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Introduction: Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) represent pediatric and adult variants of the Still's disease continuum. To determine whether clinical outcomes between patients with sJIA and AOSD were similar, Bayesian and population model-based analyses were conducted on endpoints from studies of canakinumab in both patient populations. The objective was to further support the efficacy of canakinumab in patients with AOSD. Methods: A Bayesian analysis of endpoints from a study of canakinumab in AOSD was conducted borrowing information from five pooled sJIA studies using a robust meta-analytic predictive (MAP) approach. Similarity of clinical outcomes across populations was fulfilled if the AOSD study posterior median fell within the 95% predicted credible interval for the outcome of interest, based on the pooled sJIA data. Population model-based analyses (pharmacokinetic [PK] and PK/pharmacodynamic [PKPD]) were conducted to compare the pharmacokinetics and exposure-response relationships between populations.Results: The AOSD study posterior medians for adapted American College of Rheumatology (ACR)30 response, continuous adapted ACR response, number of active joints, C-reactive protein, and absence of fever were within the 95% credible interval for the prediction of the MAP analysis from the pooled sJIA data, supporting the similarity in outcomes between patient populations. PK analysis demonstrated comparable exposure across sJIA age groups and patients with AOSD. PKPD relationships were consistent across patient populations. Analyses indicated that no therapeutic benefit can be expected from a dose increase in patients with AOSD. Conclusion:The analyses presented support the similarity of clinical outcomes following treatment with canakinumab in patients with sJIA and AOSD.

BackgroundPhase III clinical trials have shown apremilast (APR) reduced PsA signs/symptoms and improved physical function,1-3 but no study has addressed its impact on structural disease progression. MRI is a highly sensitive, validated tool to assess inflammatory and structural changes, as it can detect soft tissue inflammation, bone marrow edema (BME) lesions, bone erosion and proliferation in peripheral joints and axial skeleton. Whole-body (WB)-MRI, a relatively novel technique in musculoskeletal studies, allows assessment of all peripheral/axial joints and entheses in 1 examination.4 Recent, consensus-based and semi-quantitative scoring methods were developed and validated. This study is the first to systematically use new state-of-the-art MRI scoring methodologies to assess PsA inflammatory and structural changes in a global clinical trial.ObjectivesTo assess APR efficacy on inflammatory indices and imaging outcome measures associated with PsA structural progression by conventional static MRI and dynamic contrast-enhanced (DCE)-MRI of the most affected hand and WB-MRI.MethodsThe study aims to enroll 120 biologic-naïve adults with PsA for ≥3 mos to ≤5 yrs and prior treatment with ≤2 conventional DMARDs. Subjects must have ≥3 swollen and ≥3 tender joints, hand involvement (≥1 swollen joint or ≥1 dactylitis) and ≥1 active enthesitis site. After 4-wk screening, all eligible patients will receive APR 30 mg twice daily (titrated during the first 5 days) as monotherapy or in combination with methotrexate for 48 wks, with a 4-wk observational follow-up. Conventional MRI and optional DCE-MRI of the most affected hand and WB-MRI of the entire body will be performed at Wks 0, 24 and 48. The primary endpoint is change from BL to Wk 24 in OMERACT PsA MRI (PsAMRIS) composite score of BME + synovitis + tenosynovitis. Other imaging endpoints include change from BL to Wk 48 in PsAMRIS composite score (BME + synovitis + tenosynovitis) and change from BL to Wks 24 and 48 in PsAMRIS composite score (BME + synovitis), PsAMRIS composite inflammation score (BME + synovitis + tenosynovitis + periarticular inflammation), PsAMRIS total damage score (erosion + bone proliferation), WB-MRI indices (including peripheral joint inflammation index and peripheral enthesis inflammation index), hip and knee inflammation MRI scores (HIMRISS, KIMRISS), OMERACT heel enthesitis MRI indices, axial inflammation indices (SPARCC, CanDen), DEMRIQ-Volume and DEMRIQ-Inflammation and other DCE-MRI–derived parameters. Clinical parameters will include SJC/TJC, cDAPSA, SPARCC Enthesitis Index, Leeds Enthesitis Index, Leeds Dactylitis Index, PASDAS, PtGA, PhGA, Patient’s Assessment of Pain, HAQ-DI, and BASDAI and impact of disease (PsAID12). Safety and tolerability also will be assessed.ResultsThe study protocol was approved by an independent ethics committee and is now enrolling in the USA. Selected countries in Europe and Russia will also participate. MRI, clinical and patient-reported outcomes will be analyzed.ConclusionThis study will provide important evi...