Research ArticleArticle
Open Access
Multiple Courses of Rituximab Produce Sustained Clinical and Radiographic Efficacy and Safety in Patients with Rheumatoid Arthritis and an Inadequate Response to 1 or More Tumor Necrosis Factor Inhibitors: 5-Year Data from the REFLEX Study
Edward C. Keystone, Stanley B. Cohen, Paul Emery, Joel M. Kremer, Maxime Dougados, James E. Loveless, Carol Chung, Pamela Wong, Patricia B. Lehane and Helen Tyrrell
The Journal of Rheumatology October 2012, jrheum.120573; DOI: https://doi.org/10.3899/jrheum.120573
Edward C. Keystone
From Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada; Metroplex Clinical Research Center, Dallas, Texas, USA; the University of Leeds and Leeds Teaching Hospitals, Leeds, UK; Albany Medical College, Albany, New York, USA; René Descartes University, Paris, France; St. Luke’s Rheumatology, Boise, Idaho, USA; Genentech Inc., South San Francisco, California, USA; and Roche Products Limited, Welwyn Garden City, UK. Supported by F. Hoffmann-La Roche Ltd. Dr. Keystone has received grants/research support from and acted as a consultant for Abbott, AstraZeneca, BMS, Centocor, Roche, Merck, Pfizer and UCB, has received grants/research support from Amgen, Genzyme and Novartis, and has acted as a consultant for Biotest, Genentech and Nycomed. Dr. Cohen has received grants/research support from and acted as a consultant for Amgen, BMS, Roche, Merck and Pfizer, has received grants/research support from Abbott, AstraZeneca, Centocor, Genzyme, Novartis and UCB, and has acted as a consultant for Genentech. Dr. Emery has acted as a consultant for Pfizer, Merck, Abbott, BMS, Roche, Novartis, and UCB. Dr. Kremer has received grants/research support from Genentech and Roche, and has acted as a consultant and on speakers’ bureau for Genentech. Dr. Dougados has received grants/research support from and acted as a consultant for Roche, Abbott, Pfizer, BMS, UCB, Novartis, and Merck. Dr. Loveless has acted as a consultant and on speakers’ bureau for Roche. E.C. Keystone, MD, FRCPC, Director, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, and Professor of Medicine, University of Toronto; S.B. Cohen, MD, Medical Director, Metroplex Clinical Research Center; P. Emery, MA, MD, FRCP, Clinical Director, University of Leeds and Leeds Teaching Hospitals; J.M. Kremer, MD, Rheumatologist, Albany Medical College; M. Dougados, MD, Professor of Rheumatology, René Descartes University; J.E. Loveless, MD, Principal Investigator, St. Luke’s Rheumatology; C. Chung, PhD, Associate Director, Biostatistics; P. Wong, MPh, Biostatistician, Genentech Inc.; P.B. Lehane, PhD, BSc (Hons), Clinical Scientist; H. Tyrrell, BSc, Senior Clinical Scientist, Roche Products Ltd. Address correspondence to Dr. E.C. Keystone, Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2–006, Box 4, 60 Murray Street, Toronto, Ontario M5G 1X5, Canada. E-mail: edkeystone@mtsinai.on.ca Full Release Article. For details see Reprints/Permissions at jrheum.org Accepted for publication July 23, 2012.
