Research ArticleArticle
Longterm Safety and Efficacy of Tocilizumab in Patients with Rheumatoid Arthritis: A Cumulative Analysis of Up to 4.6 Years of Exposure
Mark C. Genovese, Andrea Rubbert-Roth, Josef S. Smolen, Joel Kremer, Majed Khraishi, Juan Gómez-Reino, Anthony Sebba, Robert Pilson, Sarah Williams and Ronald van Vollenhoven
The Journal of Rheumatology March 2013, jrheum.120687; DOI: https://doi.org/10.3899/jrheum.120687
Mark C. Genovese
From the Division of Rheumatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Internal Medicine, University of Cologne, Cologne, Germany; Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Center for Rheumatology, Albany Medical College, State University of New York, Albany, New York, USA; Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; Rheumatology Unit Hospital, Clinical Universitario, Santiago, Spain; Department of Rheumatology, University of South Florida, Palm Harbor, Florida, USA; Hoffmann-La Roche Inc., Nutley, New Jersey, USA; PDBB-Biostatistics, Roche Products Limited, Welwyn Garden City, UK; and Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Stockholm, Sweden. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd. Dr. Genovese has received grant support and consulting revenue from Roche. Dr. Rubbert-Roth has received grant support from and has served on the speakers bureau for Roche. Dr. Smolen has received grant support and consulting revenue from and has served on the speakers bureau for Roche. Dr. Kremer has received grant support and consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Khraishi has received grant support from Roche Canada and has served on the speakers bureau for Roche. Dr. Gomez-Reino has received research grant support and consulting revenue from Roche. Dr. Sebba has received consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Pilson was an employee of Hoffmann-La Roche Inc. Ms. Williams is an employee of Roche Products Ltd. Dr. van Vollenhoven has received grant support, consulting revenue, and honoraria from Roche. M.C. Genovese, MD, Professor, Division of Rheumatology, Stanford University Medical Center; A. Rubbert-Roth, PhD, Professor, Department of Internal Medicine, University of Cologne; J.S. Smolen, MD, Professor, Division of Rheumatology, Department of Medicine III, Medical University of Vienna; J. Kremer, MD, Professor, Center for Rheumatology, Albany Medical College, State University of New York; M. Khraishi, MBBCh, FRCPC, Clinical Professor of Medicine (Rheumatology), Co-chair Human Investigation Committee, Memorial University of Newfoundland; J. Gómez-Reino, MD, Professor of Medicine, Head, Rheumatology Unit, Hospital Clinical Universitario; A. Sebba, MD, Assistant Clinical Professor, Department of Rheumatology, University of South Florida; R. Pilson, MS, Clinical Science Associate, Product Development, Immunology, Hoffmann-La Roche Inc.; S. Williams, MSc, Senior Statistical Scientist, PDBB-Biostatistics, Roche Products Limited; R. van Vollenhoven, MD, PhD, Senior Physician, Associate Professor, Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna. Address correspondence to Prof. M.C. Genovese, Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. E-mail: Genovese@stanford.edu Accepted for publication December 11, 2012.
