Lupus-like syndrome infliximab

Autoimmunity Treatment with infliximab therapy may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. Discontinue treatment if a patient develops symptoms suggestive of a lupus-like syndrome following treatment with infliximab. 

An antibody directed at the murine epitope of infliximab may develop in patients. A delayed infusion reaction, which occurs 1-2 weeks after infusion, develops in approximately 5% patients who are re-treated with infliximab. Delayed infusion reaction is more common in patients with circulating anti-infliximab antibodies (20-30% of those getting multiple infusions) than in those without the antibodies. These reactions consist of myalgia arthralgia fever rash urticaria and facial, hand, and lip edema. Delayed reactions respond to symptomatic treatment with antihistamines or corticosteroids. Positive antinuclear antibodies (ANA) and anti-dsDNA develop in a small number of patients. Development of a lupus-like syndrome has been reported that resolved after discontinuation of the drug. 

Klapman JB, Ene-Stroescu D, Becker MA, Hanauer SB. A lupus-like syndrome associated with infliximab therapy. Inflamm Bowel Dis 2003 9(3) 176-8. 

The drug may increase risk of infection as noted above. An acnte infnsion reaction with symptoms including fever, chills, pmritns, and rash may occur within 1 to 2 hours after giving the dmg. Antoanti-bodies and lupus-like syndrome also have been reported. In chnical trials, the combination of methotrexate plus infliximab halted progression of joint damage in patients and was superior to methotrexate monotherapy. " ... 

Patients with rheumatoid arthritis have elevated levels of TNF-a in their joints, whereas patients with Crohn s disease have elevated levels of TNF-a in their stools. In one trial, infliximab plus methotrexate improved the signs and symptoms of rheumatoid arthritis more than methotrexate alone. Patients with active Crohn s disease who had not responded to other immunosuppressive therapies also improved when treated with infliximab, including those with Crohn s-related fistulae. Infliximab is approved in the United States for treating the symptoms of rheumatoid arthritis, and is used in combination with methotrexate in patients who do not respond to methotrexate alone. It also is approved for treatment of symptoms of moderate to severe Crohn s disease in patients who have failed to respond to conventional therapy, and in treatment to reduce the number of draining fistulae in Crohn s disease patients. About 1 of 6 patients receiving infliximab experiences an infusion reaction characterized by fever, urticaria, hypotension, and dyspnea within 1 to 2 hours after antibody administration. Serious infections also have occurred in infliximab-treated patients, most frequently in the upper respiratory and urinary tracts. The development of antinuclear antibodies, and rarely a lupus-like syndrome, have been reported after treatment with infliximab. 

The use of infliximab as a biologic response modifier raises several important considerations. Both acute (fever, chills, urticaria, or even anaphylaxis) and subacute (serum sickness—like) reactions may develop after infliximab infusion. Anti—double-stranded DNA antibodies develop in 9% of patients, but a frank lupus-like syndrome occurs only rarely. Antibodies to infliximab can decrease its clinical efficacy strategies to minimize the development of these antibodies (e.g., treatment with glucocorticoids or other immunosuppressives) may be critical to preserving infliximab efficacy for either recurrent or chronic therapy. 

About one of six patients receiving infliximab experience an infusion reaction, characterized by fever, urticaria, hypotension, and dyspnea, within 1-2 hours after antibody administration. Serious infections also have occurred in infliximab-treated patients, most frequently in the upper respiratory and urinary tracts. The development of antinuclear antibodies, and rarely a lupus-like syndrome, has been reported after treatment with infliximab. 

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. 

Immunologic Infliximab-induced lupus-like syndrome has been reported in a patient with ankylosing spondylitis [127 ]. 

Bodur H, Eser F, Konca , Arikan S. Infliximab-induced lupus-like syndrome in... 

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. 

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