Stanley B. Cohen
From Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada; Metroplex Clinical Research Center, Dallas, Texas, USA; the University of Leeds and Leeds Teaching Hospitals, Leeds, UK; Albany Medical College, Albany, New York, USA; René Descartes University, Paris, France; St. Luke’s Rheumatology, Boise, Idaho, USA; Genentech Inc., South San Francisco, California, USA; and Roche Products Limited, Welwyn Garden City, UK. Supported by F. Hoffmann-La Roche Ltd. Dr. Keystone has received grants/research support from and acted as a consultant for Abbott, AstraZeneca, BMS, Centocor, Roche, Merck, Pfizer and UCB, has received grants/research support from Amgen, Genzyme and Novartis, and has acted as a consultant for Biotest, Genentech and Nycomed. Dr. Cohen has received grants/research support from and acted as a consultant for Amgen, BMS, Roche, Merck and Pfizer, has received grants/research support from Abbott, AstraZeneca, Centocor, Genzyme, Novartis and UCB, and has acted as a consultant for Genentech. Dr. Emery has acted as a consultant for Pfizer, Merck, Abbott, BMS, Roche, Novartis, and UCB. Dr. Kremer has received grants/research support from Genentech and Roche, and has acted as a consultant and on speakers’ bureau for Genentech. Dr. Dougados has received grants/research support from and acted as a consultant for Roche, Abbott, Pfizer, BMS, UCB, Novartis, and Merck. Dr. Loveless has acted as a consultant and on speakers’ bureau for Roche. E.C. Keystone, MD, FRCPC, Director, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, and Professor of Medicine, University of Toronto; S.B. Cohen, MD, Medical Director, Metroplex Clinical Research Center; P. Emery, MA, MD, FRCP, Clinical Director, University of Leeds and Leeds Teaching Hospitals; J.M. Kremer, MD, Rheumatologist, Albany Medical College; M. Dougados, MD, Professor of Rheumatology, René Descartes University; J.E. Loveless, MD, Principal Investigator, St. Luke’s Rheumatology; C. Chung, PhD, Associate Director, Biostatistics; P. Wong, MPh, Biostatistician, Genentech Inc.; P.B. Lehane, PhD, BSc (Hons), Clinical Scientist; H. Tyrrell, BSc, Senior Clinical Scientist, Roche Products Ltd. Address correspondence to Dr. E.C. Keystone, Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2–006, Box 4, 60 Murray Street, Toronto, Ontario M5G 1X5, Canada. E-mail: edkeystone@mtsinai.on.ca Full Release Article. For details see Reprints/Permissions at jrheum.org Accepted for publication July 23, 2012.
Paul Emery
From Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada; Metroplex Clinical Research Center, Dallas, Texas, USA; the University of Leeds and Leeds Teaching Hospitals, Leeds, UK; Albany Medical College, Albany, New York, USA; René Descartes University, Paris, France; St. Luke’s Rheumatology, Boise, Idaho, USA; Genentech Inc., South San Francisco, California, USA; and Roche Products Limited, Welwyn Garden City, UK. Supported by F. Hoffmann-La Roche Ltd. Dr. Keystone has received grants/research support from and acted as a consultant for Abbott, AstraZeneca, BMS, Centocor, Roche, Merck, Pfizer and UCB, has received grants/research support from Amgen, Genzyme and Novartis, and has acted as a consultant for Biotest, Genentech and Nycomed. Dr. Cohen has received grants/research support from and acted as a consultant for Amgen, BMS, Roche, Merck and Pfizer, has received grants/research support from Abbott, AstraZeneca, Centocor, Genzyme, Novartis and UCB, and has acted as a consultant for Genentech. Dr. Emery has acted as a consultant for Pfizer, Merck, Abbott, BMS, Roche, Novartis, and UCB. Dr. Kremer has received grants/research support from Genentech and Roche, and has acted as a consultant and on speakers’ bureau for Genentech. Dr. Dougados has received grants/research support from and acted as a consultant for Roche, Abbott, Pfizer, BMS, UCB, Novartis, and Merck. Dr. Loveless has acted as a consultant and on speakers’ bureau for Roche. E.C. Keystone, MD, FRCPC, Director, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, and Professor of Medicine, University of Toronto; S.B. Cohen, MD, Medical Director, Metroplex Clinical Research Center; P. Emery, MA, MD, FRCP, Clinical Director, University of Leeds and Leeds Teaching Hospitals; J.M. Kremer, MD, Rheumatologist, Albany Medical College; M. Dougados, MD, Professor of Rheumatology, René Descartes University; J.E. Loveless, MD, Principal Investigator, St. Luke’s Rheumatology; C. Chung, PhD, Associate Director, Biostatistics; P. Wong, MPh, Biostatistician, Genentech Inc.; P.B. Lehane, PhD, BSc (Hons), Clinical Scientist; H. Tyrrell, BSc, Senior Clinical Scientist, Roche Products Ltd. Address correspondence to Dr. E.C. Keystone, Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2–006, Box 4, 60 Murray Street, Toronto, Ontario M5G 1X5, Canada. E-mail: edkeystone@mtsinai.on.ca Full Release Article. For details see Reprints/Permissions at jrheum.org Accepted for publication July 23, 2012.
