Nightingale SyabbaloDr. University of Fiji, Fiji
Title: Treatment of recurrent pericarditis with interleukin-1 antagonists
Recurrent pericarditis (RP) is defined as relapsing episodes of pericardial inflammation after a minimum symptom-free period of 4-6 weeks. It is the most common complication of acute pericarditis, and is reported in 15-40% of the patients following an episode of acute pericarditis. The cause of recurrent pericarditis is unknown. However interleukin-1? (IL-1?) plays a critical role in the pathogenesis of recurrent pericarditis. It induces expression of pro-inflammatory mediators, such as cyclo-oxygenase-2 (COX-2), and prostaglandins, which cause pericardial inflammation, hyperemia, edema, and pain. Treatment of RP is challenging because of the relapses after treatment, which may complicate into cardiac tamponade. It may require invasive treatments, such as pericardiocentesis, pericardial window, and pericardial balloon pericardiotomy or sclerosis with tetracycline, doxycycline, cisplatin, and 5-fluorouracil. Biologics inhibiting IL-1? and its receptors inflammatory pathways are potential therapeutic targets to treat recurrent pericarditis. Anakinra is a recombinant form of naturally occurring IL-1 receptor antagonist (IL-1Ra), which inhibits the activity of both IL-1? and IL-1?. Treatment with anakinra has been shown to immediately reduce pericardial inflammation and pain. Anakinra also allows patients to discontinue corticosteroids within 2 months of therapy. However, abrupt discontinuation of colchicine or anakinra is associated with relapse of pericarditis in 70% of the patients. Rilonacept is a chimeric recombinant fusion protein functioning as a soluble decoy protein that binds to IL-1?, IL-1?, and IL-1Ra. Rilonacept has been reported to rapidly and sustainably reduce pericarditis pain, and decrease inflammatory biomarkers, such as C-reactive protein. Notably, it has been shown to reduce recurrent pericarditis significantly; only 7% of the patients treated with rilonacept developed pericarditis relapse, compared to 74% in the control group. Rilonacept has also been demonstrated to allow patients taper or discontinue corticosteroids, and colchicine, without pericarditis recurrences. Additionally, rilonacept significantly improves the health-related quality of life. Early treatment of RP with IL-1 antagonists, such as rilonacept may reduce the risk of recurrences, and life-threatening complications, such as cardiac tamponade, constrictive pericarditis, which may require invasive treatments, such as pericardial window, pericardial balloon pericardiotomy, and pericardiectomy.
Nightingale Syabbalo is a Pulmonologist, and Clinical Respiratory Physiologist by training, and obtained his postgraduate training at St. George’s Hospital Medical School, University of London, UK. He was trained by one of the international distinguished Respirologist of our times. Nightingale has worked as an academician, Consultant Physician, and a Clinical Researcher in several counties, including Canada, Kuwait, Oman, South Africa, and Zambia. He has published extensively in high impact medical journals, and is an Editorial Board member of fourteen journals in Pulmonology and Respiratory Medicine; and a reviewer of four journals in Thoracic Medicine, Respiratory Research, and Internal Medicine. Prof. Syabbalo’s current area of research focuses on the role of interleukins in the pathophysiology and treatment of severe asthma. He has also interest in the mechanisms of interleukins-1? in the pathogenesis and treatment of pericardial syndromes.