Towards the Lowest Efficacious Dose: Results From a Multicenter Noninferiority Randomized Open‐Label Controlled Trial Assessing Tocilizumab or Abatacept Injection Spacing in Rheumatoid Arthritis in Remission

Abstract

ObjectiveTo assess the clinical and structural impact at 2 years of progressively spacing tocilizumab (TCZ) or abatacept (ABA) injections versus maintenance at full dose in rheumatoid arthritis (RA) patients in sustained remission.MethodsThis multicenter open‐label non‐inferiority (NI) randomized clinical trial included patients with established RA in sustained remission receiving ABA or TCZ at a stable dose. Patients were randomized to treatment maintenance at full dose (M‐arm), or progressive injection spacing driven by the Disease Activity Score in 28 joints (DAS28) every 3 months up to biologics discontinuation (S‐arm). The primary endpoint was the evolution of disease activity according to DAS44 during the 2‐year follow‐up analysed per protocol with a linear mixed‐effects model, evaluated by an NI test based on the one‐sided 95% CI of the slope difference (NI margin: 0.25). Other endpoints were flare incidence and structural damage progression (SDP).ResultsOverall, 202 of the 233 patients included were considered for per protocol analysis (90 in S‐arm, 112 in M‐arm). At the end of follow‐up, 16.2% of the S‐arm patients could discontinue their bDMARD: 46.9% tapered the dose and 36.9% returned to a full dose. NI was not demonstrated for the primary outcome, with a slope difference of 0.10 [95% CI ‐0.10; 0.31] between the two arms. NI was not demonstrated for flare incidence (difference 42.6% [95%CI: 30.0; 55.1]) or rate of SDP at 2 years (difference 13.9% [95% CI: ‐6.7; 34.4]).ConclusionsThe ToLEDo trial failed to demonstrate NI for the proposed ABA or TCZ tapering strategy.