近日,FDA批准Taltz（ixekizumab）注射液用于适合系统治疗（systemic therapy，即全身疗治）或光疗（phototherapy）的中度至重度斑块型银屑病（plaque psoriasis）成人患者的治疗。
ixekizumab是一种单克隆抗体，针对具有促炎作用的细胞因子白介素-17A（IL-17A）具有较高的亲和力和特异性，可抑制IL-17A与IL-17受体的结合。对于银屑病患者而言，IL-17A在驱动角化细胞（皮肤细胞）过度增殖和活化方面发挥了重要作用。ixekizumab不会与细胞因子IL-17B、IL-17C、IL-17D、IL-17E或IL-17F相结合。Ixekizumab通过皮下注射给药。
批准日期：2016年3月25日 公司：礼来公司
TALTZ（伊沙珠单抗[ixekizumab]）注射液，用于皮下注射
美国最初批准：2016年
最近的重大变化
适应症和用法：
银屑病关节炎：12/2017
剂量和给药：
银屑病关节炎：12/2017
警告和注意事项：
感染：12/2017
过敏症：07/2017
免疫：12/2017
作用机制
伊沙珠单抗是人源化IgG4单克隆抗体，其选择性地与白细胞介素17A（IL-17A）细胞因子结合并抑制其与IL-17受体的相互作用。
IL-17A是天然存在的细胞因子，参与正常的炎症和免疫反应。Ixekizumab抑制促炎细胞因子和细胞因子的释放趋化因子。
适应症和用法
TALTZ是一种人源化白细胞介素-17A拮抗剂，适用于治疗成人：
•中度至重度斑块状银屑病，可作为全身治疗或光疗的候选者。
•活动性银屑病关节炎。
剂量和给药
斑块状牛皮癣
•通过皮下注射给药。
•推荐剂量在第0周时为160 mg（两次80 mg注射），然后在第2,4,6,8,10和12周时为80mg，然后在第4周时为80m。
银屑病关节炎
•在第0周通过皮下注射（两次80mg注射）推荐剂量为160mg，然后每4周注射80mg。
•对于同时存在中度至重度斑块状银屑病的银屑病关节炎患者，使用剂量方案治疗斑块状银屑病。
•TALTZ可以单独给药或与常规DMARD（例如甲氨蝶呤）联合给药。
剂量形式和强度
自动注射器
•注射：单剂量预填充自动注射器中的80mg/mL溶液。
预充式注射器
•注射：单剂量预充式注射器中的80mg/mL溶液。
禁忌症
对ixekizumab或任何接受者的严重超敏反应。
警告和注意事项
•感染：发生严重感染。如果出现临床上重要的慢性或急性感染的体征或症状，请指导患者提供医疗建议。如果发生严重感染，请停止TALTZ直至感染消退。
•结核病（TB）：在开始治疗前评估结核病。
•过敏反应：如果发生严重的过敏反应，立即停止TALTZ并开始适当的治疗。
•炎症性肠病：临床试验期间发生克罗恩病和溃疡性结肠炎，包括恶化。
应密切监测用TALTZ治疗并患有炎症性肠病的患者。
不良反应
与TALTZ治疗相关的最常见（≥1％）不良反应是注射部位反应，上呼吸道感染，恶心和癣感染。
要报告疑似不良反应，请致电1-800-545-5979（1-800-LillyRx）或FDA 1-800--FDA-1088或www.fda.gov/medwatch联系Eli Lillyand公司。
药物相互作用
活疫苗：不应使用TALTZ给活疫苗。
包装提供/存储和处理
如何提供
TALTZ注射液是一种无菌，不含防腐剂，透明，无色至微黄色的溶液，可在单一剂量下使用预填充自动注射器或单剂量预填充注射器以递送80mg伊西珠单抗。
TALTZ提供：
                  包装尺寸      NDC代码
自动进样器   
80毫克单剂量      纸箱1        0002-1445-11
80毫克单剂量      纸箱2        0002-1445-27
80毫克单剂量      纸箱3        0002-1445-09
预装注射器
80毫克单剂量      纸箱1        0002-7724-11
存储和处理
TALTZ无菌且不含防腐剂。丢弃任何未使用的部分。
•使用前必须保护TALTZ避光。
•冷藏温度为2°C至8°C（36°F至46°F）。
•如果需要，患者/护理人员可将TALTZ在室温下储存至30°C（86°F），在原包装箱中储存最多5天，以防光照。一旦TALTZ在室温下储存，请不要在5天内返回冰箱并丢弃（如果未使用）。
•记录TALTZ首次从纸箱中提供的空间中取出的日期。
•对于2或3个自动注射器包，一次取出一个自动注射器，将剩余的自动注射器留在冰箱中的原始纸盒中。确保未冷藏的TALTZ免受光照。
•不要冻结。如果TALTZ已被冷冻，请勿使用。
•不要摇晃。
•使用后，将TALTZ单剂量自动注射器或注射器丢弃在防刺穿容器中。
•不是用天然橡胶乳胶制成的。
完整说明资料附件：http://pi.lilly.com/us/taltz-uspi.pdf
Taltz® (ixekizumab) Receives U.S. FDA Approval for the Treatment of Moderate-to-Severe Plaque Psoriasis
U.S. Food and Drug Administration (FDA) has approved Taltz® (ixekizumab) injection 80 mg/mL for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. Taltz should not be used in patients with a previous hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients. Taltz is designed to specifically target IL-17A, a protein that plays a role in driving underlying inflammation in psoriasis.1
Psoriasis is a chronic, immune disease that affects the skin.2 Psoriasis affects approximately 7.5 million Americans, approximately 20 percent of whom have moderate-to-severe plaque psoriasis.3 Plaque psoriasis is the most common form of the condition and appears as raised, red patches of skin covered with a silvery, white buildup of dead skin cells, which are often painful or itchy.3,4 The exact cause of psoriasis is unknown, though genetics and environmental factors are known to play a role in the development of the disease.3
