Efficacy and safety of rilonacept for recurrent pericarditis: results from a phase II clinical trial

Abstract

ObjectiveRecurrent pericarditis (RP) incurs significant morbidity. Rilonacept inhibits both interleukin-1 alpha (IL-1α) and IL-1β; these cytokines are thought to play a major role in RP. This phase II study evaluated rilonacept efficacy and safety in RP.MethodsThis multicentre, open-label study enrolled adult patients with idiopathic or postpericardiotomy RP, symptomatic (≥2 pericarditis recurrences) or corticosteroid (CS) dependent (≥2 recurrences prior).Patients received rilonacept 320 mg SC load/160 mg SC weekly maintenance in a 6-week base treatment period (TP) followed by an optional 18-week on-treatment extension period (EP) (option to wean background therapy).ResultsOutcomes: pericarditis pain (numeric rating scale (NRS)) and inflammation (C reactive protein (CRP)) for symptomatic patients; disease activity after CS taper for CS-dependent patients. Secondary outcomes: health-related quality of life (HRQOL), pericarditis manifestations and additional medications. 25 unique patients enrolled, while 23 completed the EP (seven colchicine failures and five CS failures). In symptomatic patients, NRS and CRP decreased; response was observed after first rilonacept dose. NRS decreased from 4.5 at baseline to 0.7, and CRP decreased from 4.62 mg/dL at baseline to 0.38 mg/dL at end of TP. Median time to CRP normalisation: 9 days. Pericarditis manifestations resolved. 13 patients on CS at baseline completed the EP; 11 (84.6%) discontinued CS, and 2 tapered; CRP and NRS remained low without recurrence. Mean HRQOL scores improved in symptomatic patients. One serious adverse event (SAE) resulted in discontinuation of rilonacept.ConclusionsRilonacept led to rapid and sustained improvement in pain, inflammation (CRP and pericarditis manifestations) and HRQOL. CSs were successfully tapered or discontinued; safety was consistent with known rilonacept safety profile.Trial registration numberNCT03980522.

Advances in Clinical Cardiology 2020: A Summary of Key Clinical Trials

“…Up to 30% of patients presenting with a pericarditis may have a recurrent episode despite treatment with colchicine leading to significant morbidity and use of healthcare resources. Rilonacept, an interleukin-1α and interleukin-1β cytokine trap, given by subcutaneous injection, was previously shown to reduce pericardial inflammation [ 131 ]. In the RHAPSODY trial 86 patients with recurrent pericarditis and elevated C-reactive protein level despite standard treatment were initiated on rilonacept for a 12-week run-in (with pain resolution by a median of 5 days and C-reactive protein normalisation by a median of 7 days).…”

Health-related quality of life in patients with recurrent pericarditis: results from a phase 2 study of rilonacept

“…Data will be made available upon reasonable request. 5 University of Vermont Medical Center, Burlington, VT, USA. 6 Mayo Clinic, Rochester, MN, USA.…”

“…Treatment options for patients with multiple recurrences, however, are limited, and there is a high unmet medical need for patients who have inadequate response (i.e., continued recurrence or incomplete symptom resolution) to, who cannot tolerate, standard therapy [1] or who have persistent underlying disease. Given that the cytokines interleukin-1 alpha (IL-1α) and beta (IL-1β) are implicated in RP etiology [2,4], rilonacept, an IL-1 α and IL-1 β cytokine trap, was evaluated in clinical trials for the treatment of RP [5,6] and is now the first treatment approved by FDA for RP.…”

Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease

“…The efficacy and safety of rilonacept for the treatment of RP were recently showed. A multicenter phase 2 trial enrolled 25 adults with idiopathic or post-pericardiotomy RP, who had at least a second active recurrence at the time of enrollment or who had had at least 2 recurrent events and had steroids-dependence [ 46 ]. A rapid resolution of chest pain and a concomitant reduction of CRP levels were observed.…”