FDA批准戈利木单抗静脉输液剂用于治疗类风湿性关节炎

7月18日，美国食品药品管理局(FDA)宣布，已批准戈利木单抗(golimumab)输液剂联合甲氨蝶呤用于治疗中至重度活动性类风湿性关节炎(RA)成人患者。

该批准令为这一RA药物增加了新的适应证。最初，FDA于2009年批准每月1次皮下注射戈利木单抗用于治疗中至重度活动性RA、活动性银屑病关节炎和活动性强直性脊柱炎，以商品名Simponi上市。此次批准的输液剂将以商品名Simponi Aria上市。

生产商杨森生物技术公司推荐的给药方案为：第0周和第4周以及此后每8周静脉输注给药1次，剂量为2 mg/kg ，输注时间为30分钟以上。

该公司总裁Rob Bazemore指出，这一给药方案可改善患者的输液体验。“患者现在可在较短的30分钟内接受该输液剂与抗-TNF药物的联合治疗，每8周1次。”

但加州大学洛杉矶分校风湿病学教授Daniel E. Furst博士指出，这项新的批准令对于患者在治疗选择方面并无重大影响，而更多的是给杨森带来市场利益。对于30分钟的输注时间，Furst博士认为，这可能对于部分患者具有吸引力，但与其他同类药物的输注时间相比并无显著缩短。Furst博士曾参与了多个TNF抑制剂和非TNF抑制药物的临床试验。

根据杨森公司的声明，这项批准令是基于一项名为GO-FURTHER(抗TNF-α单抗戈利木单抗联合甲氨蝶呤静脉给药治疗活动性RA) 的Ⅲ期临床试验结果。结果显示，戈利木单抗可显著该改善RA患者体征和身体功能，减缓结构性损伤进展。

在这项多中心、双盲、安慰剂对照研究中，研究者评估了592例中至重度活动性RA成人患者的治疗情况。这些患者在筛查和基线时压痛关节和肿胀关节数均至少为6个，C-反应蛋白(CRP)水平升高且至少接受了3个月的甲氨蝶呤治疗。

研究者发现，14周时近60%的戈利木单抗+甲氨蝶呤治疗患者体征显著改善，即达到美国风湿病学会提出的至少20%的改善标准(ACR 20)，这也是该研究的主要终点指标。与之相比，在接受安慰剂+甲氨蝶呤治疗的患者中，该比例仅为25%。

戈利木单抗静注患者(53%)的不良事件报告率略高于安慰剂组(49%)。0.9%的戈利木单抗静注患者出现与感染有关的严重不良事件，包括1例肺结核病例和1例社区获得性肺炎继发心梗死亡病例。安慰剂组未见严重感染病例。

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By: MARY ELLEN SCHNEIDER, Internal Medicine News Digital Network

The Food and Drug Administration has approved a new infusion-version of golimumab, in combination with methotrexate, for the treatment of adults with moderately to severely active rheumatoid arthritis.

The approval, which was announced on July 18, provides another indication for the RA drug. The FDA originally approved golimumab in 2009 as a once-monthly subcutaneous injection treatment for moderately to severely active RA, active psoriatic arthritis, and active ankylosing spondylitis. The injection version of the drug was marketed under the name Simponi, while the new infusion version will go by the trade name Simponi Aria.

The drug’s manufacturer, Janssen Biotech, recommends a dosing regimen of 2 mg/kg given as an intravenous infusion at weeks 0 and 4, then every 8 weeks after. Infusions are given over a 30-minute period.

The dosing regimen allows for an improved infusion experience, Rob Bazemore, president of Janssen Biotech, said in a statement. "Patients can now receive this form of treatment administration with an anti-TNF therapy via a short infusion time of 30 minutes with a dosing regimen of every 8 weeks," he said.

But Dr. Daniel E. Furst, professor of rheumatology at the University of California, Los Angeles, said the latest approval won’t make a major difference in terms of treatment options for patients. The approval is more of a marketing boon for Janssen, which will be able to tout its availability as an infusion. As for the 30-minute infusion time, Dr. Furst said it is likely to appeal to some patients but is not significantly shorter than other infusion times.

"It really doesn’t make a big difference," said Dr. Furst, who performs clinical trial work for several TNF inhibitor drugs and non-TNF inhibitor drugs.

The latest approval was supported by the results of the phase III trial known as GO-FURTHER (Golimumab, an Anti-TNF-alpha Monoclonal Antibody, Administered Intravenously, in Subjects with Active Rheumatoid Arthritis Despite Methotrexate Therapy). The trial showed that the drug significantly improved the signs and symptoms of RA, improved physical function, and slowed the progression of structural damage, according to a statement from Janssen.

In the multicenter, double-blind, placebo-controlled study, researchers evaluated 592 adults with moderately to severely active RA who had at least six tender and six swollen joints at screening and baseline, as well as elevated C-reactive protein (CRP) levels at screening, and who had been receiving background methotrexate for at least 3 months.

They found that at week 14, nearly 60% of the patients who received golimumab plus methotrexate had significant improvements in their signs and symptoms, as determined by at least a 20% improvement in American College of Rheumatology criteria (ACR 20), the study’s primary endpoint. In comparison, only 25% of patients receiving placebo plus methotrexate had at least an ACR 20 response.

Adverse events were reported slightly more often among patients receiving IV golimumab (53%) than among patients receiving placebo (49%). Serious adverse events involving an infection were observed in 0.9% of IV golimumab patients, including one case of tuberculosis and one death from myocardial infarction secondary to community-acquired pneumonia. No serious infections occurred in placebo-treated patients.
 

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