PDF(Pubmed)
Abstract：
UNASSIGNED: In this protocol-predefined substudy of the RHAPSODY trial, the primary aim was to assess whether pericardial late gadolinium enhancement (LGE) was associated with time to pericarditis recurrence.
UNASSIGNED: RHAPSODY was a Phase 3 double-blind, placebo-controlled, randomized-withdrawal trial that demonstrated the efficacy of rilonacept in recurrent pericarditis (RP). Patients with a history of multiple RP and an active recurrence were enrolled and had the option to participate in a cardiac magnetic resonance (CMR) imaging substudy. CMRs were interpreted by a blinded independent core laboratory with prespecified criteria to define pericardial LGE. Compared to patients with trace or mild pericardial LGE (n = 9), patients with moderate or severe pericardial LGE (n = 16) generally had a higher number of recurrent episodes per year (5.3 vs. 3.9) and a higher mean CRP level (3.6 vs. 1.1 mg/dL). Overall, 10/14 (71.4%) who received a placebo had a recurrence compared to 0/11 (0%) who received rilonacept. In patients randomized to placebo who had moderate or severe pericardial LGE, the median time to recurrence was 4.2 weeks compared to 10.7 weeks in patients who had trace or mild pericardial LGE. At the conclusion of the event-driven randomized-withdrawal period, among patients receiving a placebo, 5/7 (71.4%) with trace or mild pericardial LGE and 5/7 (71.4%) with moderate or severe pericardial LGE had a recurrence.
UNASSIGNED: Among patients with multiple RP, these preliminary findings support the concept of pericardial LGE as an imaging biomarker that may inform the duration of treatment and risk of recurrence with cessation of therapy and larger studies should be considered.
UNASSIGNED: NCT03737110.
Patients with recurrent pericarditis (RP) can suffer from debilitating pain and a poor quality of life. Rilonacept blocks interleukin 1 (IL-1), the major inflammatory driver of RP, and is highly effective at treating active episodes of RP and preventing recurrence. In pericarditis, there is the recruitment of blood vessels to the pericardium, and the extent of these new blood vessels tracks with the degree of inflammation. Cardiac magnetic resonance imaging (CMR) readily images this blood supply and can therefore assess inflammation by the magnitude of pericardial late gadolinium enhancement (LGE). In this study of RP patients with CMR, no patients who continued rilonacept had a recurrence compared to 10/14 (71.4%) patients who stopped rilonacept and received a placebo. In the patients who received a placebo, the rate of eventual recurrence was similar among patients with trace or mild pericardial LGE at baseline (5/7) compared to patients with moderate or severe pericardial LGE at baseline (5/7). However, patients who demonstrated moderate or severe pericardial LGE had a faster recurrence (∼4 weeks after stopping rilonacept) compared to patients with trace or mild pericardial LGE (∼11 weeks after stopping rilonacept). These results suggest that pericardial LGE can serve as an imaging biomarker to assess the severity of RP and raise the possibility that CMR could be studied in future clinical trials to determine appropriate therapy and treatment duration in patients with RP.
UNASSIGNED: RHAPSODY was a Phase 3 double-blind, placebo-controlled, randomized-withdrawal trial that demonstrated the efficacy of rilonacept in recurrent pericarditis (RP). Patients with a history of multiple RP and an active recurrence were enrolled and had the option to participate in a cardiac magnetic resonance (CMR) imaging substudy. CMRs were interpreted by a blinded independent core laboratory with prespecified criteria to define pericardial LGE. Compared to patients with trace or mild pericardial LGE (n = 9), patients with moderate or severe pericardial LGE (n = 16) generally had a higher number of recurrent episodes per year (5.3 vs. 3.9) and a higher mean CRP level (3.6 vs. 1.1 mg/dL). Overall, 10/14 (71.4%) who received a placebo had a recurrence compared to 0/11 (0%) who received rilonacept. In patients randomized to placebo who had moderate or severe pericardial LGE, the median time to recurrence was 4.2 weeks compared to 10.7 weeks in patients who had trace or mild pericardial LGE. At the conclusion of the event-driven randomized-withdrawal period, among patients receiving a placebo, 5/7 (71.4%) with trace or mild pericardial LGE and 5/7 (71.4%) with moderate or severe pericardial LGE had a recurrence.
UNASSIGNED: Among patients with multiple RP, these preliminary findings support the concept of pericardial LGE as an imaging biomarker that may inform the duration of treatment and risk of recurrence with cessation of therapy and larger studies should be considered.
UNASSIGNED: NCT03737110.
Patients with recurrent pericarditis (RP) can suffer from debilitating pain and a poor quality of life. Rilonacept blocks interleukin 1 (IL-1), the major inflammatory driver of RP, and is highly effective at treating active episodes of RP and preventing recurrence. In pericarditis, there is the recruitment of blood vessels to the pericardium, and the extent of these new blood vessels tracks with the degree of inflammation. Cardiac magnetic resonance imaging (CMR) readily images this blood supply and can therefore assess inflammation by the magnitude of pericardial late gadolinium enhancement (LGE). In this study of RP patients with CMR, no patients who continued rilonacept had a recurrence compared to 10/14 (71.4%) patients who stopped rilonacept and received a placebo. In the patients who received a placebo, the rate of eventual recurrence was similar among patients with trace or mild pericardial LGE at baseline (5/7) compared to patients with moderate or severe pericardial LGE at baseline (5/7). However, patients who demonstrated moderate or severe pericardial LGE had a faster recurrence (∼4 weeks after stopping rilonacept) compared to patients with trace or mild pericardial LGE (∼11 weeks after stopping rilonacept). These results suggest that pericardial LGE can serve as an imaging biomarker to assess the severity of RP and raise the possibility that CMR could be studied in future clinical trials to determine appropriate therapy and treatment duration in patients with RP.
