Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still’s Disease and Active Articular Manifestation Responding to Canakinumab

• Published in: Journal of clinical medicine 2021-09, Vol.10 (19), p.4400
• Main Authors: Ghannam, Khetam, Zernicke, Jan, Kedor, Claudia, Listing, Joachim, Burmester, Gerd-R., Foell, Dirk, Feist, Eugen
• Format: Article
• Language: English
• Subjects: Arthritis; Biomarkers; Clinical medicine; Consent; Cytokines; Drug dosages; Ethics; FDA approval; Fever; Inflammation; Monoclonal antibodies; Neutrophils; Nonsteroidal anti-inflammatory drugs; Pathogenesis; Pathogens; Patients; Tumor necrosis factor-TNF; Variance analysis
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm10194400

Adult-onset Still’s disease (AOSD) is a systemic auto-inflammatory disease characterized by the presence of immunologically mediated inflammation and deficient resolution of inflammation. Canakinumab is an approved IL-1β inhibitor in the treatment of AOSD with a balanced efficacy and safety profile. Since inflammatory cytokines play a major role in the pathogenesis of AOSD, we investigated the effects of canakinumab on the cytokine profile of AOSD patients from a randomized controlled trial. Multiplex analysis and ELISA were used to test the concentrations of several cytokines at three time points—week 0 (baseline), week 1 and week 4—in two patient groups—placebo and canakinumab. Two-way repeated-measures analysis of variance revealed a significant temporal effect on the concentrations of MRP 8/14, S100A12, IL-6 and IL-18 with a significant decrease at week 4 in the canakinumab group exclusively. Comparing responders with non-responders to canakinumab showed a significant decrease in MRP 8/14, IL-1RA, IL-18 and IL-6 in responders at week 4, while S100A12 levels decreased significantly in responders and non-responders. In summary, canakinumab showed a striking effect on the cytokine profile in patients with AOSD, exhibiting a clear association with clinical response.