OP0049 RITUXIMAB IN COMBINATION WITH METHOTREXATE (MTX) SIGNIFICANTLY INHIBITS JOINT DAMAGE IN PATIENTS WITH EARLY ACTIVE RA WHO ARE NAÏVE TO MTX: TWO-YEAR RADIOGRAPHIC OUTCOMES FROM A RANDOMIZED, ACTIVE COMPARATOR, PLACEBO-CONTROLLED TRIAL (IMAGE)

P. P. Tak ^1,*W. F. Rigby ²A. Rubbert-Roth ³C. Peterfy ⁴R. F. van Vollenhoven ⁵W. Stohl ⁶E. Hessey ⁷M. Reynard ⁷T. Shaw ⁷

¹Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, ²Medicine, Dartmouth Medical Hitchcock School, Lebanon, United States, ³Med Clinic I, University of Cologne, Cologne, Germany, ⁴Rheumatology, Synarc Inc., San Francisco, United States, ⁵Rheumatology, Karolinska University Hospital, Stockholm, Sweden, ⁶Rheumatology, USC, Los Angeles, United States, ⁷Roche Products Ltd, Welwyn Garden City, United Kingdom

Objectives: To evaluate two-year radiographic outcomes with rituximab (RTX) + MTX compared with MTX alone in patients (pts) with active RA not previously treated with MTX.

Methods: Key inclusion criteria were previously reported.¹ Pts naïve to previous MTX were randomised to either placebo (Plc) + MTX, RTX 2 x 500mg + MTX, or RTX 2 x 1000mg + MTX. MTX was initiated in all groups at 7.5mg/wk and titrated to 20mg/wk by Wk 8. RTX was given by IV infusion on Days 1 and 15 with a 24-wk repeat treatment schedule based on DAS28≥2.6. Radiographs, taken at screening, and Wks 24, 52 and 104 were centrally read using the Genant-modified Sharp method (mTSS). Based on the predefined analysis plan for multiplicity, lack of statistical significance of RTX 2 x 500mg at 1 year precluded formal statistical testing of this dose at 2 years.

Results: A total of 755 pts were randomised (716 radiographically evaluable). At 2 years, patients had received a mean of 3 courses in each treatment group. RTX 2 x 1000mg + MTX maintained a significant reduction in mTSS compared with Plc + MTX, with a 79% relative reduction in mTSS at 2 years. 82% of pts non-progressive at 1 year in the RTX 2 x 1000mg arm remained non-progressive at 2 years. The annual progression rate in mTSS from Wk 24 to Wk 104 was 0.015 compared with 0.715 in the MTX alone arm. RTX 2 x 500mg + MTX did not significantly inhibit joint damage at the 1-year primary analysis; however, exploratory analyses suggest inhibition at 2 years, with a 61% relative reduction in mTSS. 

Both doses of RTX suggest improved clinical outcomes compared with MTX alone at Wk 104 and demonstrate maintenance of response over the 2-year period. Safety data were consistent with those previously reported, with the rate of serious infections being 4.97, 4.15 and 3.25 events/100 pt-years in the Plc + MTX, RTX 2 x 500mg and RTX 2 x 1000mg arms, respectively.

***p<0.0001 compared with Plc + MTX.^†No formal statistical testing was performed with RTX 2 x 500mg + MTX due to failure to meet the primary endpoint at 1 year. 

Conclusion: In pts with early active RA not previously treated with MTX, the significant inhibition of joint damage observed with RTX 2 x 1000mg + MTX at 1 year was maintained over an extended 2-year time period.

References: 1. Tak PP, et al. Ann Rheum Dis 2009;68(Suppl3):75.

Disclosure of Interest: P. Tak Grant / Research Support from: Roche, Merck-Serono Consultant for: Roche, GenentechW. Rigby Consultant for: Genentech; Biogen/IDEC; Roche Speakers Bureau: Genentech; Biogen/IDEC; RocheA. Rubbert-Roth Consultant for: Roche, Wyeth, Abbott, UCB, Essex, BMS, Chugai Speakers Bureau: RocheC. Peterfy Shareholder of: Synarc Inc.R. van Vollenhoven Grant / Research Support from: Merck/Schering-Plough, Pfizer/Wyeth, Roche, Centocor, Inc, BMS, Abbott Consultant for: BMS, Abbott, Centocor, Inc, Roche, Pfizer/Wyeth, Merck/Schering-Plough W. Stohl Grant / Research Support from: Xencor, Genentech, Human Genome Sciences.E. Hessey Shareholder of: Roche Employee of: RocheM. Reynard Employee of: RocheT. Shaw Shareholder of: Roche Employee of: Roche