Antonio Vitale, Valeria Caggiano, Jessica Sbalchiero, Giuseppe Lopalco, Abdurrahman Tufan, Gaafar Ragab, Petros P Sfikakis, Lorenzo Dagna, Ezgi Deniz Batu, Seza Ozen, Fabrizio Conti, Federica Maiolini, Serena Bugatti, Micol Frassi, Piero Ruscitti, Maria Morrone, Francesco La Torre, Ibrahim Yahya Cakir, Nergis Akay, Elif Kilic Konte, Katerina Laskari, Yelda Bilginer, Angelica Gattamelata, Jacopo Croce, Ludovico De Stefano, Giulia Voltarel, Paola Cipriani, Maria Cristina Maggio, Sulaiman M Al-Mayouf, Lampros Fotis, Donato Rigante, Jurgen Sota, Elena Verrecchia, Giuliana Guggino, Lidia La Barbera, Matteo Piga, Giacomo Emmi, Romina Gallizzi, Giovanni Conti, Paolo Sfriso, Elena Bartoloni, Roberto Giacomelli, Patrizia Barone, Alma Nunzia Olivieri, Annachiara Alemanno, Alberto Lo Gullo, Haner Direskeneli, Fatma Alibaz-Oner, Anastasios Karamanakos, Marcella Prete, Amr Edrees, Francesco Gavioli, Paola Parronchi, Francesco Ciccia, Chiara Cardamone, José Hernández-Rodríguez, Gülen Hatemi, Cemal Bes, Ibrahim A Almaghlouth, Ángel Robles Marhuenda, Andrés Gonzáles-García, Carla Gaggiano, Amato De Paulis, Mehmet Engin Tezcan, Antonio Luca Brucato, Eugen Feist, Fernando Tornero-Romero, Benoit Suzon, Benson Ogunjimi, Maissa Thabet, Alessandro Conforti, Valentina Pucino, Oksana Boyarchuk, Tetiana Kovalchuk, Marcello Govoni, Annamaria Iagnocco, Maria Sole Chimenti, Abdelhfeez Moshrif, Emanuela Del Giudice, Francesco Carubbi, Şükran Erten, Samar Tharwat, Mohamed Tharwat Hegazy, Ewa Więsik-Szewczyk, Jiram Torres-Ruiz, Eduardo Martín-Nares, Albert Balistreri, Claudia Fabiani, Bruno Frediani, Andrea Hinojosa-Azaola, Özgür Kasapçopur, Luca Cantarini
On-label canakinumab dosing appears to increase the likelihood of study-defined LTR with subsequent treatment discontinuation, compared with underdosed treatment strategies.
OBJECTIVE: The primary aim of this study was to assess, in Still's disease, whether the employment of canakinumab at a strictly on-label dose may increase the likelihood of treatment discontinuation due to study-defined long-term remission (LTR), compared with patients receiving lower doses.
METHODS: Patients were drawn from the international Autoinflammatory Disease Alliance (AIDA) Network registry dedicated to Still's disease and stratified based on the starting canakinumab dose: the on-label group received either 300 mg every 4 weeks or 150 mg every 4 weeks (corresponding to 4 mg/kg), while the underdosed group received 150 mg every 4 weeks (corresponding to a dose not exceeding 3.5 mg/kg). Bayesian regression models were implemented to estimate the probability of achieving long-term remission with subsequent canakinumab withdrawal in the two groups, as well as the mean differences in probabilities and posterior probabilities indicating whether the on-label group was superior in achieving the endpoint.
RESULTS: In total, 131 patients (16.7%) were enrolled, 81 (61.8%) receiving the on-label posology and 50 (38.2%) the underdosed posology. The estimated marginal posterior probability of canakinumab discontinuation due to LTR was 19% (CrI 7.5%-34.6%) in the on-label group and 3.9% (CrI 0.7%-15.2%) in the underdosed group, yielding a mean difference of 15.1% (CrI 1.4%-31.4%) and a posterior probability of 98.4%. This difference remained credible, with posterior probabilities ranging from 97.9% to 99.6%, irrespective of disease course or age at disease onset.
CONCLUSION: On-label canakinumab dosing appears to increase the likelihood of study-defined LTR with subsequent treatment discontinuation, compared with underdosed treatment strategies.