Background/Purpose: Approximately one-third of RA pts treated with biologics receive them as monotherapy (ie, without other DMARDs).^1-3 Although tocilizumab (TCZ), an IL-6 receptor inhibitor, has been assessed as monotherapy in 6 trials,^4-9 direct comparison with an anti-TNF agent as monotherapy has not occurred. ADACTA is the first trial specifically designed to determine superiority of one approved biologic vs another (TCZ vs adalimumab [ADA]) as monotherapy for RA.

Methods: ADACTA was a phase 4 randomized, double-blind, 24-wk study in pts with RA of ≥6-mo duration and DAS28 >5.1 who were MTX intolerant or for whom continued treatment with MTX was considered ineffective or inappropriate. Pts received TCZ 8 mg/kg IV every 4 wks (+ placebo [PBO] ADA) or ADA 40 mg SC every 2 wks (+ PBO TCZ) for 24 wks. Primary endpoint was mean change from baseline (BL) in DAS28 at 24 wks.

Results: The ITT population included 325 pts (163, TCZ; 162, ADA). BL characteristics were similar between the TCZ and ADA arms: mean age (54.4 and 53.3 y), mean RA duration (7.3 and 6.3 y), and mean DAS28 (6.72 and 6.76). At wk 24, mean change from BL in DAS28 was significantly greater with TCZ than with ADA (p<0.0001; Table). Statistically significantly greater proportions of TCZ than ADA pts achieved DAS28 <2.6, DAS28 ≤3.2, and ACR20/50/70 responses (p<0.005; Table). A difference in favor of TCZ was observed in proportions of pts achieving Clinical Disease Activity (CDAI) and Simplified Disease Activity (SDAI) Index remission (≤2.8 and ≤3.3) at wk 24 (post hoc analysis; p<0.05; Table). From wk 16 onward, the proportion of pts achieving ACR/EULAR remission (Boolean: SJC ≤1, TJC ≤1, CRP ≤1 mg/dL, pt global VAS ≤10) was numerically greater with TCZ, and by wk 24 it reached 18% compared with 11% for ADA. For exploratory endpoints HAQ-DI, SF-36 MCS, SF-36 PCS, and FACIT Fatigue, differences in mean change from BL at wk 24 were numerically higher for TCZ than ADA. Incidences of AEs, serious AEs, and serious infection were similar between arms (TCZ, 82.1%/11.7%/ 3.1%; ADA, 82.7%/9.9%/ 3.1%). Transaminase and LDL elevations and neutrophil count reductions were more common with TCZ. Two deaths occurred in the TCZ arm: 1 due to sudden death, the other due to reported illicit drug overdose.

Conclusion: TCZ as monotherapy was superior to ADA as monotherapy in reducing RA signs/symptoms in MTX-intolerant pts or pts for whom MTX was considered ineffective or inappropriate. The overall AE profiles of the two agents were similar, and lab changes were consistent with previous reports.

References: 1. Yazici Bull NYU Hosp Jt Dis 2008;66:77; 2. Soliman Ann Rheum Dis 2011;70:583; 3. Listing. Arthritis Res Ther 2006; 8:R66; 4. Dougados Ann Rheum Dis e-pub; 5. Weinblatt Arthritis Rheum 2011;63(suppl):S864; 6. Jones Ann Rheum Dis 2010;69:88;7. Nishimoto Ann Rheum Dis 2007;66:1162; 8. Nishimoto Mod Rheumatol 2009;19:12; 9. Sibilia Ann Rheum Dis 2011;70(suppl 3):466.