Joel M. Kremer
From Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada; Metroplex Clinical Research Center, Dallas, Texas, USA; the University of Leeds and Leeds Teaching Hospitals, Leeds, UK; Albany Medical College, Albany, New York, USA; René Descartes University, Paris, France; St. Luke’s Rheumatology, Boise, Idaho, USA; Genentech Inc., South San Francisco, California, USA; and Roche Products Limited, Welwyn Garden City, UK. Supported by F. Hoffmann-La Roche Ltd. Dr. Keystone has received grants/research support from and acted as a consultant for Abbott, AstraZeneca, BMS, Centocor, Roche, Merck, Pfizer and UCB, has received grants/research support from Amgen, Genzyme and Novartis, and has acted as a consultant for Biotest, Genentech and Nycomed. Dr. Cohen has received grants/research support from and acted as a consultant for Amgen, BMS, Roche, Merck and Pfizer, has received grants/research support from Abbott, AstraZeneca, Centocor, Genzyme, Novartis and UCB, and has acted as a consultant for Genentech. Dr. Emery has acted as a consultant for Pfizer, Merck, Abbott, BMS, Roche, Novartis, and UCB. Dr. Kremer has received grants/research support from Genentech and Roche, and has acted as a consultant and on speakers’ bureau for Genentech. Dr. Dougados has received grants/research support from and acted as a consultant for Roche, Abbott, Pfizer, BMS, UCB, Novartis, and Merck. Dr. Loveless has acted as a consultant and on speakers’ bureau for Roche. E.C. Keystone, MD, FRCPC, Director, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, and Professor of Medicine, University of Toronto; S.B. Cohen, MD, Medical Director, Metroplex Clinical Research Center; P. Emery, MA, MD, FRCP, Clinical Director, University of Leeds and Leeds Teaching Hospitals; J.M. Kremer, MD, Rheumatologist, Albany Medical College; M. Dougados, MD, Professor of Rheumatology, René Descartes University; J.E. Loveless, MD, Principal Investigator, St. Luke’s Rheumatology; C. Chung, PhD, Associate Director, Biostatistics; P. Wong, MPh, Biostatistician, Genentech Inc.; P.B. Lehane, PhD, BSc (Hons), Clinical Scientist; H. Tyrrell, BSc, Senior Clinical Scientist, Roche Products Ltd. Address correspondence to Dr. E.C. Keystone, Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2–006, Box 4, 60 Murray Street, Toronto, Ontario M5G 1X5, Canada. E-mail: edkeystone@mtsinai.on.ca Full Release Article. For details see Reprints/Permissions at jrheum.org Accepted for publication July 23, 2012.
Maxime Dougados
From Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada; Metroplex Clinical Research Center, Dallas, Texas, USA; the University of Leeds and Leeds Teaching Hospitals, Leeds, UK; Albany Medical College, Albany, New York, USA; René Descartes University, Paris, France; St. Luke’s Rheumatology, Boise, Idaho, USA; Genentech Inc., South San Francisco, California, USA; and Roche Products Limited, Welwyn Garden City, UK. Supported by F. Hoffmann-La Roche Ltd. Dr. Keystone has received grants/research support from and acted as a consultant for Abbott, AstraZeneca, BMS, Centocor, Roche, Merck, Pfizer and UCB, has received grants/research support from Amgen, Genzyme and Novartis, and has acted as a consultant for Biotest, Genentech and Nycomed. Dr. Cohen has received grants/research support from and acted as a consultant for Amgen, BMS, Roche, Merck and Pfizer, has received grants/research support from Abbott, AstraZeneca, Centocor, Genzyme, Novartis and UCB, and has acted as a consultant for Genentech. Dr. Emery has acted as a consultant for Pfizer, Merck, Abbott, BMS, Roche, Novartis, and UCB. Dr. Kremer has received grants/research support from Genentech and Roche, and has acted as a consultant and on speakers’ bureau for Genentech. Dr. Dougados has received grants/research support from and acted as a consultant for Roche, Abbott, Pfizer, BMS, UCB, Novartis, and Merck. Dr. Loveless has acted as a consultant and on speakers’ bureau for Roche. E.C. Keystone, MD, FRCPC, Director, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, and Professor of Medicine, University of Toronto; S.B. Cohen, MD, Medical Director, Metroplex Clinical Research Center; P. Emery, MA, MD, FRCP, Clinical Director, University of Leeds and Leeds Teaching Hospitals; J.M. Kremer, MD, Rheumatologist, Albany Medical College; M. Dougados, MD, Professor of Rheumatology, René Descartes University; J.E. Loveless, MD, Principal Investigator, St. Luke’s Rheumatology; C. Chung, PhD, Associate Director, Biostatistics; P. Wong, MPh, Biostatistician, Genentech Inc.; P.B. Lehane, PhD, BSc (Hons), Clinical Scientist; H. Tyrrell, BSc, Senior Clinical Scientist, Roche Products Ltd. Address correspondence to Dr. E.C. Keystone, Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2–006, Box 4, 60 Murray Street, Toronto, Ontario M5G 1X5, Canada. E-mail: edkeystone@mtsinai.on.ca Full Release Article. For details see Reprints/Permissions at jrheum.org Accepted for publication July 23, 2012.
