药物名称：芬戈莫德（Gilenya）
适应症：多发性硬化症
生产厂家：诺华（Novartis）
简要说明：Gilenya可以阻止淋巴腺中的部分血细胞向大脑和脊髓移动，降低多发性硬化症患者疾病复发的频率，从而延缓多发性硬化症患者的病情恶化程度。作为多发性硬化症的首个口服药物。
药理作用：
芬戈莫德块淋巴细胞离开淋巴结肿大，外周血淋巴细胞的数量减少。在MS的影响的确切机制尚不清楚，但它可能涉及中枢神经系统的淋巴细胞迁移减少。
不良反应：
头痛，感冒，腹泻，腰痛，增加肝转氨酶，咳嗽，高血压;瞬态降低心率和房室传导，增加感染的风险，黄斑水肿，肺功能下降。
Manufacturer:
Novartis Pharmaceuticals Corp
Pharmacological Class:
Sphingosine 1-phosphate receptor modulator.
Active Ingredient(s):
Fingolimod (as HCl) 0.5mg; caps.
Indication(s):
For relapsing forms of multiple sclerosis (MS): to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.
Pharmacology:
Fingolimod blocks lymphocytes from leaving lymph nodes, reducing the numbers of circulating lymphocytes. The exact mechanism for its effects on MS is not known, but it may involve the reduction of lymphocyte migration in the CNS.
Clinical Trials:
Two studies were conducted to assess the safety and efficacy of fingolimod in treating patients with relapsing remitting MS. Study 1 was a placebo-controlled study in patients who had not received interferon-beta or glatiramer acetate for at least the previous 3 months and had not received natalizumab for at least the previous 6 months. The primary endpoint was the annualized relapse rate. At randomization, patients had an Expanded Disability Status Score (EDSS) ranging from 0–5.5 (median 2.0). Patients given fingolimod 0.5mg daily had an annualized response rate of 0.18, compared to 0.4 for those given placebo. Seventy percent of patients in the fingolimod 0.5mg group were relapse-free, compared to 46% for placebo. The 1.25mg dose did not show any additional benefit.
Study 2 was a double-dummy, active-controlled study in patients who had not received any natalizumab in the previous 6 months; prior therapy with glatiramer acetate or interferon-beta was permitted up to the time of randomization. The median baseline EDSS score was 2.0. Patients were randomized to fingolimod 0.5mg/day, fingolimod 1.25mg/day, or interferon beta-1a 30mcg IM once weekly for up to 12 months. The annualized relapse rate for patients given fingolimod 0.5mg/day was 0.16, compared to 0.33 for those given interferon. Eighty-three percent of those on fingolimod 0.5mg were relapse-free, compared to 70% of those on interferon. There was no additional benefit seen with fingolimod dosed at 1.25mg daily. A secondary endpoint, the number of new or enlarging T2 lesions seen on MRI, showed an advantage for fingolimod as well.
Legal Classification:
Rx
Adults:
≥18years: 0.5mg once daily. Monitor 1st dose (6 hours).
Children:
<18years: not recommended.
Warnings/Precautions:
Active acute or chronic infection: do not start treatment until infection resolved. Obtain recent CBC before starting treatment. Consider suspending therapy if serious infection develops; monitor for infections during treatment and for 2 months after discontinuation. Test for antibodies to varicella zoster virus; consider immunization before starting fingolimod. Immunosuppressed. Cardiac risk factors: monitor for bradycardia for 6 hours after 1st dose; consider baseline ECG. Bradycardia (<55bpm). History of syncope. Sick sinus syndrome. 2nd or 3rd degree heart block. Cardiac ischemia. CHF. QT prolongation. Arrhythmias. Diabetes, history of uveitis: increased risk of macular edema. Monitor visual acuity and for visual disturbances. Do ophthalmic exam at baseline, and at 3–4 months after starting therapy. Recent LFTs (eg, within 6 months) should be available; monitor; discontinue if liver injury occurs. Respiratory dysfunction. Renal or severe hepatic impairment. Pregnancy (Cat.C) (use effective contraception during and for 2 months after discontinuation), nursing mothers: not recommended.
