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近年，美国食品药品治理局（FDA）批准Krystexxa(peglotise)用于常规治疗无效或常规治疗无法耐受的成年痛风患者的治疗。
痛风为嘌呤代谢紊乱和(或)尿酸排泄障碍所致血尿酸增高的一组异质性疾病，其症状为关节间歇性肿胀、发红、发热、疼痛和关节僵硬。痛风患者的常规疗法是服用能够降低血液中尿酸含量的药物，例如黄嘌呤氧化酶抑制剂别嘌醇（别嘌呤醇）和Uloric(非布司他)。
Krystexxa是一种酶，能够将尿酸代谢成无害物质并经过尿液排出体外来降低痛风患者体内的尿酸水平。该药物的给药方式为静脉注射，每两周注射一次。
FDA药品审评与研究中心肺、过敏和风湿病治疗药办公室主任BadrulChowdhury说，“在3,000,000名成年痛风患者中，大约有3%的人群无法从常规治疗中获益。本次批准的这一新药物能够为这些患者提供新的治疗选择。”
两项为期6个月，有212名受试者参加的临床试验结果显示，该药物能够降低尿酸水平，并且能够减少关节及软组织中的尿酸结晶沉淀物。但该研究也同时发觉，在接受Krystexxa治疗的患者中，有1/4的患者会出现严峻过敏反应，因此医务职员在开具处方和给药时应事先给以患者类固醇和抗组胺类药，以降低患者出现过敏反应的风险。临床试验中出现的其他不良反应包括骤发痛风、恶心、注射部位青肿、鼻腔刺激、便秘、胸痛、呕吐。
FDA同时提醒医师：鉴于该药至今并未进行针对充血性心力衰竭患者的临床试验研究，因此医师在为此类患者开具处方时也需慎重。
在批准Krystexxa的同时，FDA批准了制药商制定的风险评估与降低计划（REMS），该计划包括向患者提供一份用药指南，以及给专业医护职员的相关专业信息和严峻过敏反应风险信息
批准日期：2010年9月14日：公司：Savient Pharmaceuticals, Inc.
Krystexxa注射剂，为静脉输注
初始美国批准：2010
一般描述
KRYSTEXXA(pegloticase)是一种尿酸特异性酶，它是聚乙二醇化产品，由重组修饰的哺乳动物尿酸盐氧化酶(uricase)组成，通过遗传工程修饰大肠杆菌株生产。尿酸酶被共价结合至聚乙二醇单甲醚[mPEG](分子量10 kDa)。编码尿酸酶的cDNA是根据哺乳动物序列。每个尿酸酶亚单位有分子量约34 kDa每亚单位。Pegloticase的平均分子量(四聚酶结合至mPEG)是约540 kDa。
KRYSTEXXA意向静脉输注。
KRYSTEXXA是一种无菌，澄明，无色溶液在-缓冲液生理盐水中含8 mg/mL pegloticase。
KRYSTEXXA(pegloticase)浓度是用尿酸酶蛋白浓度表示。每mL KRYSTEXXA含8 mg尿酸酶蛋白(结合至24 mg 10 kDa mPEG)，2.18 mg二水合磷酸氢二钠(Na2HPO4?2H2O)，8.77 mg氯化钠(NaCl)，0.43 mg二水磷酸二氢钠(NaH2PO4?2H2O)，和注射用水以输送8 mg pegloticase (为尿酸酶蛋白)。
作用机制
KRYSTEXXA是一种尿酸特异性酶是一种重组尿酸酶和通过催化尿酸氧化为尿囊素，因此降低血清尿酸达到其治疗作用。尿囊素是一种惰性和水溶性嘌呤代谢物。容易消除主要经肾排泄。
适应证和用途
KRYSTEXXA?(pegloticase)是一种聚乙二醇化尿酸特异性酶适用于对常规治疗难治的成年患者慢性痛风的治疗。(1)
使用的重要限制：
不推荐KRYSTEXXA对无症状高尿酸血症的治疗。(1)
剂量和给药方法
（1）对成年患者给予8 mg作为静脉输注每两周1次。(2.1)
（2）不要静脉推注或丸注给药。(2.3)
（3）每次输注前监测血清尿酸水平。(2.3)
（4）患者应用抗组织胺s和皮质激素预先给药。 (2.3, 5.1, 5.2)
（5）在医疗机构内由医疗服务提供者给药准备处理过敏反应。(2.3, 5.1, 5.2)
（6）KRYSTEXXA混合物只应通过静脉输注不短于120分钟内通过重力，注射器型泵，或输注泵给药。(2.3)
剂型和规格
（1）1 mL为稀释无菌浓缩液含8 mg pegloticase蛋白，以尿酸酶蛋白量表示。(3)
禁忌证
（1）6-磷酸葡萄糖脱氢酶(G6PD)缺乏：开始用KRYSTEXXA前，由于溶血和高铁血红蛋白症的风险应筛选G6PD缺乏较高风险患者(如，非洲和地中海祖先患者)。(4)
警告和注意事项
过敏反应：用KRYSTEXXA治疗患者中发生过敏反应。随任何输注可能发生过敏反应，包括第一次输注,和一般地在输注的2小时内出现，但是，也曾报道延迟-型超敏性反应。应医疗机构内和由医疗服务提供者给予KRYSTEXXA准备处理过敏反应。患者应用抗组织胺和皮质激素预先给药。给予KRYSTEXXA后患者应被严密监查过敏反应适当时间。(5.1)
输注反应：用KRYSTEXXA治疗患者中发生输注反应。医疗机构内和由医疗服务提供者给药准备处理输注反应。患者应抗组织胺s和皮质激素预先给药。严密监查患者输注反应的征象和症状。在输注反应事件中，应缓慢输注，或停止和在缓慢速率再开始。如发生严重输注反应，需要时停止输注和开始治疗。已丧失治疗反应患者中输注反应风险较高。(5.2)
痛风发作：抗高尿酸血症治疗的开始，包括用KRYSTEXXA治疗经常观察到痛风发作增加。如治疗期间发生痛风发作，不需要停止KRYSTEXXA。建议至少治疗的头6个月用痛风发作的预防(即，非-甾体抗炎药[NSAID]或开始用秋水仙碱[colchicine]治疗)除非医学禁忌或不能耐受。(5.3)