Andrea Rubbert-Roth
From the Division of Rheumatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Internal Medicine, University of Cologne, Cologne, Germany; Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Center for Rheumatology, Albany Medical College, State University of New York, Albany, New York, USA; Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; Rheumatology Unit Hospital, Clinical Universitario, Santiago, Spain; Department of Rheumatology, University of South Florida, Palm Harbor, Florida, USA; Hoffmann-La Roche Inc., Nutley, New Jersey, USA; PDBB-Biostatistics, Roche Products Limited, Welwyn Garden City, UK; and Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Stockholm, Sweden. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd. Dr. Genovese has received grant support and consulting revenue from Roche. Dr. Rubbert-Roth has received grant support from and has served on the speakers bureau for Roche. Dr. Smolen has received grant support and consulting revenue from and has served on the speakers bureau for Roche. Dr. Kremer has received grant support and consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Khraishi has received grant support from Roche Canada and has served on the speakers bureau for Roche. Dr. Gomez-Reino has received research grant support and consulting revenue from Roche. Dr. Sebba has received consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Pilson was an employee of Hoffmann-La Roche Inc. Ms. Williams is an employee of Roche Products Ltd. Dr. van Vollenhoven has received grant support, consulting revenue, and honoraria from Roche. M.C. Genovese, MD, Professor, Division of Rheumatology, Stanford University Medical Center; A. Rubbert-Roth, PhD, Professor, Department of Internal Medicine, University of Cologne; J.S. Smolen, MD, Professor, Division of Rheumatology, Department of Medicine III, Medical University of Vienna; J. Kremer, MD, Professor, Center for Rheumatology, Albany Medical College, State University of New York; M. Khraishi, MBBCh, FRCPC, Clinical Professor of Medicine (Rheumatology), Co-chair Human Investigation Committee, Memorial University of Newfoundland; J. Gómez-Reino, MD, Professor of Medicine, Head, Rheumatology Unit, Hospital Clinical Universitario; A. Sebba, MD, Assistant Clinical Professor, Department of Rheumatology, University of South Florida; R. Pilson, MS, Clinical Science Associate, Product Development, Immunology, Hoffmann-La Roche Inc.; S. Williams, MSc, Senior Statistical Scientist, PDBB-Biostatistics, Roche Products Limited; R. van Vollenhoven, MD, PhD, Senior Physician, Associate Professor, Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna. Address correspondence to Prof. M.C. Genovese, Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. E-mail: Genovese@stanford.edu Accepted for publication December 11, 2012.
Josef S. Smolen
From the Division of Rheumatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Internal Medicine, University of Cologne, Cologne, Germany; Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Center for Rheumatology, Albany Medical College, State University of New York, Albany, New York, USA; Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; Rheumatology Unit Hospital, Clinical Universitario, Santiago, Spain; Department of Rheumatology, University of South Florida, Palm Harbor, Florida, USA; Hoffmann-La Roche Inc., Nutley, New Jersey, USA; PDBB-Biostatistics, Roche Products Limited, Welwyn Garden City, UK; and Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Stockholm, Sweden. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd. Dr. Genovese has received grant support and consulting revenue from Roche. Dr. Rubbert-Roth has received grant support from and has served on the speakers bureau for Roche. Dr. Smolen has received grant support and consulting revenue from and has served on the speakers bureau for Roche. Dr. Kremer has received grant support and consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Khraishi has received grant support from Roche Canada and has served on the speakers bureau for Roche. Dr. Gomez-Reino has received research grant support and consulting revenue from Roche. Dr. Sebba has received consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Pilson was an employee of Hoffmann-La Roche Inc. Ms. Williams is an employee of Roche Products Ltd. Dr. van Vollenhoven has received grant support, consulting revenue, and honoraria from Roche. M.C. Genovese, MD, Professor, Division of Rheumatology, Stanford University Medical Center; A. Rubbert-Roth, PhD, Professor, Department of Internal Medicine, University of Cologne; J.S. Smolen, MD, Professor, Division of Rheumatology, Department of Medicine III, Medical University of Vienna; J. Kremer, MD, Professor, Center for Rheumatology, Albany Medical College, State University of New York; M. Khraishi, MBBCh, FRCPC, Clinical Professor of Medicine (Rheumatology), Co-chair Human Investigation Committee, Memorial University of Newfoundland; J. Gómez-Reino, MD, Professor of Medicine, Head, Rheumatology Unit, Hospital Clinical Universitario; A. Sebba, MD, Assistant Clinical Professor, Department of Rheumatology, University of South Florida; R. Pilson, MS, Clinical Science Associate, Product Development, Immunology, Hoffmann-La Roche Inc.; S. Williams, MSc, Senior Statistical Scientist, PDBB-Biostatistics, Roche Products Limited; R. van Vollenhoven, MD, PhD, Senior Physician, Associate Professor, Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna. Address correspondence to Prof. M.C. Genovese, Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. E-mail: Genovese@stanford.edu Accepted for publication December 11, 2012.
