Cosentyx (Secukinumab Injection)-成为首个白细胞介素-17A抑制剂
Pharmacological Class:
Interleukin-17A antagonist.

Active Ingredient(s):
Secukinumab 150mg/mL; soln for SC inj; and lyophilized pwd for SC inj after reconstitution; preservative-free.

Company
Novartis Pharmaceuticals Corp
Indication(s):
Moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

Pharmacology:
Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the 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. Secukinumab inhibits the release of proinflammatory cytokines and chemokines.

Clinical Trials:
Four multi-center, randomized, double-blind, placebo-controlled trials (Trials 1, 2, 3, and 4) enrolled 2,403 patients ≥18 years of age with plaque psoriasis who had minimum body surface area involvement of 10%, and Psoriasis Area and Severity Index (PASI) score ≥12, and who were candidates for phototherapy or systemic therapy.

For all trials, the endpoints were the proportion of patients who achieved a reduction in PASI score of ≥75% (PASI 75) from baseline to Week 12 and treatment success (clear or almost clear) on the Investigator's Global Assessment modified 2011 (IGA).

Other eva luated outcomes included the proportion of patients who achieved a reduction in PASI score of ≥90% (PASI 90) from baseline at Week 12, maintenance of efficacy to Week 52, and improvements in itching, pain, and scaling at Week 12 based on the Psoriasis Symptom Diary.

PASI 75 response at Week 12 was achieved with Cosentyx 300mg and 150mg compared to placebo in 82% and 71% vs. 4% of patients, respectively in Trial 1; 76% and 67% vs. 5% of patients, respectively in Trial 2; 75% and 69% vs. 0% of patients, respectively in Trial 3; and 87% and 70% vs. 3% of patients, respectively in Trial 4.

IGA outcomes of clear or almost clear were higher in the Cosentyx treatment groups vs. placebo groups across all four trials.

PASI 90 response at Week 12 was achieved with Cosentyx 300mg and 150mg compared to placebo in 59% and 39% vs. 1% of patients, respectively in Trial 1, and 54% and 42% vs. 2% of patients, respectively in Trial 2. Similar results were seen in Trials 3 and 4.

For more clinical trial data, see full labeling.

Legal Classification:
Rx

Adults:
Rotate inj site (eg, upper arms, thighs, or any quadrant of abdomen). ≥18 years: 300mg (given as two 150mg SC injections) at Weeks 0, 1, 2, 3, and 4 then 300mg every 4 weeks. For some patients, 150mg dose may be acceptable.

Children:
<18 years: not eva luated.

Warnings/Precautions:
Increased risk of infections. Chronic or history of recurrent infection. If a serious infection develops, monitor closely and discontinue until resolves. eva luate for TB infection prior to initiating; monitor for active TB during and after therapy. Patients with active TB infection: do not start. History of latent or active TB; consider anti-TB therapy prior to initiation. Active Crohn’s disease; monitor. Discontinue if anaphylaxis or serious allergic reactions occur. Latex allergy (Sensoready pen and prefilled syringe only). Pregnancy (Category B). Nursing mothers.

Interaction(s)
Concomitant live vaccines: not recommended. Non-live vaccines: may get suboptimal response. Monitor CYP450 substrates with narrow therapeutic index (eg, warfarin, cyclosporine); consider adjusting dose.

Adverse Reaction(s)
Nasopharyngitis, diarrhea, upper respiratory tract infection, rhinitis, oral herpes, pharyngitis, urticaria, rhinorrhea; Crohn’s disease exacerbation, hypersensitivity reactions, other serious infections.

How Supplied:
Single-use Sensoready pen—1, 2; Single-use prefilled syringe—1, 2; Single-use vial—1

LAST UPDATED:
6/26/2015
Cosentyx (secukinumab) 安全，有效为治疗牛皮癣患者
Novartis今天宣布了展示与Cosentyx™ (secukinumab)的新的两年的结果持续的效力与牛皮癣患者的处理的可接受的安全轮廓。 这个数据来自举足轻重的第III阶段夹具和抹除试算的扩展名研究。 结果在一个后中断的会议上第一次存在了在皮肤学 (AAD)的美国学院的第73次年会上在旧金山。 Cosentyx是被审批的只有第一个和白细胞介素17A (IL-17A)反对者治疗成人中等对严重匾牛皮癣患者。
“此两年的数据是重大的，因为它迄今表示从评估牛皮癣的处理的最长的持续第III阶段研究的结果一个 IL-17A反对者”，说安德鲁 Blauvelt、 MD、俄勒冈医学研究中心的工商管理硕士、总统和线索研究调查员。 “这个研究不仅加强对 Cosentyx效力和安全性的我们的了解，但是重申它是病人的一个重要新的更加长期的处理选项有中等对严重匾牛皮癣”。
在夹具和抹除研究的此扩展名，达到的995名患者牛皮癣地区严重级别索引(PASI)75回应在一年疗法以后(星期52)服用Cosentyx 300毫克、 Cosentyx 150毫克或者安慰剂一另外的年(星期 104)。 在二整年疗法以后， 7出于10名(70.6%)患者治疗与 Cosentyx 300 毫克有清楚对几乎清楚皮肤 (PASI 90); 4出于10(43.9%) 有清楚的皮肤 (PASI 100)和差不多9出于10名(88.2%)患者维护了他们的PASI 75回应在星期 104。
对于患者治疗与 Cosentyx 150毫克， 44.6%有清楚或几乎清楚皮肤(PASI 90); 23.5%有清楚的皮肤(PASI 100)，并且75.5% 维护了他们的 PASI 75回应在星期104。 PASI 通过评定对赤红、 psoriatic匾的比例缩放和厚度和介入的区域的减少在这个机体的每个区域估计处理效力。
在这个研究中，最初服用安慰剂的 94.8% 患者 (在扩展名的开始) 和被切换在复发以后接受 Cosentyx 300毫克，能达到PASI 75和70.3%达到的PASI 90在12个星期重新启动内 Cosentyx 处理。
“我们高兴地共享新的长期数据陈列 Cosentyx 帮助牛皮癣患者持续的效力和可接受的安全轮廓如何维护清楚地或几乎清楚皮肤在二年处理底”，说Vasant Narasimhan，发展全球经理，Novartis 配药。 “牛皮癣是导致发痒，称和痛苦的一个慢性情况; 患者需要提供替补和清楚的皮肤在一个长的时期的疗法”。
Cosentyx展示了可接受的安全轮廓。300毫克和(AEs)150条毫克处理胳膊的最公用的相反活动分别为 nasopharyngitis(24.1% 和17.0%)，上面的呼吸道传染(5.3%和5.0%)，高血压(4.3%和 5.2%)，头疼(5.6%和2.9%) 和关节痛 (4.0% 和 4.2%)。 传染和大批出没在接受Cosentyx 患者的300毫克和41.6% 53.1%患者中报告了接受150毫克。 有64(6.0%)严重的AEs(SAEs)在这个研究期间和没有死亡报告的所有Cosentyx剂量。