Piotr Wiland1, Jean Dudler2, Douglas Veale2, Hasan Tahir2, Ron Pedersen2, Jack Bukowski2, Bonnie Vlahos2, Theresa Williams2, Stefanie Gaylord2, Sameer Kotak2. 1. 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. 2. 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.
Abstract
OBJECTIVE: 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 withetanercept (ETN) plus methotrexate (MTX) therapy. METHODS: 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). RESULTS: 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). CONCLUSION: 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.
RCT Entities:
OBJECTIVE: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.
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