636 - Rituximab in Combination with Methotrexate (MTX) Significantly Inhibits Joint Damage and Improves Clinical Outcomes in Patients with Early Active RA Who Are Nave to MTX: A Randomized Active Comparator Placebo-Controlled Trial (IMAGE)

Sunday, October 18, 2009: 4:45 PM
103 A (Pennsylvania Convention Center)
Paul P. Tak1, William F. C. Rigby2, Andrea Rubbert-Roth3, Charles G. Peterfy4, Ronald F. van Vollenhoven5, William Stohl6, Eva Hessey7, Annie C. Chen8, Helen Tyrrell7 and Tim M. Shaw7, 1Academic Medical Center/ University of Amsterdam, Amsterdam, Netherlands, 2Dartmouth Hitchcock Medical Center, Lebanon, NH, 3University of Cologne, Cologne, Germany, 4Synarc Inc., San Francisco, CA, 5The Karolinska Institute, Stockholm, Sweden, 6Univ Southern California, Los Angeles, CA, 7Roche Products Ltd, Welwyn Garden City, United Kingdom, 8Genentech, Inc, South San Francisco, CA
Presentation Number: 636

Purpose: To evaluate clinical and radiographic outcomes with rituximab (RTX) plus MTX compared with MTX alone in patients (pts) with active rheumatoid arthritis (RA) not previously treated with MTX.

Methods: Key inclusion criteria were: no prior exposure to MTX; disease duration <4 years; swollen and tender joint count each ≥8; C-reactive protein (≥1.0 mg/dL), rheumatoid factor positive, or erosive damage. Pts were randomized to either placebo (Plc) + MTX, RTX (2 x 500mg) + MTX or RTX (2 x 1000 mg) + MTX. MTX was initiated in all groups at 7.5 mg/wk and titrated to 20 mg/wk by Wk 8. RTX was given by IV infusion on Days 1 and 15 with a 24-week repeat treatment schedule based on DAS28≥2.6. Radiographs, taken at screening, Wks 24 and 52, were read centrally using the Genant-modified Sharp method (mTSS). The primary endpoint was the change from screening in the mTSS at Wk 52. Secondary endpoints included Major Clinical Response (MCR; ACR70 maintained for at least 6 months).

Results: 755 pts were randomized (715 radiographically evaluable). Groups were balanced at baseline (mean RA duration of 0.9 years and DAS28 >7). At 52 wks, only RTX (2 x 1000 mg) + MTX was associated with both a significant decrease in radiographic progression and improved clinical outcomes as compared with Plc + MTX (Table). Notably, the radiographic and clinical benefits in the RTX (2 x 1000mg) + MTX group were observed by Week 24 with evidence of increased inhibition of joint damage from Wk 2452.

 

 

Plc + MTX

 

RTX
(2 x 500 mg)
+
MTX

RTX
(2 x 1000 mg) +
MTX

Radiological

n=232

n=239

n=244

Mean change in mTSS at 24 wks

0.70

0.58

0.33*

Mean change in erosion score at 24 wks

0.49

0.40

0.22**

Mean change in mTSS at 52 wks

1.08

0.65

0.36**

Mean change in erosion score at 52 wks

0.74

0.45

0.23***

Clinical

n=249

n=249

n=250

ACR50 (%)

41.8

59.4***

64.8***

ACR70 (%)

24.9

42.2***

46.8***

MCR (%)

8.0

17.3*

18.4**

DAS remission (%)

12.6

25.4**

30.5***

Mean change in DAS28

n=244

-2.06

n=247

-3.05***

n=248

-3.21***

*p<0.05, **p<0.001, ***p<0.0001 compared with Plc + MTX.

Safety data were consistent with those previously reported. The rate of serious infections was 6.09, 4.61 and 3.73 events/100 pt-years in the Plc + MTX, RTX (2 x 500 mg) and RTX (2 x 1000 mg) groups, respectively. Three deaths occurred (pneumonia [2] and cerebral infarct): all were in the Plc + MTX arm.

Conclusions: In pts with early active RA, RTX (2 x 1000 mg) + MTX significantly improved clinical outcomes and inhibited joint damage, compared with MTX alone.


Keywords: rheumatoid arthritis (RA) and rituximab

Disclosure: P. P. Tak, Roche Pharmaceuticals, 2, Merck-Serono, 2, Roche Pharmaceuticals, 5, Genentech and Biogen IDEC Inc., 5 ; W. F. C. Rigby, Genentech and Biogen IDEC Inc., 5, Genentech and Biogen IDEC Inc., 8 ; A. Rubbert-Roth, Roche Pharmaceuticals, 5, Wyeth Pharmaceuticals, 5, Abbott Laboratories, 5, UCB, 5, Essex, 5, Bristol-Myers Squibb, 5, Chugai, 5 ; C. G. Peterfy, Synarc, Inc., 4 ; R. F. van Vollenhoven, Schering-Plough, 2, Abbott Immunology Pharmaceuticals, 2, Wyeth Pharmaceuticals, 2, Roche, 2 ; W. Stohl, Xencor, Inc., 2, Xencor, Inc., 5 ; E. Hessey, Roche Pharmaceuticals, 3, Roche Pharmaceuticals, 1 ; A. C. Chen, Genentech and Biogen IDEC Inc., 1, Roche Pharmaceuticals, 1, Genentech and Biogen IDEC Inc., 3 ; H. Tyrrell, Roche Pharmaceuticals, 3 ; T. M. Shaw, Hoffmann-La Roche, 3, Hoffmann-La Roche, 1 .