Infliximab adverse effects

Infliximab (Remicade) is a chimeric monoclonal antibody directed against TNF-a. Recently, its indications have been expanded to include psoriatic arthritis and treatment of adults with chronic severe plaque psoriasis. An advantage over other systemic psoriasis treatments is that infliximab does not adversely affect blood counts, hepatic enzyme levels, or kidney function. The recommended dose is 5 mg/kg as an IV infusion at weeks 0, 2, and 6, then every 8 weeks thereafter. For psoriatic arthritis, it may be used with or without methotrexate. Adverse effects include headaches, fever, chills, fatigue, diarrhea, pharyngitis, upper respiratory and urinary tract infec-... 

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

Adverse effects Long-term use of infliximab is associated with development of anti-infliximab antibodies unless the drug is used in combination with methotrexate. Infusion reactions such as fever, chill, pruritus, or urticaria have occurred. Infections leading to pneumonia, cellulitis, and other conditions have also been reported. Whether treatment with infliximab predisposes to lymphoma, a condition that occurs with immunosuppressive or immune-altering drugs, remains to be established. 

Immediate infusion reactions to infliximab are usually defined by any significant adverse effect that occurs during or within 1-2 hours after the infusion. The sjmptoms mostly consist of flushing, rash, shortness of breath, wheeze, hotness, chest pain, vomiting, and abdominal pain. 

A 33-year-old man with a 3-year history of Crohn s disease had previously received a weU-tolerated single infusion of infliximab. When, 14 months later, he received a second infusion for exacerbation of the disease he had no immediate adverse effects, but complained of myalgia, arthralgia, nausea, and vomiting 7 days later and received diphenhydramine. After 3 days he had dyspnea, fever, and chills. An open lung biopsy showed features of eosinophilic pneumonia and no... 

In 41 patients with rheumatic disease who received a total of 300 infusions of infliximab over 9 months there were severe adverse effects in 15%, one of which was a case of histoplasmosis (58). 

Rheumatoid arthritis Single-center experience 3 months Leflunomide 100 mg/day for 3 days, then 20 mg/day plus infliximab 3 mg/ kg at 0,6, and every 8 weeks (n = 17) 20 adverse effects in 13 patients 8 discontinued (20)... 

Despite a good overall safety profile, anti-TNF antibodies can induce a number of adverse effects, including autoimmunity and infections. A trial in the treatment of Crohn s disease noted infusion reactions, transient increased of anti-dsDNA antibodies, and serum sickness-like delayed hypersensitivity with retreatment. Induction of human-antichimeric-antibodies was suggested as the cause of some of the infusion reactions [90]. A prospective study in 35 patients with Crohn s disease showed induction of ANA and anti-dsDNA autoantibodies in 53% and 35% of infliximab-treated patients [91]. A single patient showed clinical features consistent with drug-induced lupus, including the presence of ANA and anti-dsDNA autoantibodies, which quickly resolved after discontinuation of infliximab. Reports on renal adverse effects of anti-TNF antibodies are very rare. Saint Marcoux described the occurrence of crescentic GN in as few as 2 patients out of a cohort of 39 patients, treated with an anti-TNF antibody for rheumatoid arthritis [92]. A case report by Chin et al. [93] described the case of a 29-year-old Australia-born Vietnamese who presented with nephrotic syndrome. A renal biopsy showed membranous nephropathy. Symptoms attenuated after discontinuation of infliximab therapy. 

Drug intolerance often limits the usefulness of agents used to treat IBD. Many patients receiving sulfasalazine, mesalamine, corticosteroids, metronidazole, azathioprine, mercaptopurine, or infliximab experience some undesired effects. In some cases, these adverse effects can be significant and require discontinuation of the therapy. Knowledge of the common or important adverse reactions will assist in avoiding or minimizing their effects. 

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. 

The most common adverse effects of infliximab are headaches, fever, chills, fatigue, diarrhea, pharyngitis, upper respiratory and urinary tract infections, and hypersensitivity reactions (urticaria, dyspnea, and hypotension). Infliximab has been also associated with infections and lymphoproliferative disorders. It is not associated with end-organ toxicity, and blood counts, liver enzyme levels, kidney function, and complement values can be expected to remain normal during treatment. This gives it a major advantage over other systemic psoriasis treatments. 

Psoriasis New-onset psoriasis is a paradoxical adverse effect of TNF antagonists and has been described with infliximab [124 ], for example in a young woman who developed pustular psoriasis for the first time while receiving infliximab for Crohn s disease [125 ], and a 14-year-old girl with Crohn s disease who developed guttate psoriasis [126 ]. 

There is considerable discussion about whether ocular inflammation is paradoxically a potential adverse event of etanercept in either previously inflamed or previously uninflamed eyes. It is as yet imclear whether etanercept may induce new-onset uveitis or may prevent uveitis, although flares of uveitis have recently been shown to occur less than half as often in tumor necrosis factor-a-treated patients as placebo-treated control subjects. However, it seems clear that, because of a different mechanism of action, infliximab is more effective at treating certain types of ocular inflammation. 

Observational stndies In an open pilot study in 41 patients with rheumatoid ar Aritis who had previously failed infliximab therapy, neither former adverse reactions to infliximab nor baseline human antichimeric infliximab antibodies had an effect on adverse event frequency or severity [93. ... 

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