Rilonacept for the treatment of recurrent pericarditis

ABSTRACT

Introduction

Recurrent pericarditis (RP) is a debilitating disease that has an underlying autoinflammatory pathophysiology mediated by cytokine interleukin (IL)-1. Rilonacept, a recombinant dimeric fusion protein that blocks IL-1α and IL-1β signaling has emerged as a valuable therapeutic option of RP. Rilonacept has been evaluated in Phase 2 and 3 clinical trials and was recently approved for RP treatment.

Areas covered

This article reviews available clinical trials assessing the efficacy and safety of rilonacept for the treatment of RP.

Expert opinion

Findings from the Rhapsody study) trial suggest that rilonacept represents a promising new therapy for those patients with colchicine resistant or glucocorticoid-dependent disease. Treatment leads to rapid clinical response, with a median resolution of symptoms in 5 days, normalization of C-reactive protein (CRP) in a median of 7 days, and successful weaning from glucocorticoids. This novel therapy also reduces recurrence rates compared with placebo. Rilonacept has also demonstrated a good safety profile, with the most common adverse events including injection-site reactions and upper respiratory tract infections. This anti-IL 1 agent has emerged as an efficacious treatment for RP, with potential use for glucocorticoid-free regimens and as monotherapy. Future trials are needed to explore these treatment options and to clarify the appropriate therapy duration.

KEYWORDS:

• Interleukin-1 inhibitor
• recurrent pericarditis
• rilonacept

Article Highlights

● Interleukin (IL)-1 pathway is an important emerging therapeutic target in recurrent pericarditis (RP).

● Rilonacept is a recombinant fusion protein that blocks interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) signaling.

● The efficacy and safety profile of rilonacept was demonstrated in the phase 2 and pivotal phase 3 Rhapsody trial.

● This biological agent is a promising treatment for preventing relapses and refractory forms of RP with glucocorticoid-dependence (unable to taper or withdraw glucocorticoids) and colchicine resistance.

● Decisions regarding treatment continuation or cessation are anticipated in the Long-Term Extension arm of Rhapsody study.

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Declaration of Interests

A Klein has received a research grant from Kiniksa and serves as on scientific advisory boards for Kiniksa, Sobi, and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper is not funded.