Discussion
pericarditis, Idiopathic Pericarditis, RP
PERICARDITIS, DISEASE, RECURRENCE, EVENTS
Patients entering RHAPSODY were acutely symptomatic despite oral multidrug therapy. Because rilonacept, which is an IL-1α and IL-1β cytokine trap, directly targets the disease mechanism, it had been hypothesised in the trial design that the various standard oral therapies would no longer be needed and could be withdrawn relatively rapidly after rilonacept initiation. This proved to be the case, as these therapies were withdrawn, and rilonacept monotherapy was achieved in a median of 7.9 weeks without pericarditis recurrence.Given the chronicity of RP, clinicians face a conundrum when considering glucocorticoids for disease management: practice guidelines note that chronic use of glucocorticoids is associated with serious side effects, yet the data also show that discontinuation of treatment with glucocorticoids may increase the risk of pericarditis recurrence. Guidelines encourage minimising the risk of recurrence by gradually tapering off glucocorticoids: decreasing the dose by 1–2.5 mg per day every 2–6 weeks over several months when the dose is less than 15 mg/day.By contrast, use of rilonacept in RHAPSODY allowed for rapid glucocorticoid tapering without precipitating pericarditis recurrence. While clinicians often taper oral therapies taken to manage RP slowly, per available guidelines, those guidelines do not take into consideration a highly targeted, single-agent treatment such as rilonacept. In RHAPSODY, ceasing oral therapies at a rate faster than is usual in clinical practice was possible because of the overlapping and targeted disease coverage provided by rilonacept. Specifically, in patients who had been receiving glucocorticoids in combination with other treatments before study entry—including patients on long-term glucocorticoid therapy—investigators withdrew background treatments after rilonacept initiation (an overlapping approach) on the way to rilonacept monotherapy, which was achieved in a median of 7.1–8.1 weeks; the investigators chose concurrent more often than sequential tapering. This clinical trial observation, taken together with previous findings from studies using anakinra,RHAPSODY is the first IL-1 antagonist clinical trial in pericarditis in which all patients were treated with monotherapy (the Anakinra Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP) tudy did not require discontinuation of colchicine treatment during the randomised-withdrawal period).Limitations of this post hoc analysis of RHAPSODY trial data include the small patient population analysed, clinician preference, lack of run-in period events (difficult to show differences), lack of long-term follow-up, and discontinued participation of some patients during the run-in period.