"Many people living with psoriasis are still looking for a treatment that will successfully manage the magnitude of this disease," said Alex Azar, president, Lilly USA, LLC. "With the approval of Taltz, we are proud to provide patients with a new treatment that may help patients experience virtually or completely clear skin."
The FDA approval of Taltz was based on findings from the largest Phase 3 trial program approved to date—more than 3,800 patients with moderate-to-severe plaque psoriasis from 21 countries.5 This number includes patients who began the trial on Taltz or placebo, or active comparator (U.S.-approved etanercept).6 This clinical program included three double-blind, multicenter, Phase 3 studies—UNCOVER-1, UNCOVER-2 and UNCOVER-3—which demonstrated the safety and efficacy of Taltz in patients with moderate-to-severe plaque psoriasis. All three studies eva luated the safety and efficacy of Taltz (80 mg every two weeks, following a 160-mg starting dose) compared to placebo after 12 weeks. UNCOVER-2 and UNCOVER-3 included an additional comparator arm in which patients received U.S.-approved etanercept (50 mg twice a week) for 12 weeks. UNCOVER-1 and UNCOVER-2 also eva luated response rates with Taltz during the maintenance period through 60 weeks.
In these studies, the co-primary efficacy endpoints at 12 weeks were a 75 percent improvement in the composite Psoriasis Area Severity Index (PASI) score and static Physician's Global Assessment (sPGA) 0 or 1 and at least a 2-point improvement from baseline. PASI measures the extent and severity of psoriasis by assessing average redness, thickness and scaliness of skin lesions (each graded on a zero to four scale), weighted by the body surface area of involved skin, while the sPGA is the physician's assessment of severity of a patient's psoriasis lesions overall at a specific point in time and is a required measure the FDA uses to eva luate effectiveness.6
In all three studies, at 12 weeks, 87 to 90 percent of patients treated with Taltz saw a significant improvement of their psoriasis plaques (PASI 75).  In addition, 81 to 83 percent of patients treated with Taltz achieved sPGA 0 or 1. The majority of patients treated with Taltz, 68 to 71 percent, achieved virtually clear skin (PASI 90) and 35 to 42 percent of patients saw complete resolution of their psoriasis plaques (PASI 100, sPGA 0). Among those patients treated with placebo, 7 percent or fewer achieved PASI 75, 7 percent or fewer achieved sPGA 0 or 1, 3 percent or fewer achieved PASI 90 and 1 percent or fewer achieved PASI 100 and sPGA 0.
In UNCOVER-1 and UNCOVER-2, of patients who responded to Taltz (sPGA 0 or 1 and at least a 2-point improvement from baseline) at 12 weeks, 75 percent consistently maintained that response at the 60-week endpoint.
Taltz was also statistically superior to U.S.-approved etanercept at all skin clearance levels, including PASI 75 and sPGA 0 or 1 at 12 weeks. In an integrated analysis of the U.S. sites in the two active comparator studies—UNCOVER-2 and UNCOVER-3—the respective response rates for Taltz vs. U.S.-approved etanercept were 87 percent vs. 41 percent for PASI 75 and 73 percent vs. 27 percent for sPGA 0 or 1.
