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

Allan L Klein, David Lin, Paul C Cremer, Saifullah Nasir, Sushil Allen Luis, Antonio Abbate, Andrew Ertel, Martin LeWinter, Anna Beutler, Fang Fang, John F Paolini, Allan L Klein, David Lin, Paul C Cremer, Saifullah Nasir, Sushil Allen Luis, Antonio Abbate, Andrew Ertel, Martin LeWinter, Anna Beutler, Fang Fang, John F Paolini

Abstract

Objective: Recurrent 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.

Methods: This 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).

Results: Outcomes: 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.

Conclusions: Rilonacept 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 number: NCT03980522.

Keywords: inflammatory markers; pericardial disease; pericarditis.

Conflict of interest statement

Competing interests: ALK: research grant, scientific advisory board Kiniksa Pharmaceuticals, Ltd; advisory board Swedish Orphan Biovitrum AB, advisory board Pfizer, Inc. PCC: advisory board Swedish Orphan Biovitrum AB; advisory board Kiniksa Pharmaceuticals, Ltd. SAL: honoraria – advisory board member for Kiniksa Pharmaceuticals, Ltd; consultant and advisory board member for Swedish Orphan Biovitrum AB. AA: research grants from Kiniksa Pharmaceuticals, Ltd, Swedish Orphan Biovitrum AB, Olatec Therapeutics LLC, Serpin Pharma, LLC; consultant fees: Kiniksa Pharmaceuticals, Ltd, Olatec Therapeutics LLC, Serpin Pharma, LLC and Merck & Co, Inc. ML: one seminar for Kiniksa Pharmaceuticals, Ltd. AB: Kiniksa Pharmaceuticals, Ltd consultant. FF: Kiniksa Pharmaceuticals Corp employee. JFP: Kiniksa Pharmaceuticals Corp employee.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
NRS scores (pain) and CRP levels in symptomatic patients with elevated CRP. CRP, C reactive protein; NRS, numeric rating scale; RP, recurrent pericarditis.

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