Interaction(s):
Potentiated by ketoconazole. Class Ia (eg, quinidine, procainamide) or Class III antiarrhythmics (eg, amiodarone, sotalol), β-blockers, calcium channel blockers: increased risk of bradycardia. Avoid live virus vaccines during treatment and for 2 months after discontinuing fingolimod; may have suboptimal response. Caution with antineoplastic, immunosuppressant or immunomodulating therapies: increased risk of immunosuppression.
Adverse Reaction(s):
Headache, influenza, diarrhea, back pain, increased liver transaminases, cough, hypertension; transient decreased heart rate and AV conduction, increased infection risk, macular edema, decreased pulmonary function.
How Supplied:
Caps—7, 28
Gilenya(盐酸芬戈莫德)-多发性硬化症更强效新药上市
美国食品和药物管理局（FDA）批准诺华制药公司（Novartis）生产的新型多发性硬化症的治疗药物—Gilenya(盐酸芬戈莫德)上市销售。盐酸芬戈莫德是世界上第一个治疗多发性硬化症的药丸性药物。
盐酸芬戈莫德适用于复发性多发性硬化症患者(MS)的治疗减少临床加重频数和延缓身体残疾积蓄。推荐剂量为0.5 mg口服每天1次。首次剂量后应观察患者6小时以监查心动过缓的征象和症状。芬戈莫德剂量较高于0.5 mg是伴随更高不良反应发生率而效益没有增加。
芬戈莫德是一种鞘氨醇1-磷酸受体(S1PR)调节剂。药理研究证实，芬戈莫德可以作用于位于淋巴细胞上的鞘氨醇1-磷酸受体，致使循环中的淋巴细胞在淋巴结内滞留，从而减少自身反应性淋巴细胞再次进入循环的几率，进而防止这些细胞浸润中枢神经系统(CNS)。据该药的制药商诺华制药公司介绍称，芬戈莫德这种药理作用过程是可逆的，如果停止用药，循环中的淋巴细胞水平就会恢复正常。
多发性硬化症是一种使人衰弱的神经系统疾病，可能导致病人失去平衡感，出现肌肉痉挛和其他运动功能障碍，该疾病一直以来都用注射性药物进行治疗。该疾病还没有治愈的案例，但类固醇药物能在短期内减少病情的持续时间和症状的严重程度，在市场上的已经有7种药物能够成功减少症状的复发。但是，这些药物都需要每日或定期注射，给患者用药带来极大的不便。
临床II期试验数据显示，在试验的前六个月当中，每天服用一次盐酸芬戈莫德的试验组相对于服用安慰剂对照组来说可以降低80％的炎症（实验结果由磁共振成象仪器测得），也至少能够减少50％的复发率。之后的六个月当中，继续服用盐酸芬戈莫德的病人炎症活动和复发率保持在一个较低的水平，同样的结果也出现在试验后期由服用安慰剂转服盐酸芬戈莫德的病人身上。
在两项总计纳入超过2,500例复发-缓解型MS患者的研究中，研究者对芬戈莫德(给药剂量为0.5与1.25mg/d)和安慰剂或干扰素β-1a进行了对比，两项研究的主要终点均为年化复发率，其中一项研究的评估时间在研究开始1年后，另一项则在研究开始2年后。在两项研究中，与安慰剂或干扰素β-1a相比，盐酸芬戈莫德在两种给药剂量下均能使患者的复发率显著降低，并减缓患者肢体残疾的病程进展速度。
多发性硬化症是目前医学上公认的难治性疾病，现行一线治疗多发性硬化的药物，只能减少复发率30%左右。盐酸芬戈莫德的出现，打破了现行一线治疗多发性硬化的药物全是注射剂的局面，给患者自行用药带来了极大的方便，更有利于患者长期治疗，并能提高疗效，更好改善患者症状，提高生活质量，为是人类治疗多发性硬化历史上的一个新的里程碑。