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
Authors: C.J. Edwards, P. Kiely, A. Ostor, B. Naisbett-Groet
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> 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 preference<sup>1–4</sup>. Previous data showed tocilizumab (TCZ) was effective as monotherapy in MTX-intolerant pts or pts for whom MTX was ineffective or inappropriate<sup>4,5</sup>. In addition, the ACT-RAY study suggested tapering MTX may result in maintained efficacy and an improved safety profile. <h3>Objectives</h3> 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]. <h3>Methods</h3> 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 &gt;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. <h3>Results</h3> 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 &lt;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. <h3>Conclusions</h3> 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. <h3>References</h3> 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 <h3>Acknowledgement</h3> Study sponsored by Roche Products Ltd <h3>Disclosure of Interest</h3> C. Edwards: None declared, P. Kiely: None declared, A. Ostor: None declared, B. Naisbett-Groet Employee of: Roche Products Ltd