Incidence of Antibodies to Double-Stranded DNA Following Treatment with Infliximab (Remicade™)
In clinical trials with infliximab (a monoclonal antibody to tumor necrosis factor alpha) for the treatment of rheumatoid arthritis (RA), there have been reports about the de novo development of antibodies to anti-double stranded DNA (anti-dsDNA). Because antibodies to dsDNA classicially have been thought to be specific for lupus, there has been concern that treatment with infliximab could potentially induce clinical lupus.
In a study by Charles et al (Arthritis Rheum. 43:2383-90, 2000), investigators quantified the incidence of anti-dsDNA antibodies in RA patients receiving either single or multiple doses of infliximab (with or without methotrexate) in open-label, randomized placebo-controlled trials. Multiple sera obtained from 156 patients before and after treatment with infliximab and from 37 patients treated with placebo infusions were tested for anti-dsDNA antibodies by three methods: 1) Crithidia lucilae indirect immunofluorescence test (CLIFT); 2) a commercial Farr assay using mammalian DNA); and, 3) a Farr assay using 125I-labeled circular plasmid DNA.
Results: None of the RA patients had a serum sample that was positive for anti-dsDNA antibodies by the CLIFT assay prior to infliximab therapy. Twenty-two patients (14%) developed a positive CLIFT assay after infliximab treatment. Of these, 11 (7%) were also positive by the commercial Farr assay. In all but 1 patient, the anti-dsDNA antibodies were solely of the IGM isotype. Only 1 patient had detectable anti-dsDNA antibodies by the plasmid DNA assay. One patient developed anti-dsDNA antibodies of IgG, IgA, and IgM isotype and had positive results on both Farr assays; this was associated with a reversible lupus syndrome.
Conclusion: Anti-dsDNA antibodies of IgM class are induced by infliximab therapy; the frequency is dependent on the assay method used. Only 1 of the 156 patients who were treated with infliximab developed a self-limiting cinical lupus syndrome; that patient developed high titiers of anti-ds DNA antibodies of IgG, IgM, and IgA class, as detected by the CLIFT and by 2 different Farr assays.
Editorial Comment: These results are reassuring in that, while a fair number of patients developed antibodies to dsDNA, only one patient developed a lupus like syndrome. Because most patients in whom anti-dsDNA antibodies developed did not develop a clinical syndrome of lupus, routine anti-dsDNA screening of infliximab-treated patients does not seem warranted at this time. However, continued close observation of patients treated with anti-TNF agents remains advisable. Finally, no single assay for detection of anti-dsDNA antibodies proved superior to the others.