James E. Loveless
From Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada; Metroplex Clinical Research Center, Dallas, Texas, USA; the University of Leeds and Leeds Teaching Hospitals, Leeds, UK; Albany Medical College, Albany, New York, USA; René Descartes University, Paris, France; St. Luke’s Rheumatology, Boise, Idaho, USA; Genentech Inc., South San Francisco, California, USA; and Roche Products Limited, Welwyn Garden City, UK. Supported by F. Hoffmann-La Roche Ltd. Dr. Keystone has received grants/research support from and acted as a consultant for Abbott, AstraZeneca, BMS, Centocor, Roche, Merck, Pfizer and UCB, has received grants/research support from Amgen, Genzyme and Novartis, and has acted as a consultant for Biotest, Genentech and Nycomed. Dr. Cohen has received grants/research support from and acted as a consultant for Amgen, BMS, Roche, Merck and Pfizer, has received grants/research support from Abbott, AstraZeneca, Centocor, Genzyme, Novartis and UCB, and has acted as a consultant for Genentech. Dr. Emery has acted as a consultant for Pfizer, Merck, Abbott, BMS, Roche, Novartis, and UCB. Dr. Kremer has received grants/research support from Genentech and Roche, and has acted as a consultant and on speakers’ bureau for Genentech. Dr. Dougados has received grants/research support from and acted as a consultant for Roche, Abbott, Pfizer, BMS, UCB, Novartis, and Merck. Dr. Loveless has acted as a consultant and on speakers’ bureau for Roche. E.C. Keystone, MD, FRCPC, Director, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, and Professor of Medicine, University of Toronto; S.B. Cohen, MD, Medical Director, Metroplex Clinical Research Center; P. Emery, MA, MD, FRCP, Clinical Director, University of Leeds and Leeds Teaching Hospitals; J.M. Kremer, MD, Rheumatologist, Albany Medical College; M. Dougados, MD, Professor of Rheumatology, René Descartes University; J.E. Loveless, MD, Principal Investigator, St. Luke’s Rheumatology; C. Chung, PhD, Associate Director, Biostatistics; P. Wong, MPh, Biostatistician, Genentech Inc.; P.B. Lehane, PhD, BSc (Hons), Clinical Scientist; H. Tyrrell, BSc, Senior Clinical Scientist, Roche Products Ltd. Address correspondence to Dr. E.C. Keystone, Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2–006, Box 4, 60 Murray Street, Toronto, Ontario M5G 1X5, Canada. E-mail: edkeystone@mtsinai.on.ca Full Release Article. For details see Reprints/Permissions at jrheum.org Accepted for publication July 23, 2012.
