A Toolkit for Health Care Professionals Recurrent Pericarditis after a 12-week run-in period.77 Rilonacept resolved or nearly resolved chest pain after only a median of 5 days and normalized hs-CRP after a median of 7 days. At the end of the study period, 7% of patients in the rilonacept group and 74% in the placebo group experienced a recurrent episode, yielding a relative risk reduction of 90.5%.77 Other therapies Canakinumab, a monoclonal antibody that binds to IL-1 beta, 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-1 alpha and beta 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 4-week screening phase, a 12- or 24-week run-in phase based on background therapies and included 10 weeks of goflikicept monotherapy, a 24-week placebocontrolled randomized withdrawal phase and an 8-week safety follow-up period. Goflikicept was dosed at 80 mg subcutaneously every 2 weeks. During the run-in phase, treatment with goflikiciept 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 Table 5. Dosing of IL-1 blockers in recurrent pericarditis Anakinra (KINERET)13 1-2 mg/kg (max: 100 mg) subcutaneously every day. Consider dosing every other day in patients with creatinine clearance less than 30 mL/min. Rilonacept (ARCALYST)14 Initial: 320 mg (divided into 2 x 160 mg doses administered at different injection sites). Maintenance: 160 mg once weekly, starting 1 week after initial dose. 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.) Anakinra and rilonacept also increase the risk of infections, though treatment may be continued if very mild infections occur (e.g., common cold). If a serious illness or fever occurs, therapy should be withheld until illness resolves. IL-1 blockers should also be avoided with live vaccines and anti-tumor necrosis factor (TNF) agents. Active infections, including latent tuberculosis, should be identified and treated before treatment initiation, and patients should be routinely monitored for neutropenia. Duration of therapy and tapering In the AIRTRIP trial, patients continued anakinra therapy for 6 months after the 2-month lead-in period.76 In the RHAPSODY trial, the median duration of treatment with rilonacept was 9 months (range 3 to 14 months), although the long-term extension study investigated therapy for up to 24 months. Data suggests that at least 18 months of therapy decreased recurrences by 98%, while receiving ongoing treatment with rilonacept.77,78 Tapering of aspirin/NSAIDs and corticosteroids can typically be commenced 7 days after addition of an IL-1 receptor blocker.18 Thereafter, NSAIDs may be withdrawn over the next 2 weeks and corticosteroids within 6 to 10 weeks following IL-1 receptor blocker commencement. Colchicine may also be withdrawn, as its use does not alter pericarditis recurrence risk while receiving IL-1 receptor blocker therapy employed after adequate response to IL-1 blockers, though data on the optimal approach are lacking. It should be noted that IL-1 receptor blocker therapy discontinuation is associated with a high risk of recurrent pericarditis. In the International Registry of Anakinra for Pericarditis (IRAP), anakinra discontinuation was associated with a 57% risk of recurrence at 36-month follow-up.79 Similarly, rilonacept discontinuation during the long-term extension phase of the RHAPSODY study was associated with a recurrence rate of 75% with a median time to recurrence of 11.8 weeks.80 Potential strategies to reduce the risk of pericarditis recurrence following IL-1 receptor blocker discontinuation include longer duration of IL-1 receptor blocker therapy and medication tapering.79 Due to a longer elimination half-life (~7 days), the impact of rilonacept tapering on subsequent pericarditis recurrence risk is unknown. Potential tapering strategies for anakinra81 • Reduce by one administration day per week. • Reduce to every other day dosing for 3 months, followed by half dose every other day for 1 to 3 months. 23
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