Background For most DMARD-IR patients (pts) with severe active RA, therapy with a biologic and methotrexate (MTX) is effective. However, nearly 1/3 discontinue or are non-compliant with MTX because of toxicity or preference1–4. Previous data showed tocilizumab (TCZ) was effective as monotherapy in MTX-intolerant pts or pts for whom MTX was ineffective or inappropriate4,5. In addition, the ACT-RAY study suggested tapering MTX may result in maintained efficacy and an improved safety profile.
Objectives To explore if TCZ + tapering MTX has comparable efficacy and safety vs TCZ + stable MTX in pts with inadequate response to MTX [EudraCT 2011–005260–20].
Methods ACT-TAPER was a randomised, placebo-controlled non-inferiority study investigating efficacy and safety of tapering MTX vs stable MTX in DMARD-IR pts with severe active RA (DAS28 >5.1) who had initiated TCZ + MTX at study start. At Week (Wk) 0, DMARDs except MTX were discontinued; pts started open-label TCZ (8 mg/kg IV 4 weekly) and open-label MTX. At Wk 24, pts achieving good/moderate EULAR response were randomised to Group A (double-blind MTX taper) or Group B (double-blind MTX maintenance). Both continued open-label TCZ. Pts achieving adequate improvement stayed in treatment groups to Week 72. Primary analysis: proportion of pts maintaining good/moderate EULAR from wks 24–60 in TCZ + MTX taper vs TCZ + stable MTX. Secondary analyses included safety outcome measures.
Results The study stopped early due to low recruitment; 427 pts entered the initial open-label phase (IP) of the study and 272 pts were randomised (36% withdrew or were not eligible to be randomised; protocol required 494 pts to be randomised), 136 in each arm. Of the IP population, 64.4% achieved good/moderate EULAR at Wk 24, with 45.0% achieving DAS28 ≤3.2, 33.5% remission (DAS28 <2.6) and 64.2% with DAS28 change ≥1.2. After Wk 24 randomisation, the proportion of pts maintaining good/moderate EULAR to Week 60 was greater for MTX taper vs stable MTX (76.5% vs 65.4%). This allowed the pre-determined criteria for non-inferiority to be fulfilled despite the reduced recruitment. The proportion of pts achieving a change ≥1.2 DAS28 at Wk 60 did not differ significantly between groups; mean (SD) change from Wk 24–60 was -0.179 (1.1702) Group A and -0.233 (1.5156) Group B. The proportion of pts with DAS28 ≤3.2 at Wks 60 and 72 did not differ significantly between groups (59.6% and 61.0% for Group A; 62.5% and 60.3% for Group B). The proportion of pts in remission at Wks 60 and 72 did not differ significantly between treatments. Safety analysis revealed no unexpected TCZ safety signals.
Conclusions Tapering MTX in RA pts using TCZ was non-inferior to continuing stable MTX in maintaining a good/moderate EULAR response. No significant change in DAS28 was observed between groups. There were no unexpected safety signals; TCZ and MTX therapy was generally well tolerated in both groups.
Yazici Bull NYU Hosp Jt Dis 2008;66:77;
Soliman Ann Rheum Dis 2011;70:583;
Listing. Arthritis Res Ther 2006;8:R66;
Dougados Ann Rheum Dis 2013;72:43.
Jones Ann Rheum Dis 2013;72(suppl):457
Acknowledgement Study sponsored by Roche Products Ltd
Disclosure of Interest C. Edwards: None declared, P. Kiely: None declared, A. Ostor: None declared, B. Naisbett-Groet Employee of: Roche Products Ltd