Multiyear Recurrent Pericarditis Disease Duration: Clinical Outcomes After Cessation of Long‐Term Interleukin‐1 Pathway Inhibition Provide Insights for Chronic Management

BACKGROUND: Recurrent pericarditis is an interleukin-1-mediated chronic autoinflammatory disease. The phase 3 study RHAPSODY (Rilonacept Inhibition of IL-1 Alpha and IL-1 Beta for Recurrent Pericarditis: a Pivotal Symptomatology and Outcomes Study; NCT03737110) and long-term extension demonstrated that rilonacept reduced the risk of recurrence. After 3 years of rilonacept treatment in RHAPSODY, Italian patients returned to standard management, as rilonacept was not commercially available. METHODS: Clinical records from Italian RHAPSODY patients were retrospectively reviewed for the 18-month period post-long-term extension completion to assess recurrent pericarditis disease persistence and time to recurrence after rilonacept cessation/washout. The primary outcome was pericarditis recurrence (ie, pericarditis pain plus C-reactive protein elevation). Safety was also assessed. RESULTS: Seventeen patients were included in this analysis. The median disease duration (from incident episode to long-term extension completion) was 48 (interquartile range, 41-56) months; the median duration of continuous rilonacept treatment was 28 (interquartile range, 27-30) months. Fourteen (82%) of 17 patients experienced a post-trial off-treatment recurrence; the remaining patients (n=3) had no pericarditis recurrences and remained offtreatment. The median time to recurrence (n=14) was 8.0 (interquartile range, 6.0-9.0 weeks). Most patients' (n=8) post-trial off-treatment recurrences were managed with interleukin-1 pathway inhibition. Some (n=4) were managed with glucocorticoids, and few (n=2) were managed with NSAIDs/colchicine. No serious adverse events were experienced. CONCLUSIONS: The vast majority (86%) of the patients who experienced an off-treatment recurrence after 28 months of rilonacept restarted interleukin-1 pathway inhibition or corticosteroids, suggesting that NSAIDs/colchicine are insufficient in the management of patients with prolonged advanced disease. Rilonacept cessation and subsequent passive gradual washout is an evidence-based pragmatic approach to determine if continued therapy is warranted to prevent subsequent recurrences.