充血性心衰：尚未正式在充血性心衰患者中研究KRYSTEXXA，但临床试验中某些患者经受加重。当充血性心衰患者中使用KRYSTEXXA小心对待和输注后严密监查患者。(5.4)
不良反应
最常见不良反应(发生至少5% KRYSTEXXA-治疗患者)是痛风发作、输注反应、恶心、挫伤或瘀癍、鼻咽炎、便秘、胸痛、过敏反应和呕吐。(6.1)
WARNING: ANAPHYLAXIS and INFUSION REACTIONS
See full prescribing information for complete boxed warning.
Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA.
KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions.
Patients should be pre-medicated with antihistamines and corticosteroids.
Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA.
Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6mg/dL, particularly when 2 consecutive levels above 6 mg/dL
are observed.
CONTRAINDICATIONS
Glucose-6-phosphate dehydrogenase (G6PD) Deficiency: Before starting KRYSTEXXA, patients at higher risk for G6PD deficiency (e.g., those of African and Mediterranean ancestry) should be screened due to the risk of hemolysis and methemoglobinemia.
WARNINGS AND PRECAUTIONS
Anaphylaxis: Anaphylaxis occurred in patients treated with KRYSTEXXA. Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion.
However, delayed-type hypersensitivity reactions have also been reported. KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis.
Patients should be pre-medicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA.
Infusion Reactions: Infusion reactions occurred in patients treated with KRYSTEXXA. KRYSTEXXA should be administered in a healthcare setting and by healthcare providers prepared to manage infusion reactions. Patients should be pre-medicated with antihistamines and corticosteroids.
Monitor patients closely for signs and symptoms of infusion reactions.
In the event of an infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate.
If a severe infusion reaction occurs, discontinue infusion and institute treatment as needed. The risk of an infusion reaction is higher in patients who have lost therapeutic response.
Gout Flares: An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, including treatment with KRYSTEXXA.
If a gout flare occurs during treatment, KRYSTEXXA need not be discontinued. Gout flare prophylaxis (i.e., non-steroidal anti-inflammatory drugs [NSAIDs] or colchicine upon initiation of treatment) is recommended for at least the first 6 months of therapy unless
medically contraindicated or not tolerated.
