比利时UCB公司宣布，已收到美国FDA关于新药Cimzia（certolizumab pegol）的生物制剂新药上市申请的回复函。该药为第一个用聚乙二醇修饰的抗肿瘤坏死因子药物，用于治疗类风湿性关节炎。
作为批准Cimzia上市的前提条件，FDA要求UCB公司提供更新的、可靠的临床研究资料，包括从申请生物制剂上市许可以来的最新数据。

UCB公司表示，Cimzia可适用于中到重度类风湿性关节炎患者及其他炎性疾病，UCB公司一定会尽力达到FDA的要求。2008年2月，UCB公司向FDA递交该药治疗类风湿性关节炎的生物制剂上市申请之前，已进行了包含超过2300名受试者的多中心对照Ⅲ期临床试验。

2008年4月，美国FDA已批准Cimzia用于治疗对传统治疗方法不敏感的克罗恩病中到重度患者。其治疗克罗恩病的效果在瑞士也得到了认可。目前，欧洲EMEA正在对Cimzia治疗类风湿性关节炎的效用进行积极审查
      
UCB公司的单克隆抗体Cimzia对克罗恩病有疗效
根据初步临床研究的结果,由优时比(UCB)公司研制的一种单隆抗体——Cimzia(certolizumab pegol,赛妥珠单抗)可以减轻采用常规治疗不能完全缓解病情的成年中、重度克罗恩病(Crohn′sdisease,又称局限性回肠炎、局限性肠炎、节段性肠炎和肉芽肿性肠炎)活动期病人的临床症状,而且该药对于那些不能耐受英利昔单抗(infliximab, Centocor公司的产品,商品名为Remicade)或使用英利昔单抗无效的病人也有一定疗效。

- UCB公司的单克隆抗体Cimzia对克罗恩病有疗效_
         
Cimzia与英利昔单抗和雅培(Abbott)公司的阿达木单抗(adalimumab,商品名为Humira)一样,也是一种肿瘤坏死因子(TNF)抑制剂,可缓解克罗恩病症状。目前用于治疗克罗恩病的生物制剂常会在病人使用一段时间后失效,无法阻止病情的发展,而且病人还会对这些特殊的生物制剂产生免疫介导反应。因而此时医生通常需使用一系列的药物,并且在几种药物之间不断地进行更换。
         
此次名为“Welcome研究”的临床试验对象为539名曾对英利昔单抗产生应答、但现已不再产生应答或是因为急性或迟发性输液反应而对其不能耐受的病人,研究分为两期:一是开标记诱导期,即在试验开始、2周和4周时分别给予赛妥珠单抗400mg；然后是双盲维持期,即连续6～24周使用赛妥珠单抗400 mg。试验的首个终点指标为:用药第6周时,病人的克罗恩病活动指数(Crohnsdisease activity index, CDAI)至少降低至100,若降低至150则可视为症状缓解。

初步研究结果显示,用药6周后,有62.2%的病人对赛妥珠单抗产生了应答, 39.3%的病人症状减轻;而在用药第2周,产生应答的病人比例即达到33.2%,在第4周时,有43.8%的病人产生了应答。

这一结果与另一项名为“Precise 2 试验”的结果(病人应答率为64%)相近。由于参加Precise 2试验的病人在使用赛妥珠单抗前并未使用过英利昔单抗,故这两项研究的结果提示,赛妥珠单抗对使用过英利昔单抗的病人仍有较好疗效。
Manufacturer:
UCB, Inc.
Pharmacological Class:
Tumor necrosis factor (TNF) blocker
Active Ingredient(s):
Certolizumab pegol 200mg/vial; pwd for SC inj after reconstitution;
preservative-free.
Indication(s):
In moderately to severely active Crohn's disease: to reduce signs and
symptoms and to maintain clinical response in adult patients with inadequate response to conventional therapy.
Pharmacology:
Elevated levels of TNFα have been implicated in the pathology of Crohn's disease. Certolizumab pegol is a recombinant, humanized antibody Fab'fragment that has an affinity for human TNFα, a proinflammatory cytokine that plays a key role in the inflammatory process.
TNFα stimulates the production of interleukin-1, prostaglandins, platelet activating factor, and nitric oxide. After treatment with certolizumab pegol, patients with Crohn's disease had a decrease in C-reactive protein.
Clinical Trials:
Two placebo-controlled trials were conducted in patients with moderately to severely active Crohn's disease. In the first study, 662 patients were given either certolizumab pegol 400mg or placebo at weeks 0, 2, 4, and then every 4 weeks to week 24. At week 6, the proportion of clinical responders in patients on the study drug was 35%, compared to 27% for placebo; clinical remission was noted in 22% of patients given the study drug versus 17% for those given placebo. The difference in the proportion of patients who were in clinical response at weeks 6 and 26 was also significant (23% vs. 16%), indicating a maintenance of clinical response.
Legal Classification:
Rx
Adults:
Give by SC inj in abdomen or thigh. 400mg (two 200mg inj) on day 1, then at weeks 2 and 4; maintenance 400mg every 4 weeks.
Children:Not recommended.
      
Precaution(s):
Active infections: not recommended. Chronic or history of recurring infections. Conditions that predispose to infection.
Test for tuberculosis, treat TB first. Monitor closely for new infections, discontinue if serious infection develops. History of TB or histoplasmosis exposure.
Immunosuppressed. Hepatitis B infection; discontinue if reactivation occurs. Malignancies. CNS demyelinating disorders.
Hematological abnormalities. CHF. Discontinue if lupus-like syndrome or serious hypersensitivity reaction occurs. Pregnancy (Cat.B). Nursing mothers:
not recommended.
Interaction(s):
Concurrent anakinra, live vaccines or other TNF blockers: not recommended.
Immunosuppressants increase risk of infection. May interfere with coagulation tests (eg, aPPT).
Adverse Reaction(s):
Upper respiratory infections, UTI, arthralgia, other infections; rare: TB, HBV reactivation, hypersensitivity reactions, malignancies, antibody formation.