Carol Chung
From Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada; Metroplex Clinical Research Center, Dallas, Texas, USA; the University of Leeds and Leeds Teaching Hospitals, Leeds, UK; Albany Medical College, Albany, New York, USA; René Descartes University, Paris, France; St. Luke’s Rheumatology, Boise, Idaho, USA; Genentech Inc., South San Francisco, California, USA; and Roche Products Limited, Welwyn Garden City, UK. Supported by F. Hoffmann-La Roche Ltd. Dr. Keystone has received grants/research support from and acted as a consultant for Abbott, AstraZeneca, BMS, Centocor, Roche, Merck, Pfizer and UCB, has received grants/research support from Amgen, Genzyme and Novartis, and has acted as a consultant for Biotest, Genentech and Nycomed. Dr. Cohen has received grants/research support from and acted as a consultant for Amgen, BMS, Roche, Merck and Pfizer, has received grants/research support from Abbott, AstraZeneca, Centocor, Genzyme, Novartis and UCB, and has acted as a consultant for Genentech. Dr. Emery has acted as a consultant for Pfizer, Merck, Abbott, BMS, Roche, Novartis, and UCB. Dr. Kremer has received grants/research support from Genentech and Roche, and has acted as a consultant and on speakers’ bureau for Genentech. Dr. Dougados has received grants/research support from and acted as a consultant for Roche, Abbott, Pfizer, BMS, UCB, Novartis, and Merck. Dr. Loveless has acted as a consultant and on speakers’ bureau for Roche. E.C. Keystone, MD, FRCPC, Director, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, and Professor of Medicine, University of Toronto; S.B. Cohen, MD, Medical Director, Metroplex Clinical Research Center; P. Emery, MA, MD, FRCP, Clinical Director, University of Leeds and Leeds Teaching Hospitals; J.M. Kremer, MD, Rheumatologist, Albany Medical College; M. Dougados, MD, Professor of Rheumatology, René Descartes University; J.E. Loveless, MD, Principal Investigator, St. Luke’s Rheumatology; C. Chung, PhD, Associate Director, Biostatistics; P. Wong, MPh, Biostatistician, Genentech Inc.; P.B. Lehane, PhD, BSc (Hons), Clinical Scientist; H. Tyrrell, BSc, Senior Clinical Scientist, Roche Products Ltd. Address correspondence to Dr. E.C. Keystone, Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2–006, Box 4, 60 Murray Street, Toronto, Ontario M5G 1X5, Canada. E-mail: edkeystone@mtsinai.on.ca Full Release Article. For details see Reprints/Permissions at jrheum.org Accepted for publication July 23, 2012.
Pamela Wong
From Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada; Metroplex Clinical Research Center, Dallas, Texas, USA; the University of Leeds and Leeds Teaching Hospitals, Leeds, UK; Albany Medical College, Albany, New York, USA; René Descartes University, Paris, France; St. Luke’s Rheumatology, Boise, Idaho, USA; Genentech Inc., South San Francisco, California, USA; and Roche Products Limited, Welwyn Garden City, UK. Supported by F. Hoffmann-La Roche Ltd. Dr. Keystone has received grants/research support from and acted as a consultant for Abbott, AstraZeneca, BMS, Centocor, Roche, Merck, Pfizer and UCB, has received grants/research support from Amgen, Genzyme and Novartis, and has acted as a consultant for Biotest, Genentech and Nycomed. Dr. Cohen has received grants/research support from and acted as a consultant for Amgen, BMS, Roche, Merck and Pfizer, has received grants/research support from Abbott, AstraZeneca, Centocor, Genzyme, Novartis and UCB, and has acted as a consultant for Genentech. Dr. Emery has acted as a consultant for Pfizer, Merck, Abbott, BMS, Roche, Novartis, and UCB. Dr. Kremer has received grants/research support from Genentech and Roche, and has acted as a consultant and on speakers’ bureau for Genentech. Dr. Dougados has received grants/research support from and acted as a consultant for Roche, Abbott, Pfizer, BMS, UCB, Novartis, and Merck. Dr. Loveless has acted as a consultant and on speakers’ bureau for Roche. E.C. Keystone, MD, FRCPC, Director, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, and Professor of Medicine, University of Toronto; S.B. Cohen, MD, Medical Director, Metroplex Clinical Research Center; P. Emery, MA, MD, FRCP, Clinical Director, University of Leeds and Leeds Teaching Hospitals; J.M. Kremer, MD, Rheumatologist, Albany Medical College; M. Dougados, MD, Professor of Rheumatology, René Descartes University; J.E. Loveless, MD, Principal Investigator, St. Luke’s Rheumatology; C. Chung, PhD, Associate Director, Biostatistics; P. Wong, MPh, Biostatistician, Genentech Inc.; P.B. Lehane, PhD, BSc (Hons), Clinical Scientist; H. Tyrrell, BSc, Senior Clinical Scientist, Roche Products Ltd. Address correspondence to Dr. E.C. Keystone, Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2–006, Box 4, 60 Murray Street, Toronto, Ontario M5G 1X5, Canada. E-mail: edkeystone@mtsinai.on.ca Full Release Article. For details see Reprints/Permissions at jrheum.org Accepted for publication July 23, 2012.
