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 - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Arthritis & rheumatology Année : 2024

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

1 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
2 PHERE (UMR_S_1152 / U1152) - Physiopathologie et Epidémiologie des Maladies Respiratoires
3 Service de Rhumatologie
4 CHU Pitié-Salpêtrière [AP-HP]
5 SAINBIOSE - Santé Ingénierie Biologie Saint-Etienne
6 Service de Rhumatologie
7 CHU de Bordeaux Pellegrin [Bordeaux]
8 Service de rhumatologie [Rennes] = Rheumatology [Rennes]
9 Service de Rhumatologie [CHU Clermont-Ferrand]
10 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
11 Service de Rhumatologie [CHRU Montpellier]
12 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
13 UT3 - Université Toulouse III - Paul Sabatier
14 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
15 Service de Rhumatologie [CH Le Mans]
16 Hôpitaux de Chartres [Chartres]
17 VIEFRA - EA 3797 - Vieillissement, Fragilité
18 Hôpital Maison Blanche
19 Hôpitaux Sud - Rhumatologie [Sainte- Marguerite - APHM]
20 Service de rhumatologie [Strasbourg]
21 Höpital NOVO
22 ECaMO - [CRESS - U1153 / UMR_A 1125] - Clinical Epidemiology Applied to Osteoarticular Diseases | Épidémiologie clinique appliquée aux maladies rhumatismales et musculo-squelettiques
23 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
24 Service de Rhumatologie [CHU de Grenoble]
25 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
26 CIC - Centre d’Investigation Clinique [Tours] CIC 1415
27 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
28 Service de Rhumatologie [CHU Bicêtre]
29 CRSA - Centre de Recherche Saint-Antoine
30 Groupe Hospitalier du Havre
31 Centre hospitalier de Châteaudun
32 Service de rhumatologie [Nantes]
33 CHCB - Centre Hospitalier de la Côte Basque
34 Service de Rhumatologie (CHU de Dijon)
35 BIOSCAR (UMR_S_1132 / U1132) - Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques
36 Service de Rhumatologie [CHU Lariboisière]
37 Rhumatologie
38 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
39 IDESP - Institut Desbrest de santé publique
40 Service de Rhumatologie [CHRU Nancy]
Carine Salliot
Edouard Pertuiset
  • Fonction : Auteur
Jean‐Marie Berthelot

Résumé

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.
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Dates et versions

hal-04279434 , version 1 (30-01-2024)

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Citer

Joanna Kedra, Philippe Dieudé, Caroline Giboin, Hubert Marotte, Carine Salliot, et al.. 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 & rheumatology, 2024, ⟨10.1002/art.42752⟩. ⟨hal-04279434⟩
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