Joel Kremer
From the Division of Rheumatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Internal Medicine, University of Cologne, Cologne, Germany; Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Center for Rheumatology, Albany Medical College, State University of New York, Albany, New York, USA; Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; Rheumatology Unit Hospital, Clinical Universitario, Santiago, Spain; Department of Rheumatology, University of South Florida, Palm Harbor, Florida, USA; Hoffmann-La Roche Inc., Nutley, New Jersey, USA; PDBB-Biostatistics, Roche Products Limited, Welwyn Garden City, UK; and Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Stockholm, Sweden. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd. Dr. Genovese has received grant support and consulting revenue from Roche. Dr. Rubbert-Roth has received grant support from and has served on the speakers bureau for Roche. Dr. Smolen has received grant support and consulting revenue from and has served on the speakers bureau for Roche. Dr. Kremer has received grant support and consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Khraishi has received grant support from Roche Canada and has served on the speakers bureau for Roche. Dr. Gomez-Reino has received research grant support and consulting revenue from Roche. Dr. Sebba has received consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Pilson was an employee of Hoffmann-La Roche Inc. Ms. Williams is an employee of Roche Products Ltd. Dr. van Vollenhoven has received grant support, consulting revenue, and honoraria from Roche. M.C. Genovese, MD, Professor, Division of Rheumatology, Stanford University Medical Center; A. Rubbert-Roth, PhD, Professor, Department of Internal Medicine, University of Cologne; J.S. Smolen, MD, Professor, Division of Rheumatology, Department of Medicine III, Medical University of Vienna; J. Kremer, MD, Professor, Center for Rheumatology, Albany Medical College, State University of New York; M. Khraishi, MBBCh, FRCPC, Clinical Professor of Medicine (Rheumatology), Co-chair Human Investigation Committee, Memorial University of Newfoundland; J. Gómez-Reino, MD, Professor of Medicine, Head, Rheumatology Unit, Hospital Clinical Universitario; A. Sebba, MD, Assistant Clinical Professor, Department of Rheumatology, University of South Florida; R. Pilson, MS, Clinical Science Associate, Product Development, Immunology, Hoffmann-La Roche Inc.; S. Williams, MSc, Senior Statistical Scientist, PDBB-Biostatistics, Roche Products Limited; R. van Vollenhoven, MD, PhD, Senior Physician, Associate Professor, Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna. Address correspondence to Prof. M.C. Genovese, Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. E-mail: Genovese@stanford.edu Accepted for publication December 11, 2012.
Majed Khraishi
From the Division of Rheumatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Internal Medicine, University of Cologne, Cologne, Germany; Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Center for Rheumatology, Albany Medical College, State University of New York, Albany, New York, USA; Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; Rheumatology Unit Hospital, Clinical Universitario, Santiago, Spain; Department of Rheumatology, University of South Florida, Palm Harbor, Florida, USA; Hoffmann-La Roche Inc., Nutley, New Jersey, USA; PDBB-Biostatistics, Roche Products Limited, Welwyn Garden City, UK; and Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Stockholm, Sweden. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd. Dr. Genovese has received grant support and consulting revenue from Roche. Dr. Rubbert-Roth has received grant support from and has served on the speakers bureau for Roche. Dr. Smolen has received grant support and consulting revenue from and has served on the speakers bureau for Roche. Dr. Kremer has received grant support and consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Khraishi has received grant support from Roche Canada and has served on the speakers bureau for Roche. Dr. Gomez-Reino has received research grant support and consulting revenue from Roche. Dr. Sebba has received consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Pilson was an employee of Hoffmann-La Roche Inc. Ms. Williams is an employee of Roche Products Ltd. Dr. van Vollenhoven has received grant support, consulting revenue, and honoraria from Roche. M.C. Genovese, MD, Professor, Division of Rheumatology, Stanford University Medical Center; A. Rubbert-Roth, PhD, Professor, Department of Internal Medicine, University of Cologne; J.S. Smolen, MD, Professor, Division of Rheumatology, Department of Medicine III, Medical University of Vienna; J. Kremer, MD, Professor, Center for Rheumatology, Albany Medical College, State University of New York; M. Khraishi, MBBCh, FRCPC, Clinical Professor of Medicine (Rheumatology), Co-chair Human Investigation Committee, Memorial University of Newfoundland; J. Gómez-Reino, MD, Professor of Medicine, Head, Rheumatology Unit, Hospital Clinical Universitario; A. Sebba, MD, Assistant Clinical Professor, Department of Rheumatology, University of South Florida; R. Pilson, MS, Clinical Science Associate, Product Development, Immunology, Hoffmann-La Roche Inc.; S. Williams, MSc, Senior Statistical Scientist, PDBB-Biostatistics, Roche Products Limited; R. van Vollenhoven, MD, PhD, Senior Physician, Associate Professor, Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna. Address correspondence to Prof. M.C. Genovese, Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. E-mail: Genovese@stanford.edu Accepted for publication December 11, 2012.
