Ertel, Andrew

Introduction: The magnitude of pericardial delayed hyperenhancement (DHE) by cardiac magnetic resonance imaging (CMR) illustrates the severity of inflammation in pericarditis. We report exploratory CMR data from an open-label Phase 2 study of rilonacept (IL-1α/IL-1β inhibitor) in recurrent pericarditis (RP). Methods: Patients (pts) with idiopathic RP or post-pericardiotomy syndrome (PPS) enrolled in the study. A subset had CMR at baseline (BL) and final visit (FV, 6 mo). Pain (NRS) and inflammation (CRP) were also collected. CMR images were graded (none, mild, moderate, or severe DHE) by a central core lab blinded to clinical data. Results: Of 25 study pts, 11 had CMR at BL and FV; 6 active idiopathic RP, and 5 corticosteroid (CS)-dependent non-active RP (4 idiopathic, 1 PPS). At BL, DHE was severe (3), moderate (2), and none (1) in active RP pts and moderate (1) or mild/none (4) in CS-dependent pts (Figure 1). At FV, DHE was improved (2), resolved (2; one pt example in Figure C/D), or unchanged (2) in active RP pts and was improved (1), resolved (1), unchanged (2) or worsened from none to mild (1) in CS-dependent pts. DHE improvements were associated with decreased pain and CRP and occurred despite discontinuation of CS or reduction in dose level. One pt with severe DHE at baseline and mild DHE at FV experienced a recurrence ~8 weeks after rilonacept discontinuation and enrolled a second time with severe DHE; the patient had reduced CRP and pain NRS during both enrollments and ended the second enrollment with moderate DHE. Conclusions: Serial CMR demonstrated improvement in pericardial DHE after 6 mo of rilonacept treatment, consistent with clinical improvement, while corticosteroids were tapered/discontinued. Recurrence in one pt with incompletely resolved DHE after 6 months of rilonacept treatment could indicate that a longer treatment duration is warranted in patients with unresolved DHE. These preliminary results may inform future CMR-guided treatment studies in RP.

Abstract Background: Impact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1β blocker) to treat RP.Methods: Qualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS Global) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n=16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n=9). All participants received rilonacept weekly for 6 weeks during a base treatment period (TP) plus an optional 18-week extension period (EP). Concomitant medications, including corticosteroids (CS), were tapered, if possible, during EP. HRQoL was assessed using the PROMIS Global, and patient-reported pain and blood levels of c-reactive protein (CRP) were also collected at Baseline and follow-up periods. Results: Information from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline [mean PROMIS Global Physical Health (GPH) and Global Mental Health (GMH), were lower than population norm average]. In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved at EP, during CS tapering or discontinuation, without disease recurrence (low pain scores and CRP levels continued during the TP and EP). Conclusion: This is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to corticosteroids. Trial Registration: ClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522

Background: Recurrent pericarditis (RP) episodes and conventional treatments result in morbidity, but the impact on patient health-related quality of life (HRQoL) has not been quantified. The Phase 2 trial NCT03980522 of rilonacept (IL-1α/IL-1β inhibitor) evaluated HRQoL. Methods: Patients with active RP who were symptomatic at Baseline (A-RP, n=16) and RP patients who were not currently experiencing a recurrence but were corticosteroid-dependent at Baseline (CSD-RP, n=9) were enrolled. All received rilonacept weekly for 6 weeks to end of base treatment period (TP) plus an optional 18-week extension treatment period (EP). Corticosteroid tapering occurred in the EP. Physical and mental HRQoL (PROMIS Global Health v1.2 Physical and Mental Component Scores [PCS/MCS]) were assessed at baseline and follow-up. Results: Figure 1 presents the PROMIS PCS/MCS and pain scale scores (both patient-reported) as well as C-reactive protein levels over time. Mean PCS/MCS scores at baseline were 39.9/44.5 and 43.3/46.5 for A-RP and CSD-RP groups respectively (versus the norm mean of 50). In A-RP, PCS/MCS scores improved by 11.4/5.6 points by end of base TP, and this improvement was sustained throughout the EP (increase of 11.4/6.0 points from baseline at end of EP). In CSD-RP, PCS/MCS scores increased by 1.8/1.4 points by end of TP and improved by 3.5/4.2 points at end of study, after tapering or discontinuation of corticosteroid without disease recurrence. Conclusion: Impaired baseline HRQoL suggests negative impact of RP. For A-RP, rilonacept rapidly improved pericarditis signs and symptoms which was associated with HRQoL improvements. For CSD-RP, rilonacept supported tapering/withdrawal of corticosteroids without recurrence, with maintained/improved HRQoL. These results suggest rilonacept can improve RP patient HRQoL while providing an alternative to corticosteroids.