Centocor公司于2005年5月17日宣布，美国FDA批准英利昔单抗（infliximab，Remicade）用于控制银屑病关节炎患者活动性关节炎的体征和症状。这是FDA第九次批准本品用于一项新适应证。本品现已获准用于治疗节段性肠炎、类风湿性关节炎、强直性脊柱炎和银屑病关节炎等炎症性疾病。自1998年首次获准用于节段性肠炎以来，本品已被用于治疗全球50多万患者。
一项随机双盲安慰剂对照的III期研究IMPACT 2包括200例活动性银屑病关节炎患者，在第0、2、6周和每隔8周随机给予本品5mg/kg或安慰剂，直至第22周。研究数据显示，早在第2周在本品组患者中可见ACR 20和PASI 75改善，且在24周内进一步改善。在第14周，根据美国风湿病学会评分标准，58%的本品组患者的关节炎症状至少改善20%（ACR 20），安慰剂组为11%（P < 0.001）。在第24周，27%的本品组患者至少改善70%（ACR 70），安慰剂组为2%（P < 0.001）。此外，在第24周，根据银屑病皮损面积严重度指数，60%的本品组患者的银屑病至少较基线改善75%（PASI 75），安慰剂组为1%。在第24周，39%的本品组患者达到PASI 90，即银屑病症状显著改善，而安慰剂组为0。

重要的是，本品组发生指炎和腱端病的患者亦减少。据估计，超过1/3的银屑病关节炎患者受指炎和腱端病侵袭。研究中，40%的本品组患者和41%的安慰剂组患者在基线时至少一个手指有指炎。24周后，只有15%的本品组患者症状继续存在，安慰剂组为33%（P 3 0.05）。基线时，在42%的本品组患者和35%的安慰剂组患者中可见腱端病。24周时，只有22%的本品组患者仍有腱端病，安慰剂组为36%（P = 0.004）。

据2004年美国银屑病基金会（National Psoriasis Foundation）对1000多例银屑病和银屑病关节炎患者的调查显示，约85%的银屑病关节炎患者称疾病影响了他们的日常生活。此外，只有不到20%的患者表示对治疗很满意。

“我们的调查表明患者一向指出银屑病关节炎在身体和情绪方面对他们的生活质量产生负面影响。” 美国银屑病基金会会长兼CEO Gail Zimmerman说，“Remicade的获准很重要，因为它为众多银屑病关节炎患者提供了新生的希望。”

2004年9月，本品在欧盟获准与甲氨蝶呤合用于治疗对缓解疾病抗风湿药缺乏应答的活动性和进展性银屑病关节炎患者。

Indications for REMICADE^® (infliximab)

Rheumatoid Arthritis

REMICADE^®, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis.

Crohn's Disease

REMICADE^® is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy.

REMICADE^® is indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn's disease.

Ankylosing Spondylitis

REMICADE^® is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.

Psoriatic Arthritis

REMICADE^® is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis.

Plaque Psoriasis

REMICADE^® is indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. REMICADE^® should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

Ulcerative Colitis

REMICADE^® is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.

IMPORTANT SAFETY INFORMATION FOR REMICADE^® (infliximab)

SERIOUS INFECTIONS

Patients treated with REMICADE^® (infliximab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue REMICADE^® if a patient develops a serious infection or sepsis.

Reported infections include:

• Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with REMICADE^®.^{1, 2} Treatment for latent infection should be initiated prior to treatment with REMICADE^®.
• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
• Bacterial, viral, and other infections due to opportunistic pathogens.

The risks and benefits of treatment with REMICADE^® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with REMICADE^®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

In clinical trials, other serious infections observed in patients treated with REMICADE^® included pneumonia, cellulitis, abscess, and skin ulceration.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including REMICADE^®. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including REMICADE^®. These cases have had a very aggressive disease course and have been fatal. All reported REMICADE^® cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. All of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE^® at or prior to diagnosis. Carefully assess the risks and benefits of treatment with REMICADE^®, especially in these patient types.

In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn's disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including REMICADE^®, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with REMICADE^® was similar to that expected in the general population whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).

CONTRAINDICATIONS

REMICADE^® is contraindicated in patients with moderate to severe (NYHA Class III/IV) congestive heart failure (CHF) at doses greater than 5 mg/kg. Higher mortality rates at the 10 mg/kg dose and higher rates of cardiovascular events at the 5 mg/kg dose have been observed in these patients. REMICADE^® should be used with caution and only after consideration of other treatment options. Patients should be monitored closely. Discontinue REMICADE^® if new or worsening CHF symptoms appear. REMICADE^® should not be (re)administered to patients who have experienced a severe hypersensitivity reaction or to patients with hypersensitivity to murine proteins or other components of the product.

HEPATITIS B REACTIVATION

TNF inhibitors, including REMICADE^®, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating REMICADE^®. Exercise caution when prescribing REMICADE^® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with REMICADE^®. Discontinue REMICADE^® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of REMICADE^® and monitor patients closely.

HEPATOTOXICITY

Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported rarely in patients receiving REMICADE^® postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (e.g., > 5 times the upper limit of normal) develop, REMICADE^® should be discontinued, and a thorough investigation of the abnormality should be undertaken.

HEMATOLOGIC EVENTS

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to REMICADE^® therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of REMICADE^® in patients who develop significant hematologic abnormalities.

HYPERSENSITIVITY

REMICADE^® has been associated with hypersensitivity reactions that differ in their time of onset. Acute urticaria, dyspnea, and hypotension have occurred in association with infusions of REMICADE^®. Serious infusion reactions including anaphylaxis were infrequent. Medications for the treatment of hypersensitivity reactions should be available.

NEUROLOGIC EVENTS

TNF inhibitors, including REMICADE^®, have been associated in rare cases with CNS manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering REMICADE^® in patients with these disorders and consider discontinuation if these disorders develop.

AUTOIMMUNITY

Treatment with REMICADE^® may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.

ADVERSE REACTIONS

In clinical trials, the most common REMICADE^® adverse reactions occurring in >10% of patients included infections (e.g., upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.

USE WITH OTHER DRUGS

The use of REMICADE^® in combination with anakinra, abatacept or tocilizumab is not recommended. Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection. Live vaccines should not be given with REMICADE^®. Bring pediatric Crohn's patients up to date with all vaccinations prior to initiating REMICADE^®.

Please see full Prescribing Information and Medication Guide for REMICADE^®. Provide the Medication Guide to your patients and encourage discussion.