Tuberculosis infliximab

Prior to initiating infliximab, obtain a tuberculin skin test to rule out latent tuberculosis. Assure that patients do not have a clinically significant systemic infection or New York Heart Association Class III or IV heart failure. 

Infliximab (Remicade) 3-1 0 mg/kg at 0, 2, and 6 weeks then q 8 weeks IV infusion 1 -4 weeks IR (rash, urticaria, flushing, HA, fever, chills, nausea, tachycardia, dyspnea) Monitor for infection Screen for tuberculosis... 

Infliximab has been associated with infusion reactions, serum sickness, sepsis, and reactivation of latent tuberculosis. Adalimumab carries risks similar to infliximab. 

Tuberculosis (frequently disseminated or extrapulmonary at clinical presentation), invasive fungal infections, and other opportunistic infections have been observed in patients receiving infliximab. Some of these infections have been fatal (see Warnings). 

Evaluate patients for latent tuberculosis infection with a tuberculin skin test. Initiate treatment of latent tuberculosis infection prior to therapy with infliximab. 

IX.b.3.4. Genetically engineered antibodies. Anti-TNF antibody treatment with infliximab or adalimumab is now accepted as of value in treating severe and fistulating exacerbations of Crohn s disease when standard treatments are not tolerated or have failed. Adverse effects which limit usefulness include the occurrence of tuberculosis and septicaemia, leucopenia and pancytopenia, and risk of exacerbation of demyelinating disease. Considerations of benefits versus risks of such treatment are complex, but probably positive. 

The most common side effects, which are related to the intravenous infusion itself, include rash, low blood pressure, chills, and chest pain. These symptoms are generally temporary and often respond to a decrease in infusion rate. In addition, some patients develop antibodies, which have been associated in rare cases with symptoms similar to those of patients with systemic lupus erythematosus. These symptoms were also temporary. Another side effect is increased risk of infections. Fatal cases of tuberculosis have been reported following infliximab therapy. Another potential side effect is an increased risk of lymphoma. Its occurrence remains controversial. 

Anti-TNF antibodies, eg, infliximab, others Bind tumor necrosis factor and prevent it from binding to its receptors Suppression of several aspects of immune function, especially ThI lymphocytes Infliximab Moderately severe to severe Crohn s disease and ulcerative colitis others approved in Crohn s disease Infusion reactions reactivation of latent tuberculosis increased risk of dangerous systemic fungal and bacterial infections... 

The most important adverse effect of infliximab therapy is infection due to suppression of the THl inflammatory response. Reactivation of latent tuberculosis, with dissemination, has occurred. 

Before administering infliximab, all patients must undergo purified protein derivative (PPD) testing prophylactic therapy for tuberculosis is warranted for patients with positive test results. Other infections include pneumonia, sepsis, pneumocystosis, and listeriosis. 

Adverse reactions that have been reported include infections, fever, headache, vertigo, hypertension, skin reactions, fatigue, chest pain and worsening congestive cardiac failure, gastrointestinal upset. Active tuberculosis may develop soon after starting treatment with infliximab and patients should be screened for latent infection or disease. 

In contrast to infliximab, etanercept is rarely associated with severe infectious complications. This has been attributed to different mechanisms of tumor necrosis factor alfa neutralization by the two drugs. Indeed, only nine cases of tuberculosis have previously been reported to the FDA from more than 100 000 patients treated worldwide (30). However, severe or uncommon infectious complications (severe viral pneumonia, fatal pneumococcal sepsis due to... 

Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, Siegel JN, Braun MM. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001 345(15) 1098-104. 

Myers A, Clark J, Foster H. Tuberculosis and treatment with infliximab. N Engl J Med 2002 346(8) 623-6. 

The safety and efficacy of infliximab have been assessed in 40 patients with severe active spondylarthropathy in a double-blind, randomized, placebo-controlled trial (43). One 65-year-old patient improved but 3 weeks after the third infusion developed a systemic illness. He had enlarged mediastinal lymph nodes and nodular lesion of the liver and spleen. Biopsy of the mediastinal lymph nodes showed tuberculosis, which was confirmed by culture. He was treated and recovered slowly. 

Reactivation of latent tuberculosis is a major concern with infliximab (SEDA-26, 402), and accounts for about one-third of infections in these patients. According to data from the manufacturers, 130 cases of active tuberculosis were notified up to October 2001. Many of the cases were disseminated or extrapulmonary tuberculosis, and several patients died. Several case reports have provided detailed information in at least seven other patients, including three who developed miliary tuberculosis and one who developed Mycobacterium tuberculosis enteritis (44-48). A detailed analysis of 70 cases of tuberculosis reported to the FDA has been published (49). Two-thirds of the cases were noted after three or fewer infusions and 57% of the patients had extrapulmonary disease. There were 64 cases from countries with a low incidence of tuberculosis. From these reports and the number of patients treated with infliximab, the estimated rate of tuberculosis in patients with rheumatoid arthritis treated with infliximab was four times higher than the background rate. Patients with evidence of active infection should not receive infliximab until the infection is under control all should be screened for tuberculosis before starting infliximab (50). From these and other data it has been estimated that the risk of tuberculosis in the first year of infliximab treatment is 0.035 in US citizens and 0.2% in non-US citizens. Further investigations, such as a chest X-ray and a Mantoux test, and prophylactic treatment with isoniazid, will show whether the incidence can be reduced in patients taking anti-TNF treatment (51). 

Liberopoulos EN, Drosos AA, Ehsaf MS. Exacerbation of tuberculosis enteritis after treatment with infliximab. Am J Med 2002 113(7) 615. 

Infliximab has been related to adverse effects such as infusion reactions, serum sickness, sepsis, and reactivation of tuberculosis. Infusion reactions and serum sickness relate to the immune response to foreign protein. Patients often develop anti-infliximab antibodies with multiple infusions. Serum sickness has occurred in patients who received infliximab doses separated by a long period of time. Sepsis and tuberculosis may occur because of the inhibition of TNF-protective mechanisms. 

Infliximab therapy is associated with increased incidence of respiratory infections of particular concern is potential reactivation of tuberculosis or other granulomatous infections with subsequent dissemination. The FDA recommends that candidates for infliximab therapy should be tested for latent tuberculosis with purified protein derivative, and patients who test positive should be treated prophylactically with isoniazid. However, anergy with a false-negative skin test has been noted in some patients with Crohn s disease, and some experts routinely perform chest radiographs to look for active or latent pulmonary disease. Infliximab also is contraindicated in patients with severe congestive heart failure. The significant cost of infliximab is an important consideration in some patients. 

Although the current protein-based TNF inhibitors have demonstrated ligand-inhibitory efficacy, they can also exhibit potentially serious adverse efiects such as a greater predisposition towards secondary infections, congestive heart failure, neurologic changes (demyelination), lymphomas, re-exacerbation of latent tuberculosis and problems related to autoimmunity such as lupus-like syndrome. With infliximab, acute allergic reactions are seen in approximately 5% of intravenous infusions as well. 

Tuberculosis In a case-control analysis, exposure to infliximab versus etanercept was an independent susceptibility factor for tuberculosis. The authors concluded that the risk of tuberculosis is higher in patients receiving anti-TNF monoclonal antibodies than in those receiving soluble TNF receptors [105 ]. 

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