Towards the Lowest Efficacious Dose (ToLEDo): Results of a Multicenter Non-Inferiority Randomized Open-Label Controlled Trial Assessing Tocilizumab or Abatacept Injection Spacing in Rheumatoid Arthritis in Remission

Arthritis Rheumatol. 2023 Nov 9. doi: 10.1002/art.42752. Online ahead of print.

Abstract

Objective: To 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.

Methods: This 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).

Results: Overall, 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]).

Conclusions: The ToLEDo trial failed to demonstrate NI for the proposed ABA or TCZ tapering strategy.