Information regarding the safety of Taltz is drawn from a database of 4,204 patients with moderate-to-severe plaque psoriasis who volunteered in both controlled and uncontrolled clinical trials.
Taltz may increase the risk of infection. Patients treated with Taltz had a higher rate of infections than patients treated with placebo (27 percent vs. 23 percent). Upper respiratory tract infections, oral candidiasis, conjunctivitis and tinea infections occurred more frequently in patients treated with Taltz compared to placebo. Serious infections have occurred. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue Taltz until the infection resolves.
Other warnings and precautions for Taltz include pre-treatment eva luation for tuberculosis, hypersensitivity reactions, inflammatory bowel disease and immunizations. See Important Safety Information below.
In UNCOVER-2 and UNCOVER-3, the rate of serious adverse events during the controlled induction period (weeks 0-12) was 0.7 percent for U.S.-approved etanercept and 2 percent for Taltz, and the rate of discontinuation from adverse events was 0.7 percent for U.S.-approved etanercept and 2 percent for Taltz. The incidence of infections was 18 percent for U.S.-approved etanercept and 26 percent for Taltz. The rate of serious infections was 0.3 percent for both U.S.-approved etanercept and Taltz.
"Complete clearance of skin plaques is an important treatment goal for psoriasis," said Craig Leonardi, M.D., lead study author and clinical professor of dermatology at St. Louis University School of Medicine. "With Taltz, physicians now have a choice that can help patients achieve virtually clear or completely clear skin; in fact, four out of 10 achieved completely clear skin. With these study results, physicians can reassure patients that consistent results can be maintained with Taltz."
Indications and Usage
Taltz® is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
Taltz is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients.
WARNINGS AND PRECAUTIONS
Infections
Taltz may increase the risk of infection. The Taltz group had a higher rate of infections than the placebo group (27% vs. 23%). Serious infections have occurred. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue Taltz until the infection resolves.
Pre-Treatment eva luation for Tuberculosis
eva luate patients for tuberculosis (TB) infection prior to initiating treatment with Taltz. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Taltz. Patients receiving Taltz should be monitored closely for signs and symptoms of active TB during and after treatment.
Hypersensitivity
Serious hypersensitivity reactions, including angioedema and urticaria (each <</span> 0.1%), occurred in the Taltz group in clinical trials. If a serious hypersensitivity reaction occurs, discontinue Taltz immediately and initiate appropriate therapy.
Inflammatory Bowel Disease
Crohn's disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the Taltz group (Crohn's disease 0.1%, ulcerative colitis 0.2%) than in the placebo group (0%) during clinical trials. During Taltz treatment, monitor patients for onset or exacerbations of inflammatory bowel disease.
Immunizations
Prior to initiating therapy with Taltz, consider completion of all age appropriate immunizations according to current immunization guidelines. Live vaccines should not be given with Taltz.
ADVERSE REACTIONS
Most common adverse reactions (>1%) associated with Taltz treatment are injection site reactions, upper respiratory tract infections, nausea, and tinea infections.
See accompanying Prescribing Information and Medication Guide. See Instructions for Use included with the device.
IX HCP ISI 22MAR2016
About Taltz®
Taltz® (ixekizumab) is a humanized IgG4 monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses.  Taltz inhibits the release of pro-inflammatory cytokines and chemokines.
About the UNCOVER Studies
The UNCOVER-1, UNCOVER-2 and UNCOVER-3 studies are double-blind, multicenter, Phase 3 studies eva luating more than 3,800 patients with moderate-to-severe plaque psoriasis from 21 countries. All three studies eva luated the safety and efficacy of different dosing regimens of Taltz (80 mg every two or four weeks, following a 160-mg starting dose) compared to placebo after 12 weeks. UNCOVER-2 and UNCOVER-3 included an additional comparator arm in which patients received U.S.-approved etanercept (50 mg twice a week) for 12 weeks. In UNCOVER-1 and UNCOVER-2, safety and efficacy of Taltz was further eva luated through 60 weeks.
About Moderate-to-Severe Plaque Psoriasis
Psoriasis is a chronic, immune disease that affects the skin.3 It occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells.3 It is the most common inflammatory disease in the United States, affecting as many as 7.5 million Americans and an estimated 125 million people worldwide.3 The most common form of psoriasis, plaque psoriasis, appears as raised, red patches covered with a silvery white buildup of dead skin cells.3 Approximately 20 percent of people with psoriasis have moderate-to-severe plaque psoriasis.