Background/Purpose: Recent recommendations support intensive treatment of patients (pts) with early rheumatoid arthritis (RA) to achieve remission or low disease activity.^1-3 Tocilizumab (TCZ) was not previously studied exclusively in an early RA population. The purpose of this study was to assess the efficacy and safety of TCZ ± methotrexate (MTX) vs MTX in MTX-naive pts with early RA (defined as ≤2 y since diagnosis).

Methods: Pts were randomized 1:1:1:1 (double-dummy, double-blind) to receive TCZ 8 mg/kg (TCZ8) + MTX (primary intervention), TCZ8 monotherapy (TCZ8 MONO), TCZ 4 mg/kg (TCZ4) + MTX, or MTX for 104 wks. Pts received IV TCZ q4w, and MTX starting at 7.5 mg qw and escalating to 20 mg qw by wk 8. Inclusion criteria included RA duration ≤2 y, DAS28 >3.2, MTX-naive, elevated ESR or CRP, and presence of RF or anti-CCP antibodies or radiographic erosion(s). Primary endpoint was proportion of pts achieving DAS28 remission (DAS28 <2.6) at wk 24. Key secondary endpoints included mean changes from baseline (BL) to wk 52 in van der Heijde–modified Total Sharp Score (mTSS) and improvement in physical function (using HAQ-DI). A hierarchy of statistical testing was implemented to control the type 1 error rate for multiplicity. This trial is ongoing; 52-wk data are reported here.

Results: The intent-to-treat population consisted of 1157 pts. BL characteristics were similar in all treatment groups: mean RA duration, 0.4-0.5 y; mean DAS28, 6.6-6.7; mTSS, 5.66-7.72. Statistically significantly greater proportions of TCZ8 + MTX vs MTX pts achieved DAS28 remission and ACR20/50/70 responses at wks 24 and 52 (p < 0.05); statistically significant improvements in mean mTSS and HAQ-DI were also observed at wk 52 (p < 0.05; Table). TCZ8 MONO was also statistically significant for the primary endpoint of percentage of DAS28 remission responders in comparison to MTX at wk 24 (p < 0.05). Both TCZ8 MONO and TCZ4 + MTX exhibited numerically greater improvements vs MTX across key secondary endpoints and were more efficacious than MTX in preventing structural joint damage (Table). Adverse events (AEs) observed with TCZ were consistent with its known safety profile. Incidences of AEs and serious AEs were similar across groups, while serious infections were highest with combination therapy (Table). Overall, 9 deaths were observed across all groups; causes of death were variable.

Conclusion: TCZ is effective as combination therapy and monotherapy in MTX-naive pts with early active RA. TCZ resulted in greater improvements from BL in signs, symptoms, and physical function and in inhibition of structural joint damage in all treatment groups vs MTX alone. Of the 3 TCZ treatment groups, efficacy outcomes for TCZ vs MTX were consistently greatest in the TCZ8 + MTX group. The overall safety of TCZ was consistent with its known profile.

References: 1. Arthritis Care Res 2012;64:625; 2. Ann Rheum Dis 2010;69:631; 3.Ann Rheum Dis 2010;69:964