Interleukin-1 Blockers: A Paradigm Shift in the Treatment of Recurrent Pericarditis

Abstract

Recurrent pericarditis is a problematic clinical condition that impairs the quality of life of the affected patients due to the need for repeated hospital admissions, emergency department visits, and complications from medications, especially glucocorticoids. Unfortunately, available treatments for recurrent pericarditis are very limited, including only a handful of medications such as aspirin/NSAIDs, glucocorticoids, colchicine, and immunosuppressants (such as interleukin-1 (IL-1) blockers, azathioprine, and intravenous human immunoglobulins). Until recently, the clinical experience with the latter class of medications was very limited. Nevertheless, in the last decade, experience with IL-1 blockers has consistently grown, and valid clinical data have emerged from randomized clinical trials. Accordingly, IL-1 blockers are a typical paradigm shift in the treatment of refractory recurrent pericarditis with a clearly positive cost/benefit ratio for those unfortunate patients with multiple recurrences. A drawback related to the above-mentioned medications is the absence of universally accepted and established treatment protocols regarding the full dose administration period and the need for a tapering protocol for individual medications. Another concern is the need for long-standing treatments, which should be discussed with the patients. The above-mentioned unmet needs are expected to be addressed in the near future, such as further insights into pathophysiology and an individualized approach to affected patients.

Keywords: NLRP3 inflammasome; interleukin-1 blockers; pathophysiology; recurrent pericarditis; steroid dependence.

Figure 1

The role of interleukin-1 and NLRP3 inflammasome in pericarditis and the mechanism of action of IL-1-targeted therapeutics. DAMP: damage-associated molecular pattern; PAMP: pathogen-associated molecular pattern; IL: interleukin; IL-1R: interleukin-1 receptor; and AK: anakinra.

Figure 2

Proposed algorithm for the treatment of patients with recurrent pericarditis according to the 2015 European Society of Cardiology Guidelines for the diagnosis and management of pericardial diseases. PPI = protein pump inhibitors; NSAIDs = non-steroidal anti-inflammatory drugs; and IVIG = intravenous immunoglobulin. * This step consists of administering intermediate doses of aspirin/NSAIDs—steroids (and a standard dose of colchicine) to achieve remission, avoiding side effects related to high doses of the latter medication.