Juan Gómez-Reino
From the Division of Rheumatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Internal Medicine, University of Cologne, Cologne, Germany; Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Center for Rheumatology, Albany Medical College, State University of New York, Albany, New York, USA; Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; Rheumatology Unit Hospital, Clinical Universitario, Santiago, Spain; Department of Rheumatology, University of South Florida, Palm Harbor, Florida, USA; Hoffmann-La Roche Inc., Nutley, New Jersey, USA; PDBB-Biostatistics, Roche Products Limited, Welwyn Garden City, UK; and Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Stockholm, Sweden. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd. Dr. Genovese has received grant support and consulting revenue from Roche. Dr. Rubbert-Roth has received grant support from and has served on the speakers bureau for Roche. Dr. Smolen has received grant support and consulting revenue from and has served on the speakers bureau for Roche. Dr. Kremer has received grant support and consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Khraishi has received grant support from Roche Canada and has served on the speakers bureau for Roche. Dr. Gomez-Reino has received research grant support and consulting revenue from Roche. Dr. Sebba has received consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Pilson was an employee of Hoffmann-La Roche Inc. Ms. Williams is an employee of Roche Products Ltd. Dr. van Vollenhoven has received grant support, consulting revenue, and honoraria from Roche. M.C. Genovese, MD, Professor, Division of Rheumatology, Stanford University Medical Center; A. Rubbert-Roth, PhD, Professor, Department of Internal Medicine, University of Cologne; J.S. Smolen, MD, Professor, Division of Rheumatology, Department of Medicine III, Medical University of Vienna; J. Kremer, MD, Professor, Center for Rheumatology, Albany Medical College, State University of New York; M. Khraishi, MBBCh, FRCPC, Clinical Professor of Medicine (Rheumatology), Co-chair Human Investigation Committee, Memorial University of Newfoundland; J. Gómez-Reino, MD, Professor of Medicine, Head, Rheumatology Unit, Hospital Clinical Universitario; A. Sebba, MD, Assistant Clinical Professor, Department of Rheumatology, University of South Florida; R. Pilson, MS, Clinical Science Associate, Product Development, Immunology, Hoffmann-La Roche Inc.; S. Williams, MSc, Senior Statistical Scientist, PDBB-Biostatistics, Roche Products Limited; R. van Vollenhoven, MD, PhD, Senior Physician, Associate Professor, Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna. Address correspondence to Prof. M.C. Genovese, Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. E-mail: Genovese@stanford.edu Accepted for publication December 11, 2012.
