Association between canakinumab dose and long-term remission in Still's disease: insights from the AIDA network registry

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.