新药Arcalyst（rilonacept）白介素-1（IL-1）阻滞剂 是一种皮下注射的可溶性融合蛋白，由IL-1受体1（IL-1R1）胞外部分的配体结合域，和IL-1受体辅助蛋白（IL-1RAcP），呈线性连接至人免疫球蛋白G1（IgG1）的Fc结合域。它通过充当一种可与IL-1α和IL-1β结合的受体来抑制IL-1的信号传导，从而阻断它们与细胞表面IL-1受体相互作用。Rilonacept是由再生元（Regeneron）公司发现并开发，Kiniksa公司获得其独家许可后进一步开发治疗RP患者。
2021年03月18日，Kiniksa Pharmaceuticals宣布，美国FDA已批准该公司开发的IL-1抑制剂Arcalyst（rilonacept）上市，用于治疗12岁以上复发性心包炎（recurrent pericarditis）患者和减轻心包炎的复发风险。
Arcalyst（rilonacept）是首款获得FDA批准的复发性心包炎疗法。
FDA的批准是基于名为RHAPSODY的关键性3期临床试验结果。
试验结果显示：97%的患者对rilonacept治疗产生应答，接受rilonacept治疗的患者出现复发心包炎事件的风险与安慰剂组相比降低了96%。Rilonacept组的患者在临床试验中，92%的时间没有疼痛或者痛感非常轻微，安慰剂组这一数值为40%。
这一结果已经发布在《新英格兰医学杂志》上。
在美国，Arcalyst（rilonacept）220mg皮下注射冻干粉剂的花费约为$20,890美元。
复发性心包炎是一种影响心脏周围组织的炎症性疾病，它影响15%至30%的急性心包炎患者。复发性心包炎是一种失能性疾病，患者会有反复的胸痛发作，且伴有危及生命的并发症，严重限制患者的身体活动和日常生活。
目前，标准疗法有非甾体类抗炎药（NSAIDs），秋水仙碱，和皮质类固醇（CS）药物，长期使用这些药物会对患者造成安全问题，尤其是CS药物。白介素-1（IL-1）是介导这种疾病的病理生理的细胞因子之一，心包中的IL-1α和IL-1β引起的组织损伤受刺激后会分泌额外的IL-1α和IL-1β，从而造成心包炎症的延续。
ARCALYST®(rilonacept) for injection, for subcutaneous use
Initial U.S. Approval: 2008
IMPORTANT SAFETY INFORMATION
Warning and Precautions
Interleukin-1 (IL-1) blockade may interfere with the immune response to infections. Treatment with another medication that works through inhibition of IL-1 has been associated with an increased risk of serious infections, and serious infections have been reported in patients taking ARCALYST. ARCALYST is not recommended for use with tumor necrosis factor (TNF) inhibitors because this may increase risk of serious infections. ARCALYST should be discontinued if a patient develops a serious infection. Treatment with ARCALYST should not be initiated in patients with an active or chronic infection.
It is possible that taking drugs that block IL-1 increase the risk of tuberculosis (TB) or other atypical or opportunistic infections. Refer to current practice guidelines to eva luate and to treat possible latent TB infections before initiating therapy.
The impact of ARCALYST on infections and the development of malignancies is not known. However, treatment with immunosuppressants may result in an increase in the risk of malignancies.
Hypersensitivity reactions occurred in clinical trials. If a hypersensitivity reaction occurs, discontinue ARCALYST and initiate appropriate therapy.
Patients should be monitored for changes in their lipid profiles and provided with medical treatment if warranted.
Since no data are available, avoid administration of live vaccines while patients are receiving ARCALYST. Because IL-1 blockade may interfere with immune response to infections, it is recommended that, prior to initiation of therapy with ARCALYST, patients receive all recommended vaccinations, as appropriate.
Adverse Reactions
The most common adverse reactions (≥10%) include injection-site reactions, upper respiratory tract infections, arthralgia, and myalgia.
Drug Interactions
Concomitant administration of ARCALYST with TNF-blocking agents or other agents that block IL-1 or its receptor is not recommended, as this may increase the risk of serious infections.
In patients being treated with CYP450 substrates with narrow therapeutic indices, therapeutic monitoring of the effect or drug concentration should be performed, and the individual dose of the medicinal product may need to be adjusted as needed.
Use in Specific Populations
Pregnancy outcomes reported post marketing and during clinical trials were rare, therefore, the effect of using ARCALYST during pregnancy is not known.
There is no information on the presence of ARCALYST in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.
https://www.arcalyst.com/sites/arcalyst.com/files/2021-03/PI.pdf |