Anthony Sebba
From the Division of Rheumatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Internal Medicine, University of Cologne, Cologne, Germany; Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Center for Rheumatology, Albany Medical College, State University of New York, Albany, New York, USA; Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; Rheumatology Unit Hospital, Clinical Universitario, Santiago, Spain; Department of Rheumatology, University of South Florida, Palm Harbor, Florida, USA; Hoffmann-La Roche Inc., Nutley, New Jersey, USA; PDBB-Biostatistics, Roche Products Limited, Welwyn Garden City, UK; and Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Stockholm, Sweden. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd. Dr. Genovese has received grant support and consulting revenue from Roche. Dr. Rubbert-Roth has received grant support from and has served on the speakers bureau for Roche. Dr. Smolen has received grant support and consulting revenue from and has served on the speakers bureau for Roche. Dr. Kremer has received grant support and consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Khraishi has received grant support from Roche Canada and has served on the speakers bureau for Roche. Dr. Gomez-Reino has received research grant support and consulting revenue from Roche. Dr. Sebba has received consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Pilson was an employee of Hoffmann-La Roche Inc. Ms. Williams is an employee of Roche Products Ltd. Dr. van Vollenhoven has received grant support, consulting revenue, and honoraria from Roche. M.C. Genovese, MD, Professor, Division of Rheumatology, Stanford University Medical Center; A. Rubbert-Roth, PhD, Professor, Department of Internal Medicine, University of Cologne; J.S. Smolen, MD, Professor, Division of Rheumatology, Department of Medicine III, Medical University of Vienna; J. Kremer, MD, Professor, Center for Rheumatology, Albany Medical College, State University of New York; M. Khraishi, MBBCh, FRCPC, Clinical Professor of Medicine (Rheumatology), Co-chair Human Investigation Committee, Memorial University of Newfoundland; J. Gómez-Reino, MD, Professor of Medicine, Head, Rheumatology Unit, Hospital Clinical Universitario; A. Sebba, MD, Assistant Clinical Professor, Department of Rheumatology, University of South Florida; R. Pilson, MS, Clinical Science Associate, Product Development, Immunology, Hoffmann-La Roche Inc.; S. Williams, MSc, Senior Statistical Scientist, PDBB-Biostatistics, Roche Products Limited; R. van Vollenhoven, MD, PhD, Senior Physician, Associate Professor, Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna. Address correspondence to Prof. M.C. Genovese, Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. E-mail: Genovese@stanford.edu Accepted for publication December 11, 2012.
Robert Pilson
From the Division of Rheumatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Internal Medicine, University of Cologne, Cologne, Germany; Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Center for Rheumatology, Albany Medical College, State University of New York, Albany, New York, USA; Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; Rheumatology Unit Hospital, Clinical Universitario, Santiago, Spain; Department of Rheumatology, University of South Florida, Palm Harbor, Florida, USA; Hoffmann-La Roche Inc., Nutley, New Jersey, USA; PDBB-Biostatistics, Roche Products Limited, Welwyn Garden City, UK; and Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Stockholm, Sweden. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd. Dr. Genovese has received grant support and consulting revenue from Roche. Dr. Rubbert-Roth has received grant support from and has served on the speakers bureau for Roche. Dr. Smolen has received grant support and consulting revenue from and has served on the speakers bureau for Roche. Dr. Kremer has received grant support and consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Khraishi has received grant support from Roche Canada and has served on the speakers bureau for Roche. Dr. Gomez-Reino has received research grant support and consulting revenue from Roche. Dr. Sebba has received consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Pilson was an employee of Hoffmann-La Roche Inc. Ms. Williams is an employee of Roche Products Ltd. Dr. van Vollenhoven has received grant support, consulting revenue, and honoraria from Roche. M.C. Genovese, MD, Professor, Division of Rheumatology, Stanford University Medical Center; A. Rubbert-Roth, PhD, Professor, Department of Internal Medicine, University of Cologne; J.S. Smolen, MD, Professor, Division of Rheumatology, Department of Medicine III, Medical University of Vienna; J. Kremer, MD, Professor, Center for Rheumatology, Albany Medical College, State University of New York; M. Khraishi, MBBCh, FRCPC, Clinical Professor of Medicine (Rheumatology), Co-chair Human Investigation Committee, Memorial University of Newfoundland; J. Gómez-Reino, MD, Professor of Medicine, Head, Rheumatology Unit, Hospital Clinical Universitario; A. Sebba, MD, Assistant Clinical Professor, Department of Rheumatology, University of South Florida; R. Pilson, MS, Clinical Science Associate, Product Development, Immunology, Hoffmann-La Roche Inc.; S. Williams, MSc, Senior Statistical Scientist, PDBB-Biostatistics, Roche Products Limited; R. van Vollenhoven, MD, PhD, Senior Physician, Associate Professor, Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna. Address correspondence to Prof. M.C. Genovese, Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. E-mail: Genovese@stanford.edu Accepted for publication December 11, 2012.