Patricia B. Lehane
From Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada; Metroplex Clinical Research Center, Dallas, Texas, USA; the University of Leeds and Leeds Teaching Hospitals, Leeds, UK; Albany Medical College, Albany, New York, USA; René Descartes University, Paris, France; St. Luke’s Rheumatology, Boise, Idaho, USA; Genentech Inc., South San Francisco, California, USA; and Roche Products Limited, Welwyn Garden City, UK. Supported by F. Hoffmann-La Roche Ltd. Dr. Keystone has received grants/research support from and acted as a consultant for Abbott, AstraZeneca, BMS, Centocor, Roche, Merck, Pfizer and UCB, has received grants/research support from Amgen, Genzyme and Novartis, and has acted as a consultant for Biotest, Genentech and Nycomed. Dr. Cohen has received grants/research support from and acted as a consultant for Amgen, BMS, Roche, Merck and Pfizer, has received grants/research support from Abbott, AstraZeneca, Centocor, Genzyme, Novartis and UCB, and has acted as a consultant for Genentech. Dr. Emery has acted as a consultant for Pfizer, Merck, Abbott, BMS, Roche, Novartis, and UCB. Dr. Kremer has received grants/research support from Genentech and Roche, and has acted as a consultant and on speakers’ bureau for Genentech. Dr. Dougados has received grants/research support from and acted as a consultant for Roche, Abbott, Pfizer, BMS, UCB, Novartis, and Merck. Dr. Loveless has acted as a consultant and on speakers’ bureau for Roche. E.C. Keystone, MD, FRCPC, Director, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, and Professor of Medicine, University of Toronto; S.B. Cohen, MD, Medical Director, Metroplex Clinical Research Center; P. Emery, MA, MD, FRCP, Clinical Director, University of Leeds and Leeds Teaching Hospitals; J.M. Kremer, MD, Rheumatologist, Albany Medical College; M. Dougados, MD, Professor of Rheumatology, René Descartes University; J.E. Loveless, MD, Principal Investigator, St. Luke’s Rheumatology; C. Chung, PhD, Associate Director, Biostatistics; P. Wong, MPh, Biostatistician, Genentech Inc.; P.B. Lehane, PhD, BSc (Hons), Clinical Scientist; H. Tyrrell, BSc, Senior Clinical Scientist, Roche Products Ltd. Address correspondence to Dr. E.C. Keystone, Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2–006, Box 4, 60 Murray Street, Toronto, Ontario M5G 1X5, Canada. E-mail: edkeystone@mtsinai.on.ca Full Release Article. For details see Reprints/Permissions at jrheum.org Accepted for publication July 23, 2012.
Helen Tyrrell
From Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada; Metroplex Clinical Research Center, Dallas, Texas, USA; the University of Leeds and Leeds Teaching Hospitals, Leeds, UK; Albany Medical College, Albany, New York, USA; René Descartes University, Paris, France; St. Luke’s Rheumatology, Boise, Idaho, USA; Genentech Inc., South San Francisco, California, USA; and Roche Products Limited, Welwyn Garden City, UK. Supported by F. Hoffmann-La Roche Ltd. Dr. Keystone has received grants/research support from and acted as a consultant for Abbott, AstraZeneca, BMS, Centocor, Roche, Merck, Pfizer and UCB, has received grants/research support from Amgen, Genzyme and Novartis, and has acted as a consultant for Biotest, Genentech and Nycomed. Dr. Cohen has received grants/research support from and acted as a consultant for Amgen, BMS, Roche, Merck and Pfizer, has received grants/research support from Abbott, AstraZeneca, Centocor, Genzyme, Novartis and UCB, and has acted as a consultant for Genentech. Dr. Emery has acted as a consultant for Pfizer, Merck, Abbott, BMS, Roche, Novartis, and UCB. Dr. Kremer has received grants/research support from Genentech and Roche, and has acted as a consultant and on speakers’ bureau for Genentech. Dr. Dougados has received grants/research support from and acted as a consultant for Roche, Abbott, Pfizer, BMS, UCB, Novartis, and Merck. Dr. Loveless has acted as a consultant and on speakers’ bureau for Roche. E.C. Keystone, MD, FRCPC, Director, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, and Professor of Medicine, University of Toronto; S.B. Cohen, MD, Medical Director, Metroplex Clinical Research Center; P. Emery, MA, MD, FRCP, Clinical Director, University of Leeds and Leeds Teaching Hospitals; J.M. Kremer, MD, Rheumatologist, Albany Medical College; M. Dougados, MD, Professor of Rheumatology, René Descartes University; J.E. Loveless, MD, Principal Investigator, St. Luke’s Rheumatology; C. Chung, PhD, Associate Director, Biostatistics; P. Wong, MPh, Biostatistician, Genentech Inc.; P.B. Lehane, PhD, BSc (Hons), Clinical Scientist; H. Tyrrell, BSc, Senior Clinical Scientist, Roche Products Ltd. Address correspondence to Dr. E.C. Keystone, Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2–006, Box 4, 60 Murray Street, Toronto, Ontario M5G 1X5, Canada. E-mail: edkeystone@mtsinai.on.ca Full Release Article. For details see Reprints/Permissions at jrheum.org Accepted for publication July 23, 2012.
