, Pfizer; J. Bukowski, MD, PhD, Medical Director, Pfizer; B. Vlahos, MBA, BSN, RN, Medical Director, Clinical Lead, Pfizer; T. Williams, PA, MS, Study Clinician, Pfizer; S. Gaylord, BSN, RN, Assistant Director, Clinical Scientist, Pfizer; S. Kotak, MBA, MS, Director, Pfizer.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Vlahos
authors.affiliation: From the Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland; Clinic of Rheumatology, HFR Fribourg - Hôpital Cantonal, Fribourg, Switzerland; Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland; Barts Health National Health Service (NHS) Trust, London, UK; Pfizer Inc., Collegeville, Pennsylvania; Pfizer Inc., New York, New York, USA.P. Wiland, MD, PhD, Professor, Head of Department, Department of Rheumatology and Internal Medicine, Wroclaw Medical University; J. Dudler, MD, Professor, Head of Department, Department of Rheumatology, HFR Fribourg - Hôpital Cantonal; D. Veale, MD, Professor, Director of Translational Research, Dublin Academic Medical Centre; H. Tahir, MFSEM (UK), FRCP (UK), Professor, Consultant Rheumatologist, Sports Physician, Barts Health NHS Trust; R. Pedersen, MS, Director of Statistics, Pfizer; J. Bukowski, MD, PhD, Medical Director, Pfizer; B. Vlahos, MBA, BSN, RN, Medical Director, Clinical Lead, Pfizer; T. Williams, PA, MS, Study Clinician, Pfizer; S. Gaylord, BSN, RN, Assistant Director, Clinical Scientist, Pfizer; S. Kotak, MBA, MS, Director, Pfizer.
authors.forename: Theresa
authors.initials: T
authors.lastname: Williams
authors.affiliation: From the Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland; Clinic of Rheumatology, HFR Fribourg - Hôpital Cantonal, Fribourg, Switzerland; Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland; Barts Health National Health Service (NHS) Trust, London, UK; Pfizer Inc., Collegeville, Pennsylvania; Pfizer Inc., New York, New York, USA.P. Wiland, MD, PhD, Professor, Head of Department, Department of Rheumatology and Internal Medicine, Wroclaw Medical University; J. Dudler, MD, Professor, Head of Department, Department of Rheumatology, HFR Fribourg - Hôpital Cantonal; D. Veale, MD, Professor, Director of Translational Research, Dublin Academic Medical Centre; H. Tahir, MFSEM (UK), FRCP (UK), Professor, Consultant Rheumatologist, Sports Physician, Barts Health NHS Trust; R. Pedersen, MS, Director of Statistics, Pfizer; J. Bukowski, MD, PhD, Medical Director, Pfizer; B. Vlahos, MBA, BSN, RN, Medical Director, Clinical Lead, Pfizer; T. Williams, PA, MS, Study Clinician, Pfizer; S. Gaylord, BSN, RN, Assistant Director, Clinical Scientist, Pfizer; S. Kotak, MBA, MS, Director, Pfizer.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Gaylord
authors.affiliation: From the Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland; Clinic of Rheumatology, HFR Fribourg - Hôpital Cantonal, Fribourg, Switzerland; Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland; Barts Health National Health Service (NHS) Trust, London, UK; Pfizer Inc., Collegeville, Pennsylvania; Pfizer Inc., New York, New York, USA.P. Wiland, MD, PhD, Professor, Head of Department, Department of Rheumatology and Internal Medicine, Wroclaw Medical University; J. Dudler, MD, Professor, Head of Department, Department of Rheumatology, HFR Fribourg - Hôpital Cantonal; D. Veale, MD, Professor, Director of Translational Research, Dublin Academic Medical Centre; H. Tahir, MFSEM (UK), FRCP (UK), Professor, Consultant Rheumatologist, Sports Physician, Barts Health NHS Trust; R. Pedersen, MS, Director of Statistics, Pfizer; J. Bukowski, MD, PhD, Medical Director, Pfizer; B. Vlahos, MBA, BSN, RN, Medical Director, Clinical Lead, Pfizer; T. Williams, PA, MS, Study Clinician, Pfizer; S. Gaylord, BSN, RN, Assistant Director, Clinical Scientist, Pfizer; S. Kotak, MBA, MS, Director, Pfizer.
authors.forename: Sameer
authors.initials: S
authors.lastname: Kotak
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068800:Etanercept / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D000071066:Patient Reported Outcome Measures; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D000068800:Etanercept; D008727:Methotrexate
keywords: CLINICAL TRIAL; DOSE-RESPONSE RELATIONSHIP; ETANERCEPT; METHOTREXATE; RHEUMATOID ARTHRITIS