Longterm safety, efficacy, and inhibition of structural damage progression over 5 years of treatment with abatacept in patients with rheumatoid arthritis in the abatacept in inadequate responders to methotrexate trial.
OBJECTIVE
Evaluate the safety and efficacy of longterm abatacept (ABA) treatment over 5 years in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA).


METHODS
Patients from the 1-year, double-blind Abatacept in Inadequate Responders to Methotrexate (AIM) study (NCT00048568) received open-label ABA (∼10 mg/kg) in the longterm extension (LTE). Safety was assessed for patients who received ≥ 1 ABA dose, and efficacy for patients randomized to ABA and treated in the LTE. Radiographs were evaluated for changes in Genant-modified Sharp scores.


RESULTS
Out of 652 patients, 539 entered the LTE (ABA, n = 378; placebo, n = 161). At Year 5, 72.4% were ongoing; discontinuation rates declined over time. Incidence rates of serious adverse events, serious infections, malignancies, and autoimmune events were 13.87, 2.84, 1.45, and 0.99 events/100 patient-years exposure, respectively. American College of Rheumatology 20 response was 82.3% (n = 373) and 83.6% (n = 268) at years 1 and 5, respectively. Disease Activity Score 28 C-reactive protein (DAS28-CRP) < 2.6 and ≤ 3.2 were achieved by 25.4% and 44.1% of patients at Year 1 (n = 370), and 33.7% and 54.7% at Year 5 (n = 267), respectively. Mean changes in DAS28-CRP and Health Assessment Questionnaire-Disability Index at Year 1 [-2.83 (n = 365) and -0.68 (n = 369)] were maintained at Year 5 [-3.14 (n = 264) and -0.77 (n = 271)] for patients continuing treatment. Of them, 59.5% (n = 291) and 45.1% (n = 235) remained free from radiographic progression at years 1 and 5, respectively.


CONCLUSIONS
In MTX-refractory patients with RA, longterm ABA treatment was well tolerated and provided consistent safety and sustained efficacy, with high patient retention. Radiographic progression continued to be inhibited with ongoing treatment.
From the Center for Rheumatology, Albany Medical College, Albany, New York; Spire Sciences Inc., Boca Raton, Florida, USA; Division of Rheumatology, University of Alberta Hospital, Edmonton, Alberta, Canada; Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust, Leeds, UK; Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí, San Luis Potosí, México; Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre, Strasbourg, France; Bristol-Myers Squibb, Princeton, New Jersey, USA; Department of Rheumatology, Universitaire Ziekenhuizenn Leuven, Leuven, Belgium; UCSF/Synarc, San Francisco, California, USA.Professional medical writing and editorial assistance funded by Bristol-Myers Squibb, Princeton, New Jersey, USA, and provided by Eve Guichard BSc (hons) of Caudex Medical, Oxford, UK.J.M. Kremer, MD, Center for Rheumatology, Albany Medical College; C. Peterfy, MD, PhD, FRCPC, Spire Sciences Inc.; A.S. Russell, FRCP, FRCPC, Division of Rheumatology, University of Alberta Hospital; P. Emery, MA, MD, FRCP, FRCPE, Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust; C. Abud-Mendoza, MD, Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí; J. Sibilia, MD, Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre; J-C. Becker, MD, Bristol-Myers Squibb*; R. Westhovens, MD, Department of Rheumatology, Universitaire Ziekenhuizenn Leuven; H.K. Genant, MD, UCSF/Synarc. jkremer@joint-docs.com.
Joel M
JM
Kremer
From the Center for Rheumatology, Albany Medical College, Albany, New York; Spire Sciences Inc., Boca Raton, Florida, USA; Division of Rheumatology, University of Alberta Hospital, Edmonton, Alberta, Canada; Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust, Leeds, UK; Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí, San Luis Potosí, México; Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre, Strasbourg, France; Bristol-Myers Squibb, Princeton, New Jersey, USA; Department of Rheumatology, Universitaire Ziekenhuizenn Leuven, Leuven, Belgium; UCSF/Synarc, San Francisco, California, USA.Professional medical writing and editorial assistance funded by Bristol-Myers Squibb, Princeton, New Jersey, USA, and provided by Eve Guichard BSc (hons) of Caudex Medical, Oxford, UK.J.M. Kremer, MD, Center for Rheumatology, Albany Medical College; C. Peterfy, MD, PhD, FRCPC, Spire Sciences Inc.; A.S. Russell, FRCP, FRCPC, Division of Rheumatology, University of Alberta Hospital; P. Emery, MA, MD, FRCP, FRCPE, Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust; C. Abud-Mendoza, MD, Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí; J. Sibilia, MD, Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre; J-C. Becker, MD, Bristol-Myers Squibb*; R. Westhovens, MD, Department of Rheumatology, Universitaire Ziekenhuizenn Leuven; H.K. Genant, MD, UCSF/Synarc.
