학술논문
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.
Document Type
Academic Journal
Author
Kedra J; Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Paris, France.; Dieudé P; Université de Paris Cité, INSERM UMR 1152 and Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.; Giboin C; Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Paris, France.; Marotte H; Université Jean Monnet Saint-Étienne, Centre Hospitalier Universitaire de Saint-Etienne, Mines Saint-Etienne, INSERM, SAINBIOSE U1059, Saint-Étienne, France.; Salliot C; Orleans Regional Hospital, Orleans, France.; Schaeverbeke T; Bordeaux-Pellegrin University Hospital, Bordeaux, France.; Perdriger A; Rennes University Hospital, Rennes, France.; Soubrier M; Clermont-Ferrand University Hospital, Clermont-Ferrand, France.; Morel J; Montpellier University Hospital and University of Montpellier, INSRM, CNRS, Montpellier, France.; Constantin A; Pierre-Paul Riquet University Hospital, Toulouse III - Paul Sabatier University, and INSERM UMR 1291, Purpan University Hospital, Toulouse, France.; Dernis E; Le Mans General Hospital, Le Mans, France.; Royant V; Chartres Hospital, Chartres, France.; Salmon JH; University of Reims Champagne-Ardenne, Faculty of Medicine, UR 3797 and Maison Blanche Hospital, Reims University Hospitals, Reims, France.; Pham T; Sainte-Marguerite Hospital, Assistance Publique - Hôpitaux de Marseille, Marseille, France.; Gottenberg JE; Hautepierre Hospital, Strasbourg University Hospital, Strasbourg, France.; Pertuiset E; Nord-Ouest Val-d'Oise Hospital, Pontoise, France.; Dougados M; University of Paris, Hôpital Cochin. AP-HP, INSERM U1153, pôle de recherche et d'enseignement supérieur Sorbonne Paris-Cité, Paris, France.; Devauchelle-Pensec V; Brest University Hospital, INSERM U1227, Brest, France.; Gaudin P; Grenoble Alpes University Hospital, Grenoble, France.; Cormier G; La Roche sur Yon Hospital, La Roche sur Yon, France.; Goupille P; University Hospital of Tours and University of Tours, Tours, France.; Mariette X; Université Paris-Saclay, Hôpital Bicêtre, AP-HP, INSERM UMR1184, Le Kremlin Bicêtre, France.; Berenbaum F; Sorbonne University-INSERM Centre De Recherche scientifique Saint-Antoine, AP-HP Saint-Antoine Hospital, Paris, France.; Alcaix D; Le Havre Hospital, Le Havre, France.; Rouidi SA; Châteaudun General Hospital, Châteaudun, France.; Berthelot JM; Nantes University Hospital, Nantes, France.; Monnier A; Cote Basque Hospital, Bayonne, France.; Piroth C; Dijon University Hospital, Dijon, France.; Lioté F; Université de Paris and INSERM UMR1132 Bioscar (Centre Viggo Petersen), Hôpital Lariboisière, AP-HP, Paris, France.; Goëb V; University Hospital of Amiens, Université de Picardie Jules Verne, Amiens, France.; Gaujoux-Viala C; Institut Pierre Louis d'Epidémiologie et de Santé Publique, University of Montpellier, INSERM, Centre Hospitalier Universitaire de Nîmes, Montpellier, France.; Chary-Valckenaere I; Nancy University Hospital, Nancy, France.; Hajage D; Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Paris, France.; Tubach F; Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Paris, France.; Fautrel B; Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Paris, France.
Source
Publisher: Wiley Country of Publication: United States NLM ID: 101623795 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2326-5205 (Electronic) Linking ISSN: 23265191 NLM ISO Abbreviation: Arthritis Rheumatol Subsets: MEDLINE
Subject
Language
English
Abstract
Objective: We assess the clinical and structural impact at two years of progressively spacing tocilizumab (TCZ) or abatacept (ABA) injections versus maintenance at full dose in patients with rheumatoid arthritis in sustained remission.
Methods: This multicenter open-label noninferiority (NI) randomized clinical trial included patients with established rheumatoid arthritis in sustained remission receiving ABA or TCZ at a stable dose. Patients were randomized to treatment maintenance (M) at full dose (M-arm) or progressive injection spacing (S) driven by the Disease Activity Score in 28 joints every 3 months up to biologics discontinuation (S-arm). The primary end point was the evolution of disease activity according to the Disease Activity Score in 44 joints during the 2-year follow-up analyzed per protocol with a linear mixed-effects model, evaluated by an NI test based on the one-sided 95% confidence interval (95% CI) of the slope difference (NI margin 0.25). Other end points were flare incidence and structural damage progression.
Results: Overall, 202 of the 233 patients included were considered for per protocol analysis (90 in S-arm and 112 in M-arm). At the end of follow-up, 16.2% of the patients in the S-arm could discontinue their biologic disease-modifying antirheumatic drug, 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 structural damage progression at two years (difference 13.9%, 95% CI -6.7 to 34.4).
Conclusion: The Towards the Lowest Efficacious Dose trial failed to demonstrate NI for the proposed ABA or TCZ tapering strategy.
(© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
Methods: This multicenter open-label noninferiority (NI) randomized clinical trial included patients with established rheumatoid arthritis in sustained remission receiving ABA or TCZ at a stable dose. Patients were randomized to treatment maintenance (M) at full dose (M-arm) or progressive injection spacing (S) driven by the Disease Activity Score in 28 joints every 3 months up to biologics discontinuation (S-arm). The primary end point was the evolution of disease activity according to the Disease Activity Score in 44 joints during the 2-year follow-up analyzed per protocol with a linear mixed-effects model, evaluated by an NI test based on the one-sided 95% confidence interval (95% CI) of the slope difference (NI margin 0.25). Other end points were flare incidence and structural damage progression.
Results: Overall, 202 of the 233 patients included were considered for per protocol analysis (90 in S-arm and 112 in M-arm). At the end of follow-up, 16.2% of the patients in the S-arm could discontinue their biologic disease-modifying antirheumatic drug, 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 structural damage progression at two years (difference 13.9%, 95% CI -6.7 to 34.4).
Conclusion: The Towards the Lowest Efficacious Dose trial failed to demonstrate NI for the proposed ABA or TCZ tapering strategy.
(© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)