The FDA has approved lesinurad (Zurampic) – to be used in combination with allopurinol (Zyloprim)或非布司他(Uloric) -用于治疗高尿酸血症相关的痛风．Lesiunard is the first in a new class of drugs called selective uric acid reabsorption inhibitors (SURIs) to be approved in the United States.
阿拉巴马大学伯明翰分校(UAB)的风湿病学家Jasvinder Singh医学博士说，这代表了对目前药物无法控制痛风患者的治疗的一个重要进步，他也是莱西纳尔德批准的临床试验的研究人员之一。痛风是一种痛苦的、可能使人衰弱的炎症性关节炎，影响着多达4%的美国成年人。
Lesinurad works in a novel way to lower blood levels of uric acid, a bodily waste product responsible for gout.When uric acid reaches high levels in the blood (hyperuricemia), the acid can leak out and deposit as crystals in the joints and other tissues, resulting in intense pain and swelling.在病程早期，痛风发作通常发生在一个关节，通常是大脚趾。Repeated attacks, or flares, can lead to irreparable damage of the affected joint(s) as well as interfere with a person’s quality of life and work productivity, says Dr. Singh, who is also a professor at UAB’s division of clinical immunology and rheumatology.
Acute gout attacks are treated with anti-inflammatory medications;however, drugs to lower uric acid are needed to prevent or lessen the frequency of subsequent attacks.Unlike most current gout medications, which decrease the body’s production of uric acid, lesinurad increases its excretion.The drug works by inhibiting a protein called urate transporter 1 (URAT1), which is responsible for the majority of uric acid reabsorption by the kidneys.This difference, says Dr. Singh, makes it possible to combine lesinurad with existing drugs, such as allopurinol or febuxostat – both known as xanthine oxidase inhibitors, or XOIs – to enhance the effects for people whose gout is not controlled by XOIs alone.
“A different mechanism is always something that allows us to combine drugs without having a similar side effect or toxicity profile,” says Dr. Singh.“It gives us more of an option.It also helps us understand the disease better, not only how to treat it better now, but it probably leads to more discovery down the path,” he says.
在两项III期研究中，与单独服用别嘌呤醇的患者相比，服用莱西脲(200mg或400mg剂量)和别嘌呤醇的患者在6个月时达到目标血清尿酸水平(低于6.0 mg/dL)的比例明显更高。辛格博士说:“这个目标很重要，因为研究表明，这个目标与疾病发作次数、成本、生产力损失以及人们如何应对这种疾病非常相关。”“这个水平是有意义的，保持在这个水平以下可以让人们更正常地工作。”
At 200 mg doses (the dose approved by the FDA), lesinurad compared favorably in safety to allopurinol alone, with a couple of exceptions, says Dr. Singh.The group taking lesinurad with allopurinol had worse numbers in a test that measures kidney function, which was reversible, and an increased risk of cardiovascular events.
The FDA is requiring the drug maker to continue to evaluate the kidney and cardiovascular safety of lesinurad in a postmarketing study.Dr. Singh says he also hopes to see studies of the drug in different populations to determine if more people can benefit from it.For now, he says, lesinurad is an important addition for people whose gout is not controlled by allopurinol alone.
北达科他州立大学药学实践系教授唐纳德·米勒(Donald Miller)对此表示赞同。“Lesinurad将为痛风患者提供一个重要的新选择，以获得更好的控制病情，”Miller说，他是FDA关节炎咨询委员会的成员，该委员会在10月以10比4的投票结果推荐批准Lesinurad与一种XOI联合治疗痛风相关的高尿酸血症。“它不是一线疗法，但当别嘌呤醇或非布司他单独使用不能控制高血尿酸水平时，可以添加到这些药物中。然而，重要的是，患者应该意识到应该采取的预防措施，如保持充足的水分，以避免肾结石的形成。”