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

Abstract

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 -β 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.

Keywords: inflammation; interleukin‐1; patient‐reported outcome measures; pericarditis; quality of life; rilonacept; surveys and questionnaires.

Figure 1. Effect size and 95% CIs for change in PRO scores between RI BL to RI Week 12.

Cohen's effect size d=(mean RI week 12–mean RI BL)/SD RI BL. *P<0.001. BL indicates baseline; ISI, Insomnia Severity Index; NRS, numeric rating scale; PGIPS, Patient Global Impression of Pericarditis Symptom Severity; PRO, patient‐reported outcome; RI, run‐in; and VAS, Visual Analogue Scale.

Figure 2. Percentage of participants for each ISI total score severity category over time, and by treatment group.

ISI total score categories are noted by color; Green=“absence of insomnia” (0–7), Yellow=“sub‐threshold insomnia” (8–14), Orange=“moderate insomnia” (15–21), Red=“severe insomnia” (22–28). EOS indicates End of Study; ISI, Insomnia Severity Index; RI, run‐in; and RW, randomized withdrawal.

Figure 3. Daily pain scores for participants in placebo group who experienced recurrence before Week 24 of the RW (n=22), before and after Recurrence visit.

NRS indicates numeric rating scale; and RW, randomized withdrawal.

Figure 4. Spider plot for SF‐36v2 scores over study timepoints for participants in placebo group who experienced recurrence Before Week 24 of the RW (n=22).

Each spoke corresponds to a subscale or domain score on the SF‐36v2; scores closer to the center indicate worse HRQoL, and scores further on each spoke correspond to better HRQoL; all scores are normed such that a score of 50 is the population average. EOS indicates End of Study; HRQoL, health‐related quality of life; RI, run‐in; and RW, randomized withdrawal.

Figure 5. Mean scores (and 95% CI error bars) for SF‐36v2 Bodily Pain domain for RI BL, RW BL, Recurrence visit, and RW Week 24/EOS, for 3 groups of participants: Rilonacept only, placebo, and placebo without recurrence before Week 24.

BL indicates baseline; BP, bodily pain; EOS, End of Study; NR, no recurrence; RI, run‐in; and RW, randomized withdrawal.