How Supplied:
Kit—1 (2 single-dose vials w. syringes, needles, supplies)

Last Updated:
1/15/2

What is CIMZIA? CIMZIA is a medicine called a tumor necrosis factor (TNF)-blocker. CIMZIA is used in adult patients to: Lessen the signs and symptoms of moderately to severely active Crohn’s disease (CD) in adults who have not been helped enough by usual treatments Treat moderately to severely active rheumatoid arthritis (RA) What is the most important information I should know about CIMZIA? CIMZIA is a medicine that affects your immune system. CIMZIA can lower the ability of the immune system to fight infections. Serious infections have happened in patients taking CIMZIA, including tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients have died from these infections. Your doctor should test you for TB before starting CIMZIA Your doctor should monitor you closely for signs and symptoms of TB during treatment with CIMZIA Before starting CIMZIA, tell your doctor about all of your medical conditions, including if you: Think you have an infection. You should not start taking CIMZIA if you have any kind of infection (See "What is the most important information I should know about CIMZIA?") Are being treated for an infection Have signs of an infection, such as a fever, cough, or flu-like symptoms Have any open cuts or sores on your body Get a lot of infections or have infections that keep coming back Have diabetes Have HIV Have TB, or have been in close contact with someone with TB Were born in, lived in, or traveled to countries where there is more risk of getting TB. Ask your doctor if you are not sure Live or lived in certain parts of country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections(histoplasmosis,coccidioidomycosis,blastomycosis). These infections may develop or become severe if you take CIMZIA. If you do not know if you have lived in these types of areas, ask your doctor Have or have had hepatitis B Have or have had any type of cancer Have congestive heart failure Have seizures, any numbness or tingling, or a disease that affects your nervous system such as multiple sclerosis Are scheduled to receive a vaccine. Do not receive a live vaccine while taking CIMZIA Arepregnant,planning to become pregnant, or breastfeeding. CIMZIA has not been studied in pregnant or nursing women Are allergic to any of the ingredients in CIMZIA Are taking any medicines, including prescription and nonprescription medicines, vitamins, and herbal supplements. Your doctor will tell you if it is okay to take your other medicines while taking CIMZIA Especially tell your doctor if you take: Kineret® (anakinra), Orencia® (abatacept),Rituxan® (rituximab), Tysabri® (natalizumab). You have a higher chance for serious infections when taking CIMZIA with these medicines A TNF-blocker:Remicade® (infliximab), Humira® (adalimumab), Enbrel® (etanercept) How should I use CIMZIA? CIMZIA is available as a lyophilized powder for reconstitution or in a prefilled syringe. If your doctor prescribes the lyophilized pack, CIMZIA should be injected by a healthcare provider. If your doctor prescribes the prefilled syringe, see the section "Patient Instructions for Use" at the end of the Medication Guide for complete instructions for use. Do not give yourselfaninjection of CIMZIA unless you have been shown how by your doctor or nurse—or they can train someone you know to help you with your injection. CIMZIA is given by an injection under the skin. Your doctor will tell you how much CIMZIA to inject and how often, based on your condition to be treated. Make sure to keep all of your injection and follow-up appointments with your doctor. After starting CIMZIA, if you get an infection, any sign of an infection including a fever, cough, or flu-like symptoms, or have open cuts or sores on your body, call your doctor right away. CIMZIA can make you more likely to get infections or make any infection that you may have worse. What are the possible side effects of CIMZIA? Serious side effects have happened in patients taking CIMZIA including: Serious infections including TB. See "What is the most important information I should know about CIMZIA?" Certain types of cancer. There have been cases of certain types of cancer in people taking CIMZIA or other TNF-blockers. People with RA, especially more serious RA, may have a higher chance for getting a kind of cancer called lymphoma Heart failure including new heart failure or worsening of heart failure you already have. Symptoms include shortness of breath or swelling of your ankles or feet Nervous system problems such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes. Symptoms include dizziness, numbness or tingling, problems with your vision, and weakness in your arms or legs Allergic reactions. Signs of an allergic reaction include a skin rash, swollen face, or trouble breathing Hepatitis B virusreactivation in patients who carry the virus in their blood. In some cases, patients have died as a result of hepatitis B virus being reactivated. Your doctor should monitor you carefully during treatment with CIMZIA if you carry the hepatitis B virus in your blood. Tell your doctor if you have any of the following symptoms: feel unwell, poor appetite, tiredness (fatigue), fever, skin rash, or joint pain Blood problems. Your body may not make enough of the blood cells that help fight infections or help stop bleeding. Symptoms include a fever that doesn't go away, bruising or bleeding very easily, or looking very pale Immune reactions including a lupus-like syndrome. Symptoms include shortness of breath, joint pain, or a rash on the cheeks or arms that worsens with sun exposure Call your doctor right away if you develop any of the above side effects or symptoms. The most common side effects of CIMZIA are upper respiratory infections (flu, cold), rash, and urinary tract infections (bladder infections). Injection site reactions happen in some people. Tell your doctor about any side effect that bothers you or does not go away. These are not all of the side effects with CIMZIA. Ask your doctor or pharmacist for more information.