Rheumatoid arthritis antibody treated patients with

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. 

Infliximab is given by intravenous infusion at a dose of 3 mg/kg at 0, 2, and 6 weeks, and then every 8 weeks. To prevent the formation of antibodies to this foreign protein, methotrexate shonld be given orally in doses typically used to treat rheumatoid arthritis for as long as the patient continues on infliximab. The clinical significance of these antibodies in rheumatoid arthritis has not been demonstrated, bnt in Crohn s disease they are associated with infnsion reactions and reduce the duration of response. Infusion reactions may occnr in any patient treated with the drug. Loss of response may be seen in patients with rheumatoid arthritis who have initial good response, which requires increased doses or shorter intervals between doses to maintain response. 

Alemtuzumab (campath-lH) is a humanized monoclonal antibody specific for the CDw52 antigen, present on cell membranes of lymphocytes and monocytes. It has been used for treatment of patients with rheumatoid arthritis and vasculitis, is being investigated for the treatment of chronic lymphocytic leukemia, and has been used to deplete circulating lymphocytes in patients with multiple sclerosis (1). In 2001, alemtuzumab was approved in Europe for the treatment of chronic B cell lymphocytic leukemia that had been treated previously with alkylating agents and was refractory to fludarabine (2). It has also been used for induction of immunosuppression/tolerance in liver transplant recipients (3,4) and kidney/pancreas transplant recipients (5). 

Anakinra is an interleukin-1 receptor antagonist. It has been used to treat rheumatoid arthritis (1,2). It has been tried in graft-versus-host disease, but without success (3). According to published trial data, moderate injection site reactions were the primary adverse effect and required treatment withdrawal in under 5% of patients. An erythematous rash was seldom observed. Although a few patients have developed antibodies to anakinra, these have not so far been associated with lack of efficacy or allergic skin reactions. 

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. 

Following treatment of patients with rheumatoid arthritis with low and high dose anti tumor necrosis factor-a (TNF) or placebo, serum MMP-1 and MMP-3 levels were assessed by Brennan et al. (BIO). In both antibody-treated groups, a significant decrease in serum MMP-3 levels at all time points was observed, reduced maximally to 41% of pre-infusion values at day 7. MMP-1 levels were also reduced, but less dramatically than with MMP-3. While serum MMP-3 levels correlated with C-reactive protein both prior to and following therapy, Brennan et al. concluded that it remains to be demonstrated that serum MMP-3 and/or MMP-1 levels reflect the cartilage and bone resorptive processes which are evident in this disease. Catrina et al. (C2) also examined the effect of anti-tumor necrosis factor-a therapy (etanercept) on MMPs. Etanercept therapy downregulated serum... 

Secher et al. (1978) report the appearance of the granular deposition of IgG and C3 at dermal-epidermal junctions in a patient who experienced a pruritic rash when being treated with levamisole a provocation dose of levamisole resulted in further complex deposition. The authors comment on the possibility that these complexes were related more to the patient s underlying disease, rheumatoid arthritis, than to drug-specific complexes but on balance, they believe that they were in fact due to levamisole-specific antibodies. The view was strengthened by the... 

Smith MA. Bains SK. Betts JC. Choy EHS. Zanders ED. Use of two-dimensional gel electrophoresis to measure changes in novial fluid proteins from patients with rheumatoid arthritis treated with antibody to CD4. Clinical and Diagnostic Laboratory Immunology January 1. 2001 8(1) 105-11. 

The patient, a 66-year-old man, was treated with 500 mg penicillamine daily for rheumatoid arthritis. After 6 months of treatment a bullous and crythcmatosquamous eruption developed on the trunk, scalp and arms. The Nikolsky phenomenon was positive. An erythematosquamous balanitis was present stomatitis did not develop. On cytological examination acantholytic cells were present. Histological examination revealed both aspects of toxicoderma and pemphigus. Intercellular immunofluorescence was positive in the superficial layers of both affected and apparently normal skin. Electron microscopic examination confirmed acantholysis. Anti-intercellular substances and anti-striational antibodies were detected in the serum ANF and LE cells were absent. The disorder rapidly disappeared after withdrawal of penicillamine, and a course of treatment with a corticosteroid. 

---