Objective To evaluate efficacy of tocilizumab in US patients with moderate to severe active rheumatoid arthritis (RA) and inadequate clinical response to disease-modifying antirheumatic drugs (DMARD). Safety-related outcomes were also analysed.
Methods The rapid onset and systemic efficacy study was a 24-week, randomised, double-blind trial. Patients were randomly assigned 2:1 to tocilizumab 8 mg/kg (n=412) or placebo (n=207) every 4 weeks while continuing background DMARD in both groups.
Results The primary efficacy endpoint, percentage of patients achieving ACR50 response at week 24, was higher with tocilizumab versus placebo (30.1% vs 11.2%; p<0.0001). Percentages of ACR20 and ACR50 responders were significantly higher with tocilizumab versus placebo as early as week 4 and continued to week 24; more patients in the tocilizumab versus placebo group also achieved ACR70 responses beginning at week 8 (p<0.01). Significant improvements associated with tocilizumab versus placebo were seen in routine assessment of patient index data responses, EULAR good response, DAS28 and percentages of patients achieving low disease activity and clinical remission (based on DAS28). A substudy examining early response to therapy showed improved patient global assessment of disease activity (p=0.005) and pain (p=0.01) and DAS28 (p=0.007) with tocilizumab versus placebo at day 7. Safety findings were consistent with the known tocilizumab safety profile; rates of serious infections (per 100 patient-years) were 7.87 (95% CI 4.30 to 13.2) and 1.20 (95% CI 0.03 to 6.66) in the tocilizumab and placebo groups, respectively.
Conclusions This study demonstrated the efficacy of tocilizumab in improving measures of disease activity in patients with RA who failed to respond adequately to DMARD therapy. Rapid improvement in clinical outcomes was demonstrated in a substudy as early as week 1 as shown by DAS28 scores, patient measures and C-reactive protein.
Trial Registry no NCT00531817
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Funding This study was funded by Roche. Support for third-party writing assistance for this manuscript, furnished by Marci Mikesell, PhD, was provided by Embryon. Third-party writing assistance for this paper was provided by F Hoffmann-La Roche.
Competing interests YY has received research grants and consulting fees from Genentech, a member of the Roche Group. He has received consulting fees from Bristol-Myers Squibb, Celgene, Centocor and UCB and has ownership/partnership in UCB. YY is a speaker for Bristol-Myers Squibb and Pfizer. JRC has received research grants and consulting fees from Amgen, Centocor, Corrona, Abbott, Roche and UCB. AI is a speaker for Amgen and Wyeth Pharmaceuticals. HB has received research grants and consulting fees from Roche. He is also a speaker for Roche. RLM is an employee of Genentech. LLT is a consultant of Roche. AK has received research grants and consulting fees from Roche.
Ethics approval This study was conducted with the approval of the ROSE protocol and study design were approved by a central institutional review board and by individual institutional review boards.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.