Interleukin-1 Trap Rilonacept Improved Health-Related Quality of Life and Sleep in Patients With Recurrent Pericarditis: Results From the Phase 3 Clinical Trial RHAPSODY.

Background Recurrent pericarditis is characterized by painful flares and inflammation, which negatively impact health-related quality of life. RHAPSODY (rilonacept inhibition of interleukin-1 alpha and beta for recurrent pericarditis: a pivotal symptomatology and outcomes study) evaluated the efficacy and safety of rilonacept (IL-1α and -ß cytokine trap) in recurrent pericarditis. A secondary analysis of these data evaluated the patient-reported outcome questionnaire score change during the trial. Methods and Results Participants completed 5 patient-reported outcome (PRO) questionnaires assessing pericarditis pain, health-related quality of life, general health status, sleep impact, and overall symptom severity. PRO score changes during the treatment run-in period (12 weeks) and the blinded randomized withdrawal period (up to 24 weeks) were evaluated using descriptive statistics and mixed model repeated measures analyses. Participants with PRO data from the run-in period (n=84) and the randomized withdrawal period (n=61; 30 rilonacept, 31 placebo) were included in analyses. Run-in baseline PRO scores indicated that pericarditis symptoms during pericarditis recurrence impacted health-related quality of life. All PRO scores significantly improved (P<0.001) on rilonacept treatment during the run-in period. For the randomized withdrawal period, PRO scores were maintained for participants receiving rilonacept. For those receiving placebo and who experienced a recurrence, PRO scores deteriorated at the time of recurrence and then improved following rilonacept bailout. At randomized withdrawal Week 24/End of Study, scores of participants who received bailout rilonacept were similar to those of participants who had continued rilonacept. Conclusions These results demonstrate the burden of pericarditis recurrences and the improved physical and emotional health of patients with recurrent pericarditis while on rilonacept treatment. These findings extend prior rilonacept efficacy results, demonstrating improvements in patient-reported health-related quality of life, sleep, pain, and global symptom severity while on treatment. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110.

Disease and Economic Burden Associated with Recurrent Pericarditis in a Privately Insured United States Population.

INTRODUCTION: Approximately 30% of patients with a first acute pericarditis episode experience a recurrence ≤ 18 months; ~ 15% experience multiple recurrences. This study assessed the recurrence and economic burden among patients with multiple recurrences. METHODS: Adults with idiopathic pericarditis were identified in the OptumHealth Care Solutions, Inc., database (2007-2017). Recurrent pericarditis (RP) was defined as ≥ 2 episodes of care separated by > 28 days; multiple recurrences were defined as ≥ 2 recurrences. RESULTS: Among 944 patients with RP, 375 (39.7%) experienced multiple recurrences and were propensity score-matched 1:1 to 375 patients without recurrence. Among patients with multiple recurrences, median disease duration (time from first episode to end of last recurrence, confirmed by a 1.5-year recurrence-free period) was 2.84 years. The multiple recurrences cohort had higher rates of hospitalizations per-patient-per-month (PPPM) than the no recurrence cohort (rate ratio [95% confidence interval (CI)] = 2.22 [1.35-3.65]). Mean total healthcare costs were significantly higher in the multiple recurrences versus no recurrence cohort ($2728 vs. $1568 PPPM, cost ratio [95% CI] = 1.74 [1.29-2.32]), mainly driven by higher hospitalization costs in the multiple recurrences cohort (mean: $1180 vs. $420 PPPM, cost ratio [95% CI] = 2.81 [1.80-4.66]). Mean work loss costs were higher in the multiple recurrences versus no recurrence cohort ($696 vs. $169 PPPM, cost ratio [95% CI] = 4.12 [1.64-9.61]). In patients with multiple recurrences, mean cost of the first episode was $19,189; subsequent recurrences ranged from $2089 to $7366 (second recurrence = $6222). CONCLUSION: In conclusion, among patients with multiple pericarditis recurrences, disease symptoms persisted several years, and healthcare and work loss costs were further compounded in this subset of patients.

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

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-1ß 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://clinicaltrials.gov/ct2/show/NCT03980522 .

Burden of Recurrent Pericarditis on Health-Related Quality of Life.

The extent to which recurrences of pericarditis episodes impact patients' health-related quality of life (HRQOL) remains poorly understood. This study aimed to evaluate HRQOL and work productivity in patients with recurrent pericarditis (RP). Adult patients from a centralized recruitment database for the rilonacept Phase 2/3 clinical trials were invited to participate in a survey. Inclusion criteria were confirmed RP diagnosis and ≥1 recurrence within the previous 12 months. The 11-Point Pain Numeric Rating Scale, Patient Global Impression of Pericarditis Severity, Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health v1.2, PROMIS Short Form Sleep Disturbance 8b, Work Productivity and Activity Impairment v2.0, and customized questions about fear and economic impact were used. In total, 83 patients (55% female, average age = 49.3 years) completed the survey. The median time since pericarditis diagnosis was 3.0 years at the time of survey completion; 49% experienced ≥3 recurrences in the previous 12 months. Forty percent had an emergency room visit, and 25% were hospitalized for their most recent recurrence. Sixty-six percent of participants rated the symptoms of their last recurrence as severe. The mean value for worst pericarditis pain (0 to 10 scale) during the most recent recurrence was 6.1. The average T-scores for PROMIS physical and mental health were 37.6 and 42.8, respectively, compared with 50 in the general population. Participants reported 50% of overall work impairment and 62% of activity impairment due to RP. In conclusion, patients with RP experienced a high number of recurrences with severe symptoms that substantially reduced their HRQOL and work productivity.