Garshick, Michael

Abstract Background Recurrent pericarditis (RP) is an IL-1-mediated chronic autoinflammatory disease (1,2). The phase 3 trial RHAPSODY demonstrated that rilonacept (IL-1α and IL-1β cytokine trap), the first and only FDA-approved treatment for RP, was effective in treating RP not only as a third-line agent (3L; after corticosteroids) but also as a second-line agent (2L; instead of corticosteroids) and reduced recurrence risk as monotherapy (3). The REgiStry Of the NAtural history of recurreNt periCarditis in pEdiatric and adult patients (RESONANCE) has been collecting long-term combined prospective and retrospective data from US-based pericardial-disease-dedicated programs since 2020 (4). Purpose To assess the efficacy of rilonacept in RP in a real-world setting, extending the clinical trial findings of RHAPSODY. Methods Database cut-off (DCO) was 05 February 2025. Data on RP management were collected and analyzed from pts with ≥2 years of observation in RESONANCE. Disease duration at DCO was defined as time from RP diagnosis to either disease resolution (no disease flares while off all RP treatments for ≥6 months before DCO) or last follow-up (for pts with ongoing treatment at DCO). Pericarditis recurrences (investigator-assessed) were confirmed based on RP symptom data and/or objective findings. Annualized recurrence rates were calculated per RP treatment regimen as total pericarditis recurrences divided by total patient-years (PY) while receiving that treatment. Wilcoxon signed-rank test was utilized to analyze the significance in change of annualized recurrence rates before and after rilonacept initiation. Results At DCO, 81 pts had ≥2 years of follow-up data in RESONANCE; mean (SD) age was 51.0 (16.8) years; most (66.7%) were female; 84% had idiopathic etiology; median (Q1-Q3) disease duration was 3.1 (2.6-3.7) years; and median observation was 2.93 (2.54-3.38) years. Patient-year treatment exposures per treatment were: NSAIDS ± colchicine (n=79; 187.8 PY), corticosteroids (n=30; 61.1 PY), anakinra (n=1; 1.2 PY) and rilonacept (n=35; 72.8 PY). Of the 35 pts treated with rilonacept for any duration (median observation: 3.2 years; median time on rilonacept: 2.08 years), the most common reason for rilonacept initiation was chest pain/recurrence on prior treatment (n=28). The annualized recurrence rate while receiving rilonacept was significantly lower versus all combined prior lines of treatment (4.00 vs. 0.02 events per PY; p=0.002); this outcome was consistent across line of treatment for rilonacept use (2L: 3.73 vs. 0.06 events per PY, p=0.02; 3L: 4.14 vs. 0 events per PY, p<0.001; Table 1). Conclusions This first report of real-world outcomes from RESONANCE shows that rilonacept-containing regimens for RP as 1st, 2nd, or 3rd line therapy reduced recurrence risk over long- term (>2 year) treatment, supporting prolonged management during RP natural history.

Patients with psoriasis (PsO) and psoriatic arthritis (PsA) are at significantly increased risk for cardiovascular (CV) disease, attributed to chronic systemic inflammation and a high burden of cardiometabolic comorbidities. Despite this, CV risk factors in this population are frequently underdiagnosed and undertreated. This consensus document, developed by the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN), provides practical recommendations for dermatologists, rheumatologists, and primary care physicians to improve CV risk assessment and management in PsO and PsA. Key recommendations include conducting baseline CV risk assessments at diagnosis—particularly for patients with moderate-to-severe PsO, PsA, or those requiring biologic therapy—and routine screening for hypertension, diabetes, dyslipidemia, smoking, obesity, and metabolic syndrome. The use of biomarkers such as high-sensitivity C-reactive protein and lipoprotein(a) may help refine risk stratification. Patients at elevated risk should be referred to their primary care provider or a cardiologist for further evaluation and may require additional imaging, including coronary artery calcium scoring. Lifestyle counseling on diet, exercise, weight management, and smoking cessation is essential. Pharmacologic strategies, such as earlier initiation of statins and consideration of glucagon-like peptide-1 (GLP-1) receptor agonists, are encouraged when clinically appropriate. Systemic inflammation should be reduced using anti-inflammatory therapies, although outcome data remain mixed. Clinicians must carefully assess the risks and benefits of NSAIDs, corticosteroids, and Janus kinase (JAK) inhibitors. This document aims to bridge existing gaps in interdisciplinary care and facilitate earlier, more aggressive CV risk management in psoriatic disease, aligning with current cardiology and dermatology guidelines to reduce morbidity and mortality.

Abstract Background Recurrent pericarditis (RP) is a chronic autoinflammatory disease mediated by IL-1 that requires long-term treatment. While the 2015 European Society of Cardiology Guidelines position IL-1 pathway inhibition only after corticosteroids, complications associated with long-term steroid use underscore the importance of steroid-sparing strategies. Rilonacept, an IL-1α and IL-1β cytokine trap, is the only FDA-approved treatment for RP (available since April 2021). RESONANCE, an ongoing 5-year non-interventional US registry of patients (pts) with RP, has collected real-world data from pts cared for by cardiologists with a focus on pericardial disease, with a goal of informing contemporary RP clinical management. Purpose Analysis of temporal trends in RP management from RESONANCE. Methods From a database cut-off (DCO) on 21 December 2023, patient demographics and disease characteristics are reported for 242 active RP pts (excluding RHAPSODY prior participants) at 20 US sites (median [Q1:Q3] 2.1 [1.5:2.6] years and 556 patient-years [PY] of observation). Complete medication class use data were available for 239 pts (total 546 PY). Proportional medication class use prior to initiating rilonacept was analyzed annually across the observation period. Results Mean (standard deviation) age at DCO was 50.2 (16.6) years; 58.1% were female. Median [Q1:Q3] disease duration at DCO from index pericarditis episode was 3.1 [2.2:5] years. Median [Q1:Q3] number of prior recurrences at enrollment was 3 [2:5]. Prior to rilonacept availability, NSAIDs/Colchicine/Aspirin represented the highest proportion of treatment (73% of PY); steroid use was 9% of PY, IL-1 pathway inhibition (anakinra) was 13% of PY, and conventional synthetic disease modifying antirheumatic drugs (csDMARDs) were 0.46% PY (no RP-specific treatment was 5% of PY) (Fig 1). In the years since rilonacept availability, proportional IL-1 pathway inhibition use has increased, from 13% of PY in 2020-21 to 26% of PY in 2023, driven by an increase in rilonacept use (6%, 13%, 16% of PY in 2021, 2022, and 2023, respectively). Over that same period, proportional NSAIDs/Colchicine/Aspirin use (57%-63% of PY) has been consistently 6-times more than proportional steroid use (10%-11% of PY). Among pts who initiated rilonacept (n=81), similar proportions transitioned from NSAIDs/Colchicine/Aspirin as from corticosteroids (Fig 2), a robust trend observed each year. Of those pts transitioning from corticosteroids, 1/3 had used corticosteroids for <30 days and 1/3 for >6 months. Conclusions Real-world data from the RESONANCE registry reveal a temporal shift in RP management in US centers with RP-focused cardiologists, with increased proportional IL-1 pathway inhibition use since rilonacept availability in 2021. Advancing beyond 2015 guideline recommendations, IL-1 pathway inhibition is often being used as steroid-sparing treatment, i.e., after colchicine instead of chronic corticosteroids.