- Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features results from the 5-year long-term extension of the phase III pivotal trials. Annals of the rheumatic diseases. 2018; 77(12):1710-1719. .
- Currently available therapies for systemic juvenile idiopathic arthritis (sJIA) include non-steroidal anti-inflammatory drugs, glucocorticoids, synthetic disease-modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs that inhibit primarily interleukin 6 and Interleukin 1. The management of sJIA is aimed at achieving and maintaining clinical remission. Canakinumab is a fully human monoclonal antibody that selectively binds to IL-1β, inactivating its downstream signaling cascade. Previous Phase II-III trials have demonstrated the short-term efficacy and safety of canakinumab in patients with sJIA (Ruperto & Brunner et al; NEJM 2012). To evaluate the long-term efficacy and safety of canakinumab 144 patients with SJIA were followed up to 5 years and evaluated every 3 months. At 2 years after starting canakinumab treatment more than one of every 3 patients taking canakinumab achieved inactive disease status, meaning had no signs and symptoms of SJIA when evaluated. A more pronounced improvement of SJIA disease activity was observed in SJIA patients who had not been treated with other biologic drugs previously. Patients treated with canakinumab while on methotrexate background therapy and those treated with canakinumab alone showed similar degrees of sJIA improvement of disease activity and rates of achieving inactive disease status. Over 70% of children who required steroid treatment when starting canakunumab were able to stop steroids by 2 years of receiving canakinumab injections every one month. Therefore, response to canakinumab treatment was sustained and associated with substantial glucocorticoid discontinuation. No new safety findings were observed upon long-term use of canakinumab.
- Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease. Arthritis and Rheumatology. 2018; 70(9):1508-1518. .
- Current biologic therapies for Juvenile Idiopathic Arthritis (JIA) result in many JIA patients that are symptom free and without clinical evidence of active arthritis, i.e., have inactive disease. Biologic therapies for JIA can have short term toxicity; long-term safety is not fully understood; and they are expensive. It is unknown if children in clinical remission need to continue the biologic therapy. This clinical trial addressed this issue by systematically discontinuing the biologic drugs in JIA patients who had demonstrated at least 6 months of inactive disease under observation in this clinical trial. The study demonstrated that within 8 months after stopping the biologic therapy 37% of the patients will reactivate the JIA. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05). This study defined the risk for reactivation of JIA after stopping biologic therapy and clinical parameters that are associated with a lower risk for reactivation. This study will help inform the decision making about consideration of stopping biologic therapy in children with JIA.
- Long-term outcomes of adolescents with juvenile-onset fibromyalgia into adulthood and impact of depressive symptoms on functioning over time. Pain. 2019; 160(2):433-441. .
- This study offers evidence that although Juvenile Fibromyalgia (JFM) symptoms persist for most individuals, pain severity tends to decrease over time. However, depressive symptoms appear to follow specific trajectories, indicating possible subgroups of JFM. In particular, JFM patients with worsening depressive symptoms had decreasing physical functioning and therefore may require more intensive and consistent intervention to prevent long-term disability.
- Neutrophils From Children With Systemic Juvenile Idiopathic Arthritis Exhibit Persistent Proinflammatory Activation Despite Long-Standing Clinically Inactive Disease. Frontiers in Immunology. 2018; 9. .
- This study examined the phenotypes of neutrophils in children with systemic juvenile idiopathic arthritis (sJIA). We identified features of neutrophil activation in sJIA patients with both active and inactive disease, reflecting persistent innate immune activation. Taken together, this work expands the understanding of neutrophil function in chronic autoinflammatory disorders such as sJIA.
- A Multiparameter Flow Cytometry Analysis Panel to Assess CD163 mRNA and Protein in Monocyte and Macrophage Populations in Hyperinflammatory Diseases. Journal of immunology (Baltimore, Md. : 1950). 2019; 202(5):1635-1643. .
- In this study we developed a multi-parameter flow cytometry panel that includes analysis of mRNA and protein expression of CD163, a key monocyte/macrophage polarization marker, at the single cell level. Our studies indicate distinct changes in CD163 mRNA and protein expression in response to specific stimuli in a time and dose dependent manner. Finally, this mRNA probe can be utilized in conjunction with other monocyte/macrophage polarization markers to aid in defining underlying mechanisms of disease pathogenesis in hyperinflammatory syndromes.