ST LOUIS (MD Consult) - On September 22, 2010, Novartis announced that the US Food and Drug Administration (FDA) has approved Gilenya (fingolimod) as a first-line treatment for relapsing forms of multiple sclerosis (MS). According to Novartis, Gilenya is the first oral medication approved for this indication.

 

Gilenya is considered a sphingosine 1-phosphate receptor modulator. Gilenya's mechanism of action in the treatment of MS is unknown. It is believed that the drug reduces the immune system's attack on the central nervous system by retaining lymphocytes in the lymph nodes, thus helping reduce demyelination. This action is reversible if Gilenya treatment is discontinued.

 

According to Novartis, Gilenya has a well-studied safety and tolerability profile, which has been characterized in over 2,600 clinical trial patients, some of whom are in their seventh year of treatment.

 

The FDA regulatory application for approval of Gilenya included data showing that use of the drug (at an oral dose of 0.5 mg daily) reduced relapses by 52% (P < .001) at 1 year compared with the use of intramuscularly administered interferon beta-1a (Avonex). Gilenya use was also associated with a reduction in disease activity as measured by the number of new and newly enlarged T2 lesions seen on magnetic resonance imaging, compared with the use of interferon beta-1a (1.6 vs 2.6, respectively, P = .002) at 1 year. In addition, data from a 2-year placebo-controlled study showed a reduction in relapse rate (54% reduction [P < .001] compared with placebo) and in the risk of disability progression among patients treated with Gilenya (30% reduction confirmed at 3-month follow-up visit [P = .02] compared with placebo).

 

The most common adverse effects experienced by patients receiving Gilenya were headache, influenza, diarrhea, back pain, cough, and abnormal liver studies.

 

Before treatment with Gilenya is started, consideration should be given to obtaining white blood cell counts and liver function studies. After the first dose, patients should be observed for 6 hours so that they may be appropriately monitored for serious adverse events.

 

Bradycardia can occur with the use of Gilenya and may be especially evident after the first dose. Bradycardia will usually resolve within approximately 1 month of Gilenya therapy. Patients should be instructed to contact their physician if they experience dizziness, fatigue, or heart rhythm disturbances.

 

Patients receiving Gilenya have an increased risk of serious infections, but this risk is ameliorated within about 2 months of stopping therapy. Patients should be advised to contact their physician immediately if they experience fever, fatigue, body aches, chills, nausea, or vomiting.

 

A patient's vision should be tested before starting Gilenya, after 3 to 4 months of treatment, or any time they notice vision changes during treatment because a risk for macular edema exists. This risk may be higher in patients with diabetes or uveitis. Patients should be advised to contact their physician if they experience blurred vision, shadows or blind spots in their visual field, light sensitivity, or changes in color perception.

圣路易斯(MD Consult) – 2010年9月22日，诺华宣布美国食品药品管理局(FDA)已批准了Gilenya (fingolimod)作为一线药物用于治疗复发型多发性硬化症。诺华称，Gilenya是首个被批准用于该症的口服药物。

 

Gilenya为鞘氨醇-1-磷酸受体调节剂，其治疗多发性硬化症的作用机制尚不清楚。据认为该药物通过将淋巴细胞保留在淋巴结中，减少免疫系统对中枢神经系统的攻击，从而有助于减少脱髓鞘作用。Gilenya停药后该作用是可逆的。

 

诺华称，Gilenya的安全性和耐受性得到了充分研究，在超过2,600例患者参与的临床试验中得以确认，其中部分患者已接受治疗7年。

 

向FDA提交的Gilenya申报资料显示，与肌肉注射干扰素β-1a (Avonex)相比，Gilenya（口服，每天0.5 mg）用药1年可减少52%的复发 (P < 0.001)；Gilenya用药还与疾病活动(以MRI所示新增和增大的T2病变数量作为指标) 降低具有相关性(分别为1.6 和 2.6， P = 0.002)。此外，一项为期两年的安慰剂对照研究数据显示，接受Gilenya治疗的患者复发率降低(与安慰剂相比降低54%  [P < 0.001])，残疾进展风险下降(与安慰剂相比，3个月随访确认下降30% [P =0 .02])。

 

服用Gilenya患者最常见不良反应是头痛、流行性感冒、腹泻、背痛、咳嗽以及肝功能异常。

 

在接受Gilenya治疗之前，应考虑进行白细胞计数和肝功能检测。首次服药后，应对患者观察6 h 以便对严重不良事件进行相应监测。

 

使用Gilenya可能出现心动过缓症状，特别是在首次服用之后。心动过缓症状通常在接受Gilenya治疗1个月之内消退。如果患者出现头晕、疲劳或心律不齐，应与医生联系。

 

服用Gilenya的患者其严重感染的风险增大，但是该风险在停药后2个月之内可得到改善。患者如果出现发热、疲劳、身体疼痛、寒颤、恶心或呕吐症状，建议患者应立即与医生联系。

 

由于存在黄斑水肿风险，患者在开始服用Gilenya之前、服药后3~4个月或在治疗期间视力出现变化的任何时候，均应进行视力检查。糖尿病或葡萄膜炎患者该风险可能较高。患者如果出现视物模糊、视野中出现阴影或盲斑、光敏感或光感变化，建议与医生联系。