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.