TY - JOUR
T1 - Non-inferiority of dose reduction versus standard dosing of TNF-inhibitors in axial spondyloarthritis
AU - Gratacós, Jordi
AU - Pontes, Caridad
AU - Juanola, Xavier
AU - Sanz, Jesús
AU - Torres, Ferran
AU - Avendaño, Cristina
AU - Vallano, Antoni
AU - Calvo, Gonzalo
AU - De Miguel, Eugenio
AU - Sanmartí, Raimon
AU - Almirall, Miriam
AU - Aparicio, Maria
AU - Sellas, Agustí
AU - Vives, Roser
AU - Albiñana, Nestor
AU - Moreno, Mireia
AU - Clavaguera, Teresa
AU - Torre-Alonso, Juan Carlos
AU - Veroz, Raúl
AU - Rodríguez-Lozano, Carlos
AU - Linares, Luís Francisco
AU - Urruticoechea, Ana
AU - Collantes, Eduardo
AU - Morlà, Rosa María
AU - Reina, Dèlia
AU - Cuende, Eduardo
AU - Zarco, Pedro
AU - Fernández-Espartero, Maria Cruz
AU - García-Vicuña, Rosario
AU - Montilla, Carlos Alberto
AU - Villalba, Alejandro
AU - Pascual, Dora
AU - Campos, Cristina
AU - Juan, Antonio
AU - Ariza, Rafael
AU - Díaz-Miguel, Consuelo
AU - Maqueda, Manuel
AU - Fernández-Dapica, Maria Pilar
AU - Fernández-Prada, Manuel
AU - Batlle, Enrique
AU - González-Fernández, Carlos
AU - Queiro, Rubén
N1 - Funding Information:
The study was fully funded by grants from the Spanish Ministry of Health within the programme “Ayudas para el fomento de la investigación clínica independiente del Ministerio de Salud, Política Social e Igualdad - Orden SPI/ 2885/2011, de 20 de octubre” (project ID: EC11–229) and from the Ministerio de Economia y Consumo (MINECO)-Instituto de Salud Carlos III-Subdirección General de Evaluación and the European Fund for Regional Development (Project ID: PI13/02680).
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/1/8
Y1 - 2019/1/8
N2 - Objective: The objective was to determine if dose reduction is non-inferior to full-dose TNFi to maintain low disease activity (LDA) in patients already in remission with TNFi, in axial spondyloarthritis. Methods: Randomized, parallel, non-inferiority, open-label multicentre clinical trial. Patients were eligible if they had axial spondyloarthritis and had been in clinical remission for ≥ 6 months with any available TNFi (adalimumab, etanercept, infliximab, golimumab) at the dose recommended by product labelling. Patients were randomized by automated central allocation to continue the same TNFi dose schedule, or to reduce the dose by roughly half according to the protocol. The main outcome was the proportion of subjects with LDA after 1 year. Serious adverse reactions or infections were recorded. Results: The trial stopped due to end of the funding period, after 126 patients were randomized; 113 patients (84.1% male, mean age (SD) 45.6 (13.0) years) were included in the main per-protocol subset. Non-inferiority was concluded for LDA at 1 year (47/55 (83.8%) patients in the full-dose and 48/58 (81.3%) patients in the reduced-dose arm, adjusted difference (95% CI) - 2.5% (- 16.6% to 11.7%)). Serious adverse reactions or infections were reported in 7/62 patients (11.3%) assigned to full dose and 2/61 patients (3.3%) assigned to reduced dose (p value = 0.164). Conclusion: In patients with ankylosing spondylitis in clinical remission for at least 6 months, dose reduction is non-inferior to full TNF inhibitor doses to maintain LDA after 1 year. Serious adverse events may be less frequent with reduced doses. Trial registration: EU Clinical Trials Registry, EudraCT 2011-005871-18 and ClinicalTrials.gov, NCT01604629.
AB - Objective: The objective was to determine if dose reduction is non-inferior to full-dose TNFi to maintain low disease activity (LDA) in patients already in remission with TNFi, in axial spondyloarthritis. Methods: Randomized, parallel, non-inferiority, open-label multicentre clinical trial. Patients were eligible if they had axial spondyloarthritis and had been in clinical remission for ≥ 6 months with any available TNFi (adalimumab, etanercept, infliximab, golimumab) at the dose recommended by product labelling. Patients were randomized by automated central allocation to continue the same TNFi dose schedule, or to reduce the dose by roughly half according to the protocol. The main outcome was the proportion of subjects with LDA after 1 year. Serious adverse reactions or infections were recorded. Results: The trial stopped due to end of the funding period, after 126 patients were randomized; 113 patients (84.1% male, mean age (SD) 45.6 (13.0) years) were included in the main per-protocol subset. Non-inferiority was concluded for LDA at 1 year (47/55 (83.8%) patients in the full-dose and 48/58 (81.3%) patients in the reduced-dose arm, adjusted difference (95% CI) - 2.5% (- 16.6% to 11.7%)). Serious adverse reactions or infections were reported in 7/62 patients (11.3%) assigned to full dose and 2/61 patients (3.3%) assigned to reduced dose (p value = 0.164). Conclusion: In patients with ankylosing spondylitis in clinical remission for at least 6 months, dose reduction is non-inferior to full TNF inhibitor doses to maintain LDA after 1 year. Serious adverse events may be less frequent with reduced doses. Trial registration: EU Clinical Trials Registry, EudraCT 2011-005871-18 and ClinicalTrials.gov, NCT01604629.
KW - Dose-tapering
KW - Non-inferiority
KW - Spondyloarthritis
KW - TNF inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85059766002&partnerID=8YFLogxK
U2 - 10.1186/s13075-018-1772-z
DO - 10.1186/s13075-018-1772-z
M3 - Article
C2 - 30621746
SN - 1478-6354
VL - 21
SP - 11
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 11
ER -