Charles
C
Peterfy
From the Center for Rheumatology, Albany Medical College, Albany, New York; Spire Sciences Inc., Boca Raton, Florida, USA; Division of Rheumatology, University of Alberta Hospital, Edmonton, Alberta, Canada; Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust, Leeds, UK; Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí, San Luis Potosí, México; Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre, Strasbourg, France; Bristol-Myers Squibb, Princeton, New Jersey, USA; Department of Rheumatology, Universitaire Ziekenhuizenn Leuven, Leuven, Belgium; UCSF/Synarc, San Francisco, California, USA.Professional medical writing and editorial assistance funded by Bristol-Myers Squibb, Princeton, New Jersey, USA, and provided by Eve Guichard BSc (hons) of Caudex Medical, Oxford, UK.J.M. Kremer, MD, Center for Rheumatology, Albany Medical College; C. Peterfy, MD, PhD, FRCPC, Spire Sciences Inc.; A.S. Russell, FRCP, FRCPC, Division of Rheumatology, University of Alberta Hospital; P. Emery, MA, MD, FRCP, FRCPE, Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust; C. Abud-Mendoza, MD, Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí; J. Sibilia, MD, Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre; J-C. Becker, MD, Bristol-Myers Squibb*; R. Westhovens, MD, Department of Rheumatology, Universitaire Ziekenhuizenn Leuven; H.K. Genant, MD, UCSF/Synarc.
Anthony S
AS
Russell
From the Center for Rheumatology, Albany Medical College, Albany, New York; Spire Sciences Inc., Boca Raton, Florida, USA; Division of Rheumatology, University of Alberta Hospital, Edmonton, Alberta, Canada; Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust, Leeds, UK; Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí, San Luis Potosí, México; Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre, Strasbourg, France; Bristol-Myers Squibb, Princeton, New Jersey, USA; Department of Rheumatology, Universitaire Ziekenhuizenn Leuven, Leuven, Belgium; UCSF/Synarc, San Francisco, California, USA.Professional medical writing and editorial assistance funded by Bristol-Myers Squibb, Princeton, New Jersey, USA, and provided by Eve Guichard BSc (hons) of Caudex Medical, Oxford, UK.J.M. Kremer, MD, Center for Rheumatology, Albany Medical College; C. Peterfy, MD, PhD, FRCPC, Spire Sciences Inc.; A.S. Russell, FRCP, FRCPC, Division of Rheumatology, University of Alberta Hospital; P. Emery, MA, MD, FRCP, FRCPE, Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust; C. Abud-Mendoza, MD, Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí; J. Sibilia, MD, Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre; J-C. Becker, MD, Bristol-Myers Squibb*; R. Westhovens, MD, Department of Rheumatology, Universitaire Ziekenhuizenn Leuven; H.K. Genant, MD, UCSF/Synarc.
Paul
P
Emery
From the Center for Rheumatology, Albany Medical College, Albany, New York; Spire Sciences Inc., Boca Raton, Florida, USA; Division of Rheumatology, University of Alberta Hospital, Edmonton, Alberta, Canada; Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust, Leeds, UK; Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí, San Luis Potosí, México; Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre, Strasbourg, France; Bristol-Myers Squibb, Princeton, New Jersey, USA; Department of Rheumatology, Universitaire Ziekenhuizenn Leuven, Leuven, Belgium; UCSF/Synarc, San Francisco, California, USA.Professional medical writing and editorial assistance funded by Bristol-Myers Squibb, Princeton, New Jersey, USA, and provided by Eve Guichard BSc (hons) of Caudex Medical, Oxford, UK.J.M. Kremer, MD, Center for Rheumatology, Albany Medical College; C. Peterfy, MD, PhD, FRCPC, Spire Sciences Inc.; A.S. Russell, FRCP, FRCPC, Division of Rheumatology, University of Alberta Hospital; P. Emery, MA, MD, FRCP, FRCPE, Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust; C. Abud-Mendoza, MD, Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí; J. Sibilia, MD, Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre; J-C. Becker, MD, Bristol-Myers Squibb*; R. Westhovens, MD, Department of Rheumatology, Universitaire Ziekenhuizenn Leuven; H.K. Genant, MD, UCSF/Synarc.
Carlos
C
Abud-Mendoza
From the Center for Rheumatology, Albany Medical College, Albany, New York; Spire Sciences Inc., Boca Raton, Florida, USA; Division of Rheumatology, University of Alberta Hospital, Edmonton, Alberta, Canada; Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust, Leeds, UK; Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí, San Luis Potosí, México; Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre, Strasbourg, France; Bristol-Myers Squibb, Princeton, New Jersey, USA; Department of Rheumatology, Universitaire Ziekenhuizenn Leuven, Leuven, Belgium; UCSF/Synarc, San Francisco, California, USA.Professional medical writing and editorial assistance funded by Bristol-Myers Squibb, Princeton, New Jersey, USA, and provided by Eve Guichard BSc (hons) of Caudex Medical, Oxford, UK.J.M. Kremer, MD, Center for Rheumatology, Albany Medical College; C. Peterfy, MD, PhD, FRCPC, Spire Sciences Inc.; A.S. Russell, FRCP, FRCPC, Division of Rheumatology, University of Alberta Hospital; P. Emery, MA, MD, FRCP, FRCPE, Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust; C. Abud-Mendoza, MD, Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí; J. Sibilia, MD, Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre; J-C. Becker, MD, Bristol-Myers Squibb*; R. Westhovens, MD, Department of Rheumatology, Universitaire Ziekenhuizenn Leuven; H.K. Genant, MD, UCSF/Synarc.
