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

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 cytokine trap) 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 GH) 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 during a 6-week base treatment period (TP) plus an optional 18-week extension period (EP). Tapering of concomitant medications, including corticosteroids (CS), was permitted during EP. HRQoL was assessed using the PROMIS GH, and patient-reported pain and blood levels of c-reactive protein (CRP) were collected at Baseline and follow-up periods. A secondary, descriptive analysis of the Phase 2 trial efficacy results was completed using HRQoL measures to characterize both the impact of RP and the treatment effect of rilonacept.

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 during 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 CS.

Trial registration: ClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://ichgcp.net/clinical-trials-registry/NCT03980522 .

Keywords: Health-related quality of life; Interleukin-1 cytokine trap; Pericarditis; Recurrent pericarditis.

Conflict of interest statement

David Lin: None. Allan Klein: Research grant, scientific advisory board Kiniksa Pharmaceuticals, Ltd., advisory board Swedish Orphan Biovitrum AB, advisory board Pfizer, Inc., modest. David Cella: Consultant for Kiniksa Pharmaceuticals, Ltd., modest. Anna Beutler: Kiniksa Pharmaceuticals, Ltd. consultant. Fang Fang: Kiniksa Pharmaceuticals, Corp. employee. Matt Magestro: Kiniksa Pharmaceuticals, Corp. employee. Paul Cremer: Advisory board Swedish Orphan Biovitrum AB, advisory board Kiniksa Pharmaceuticals, Ltd., modest. Martin M. LeWinter: One seminar for Kiniksa Pharmaceuticals, Ltd., modest. Sushil Allen Luis: Advisory board member for Kiniksa Pharmaceuticals, Ltd., modest. Consultant and advisory board member for Swedish Orphan Biovitrum AB, significant. Antonio Abbate: 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, Merck & Co., Inc., modest. Andrew Ertel: None. Leighann Litcher-Kelly: Employed by Adelphi Values, which received funding from Kiniksa Pharmaceuticals, Ltd. for PRO work in pericarditis. Brittany Klooster: Employed by Adelphi Values, which received funding from Kiniksa Pharmaceuticals, Ltd. for PRO work in pericarditis. John F. Paolini: Kiniksa Pharmaceuticals, Corp. Employee.

Figures

Fig. 1

Patient-centric conceptual model for recurrent pericarditis. Proposed by Wilson and Cleary [17], a conceptual model is a heuristic classification scheme that links a specified disease state or condition to its proximal and increasingly distal health outcomes. This model presents the concepts reported by adult RP patients during qualitative interviews: RP symptoms (proximal to the disease process of RP) and impacts to daily life (organized by HRQoL domain, increasingly distal to the disease process). *Khandaker et al. [26]

Fig. 2

Mean PROMIS GPH/MPH at Baseline for A-RP and CSD-RP. This figure presents the mean and standard deviations for the baseline scores of the PROMIS GH physical (GPH) and mental (GMH) health domains. For both the A-RP (n = 16) and CSD-RP (n = 9) groups, average scores for these domains are below the US normative average score of 50. A-RP = active symptomatic recurrent pericarditis; CSD-RP = corticosteroid-dependent recurrent pericarditis with no active recurrence; GPH = Global Physical Health; GMH = Global Mental Health; PROMIS GH = Patient-Reported Outcomes Measurement Information System Global Physical Health

Fig. 3

PROMIS GH domain scores, pericardial pain, and c-reactive protein levels over time by participant group. This figure shows the change in the GPH and GMH domain scores over the study period for the A-RP group and the CSD-RP group, and the trend between these HRQoL scores and patient-reported pericardial pain and serum marker of inflammation (CRP). For the A-RP group, pain scores and CRP levels decrease over the study period, while HRQoL scores increase. For the CSD-RP group, pericardial pain and CRP (low at baseline, as expected because these participants entered the trial while not in active flare) remain low over the course of the study even while tapering and discontinuing CS, while HRQoL scores increase over time. BL = baseline; CRP = c-reactive protein; D = day; EoEP = end of extension period; EoTP = end of treatment period; NRS = numeric rating scale; QoL = quality of life; SE = standard error; W = week