Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE

Tak, Paul P; Rigby, William; Rubbert-Roth, Andrea; Peterfy, Charles; van Vollenhoven, Ronald F; Stohl, William; Healy, Emma; Hessey, Eva; Reynard, Mark; Shaw, Tim

doi:10.1136/annrheumdis-2011-200170

Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE

¹Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands
²Department of Medicine, Dartmouth Medical School/Dartmouth-Hitchcock Medical Centre, Lebanon, New Hampshire, USA
³Department of Internal Medicine, University of Cologne, Cologne, Germany
⁴Spire Sciences LLC, San Francisco, California, USA
⁵Department of Medicine, The Karolinska Institute, Stockholm, Sweden
⁶Department of Medicine, Division of Rheumatology, Los Angeles County/University of Southern California Medical Centre and University of Southern California Keck School of Medicine, Los Angeles, California, USA
⁷Roche Products, Welwyn Garden City, UK

Correspondence to Professor Paul P Tak, Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, F4-105, P O Box 22700, 1100 DE Amsterdam, The Netherlands; p.p.tak{at}amc.uva.nl

Contributorship PPT monitored data collection, analysed the data and implemented the trial. He is guarantor. WR monitored data collection, analysed the data and implemented the trial. ARR monitored data collection, analysed the data and implemented the trial. CP monitored data collection, analysed the data and implemented the trial. RFvV monitored data collection, analysed the data and implemented the trial. WS monitored data collection, analysed the data and implemented the trial. E Healy monitored data collection, cleaned and analysed the data and implemented the trial. E Hessey wrote the statistical analysis plan and cleaned and analysed the data. MR monitored data collection, cleaned and analysed the data and implemented the trial. TS designed the study and data collection tools, cleaned and analysed the data and implemented the trial. All authors contributed to the development of the manuscript and read and approved the final version. Laura Burke (Roche) monitored data collection, cleaned and analysed the data, implemented the trial and contributed to the development of the manuscript. Nicola Tyson (Roche) wrote the statistical analysis plan, cleaned and analysed the data and contributed to the development of the manuscript.

Received 13 May 2011
Accepted 10 September 2011
Published Online First 19 October 2011

Abstract

Background In the IMAGEstudy, rituximab plus methotrexate (MTX) inhibited joint damage and improved clinical outcomes at 1 year in MTX-naïve patients with early active rheumatoid arthritis.

Objective The aim of this study was to assess joint damage progression and clinical outcomes over 2 years.

Methods Patients (n=755) were randomised to receive rituximab 2×500 mg+MTX, 2×1000 mg+MTX or placebo+MTX. The placebo-controlled period continued to week 104. Two-year end points were defined as secondary or exploratory and included change in total Genant-modified Sharp score (mTSS), total erosion score and joint space narrowing score from baseline to week 104. Clinical efficacy and physical function end points were also assessed.

Results At 2 years, rituximab 2×1000 mg+MTX maintained inhibition of progressive joint damage versus MTX alone (mTSS change 0.41 vs 1.95; p<0.0001 (79% inhibition)), and a higher proportion of patients receiving rituximab 2×1000 mg+MTX had no radiographic progression over 2 years compared with those receiving MTX alone (57% vs 37%; p<0.0001). Contrary to 1-year results, exploratory analysis of rituximab 2×500 mg+MTX at 2 years showed that progressive joint damage was slowed by ∼61% versus placebo+MTX (mTSS, exploratory p=0.0041). Improvements in clinical signs and symptoms and physical function seen after 1 year in rituximab-treated patients versus those receiving placebo were maintained at year 2. Safety profiles were similar between groups.

Conclusions Treatment with rituximab 2×1000 mg+MTX was associated with sustained improvements in radiographic, clinical and functional outcomes over 2 years.

Clinical trials.gov identifier NCT00299104.

Footnotes

Funding Financial support for this study was obtained from F Hoffmann-La Roche, Genentech Inc and Biogen Idec.
Competing Interests PPT has served as a consultant to Roche and Genentech. WR has served as a paid consultant for Roche, Genentech and Biogen Idec; has been paid lecture fees by Genentech and Biogen Idec; and has received grant support from Roche. ARR has received honoraria for talks and consulting from Roche. CP is an employee and shareholder of Spire Sciences LLC and a shareholder of Synarc Inc, which provide clinical trials services for multiple pharmaceutical, biotechnology and medical device companies. RFvV has received research support and honoraria/consultancy from Abbott, Merck, Pfizer, Roche and UCB Pharma, as well as honoraria/consultancy from Bristol Myers Squibb. WS has received a research grant from Xencor. E Healy is an employee of and owns shares in Roche. E Hessey is an employee of Roche. MR was an employee of Roche at the time of trial conduct and manuscript preparation, owns shares in Roche and is now an employee of and owns shares in GlaxoSmithKline. TS was an employee of Roche at the time of trial conduct and manuscript preparation, owns shares in Roche and is now an employee of Celgene Corporation.
Provenance and peer review Not commissioned; externally peer reviewed.

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