Jean
J
Sibilia
From the Center for Rheumatology, Albany Medical College, Albany, New York; Spire Sciences Inc., Boca Raton, Florida, USA; Division of Rheumatology, University of Alberta Hospital, Edmonton, Alberta, Canada; Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust, Leeds, UK; Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí, San Luis Potosí, México; Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre, Strasbourg, France; Bristol-Myers Squibb, Princeton, New Jersey, USA; Department of Rheumatology, Universitaire Ziekenhuizenn Leuven, Leuven, Belgium; UCSF/Synarc, San Francisco, California, USA.Professional medical writing and editorial assistance funded by Bristol-Myers Squibb, Princeton, New Jersey, USA, and provided by Eve Guichard BSc (hons) of Caudex Medical, Oxford, UK.J.M. Kremer, MD, Center for Rheumatology, Albany Medical College; C. Peterfy, MD, PhD, FRCPC, Spire Sciences Inc.; A.S. Russell, FRCP, FRCPC, Division of Rheumatology, University of Alberta Hospital; P. Emery, MA, MD, FRCP, FRCPE, Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust; C. Abud-Mendoza, MD, Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí; J. Sibilia, MD, Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre; J-C. Becker, MD, Bristol-Myers Squibb*; R. Westhovens, MD, Department of Rheumatology, Universitaire Ziekenhuizenn Leuven; H.K. Genant, MD, UCSF/Synarc.
Jean-Claude
JC
Becker
From the Center for Rheumatology, Albany Medical College, Albany, New York; Spire Sciences Inc., Boca Raton, Florida, USA; Division of Rheumatology, University of Alberta Hospital, Edmonton, Alberta, Canada; Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust, Leeds, UK; Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí, San Luis Potosí, México; Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre, Strasbourg, France; Bristol-Myers Squibb, Princeton, New Jersey, USA; Department of Rheumatology, Universitaire Ziekenhuizenn Leuven, Leuven, Belgium; UCSF/Synarc, San Francisco, California, USA.Professional medical writing and editorial assistance funded by Bristol-Myers Squibb, Princeton, New Jersey, USA, and provided by Eve Guichard BSc (hons) of Caudex Medical, Oxford, UK.J.M. Kremer, MD, Center for Rheumatology, Albany Medical College; C. Peterfy, MD, PhD, FRCPC, Spire Sciences Inc.; A.S. Russell, FRCP, FRCPC, Division of Rheumatology, University of Alberta Hospital; P. Emery, MA, MD, FRCP, FRCPE, Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust; C. Abud-Mendoza, MD, Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí; J. Sibilia, MD, Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre; J-C. Becker, MD, Bristol-Myers Squibb*; R. Westhovens, MD, Department of Rheumatology, Universitaire Ziekenhuizenn Leuven; H.K. Genant, MD, UCSF/Synarc.
Rene
R
Westhovens
From the Center for Rheumatology, Albany Medical College, Albany, New York; Spire Sciences Inc., Boca Raton, Florida, USA; Division of Rheumatology, University of Alberta Hospital, Edmonton, Alberta, Canada; Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds; UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust, Leeds, UK; Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí, San Luis Potosí, México; Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre, Strasbourg, France; Bristol-Myers Squibb, Princeton, New Jersey, USA; Department of Rheumatology, Universitaire Ziekenhuizenn Leuven, Leuven, Belgium; UCSF/Synarc, San Francisco, California, USA.Professional medical writing and editorial assistance funded by Bristol-Myers Squibb, Princeton, New Jersey, USA, and provided by Eve Guichard BSc (hons) of Caudex Medical, Oxford, UK.J.M. Kremer, MD, Center for Rheumatology, Albany Medical College; C. Peterfy, MD, PhD, FRCPC, Spire Sciences Inc.; A.S. Russell, FRCP, FRCPC, Division of Rheumatology, University of Alberta Hospital; P. Emery, MA, MD, FRCP, FRCPE, Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust; C. Abud-Mendoza, MD, Regional Unit of Rheumatology, Faculty of Medicine and Central Hospital, University of San Luis Potosí; J. Sibilia, MD, Service de Rhumatologie, CHU de Strasbourg, Hôpital de Hautepierre; J-C. Becker, MD, Bristol-Myers Squibb*; R. Westhovens, MD, Department of Rheumatology, Universitaire Ziekenhuizenn Leuven; H.K. Genant, MD, UCSF/Synarc.
Harry K
HK
Genant
D000069594:Abatacept; D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D033023:Foot Joints / Q000000981:diagnostic imaging / Q000187:drug effects*; D050823:Hand Joints / Q000000981:diagnostic imaging / Q000187:drug effects*; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D019233:Retreatment; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D018796:Immunoconjugates; D000069594:Abatacept; D008727:Methotrexate
ABATACEPT; METHOTREXATE; RHEUMATOID ARTHRITIS