22 closed, two of 30 (7%) patients in the rilonacept group and 23 of 31 (74%) patients in the placebo group experienced a recurrent episode. In the RHAPSODY long-term extension (LTE), 74 out of 75 eligible patients continued and received open-label rilonacept for up to 24 additional months. For each LTE patient, 18 months after the most recent pericarditis recurrence (qualifying or RW period), a decision was made to continue rilonacept, suspend rilonacept for off-treatment observation or discontinue from LTE. For the patients that continued treatment with rilonacept past the 18-month decision milestone, there was a 98% reduction in risk of recurrence (HR, 0.02; P<0.0001), consistent with the primary efficacy endpoint. Registry of the natural history of recurrent pericarditis in pediatric and adult patients (RESONANCE) (NCT04687358), the first multicenter U.S. recurrent pericarditis patient registry, launched in March 2021 and is currently ongoing. Data from RESONANCE demonstrate that second-line management of patients failing aspirin/NSAIDs/colchicine has shifted increasingly toward IL-1 pathway inhibition, and the initiation of corticosteroids decreased each year after rilonacept approval in recurrent pericarditis. Anakinra is a recombinant human IL-1 receptor antagonist (IL-1RA) that competes with endogenous IL-1 and mimics the effects of a native human interleukin-1 receptor antagonist (IL-1RA), blunting the activity of both IL-1α and β. It has been used off-label in the treatment of recurrent pericarditis. The AIRTRIP trial randomized 21 colchicine-resistant, corticosteroid-dependent patients with a history of three or more recurrences. After an open-label phase in which all patients received anakinra for two months, patients were randomized to anakinra or receive placebo. All patients in the two-month, openlabel phase experienced a complete response to anakinra after approximately one week of therapy. During the withdrawal phase, recurrence occurred in 18% of patients receiving anakinra versus 90% of those on placebo, meaning approximately 82% of patients on anakinra remained recurrence-free (incidence rate ratio 0.055; P<0.001). Approximately half of the participants remained on colchicine, as monotherapy was not a requirement of the study.76 Other therapies Canakinumab, a monoclonal antibody that binds to IL-1β, can be considered, though evidence of its use in pericarditis is mainly limited to case reports. Goflikicept is a heterodimeric fusion protein that binds to IL-1α and β cytokines with high affinity. It has been investigated in a phase 2 and 3 randomized open-label study in adults with idiopathic recurrent pericarditis. The study consisted of four phases: a four-week screening phase, a 12- or 24week run-in phase based on background therapies and included 10 weeks of goflikicept monotherapy, a 24-week placebo-controlled randomized withdrawal phase and an eight-week safety follow-up period. Goflikicept was dosed at 80 mg subcutaneously once weekly. During the run-in phase, treatment with goflikicept significantly reduced CRP levels, chest pain and pericardial effusion size. During the randomized withdrawal period, 90% of patients in the placebo group experienced a recurrence compared to no patients in the treatment group.74 Goflikicept is approved for use only in the Russian Federation. The most common adverse effect of IL-1 blocking agents is injection site reactions, but these are typically mild and self-limiting, and patients can employ several techniques to mitigate these. (See “Patient Education Checklist” on page 24.) IL-1 blockers are associated with increased risk of infections, most commonly upper respiratory infections; they may blunt inflammatory signs, so infections should be monitored and serious infections prompt treatment interruption. Duration of therapy and tapering Decisions around treatment duration should consider the natural history of recurrent pericarditis, including how much of the expected disease course has elapsed. Discontinuation of therapy should be guided by clinical judgment and whether the underlying autoinflammatory process re-emerges upon dose reduction, dose interval elongation or treatment withdrawal. Should symptoms or inflammatory activity re-emerge, prompt re-initiation of therapy is warranted to restore disease control and continue treatment for the duration of the underlying disease course. Tapering of NSAIDs or corticosteroids is initiated after clinical improvement and CRP normalization, typically within one to two weeks of IL-1 inhibitor initiation.18 Thereafter, NSAIDs may be withdrawn over the next two weeks and
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