Regeneron制药公司的白介素(IL)-1阻滞剂Arcalyst(Rilonacept)已通过美国食品药品管理局(FDA)的批准，成为治疗cryopyrin相关周期性综合征(CAPS)这一罕见病的首个药物。其给药方式为每周一次皮下注射，因此患者可以自己给药治疗。

CAPS是一种终生疾病，包括家族性寒冷型自身炎症性综合征(FCAS)和Muckle-Wells综合征(MWS)，其特点为终生反复发作皮疹、发热/寒战、关节痛、眼睛发红/眼睛疼痛和疲劳等症状。

该药通过FDA批准是基于一项Ⅲ期临床试验结果。该临床试验有47名FCAS和MWS患者参加，其复合主要终点测定了5个CAPS体征和症状的改善情况：关节痛、皮疹、发热/寒战、眼睛发红/眼睛疼痛和疲劳。在使用该药治疗前，测定了3周内患者的平均基线症状分值，随后患者被随机分组，接受该药或者安慰剂治疗6周，并在治疗后3周测定患者的平均基线症状分值。经过6周的治疗后，治疗组的平均基线症状分值从3.08降至0.47，而安慰剂组从2.41降至2.1(P<0.0001)。

该药最常见的不良反应为注射部位反应(治疗组为48%，安慰剂组为13%)和上呼吸道感染(26%比4%)。

In February 2008, the U.S. Food and Drug Administration (FDA) approved ARCALYST Injection for Subcutaneous Use for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older.

Rilonacept is also approved for marketing, but not yet available, in the European Union for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older.

Cryopyrin-Associated Periodic Syndromes (CAPS)-a rare, hereditary condition

CAPS are generally caused by mutations in the NLRP-3 (previously known as CIAS1) gene and resultant alterations in the protein, cryopyrin, which it encodes. Cryopyrin, active in circulating, infection-fighting, white blood cells, controls the production of a protein called interleukin-1 (IL-1). As part of the body's infection-fighting defense system, IL-1 circulates throughout the body and can trigger inflammatory reactions when it binds to inflammatory cells. Researchers have found that alterations in the cryopyrin protein lead to over-production of IL-1, resulting in an inflammatory response and the symptoms of CAPS. Most, but not all, patients with CAPS have the NLRP-3 gene mutation.

The incidence of CAPS has been reported to be approximately 1 in 1,000,000 people in the United States and Europe.

Important Safety Considerations Regarding ARCALYST

IL-1 blockade may interfere with immune response to infections. Serious, life-threatening infections have been reported in patients taking ARCALYST. ARCALYST should be discontinued if a patient develops a serious infection. Taking ARCALYST with tumor necrosis factor inhibitors is not recommended because this may increase the risk of serious infections. Treatment with ARCALYST should not be initiated in patients with active or chronic infections. Patients should not receive a live vaccine while taking ARCALYST. It is recommended that patients receive all recommended vaccinations prior to initiation of treatment with ARCALYST. Patients should be monitored for changes in their lipid profiles and provided with medical treatment if warranted. Hypersensitivity reactions associated with ARCALYST administration have been rare.

Arcalyst (rilonacept)

Indications for ARCALYST

Cryopyrin-associated periodic syndromes (CAPS) including familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS).

Adult dose for ARCALYST

Give by SC inj into abdomen, thigh, or upper arm; rotate sites. ≥18yrs: Loading dose: 320mg on day 1 (split dose into 2x160mg at different sites), then 160mg as single dose once weekly.

Children's dosing for ARCALYST

Give by SC inj into abdomen, thigh, or upper arm; rotate sites. <12yrs: not recommended. 12–17yrs: Loading dose: 4.4mg/kg (max 320mg) in 1 or 2 inj (max 2mL/inj) on day 1; may split loading dose into 2 inj at different sites. Maintenance: 2.2mg/kg (max 160mg) once weekly.

Warnings/Precautions for ARCALYST

Discontinue if serious infection develops. Do not start treatment with active or chronic infection. Before starting therapy: complete recommended immunization schedules (including pneumococcal and influenza), and evaluate and treat possible latent tuberculosis. Asthma. Diabetes. HIV, hep B, or hep C infection. Renal or hepatic impairment. Monitor lipid profile. Patients <18yrs: monitor growth and development. Pregnancy (Cat.C): not recommended (may cause fetal harm). Nursing mothers.

Interactions for ARCALYST

Avoid concurrent live vaccines. Infection risk with concomitant TNF blockers (eg etanercept, infliximab, adalimumab) or other IL-1 blockers (eg, anakinra): not recommended. Monitor drugs that affect or are affected by CYP450 (eg, warfarin). Caution with other immunosuppressants (eg, corticosteroids).

Adverse Reactions for ARCALYST

Inj site reactions, infections (eg, URI; may be serious/fatal); possible increased risk of malignancies, antibody formation, changes in lipid profile.

How is ARCALYST supplied?

Single-dose vial—4

Arcalyst (rilonacept)注射剂使用说明

Arcalyst (rilonacept)注射剂 – 以前称Interleukin-1 Trap

批准日期：2008年2月27日美国FDA；2009年7月23日欧盟EMEA。公司：Regeneron Pharmaceuticals, Inc.。

一般描述：
Rilonacept是二聚体融合蛋白由由一种人白介素-1受体组分(IL-1R1)的胞外部分配体-结合结构区和IL-1受体辅助蛋白(IL-1RAcP)呈线性连接至人IgG1的Fc部分组成。Rilonacept分子量接近251 kDa。Rilonacept在重组中国仓鼠卵巢(CHO)细胞内表达。

适应证：
Arcalyst (rilonacept)是一种白介素-1阻断剂适用于治疗在成年和12岁以上儿童的Cryopyin蛋白-相关周期性综合征，包括家族性冷自身炎症综合征(FCAS)和Muckle-Wells(穆-韦二氏综合征:淀粉样变性-耳聋-荨麻疹-肢痛综合征，MWS)。

剂量和给药方法：

成年18岁和以上：起始治疗用负荷剂量320 mg分2次，2 mL皮下注射160 mg在同一天在2处不同部位。继续给药每周1次，单次2 mL皮下注射160 mg，不要给予Arcalyst超过比每周1次更频。
年龄12至17岁儿童患者：起始治疗用负荷剂量4.4 mg/kg，直至最大剂量320 mg，分1或2次，皮下注射，最大单次注射体积为2 mL。继续给药1周1次2.2 mg/kg，最大剂量160 mg，单次皮下注射给药至2 mL。如最初剂量为2次注射，它们应在相同天2处不同部位。不要给予Arcalyst超过比每周1次更频。

剂型规格：
消毒，单次用20 mL小瓶，玻璃含220 mg rilonacept为配制的冻干粉。

禁忌证：无

警告和注意事项：

白介素-1阻断剂可能干扰对感染的免疫反应。在用Arcalyst患者中曾报道危及生命感染。如患者发生严重感染中断治疗。有活动性或慢性感染患者中不要开始用Arcalyst治疗。
罕见伴Arcalyst给药超敏反应。如发生超敏反应，中断Arcalyst给药并开始适当治疗。
与Arcalyst不应同时给予活疫苗，开始用Arcalyst治疗前，患者应接受所有的免疫接种。

不良反应：
随CAPS用Arcalyst治疗，报道的最常见不良反应是注射部位反应和上呼吸道感染。

药物相互作用：
用Arcalyst未曾进行过正规的药物相互作用研究。

特殊人群中使用：
妊娠：无人类资料。基于动物资料，可能引起胎儿危害。