Abstract
Objective This 5-year observational posthoc analysis of the REFLEX study and its open-label extension assessed clinical efficacy, radiographic response, and safety of rituximab (RTX) in patients with rheumatoid arthritis (RA) who had an inadequate response to tumor necrosis factor (TNF) inhibitors.
Methods Patients in REFLEX were originally randomized to placebo (PBO) + methotrexate (MTX; PBO-randomized) or RTX + MTX (RTX-randomized). PBO-randomized patients were rescued with RTX as appropriate. Patients responding to initial RTX treatment could receive further RTX courses. For clinical efficacy and safety analyses, PBO-randomized patients were re-baselined prior to first RTX treatment and the data were pooled with RTX-randomized patient data. Efficacy outcomes 24 weeks after each course were calculated relative to first RTX pretreatment baseline. Radiographic outcomes were assessed relative to randomization baseline for both PBO-randomized and RTXrandomized groups.
Results A total of 480 patients received ≥ 1 RTX course. At 24 weeks, American College of Rheumatology 20/50/70 responses were 62.0%, 30.8%, and 13.0%, respectively at course 1 (n = 400) and 70.3%, 41.8%, and 22.0% at course 5 (n = 91). European League Against Rheumatism good/moderate responses were 77.2% and 84.4% at courses 1 (n = 390) and 5 (n = 90). Rates of adverse events (AE), serious AE, and infections generally remained stable. Rate of progressive joint damage (PJD; change in mean Total Sharp Score) decreased over time in both PBO-randomized (n = 79) and RTX-randomized (n = 105) groups. Mean change from baseline in PJD over 5 years was greater in PBO-randomized versus RTX-randomized patients (5.51 vs 3.21).
Conclusion RTX re-treatment over 5 years is associated with maintained or improved efficacy, continued inhibition of PJD, and a safety profile consistent with that previously reported. A delay in initiating RTX treatment may result in increased PJD.
In this issue
The Journal of Rheumatology
Vol. 50, Issue 12
1 Dec 2023
Multiple Courses of Rituximab Produce Sustained Clinical and Radiographic Efficacy and Safety in Patients with Rheumatoid Arthritis and an Inadequate Response to 1 or More Tumor Necrosis Factor Inhibitors: 5-Year Data from the REFLEX Study
Edward C. Keystone, Stanley B. Cohen, Paul Emery, Joel M. Kremer, Maxime Dougados, James E. Loveless, Carol Chung, Pamela Wong, Patricia B. Lehane, Helen Tyrrell
The Journal of Rheumatology Oct 2012, jrheum.120573; DOI: 10.3899/jrheum.120573
Multiple Courses of Rituximab Produce Sustained Clinical and Radiographic Efficacy and Safety in Patients with Rheumatoid Arthritis and an Inadequate Response to 1 or More Tumor Necrosis Factor Inhibitors: 5-Year Data from the REFLEX Study
Edward C. Keystone, Stanley B. Cohen, Paul Emery, Joel M. Kremer, Maxime Dougados, James E. Loveless, Carol Chung, Pamela Wong, Patricia B. Lehane, Helen Tyrrell
The Journal of Rheumatology Oct 2012, jrheum.120573; DOI: 10.3899/jrheum.120573