Sarah Williams
From the Division of Rheumatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Internal Medicine, University of Cologne, Cologne, Germany; Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Center for Rheumatology, Albany Medical College, State University of New York, Albany, New York, USA; Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; Rheumatology Unit Hospital, Clinical Universitario, Santiago, Spain; Department of Rheumatology, University of South Florida, Palm Harbor, Florida, USA; Hoffmann-La Roche Inc., Nutley, New Jersey, USA; PDBB-Biostatistics, Roche Products Limited, Welwyn Garden City, UK; and Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Stockholm, Sweden. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd. Dr. Genovese has received grant support and consulting revenue from Roche. Dr. Rubbert-Roth has received grant support from and has served on the speakers bureau for Roche. Dr. Smolen has received grant support and consulting revenue from and has served on the speakers bureau for Roche. Dr. Kremer has received grant support and consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Khraishi has received grant support from Roche Canada and has served on the speakers bureau for Roche. Dr. Gomez-Reino has received research grant support and consulting revenue from Roche. Dr. Sebba has received consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Pilson was an employee of Hoffmann-La Roche Inc. Ms. Williams is an employee of Roche Products Ltd. Dr. van Vollenhoven has received grant support, consulting revenue, and honoraria from Roche. M.C. Genovese, MD, Professor, Division of Rheumatology, Stanford University Medical Center; A. Rubbert-Roth, PhD, Professor, Department of Internal Medicine, University of Cologne; J.S. Smolen, MD, Professor, Division of Rheumatology, Department of Medicine III, Medical University of Vienna; J. Kremer, MD, Professor, Center for Rheumatology, Albany Medical College, State University of New York; M. Khraishi, MBBCh, FRCPC, Clinical Professor of Medicine (Rheumatology), Co-chair Human Investigation Committee, Memorial University of Newfoundland; J. Gómez-Reino, MD, Professor of Medicine, Head, Rheumatology Unit, Hospital Clinical Universitario; A. Sebba, MD, Assistant Clinical Professor, Department of Rheumatology, University of South Florida; R. Pilson, MS, Clinical Science Associate, Product Development, Immunology, Hoffmann-La Roche Inc.; S. Williams, MSc, Senior Statistical Scientist, PDBB-Biostatistics, Roche Products Limited; R. van Vollenhoven, MD, PhD, Senior Physician, Associate Professor, Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna. Address correspondence to Prof. M.C. Genovese, Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. E-mail: Genovese@stanford.edu Accepted for publication December 11, 2012.
Ronald van Vollenhoven
From the Division of Rheumatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Internal Medicine, University of Cologne, Cologne, Germany; Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Center for Rheumatology, Albany Medical College, State University of New York, Albany, New York, USA; Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; Rheumatology Unit Hospital, Clinical Universitario, Santiago, Spain; Department of Rheumatology, University of South Florida, Palm Harbor, Florida, USA; Hoffmann-La Roche Inc., Nutley, New Jersey, USA; PDBB-Biostatistics, Roche Products Limited, Welwyn Garden City, UK; and Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Stockholm, Sweden. