|
美国FDA2011年6月15日批准belatacept（Nulojix），以防止接受肾移植手术的成年患者产生急性排斥反应。该药物被批准用于与其他免疫抑制剂（抑制免疫系统药物）同时使用——特别是巴利昔单抗（basiliximab）、吗替麦考酚酯（mycophenolate mofetil）和糖皮质激素corticosteroids。
本品是一种称为选择性T细胞共刺激阻断剂的药物。这种药物有助于预防肾移植手术后的器官排斥。如果没有免疫抑制，身体会对被移植器官产生排异，这是由于免疫系统将新器官识别为外来者（移植排斥反应）。静脉输液本品30分钟，可通过防止排斥反应，与其他免疫抑制剂一起作用以保持新的肾脏。
“Nulojix为肾移植患者带来了新的选择，”FDA药物评价和研究中心抗菌产品办公室主任，医学博士、公共卫生硕士Edward Cox说。 “这种新的药物与其他免疫抑制剂联合使用有助于控制免疫系统，防止接受肾脏移植的患者对器官的排斥反应。”
两项开放性随机多中心III期试验研究对Nulojix进行了评估。该研究纳入了超过1200例患者，并将2种不同给药剂量的Nulojix联用其他免疫抑制剂——环孢菌素进行比较。这些研究表明，建议的本品疗法对防止急性器官排斥是安全和有效的。
本品附带一个黑框警示：本品可能增加移植后淋巴增生性障碍（PTLD）的风险，这是一种器官移植后白细胞失控增长的癌症。从未接触过EB病毒（EBV）——单核细胞增多症的病因——的接受过移植手术的患者患上PTLD的风险是很高。未接触过EBV的移植患者如果在移植后产生发生感染，那么他们产生对病毒的有效免疫应答是困难的；通常他们在移植时便暴露在病毒中，因为大约80%的捐赠器官上携带这种病毒。患者应当对EBV进行测试，如果结果显示他们已接触到EBV，那么只能使用Nulojix。另外的黑框警示，同样也是其他免疫抑制剂的黑框警示警告了可能增加产生严重感染和其他癌症的风险。
试验中，移植患者的常见不良反应包括：贫血、便秘、肾脏及膀胱感染、腿脚肿胀等症状。此外，服用者必须尽量减少日晒时间，以预防皮肤癌的发生。
根据器官获取和移植网络显示——该网络是由HHS卫生资源和服务管理局监督——在美国超过89000例患者正在等待肾脏移植。
Nulojix由施贵宝公司研发，普林斯顿销售。
- NULOJIX is associated with increased risk for post-transplant lymphoproliferative disorder (PTLD), predominantly in the central nervous system (CNS).
- NULOJIX is contraindicated in patients who are EBV seronegative or with unknown serostatus because the risk of PTLD is particularly increased in patients who are EBV seronegative.
NULOJIX is to be used only in patients who are EBV seropositive.
Patients should be monitored for new or worsening neurological, cognitive, or behavioral signs and symptoms.
Higher than recommended doses or more frequent dosing of NULOJIX and concomitant immunosuppressives is not recommended.
Immunosuppression may result in increased susceptibility to infection and development of malignancies.
NULOJIX should be prescribed only by physicians experienced in immunosuppressive therapy and management of kidney transplant patients.
Use in liver transplant patients is not recommended due to an increased risk of graft loss and death.
Dosage Formulation and Strength: 250 mg lyophilized powder for injection, for intravenous use.