Congestive Heart Failure: KRYSTEXXA has not been formally studied in patients with congestive heart failure, but some patients in clinical trials experienced exacerbation. Exercise caution when using KRYSTEXXA in patients who have congestive heart failure and monitor patients closely following infusion.
ADVERSE REACTIONS
The most common adverse reactions (occurring in at least 5% of KRYSTEXXA-treated patients) are gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis,
constipation, chest pain, anaphylaxis and vomiting.
Manufacturer:
Savient Pharmaceuticals
Pharmacological Class:
PEGylated uric acid specific enzyme.
Active Ingredient(s):
Pegloticase 8mg/mL (as uricase protein) in phosphate buffered saline; for IV infusion after dilution.
Indication(s):
Chronic gout in adult patients refractory to conventional therapy.
Pharmacology:
Pegloticase is a recombinant, modified mammalian urate oxidase conjugated to a form of polyethylene glycol. Pegloticase catalyzes the oxidation of uric acid to allantoin, thereby lowering serum uric acid. It is indicated for use in patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors or in those for whom these drugs are contraindicated.
Pegloticase should not be given to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency because they are at an increased risk of hemolysis and methemoglobinemia. To better manage gout flares, patients should be started on therapy with an NSAID or colchicine at least one week before treatment with pegloticase, continuing for at least 6 months when feasible. It is not necessary to discontinue treatment with pegloticase in the event of a gout flare.
Clinical Trials:
Two double-blind, placebo-controlled 6-month trials were conducted to assess the efficacy and safety of pegloticase (given once every 2 weeks or once every 4 weeks) in treating adults with chronic, refractory gout. Patients were pretreated with an oral antihistamine, intravenous corticosteroid, and acetaminophen, and they also received NSAIDs and/or colchicine beginning one week before treatment, unless contraindicated, to prevent gout flares. The primary endpoint in both studies was the proportion of patients who achieved plasma uric acid levels <6mg/dL for at least 80% of the time during months 3 and 6. Baseline criteria included serum uric acid ≥8mg/dL and at least 3 gout flares in the previous 18months or at least one gout tophus or gouty arthritis. A significantly greater proportion of patients treated biweekly with pegloticase achieved urate lowering to <6mg/dL than those given placebo. The benefit: risk profile was better with biweekly dosing.
Pegloticase effect on tophi was a secondary endpoint. The biweekly regimen was significantly better than placebo for the rate of tophus complete response (100% resolution of ≥1 target tophus with no new or progressive tophi).
Legal Classification:
Rx
Adults:
>18 years: Premedicate with antihistamines and corticosteroids. Give by IV infusion over at least 2 hours. 8mg once every 2 weeks. Slow rate, or stop and restart at lower rate, if infusion reaction occurs; observe at least 1hour post-infusion.
Children:
<18 years: not recommended.
Contraindication(s):
G6PD deficiency.
Warnings/Precautions:
Not for treating asymptomatic hyperuricemia. Screen patients at risk for G6PD deficiency (African or Mediterranean descent). Administer in healthcare setting by clinician prepared to manage infusion reactions and anaphylaxis. Monitor closely for anaphylaxis/ infusion reactions, esp. in patients receiving retreatment after a drug-free interval >4 weeks. CHF. Monitor serum uric acid levels before each infusion; consider discontinuing when levels >6mg/dL, particularly with 2 consecutive levels >6mg/dL (increased risk of anaphylaxis and infusion reactions). Pregnancy (Cat.C). Nursing mothers: not recommended.
Adverse Reaction(s):
Gout flares (prophylax with NSAIDs or colchicine), infusion reactions, GI upset, contusion, ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis, CHF exacerbation, antibody formation.
How Supplied:
Single-use vial—1
Last Updated:
8/12/2011
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产地国家: 美国
原产地英文商品名:
KRYSTEXXA 8mg/ml/vial
原产地英文药品名:
PEGLOTICASE
中文参考商品译名:
KRYSTEXXA 8毫克/毫升/瓶
中文参考药品译名:
聚乙二醇重组尿酸酶
生产厂家中文参考译名:
SAVIENT PHARMS
生产厂家英文名:
SAVIENT PHARMS | 
