FRI0211 Tapering MTX versus Steady-State MTX in Combination with Tocilizumab for Treatment of Rheumatoid Arthritis (ACT-TAPER): A Randomised, Double-Blind, Controlled Phase 4 Trial

BackgroundFor 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.ObjectivesTo 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].MethodsACT-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.ResultsThe 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