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd. Dr. Genovese has received grant support and consulting revenue from Roche. Dr. Rubbert-Roth has received grant support from and has served on the speakers bureau for Roche. Dr. Smolen has received grant support and consulting revenue from and has served on the speakers bureau for Roche. Dr. Kremer has received grant support and consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Khraishi has received grant support from Roche Canada and has served on the speakers bureau for Roche. Dr. Gomez-Reino has received research grant support and consulting revenue from Roche. Dr. Sebba has received consulting revenue from and has served on the speakers bureau for Genentech, a member of the Roche group. Dr. Pilson was an employee of Hoffmann-La Roche Inc. Ms. Williams is an employee of Roche Products Ltd. Dr. van Vollenhoven has received grant support, consulting revenue, and honoraria from Roche. M.C. Genovese, MD, Professor, Division of Rheumatology, Stanford University Medical Center; A. Rubbert-Roth, PhD, Professor, Department of Internal Medicine, University of Cologne; J.S. Smolen, MD, Professor, Division of Rheumatology, Department of Medicine III, Medical University of Vienna; J. Kremer, MD, Professor, Center for Rheumatology, Albany Medical College, State University of New York; M. Khraishi, MBBCh, FRCPC, Clinical Professor of Medicine (Rheumatology), Co-chair Human Investigation Committee, Memorial University of Newfoundland; J. Gómez-Reino, MD, Professor of Medicine, Head, Rheumatology Unit, Hospital Clinical Universitario; A. Sebba, MD, Assistant Clinical Professor, Department of Rheumatology, University of South Florida; R. Pilson, MS, Clinical Science Associate, Product Development, Immunology, Hoffmann-La Roche Inc.; S. Williams, MSc, Senior Statistical Scientist, PDBB-Biostatistics, Roche Products Limited; R. van Vollenhoven, MD, PhD, Senior Physician, Associate Professor, Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna. Address correspondence to Prof. M.C. Genovese, Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. E-mail: Genovese@stanford.edu Accepted for publication December 11, 2012.
Abstract
Objective To assess the longterm safety and efficacy of tocilizumab (TCZ) in patients with moderate to severe rheumatoid arthritis (RA).
Methods Patient data were from 5 randomized controlled TCZ trials (n = 4211), their open-label extension phases (n = 3512), and a drug interaction study (n = 23). All randomly assigned patients, regardless of previous RA treatment, were analyzed. Measures of safety included number of adverse events (AE), serious AE (SAE), AE leading to treatment discontinuation, laboratory tests, and deaths. Efficacy measures included American College of Rheumatology (ACR) 20/50/70 responses, tender joint count (TJC), swollen joint count (SJC), ACR core set components, and low disease activity (LDA) or Disease Activity Score in 28 joints (DAS28) remission. ACR/European League Against Rheumatism (EULAR) disease remission was a posthoc exploratory analysis.
Results Total duration of observation was 12,293 patient-years (PY). No new safety signals were identified; infections were the most common AE and SAE. The rate of serious infections was 4.5/100 PY. Improvements from baseline in clinical efficacy, measured as ACR20/50/70 responses, TJC, SJC, ACR core set components, and LDA and DAS28 remission, were generally sustained through at least 216 weeks of followup. ACR/EULAR disease remission was attained by 16.5% (Boolean) and 22.7% (index) of patients at Week 216.
Conclusion TCZ has to date been studied for up to 4.6 years (240 weeks) of treatment in patients with RA. Our analysis reveals a longer-term safety profile consistent with previous observations, no new safety signals, and durable efficacy of TCZ in a large clinical trial program.
In this issue
The Journal of Rheumatology
Vol. 48, Issue 12
1 Dec 2021
Longterm Safety and Efficacy of Tocilizumab in Patients with Rheumatoid Arthritis: A Cumulative Analysis of Up to 4.6 Years of Exposure
Mark C. Genovese, Andrea Rubbert-Roth, Josef S. Smolen, Joel Kremer, Majed Khraishi, Juan Gómez-Reino, Anthony Sebba, Robert Pilson, Sarah Williams, Ronald van Vollenhoven
The Journal of Rheumatology Mar 2013, jrheum.120687; DOI: 10.3899/jrheum.120687
Longterm Safety and Efficacy of Tocilizumab in Patients with Rheumatoid Arthritis: A Cumulative Analysis of Up to 4.6 Years of Exposure
Mark C. Genovese, Andrea Rubbert-Roth, Josef S. Smolen, Joel Kremer, Majed Khraishi, Juan Gómez-Reino, Anthony Sebba, Robert Pilson, Sarah Williams, Ronald van Vollenhoven
The Journal of Rheumatology Mar 2013, jrheum.120687; DOI: 10.3899/jrheum.120687
