Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


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)

Tak1,  Paul P., Rigby2,  William F. C., Rubbert-Roth3,  Andrea, Peterfy4,  Charles G., van Vollenhoven5,  Ronald F., Stohl6,  William, Hessey7,  Eva

Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands
Dartmouth Hitchcock Medical Center, Lebanon, NH
University of Cologne, Cologne, Germany
Synarc Inc., San Francisco, CA
The Karolinska Institute, Stockholm, Sweden
Univ Southern California, Los Angeles, CA
Roche Products Ltd, Welwyn Garden City, United Kingdom
Genentech, Inc, South San Francisco, CA

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 × 500 mg) + MTX or RTX (2 × 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 × 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 × 1000 mg) + MTX group were observed by Week 24 with evidence of increased inhibition of joint damage from Wk 24–52.

 Plc + MTXRTX (2 × 500 mg) + MTXRTX (2 × 1000 mg) + MTX
Radiologicaln=232n=239n=244
Mean change in mTSS at 24 wks0.700.580.33*
Mean change in erosion score at 24 wks0.490.400.22**
Mean change in mTSS at 52 wks1.080.650.36**
Mean change in erosion score at 52 wks0.740.450.23***
Clinicaln=249n=249n=250
ACR50 (%)41.859.4***64.8***
ACR70 (%)24.942.2***46.8***
MCR (%)8.017.3*18.4**
DAS remission (%)12.625.4**30.5***
Mean change in DAS28n=244n=247n=248
 -2.06-3.05***-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 × 500 mg) and RTX (2 × 1000 mg) groups, respectively. Three deaths occurred (pneumonia [2] and cerebral infarct): all were in the Plc + MTX arm.

Conclusion:

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

To cite this abstract, please use the following information:
Tak, Paul P., Rigby, William F. C., Rubbert-Roth, Andrea, Peterfy, Charles G., van Vollenhoven, Ronald F., Stohl, William, et al; 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) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :636
DOI: 10.1002/art.25716

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