Rituximab (RTX) in combination with methotrexate (MTX) significantly inhibits joint damage and improves clinical outcomes in patients with early active rheumatoid arthritis (ra) who are naive to mtx: a randomised active comparator placebo-controlled trial (image)

Aim: To evaluate clinical and radiographic outcomes with RTX plus MTX compared with MTX alone in patients with active RA not previously treated with MTX. Methods: Patients with 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, were randomised to placebo + MTX, RTX (2 x 500 mg) + MTX, or RTX (2 x 1000 mg) + MTX (MTX initiated at 7.5 mg/week and titrated to 20 mg/week by Week 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, Weeks 24 and 52 were read centrally using the Genant‐modified Sharp method (mTSS). Primary endpoint was change from screening in mTSS at Week 52. Secondary endpoints included major clinical response (MCR; ACR70 maintained =6 months). Results: 755 patients were randomised (715 radiographically evaluable). At 52 weeks, only RTX (2 x 1000 mg) + MTX significantly decreased radiographic progression versus placebo + MTX (mean change in mTSS 0.36 vs 1.08; p < 0.001) and significantly improved clinical outcomes (MCR 18.4% vs 8.0%; p < 0.001). Radiographic and clinical benefits with RTX (2 x 1000 mg) + MTX were observed by Week 24 with evidence of increased inhibition of joint damage from Week 24 to 52. Safety data were consistent with previous studies; serious infection rates were 6.09, 4.61 and 3.73 events/100 pt‐years for placebo + MTX, RTX (2 x 500 mg) and RTX (2 x 1000 mg), respectively. Three deaths occurred in the placebo + MTX arm (pneumonia, n >= 2; cerebral infarction). Conclusions: In patients with early active RA, RTX (2 x 1000 mg) + MTX significantly improved clinical outcomes and inhibited joint damage versus MTX alone.