摘要：
■在RHAPSODY试验的该方案预定义的子研究中，主要目的是评估心包钆晚期强化(LGE)是否与心包炎复发时间相关.
■RHAPSODY是第3阶段双盲，安慰剂对照,随机停药试验证明了利隆西普治疗复发性心包炎（RP）的疗效。有多发性RP病史和活动性复发的患者被纳入，并可以选择参加心脏磁共振（CMR）成像亚研究。CMR由盲化的独立核心实验室根据预先指定的标准进行解释，以定义心包LGE。与微量或轻度心包LGE患者（n=9）相比，患有中度或重度心包LGE（n=16）的患者每年的复发次数通常较高（5.3vs.3.9）和更高的平均CRP水平（3.6与1.1mg/dL)。总的来说,接受安慰剂的10/14（71.4％）与接受rilonacept的0/11（0％）相比复发。在随机接受安慰剂治疗的中度或重度心包LGE患者中，有微量或轻度心包LGE的患者的中位复发时间为4.2周,而至复发的中位时间为10.7周.在事件驱动的随机停药期结束时，在接受安慰剂的患者中，5/7（71.4％）伴微量或轻度心包LGE和5/7（71.4％）伴中度或重度心包LGE复发。
■在多发性RP患者中，这些初步发现支持了心包LGE作为影像学生物标志物的概念,它可以告知治疗持续时间和停止治疗后复发的风险,因此应考虑进行更大规模的研究.
■NCT03737110。
患有复发性心包炎（RP）的患者可能会遭受使人衰弱的疼痛和生活质量差的困扰。Rilonacept阻断白细胞介素1（IL-1），RP的主要炎症驱动因素，并且在治疗RP的活动性发作和预防复发方面非常有效。在心包炎中，心包血管的募集，这些新血管的程度与炎症的程度有关。心脏磁共振成像（CMR）很容易对这种血液供应进行成像，因此可以通过心包晚期钆增强（LGE）的幅度来评估炎症。在这项研究的RP患者的CMR，与10/14(71.4%)停药并接受安慰剂治疗的患者相比,继续服用利洛纳的患者没有复发.在接受安慰剂的患者中，与基线时中度或重度心包LGE患者(5/7)相比,基线时轻度或轻度心包LGE患者的最终复发率相似.然而,与有微量或轻度心包LGE的患者(停药后~11周)相比,出现中度或重度心包LGE的患者复发更快(停药后~4周).这些结果表明，心包LGE可以作为成像生物标志物来评估RP的严重程度，并提高了在未来的临床试验中研究CMR的可能性，以确定RP患者的适当治疗和治疗持续时间。
■RHAPSODY是第3阶段双盲，安慰剂对照,随机停药试验证明了利隆西普治疗复发性心包炎（RP）的疗效。有多发性RP病史和活动性复发的患者被纳入，并可以选择参加心脏磁共振（CMR）成像亚研究。CMR由盲化的独立核心实验室根据预先指定的标准进行解释，以定义心包LGE。与微量或轻度心包LGE患者（n=9）相比，患有中度或重度心包LGE（n=16）的患者每年的复发次数通常较高（5.3vs.3.9）和更高的平均CRP水平（3.6与1.1mg/dL)。总的来说,接受安慰剂的10/14（71.4％）与接受rilonacept的0/11（0％）相比复发。在随机接受安慰剂治疗的中度或重度心包LGE患者中，有微量或轻度心包LGE的患者的中位复发时间为4.2周,而至复发的中位时间为10.7周.在事件驱动的随机停药期结束时，在接受安慰剂的患者中，5/7（71.4％）伴微量或轻度心包LGE和5/7（71.4％）伴中度或重度心包LGE复发。
■在多发性RP患者中，这些初步发现支持了心包LGE作为影像学生物标志物的概念,它可以告知治疗持续时间和停止治疗后复发的风险,因此应考虑进行更大规模的研究.
■NCT03737110。
患有复发性心包炎（RP）的患者可能会遭受使人衰弱的疼痛和生活质量差的困扰。Rilonacept阻断白细胞介素1（IL-1），RP的主要炎症驱动因素，并且在治疗RP的活动性发作和预防复发方面非常有效。在心包炎中，心包血管的募集，这些新血管的程度与炎症的程度有关。心脏磁共振成像（CMR）很容易对这种血液供应进行成像，因此可以通过心包晚期钆增强（LGE）的幅度来评估炎症。在这项研究的RP患者的CMR，与10/14(71.4%)停药并接受安慰剂治疗的患者相比,继续服用利洛纳的患者没有复发.在接受安慰剂的患者中，与基线时中度或重度心包LGE患者(5/7)相比,基线时轻度或轻度心包LGE患者的最终复发率相似.然而,与有微量或轻度心包LGE的患者(停药后~11周)相比,出现中度或重度心包LGE的患者复发更快(停药后~4周).这些结果表明，心包LGE可以作为成像生物标志物来评估RP的严重程度，并提高了在未来的临床试验中研究CMR的可能性，以确定RP患者的适当治疗和治疗持续时间。