INDICATION AND IMPORTANT SAFETY INFORMATION
INDICATION
- NULOJIX® (belatacept) (in combination with basiliximab induction, mycophenolate mofetil [MMF], and corticosteroids) is indicated for prophylaxis of organ rejection in adults receiving a kidney transplant
- Use NULOJIX only in patients who are Epstein-Barr virus (EBV) seropositive
- Use of NULOJIX for prophylaxis of organ rejection in transplanted organs other than kidney has not been established
IMPORTANT SAFETY INFORMATION
Post-Transplant Lymphoproliferative Disorder (PTLD)
- NULOJIX patients are at increased risk for developing PTLD, predominantly involving the central nervous system (CNS)
- Recipients without immunity to EBV (ie, seronegative) are at particularly increased risk; therefore, NULOJIX is contraindicated in transplant recipients who are EBV seronegative or unknown serostatus
- Monitor for new or worsening neurological, cognitive, or behavioral signs and symptoms
- As the total burden of immunosuppression is a risk factor for PTLD, higher than recommended doses or more frequent dosing of NULOJIX or concomitant immunosuppressive agents are not recommended
- Other known risk factors for PTLD include cytomegalovirus (CMV) infection and T-cell-depleting therapy
- CMV prophylaxis is recommended for at least 3 months after transplantation
- Use T-cell-depleting therapy to treat acute rejection cautiously
- Patients who are EBV seropositive and CMV seronegative may be at increased risk of PTLD
- Since CMV seronegative patients are at increased risk for CMV disease (a known risk factor for PTLD), the clinical significance of CMV serology for PTLD remains to be determined; however, these findings should be considered when prescribing NULOJIX
Management of Immunosuppression
- Only physicians experienced in immunosuppressive therapy and management of kidney transplant patients should prescribe NULOJIX
- Patients should be managed in facilities with adequate laboratory and supportive medical resources
- The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient
Progressive Multifocal Leukoencephalopathy (PML)
- NULOJIX® (belatacept) patients are at increased risk for PML, often a rapidly progressive and fatal opportunistic infection
- In clinical trials, two cases were reported in patients receiving NULOJIX at higher cumulative doses and more frequently than the recommended regimen, along with MMF and corticosteroids; one occurred in a kidney transplant recipient and one occurred in a liver transplant recipient
- As PML has been associated with high levels of immunosuppression, higher than recommended doses or more frequent dosing of NULOJIX and concomitant immunosuppressive agents, including MMF, are not recommended
- Monitor for new or worsening neurological, cognitive, or behavioral signs and symptoms
- PML is usually diagnosed by brain imaging, cerebrospinal fluid testing for JC viral DNA by polymerase chain reaction, and/or brain biopsy
- Consultation with a specialist should be considered
- If PML is diagnosed, consider reduction or withdrawal of immunosuppression, weighing risk to the graft
Other Malignancies and Serious Infections
- Increased susceptibility to infection and possible development of malignancies may result from immunosuppression
- Patients should avoid prolonged exposure to ultraviolet light and sunlight
- Patients receiving immunosuppressants, including NULOJIX, are at increased risk for bacterial, viral, fungal, and protozoal infections, including opportunistic infections and tuberculosis. Some infections were fatal
- Polyoma virus-associated nephropathy can lead to deteriorating renal function and graft loss; consider reduction in immunosuppression, weighing risk to the graft
- Tuberculosis was more frequently observed in patients receiving NULOJIX. Evaluate for tuberculosis and initiate treatment for latent infection prior to NULOJIX use
- CMV and Pneumocystis jiroveci prophylaxis is recommended after transplantation
Liver Transplant: use in liver transplant patients is not recommended due to increased risk of graft loss and death in a clinical trial with more frequent administration of NULOJIX than studied in kidney transplant, along with MMF and corticosteroids
Immunizations: avoid use of live vaccines during NULOJIX treatment
Pregnancy Category C: based on animal data, NULOJIX may cause fetal harm. NULOJIX should not be used in pregnancy unless potential benefit to the mother outweighs potential risk to the fetus. To monitor maternal-fetal outcomes of pregnant women who have received NULOJIX, or whose partners have received NULOJIX, healthcare providers are strongly encouraged to register pregnant patients in the National Transplant Pregnancy Registry (NTPR) by calling 1-877-955-6877
Nursing Mothers: discontinue NULOJIX® (belatacept) or nursing, considering importance of NULOJIX to the mother
Most Common Adverse Reactions (≥20%): anemia (45%), diarrhea (39%), urinary tract infection (37%), peripheral edema (34%), constipation (33%), hypertension (32%), pyrexia (28%), graft dysfunction (25%), cough (24%), nausea (24%), vomiting (22%), headache (21%), hypokalemia (21%), hyperkalemia (20%), and leukopenia (20%) |
