Abstract and Introduction
Abstract
Introduction: The induction of antinuclear antibodies (ANAs) or anti-double-stranded (ds) -DNA antibodies (Abs) after infliximab (IFX) therapy in rheumatoid arthritis (RA) is a well-known phenomenon, but the correlation of such Abs with the clinical response to IFX has not yet been determined. The aims of this retrospective observational study were to examine the prevalence of positive ANA and anti-ds-DNA Abs before and after IFX therapy in patients with RA and to investigate whether an increased titer of such Abs is associated with the clinical efficacy of IFX.
Methods: One hundred eleven RA patients who had received IFX were studied. ANA (indirect immunofluorescence with HEp-2 cells) and anti-ds-DNA Abs (Farr assay) results were examined before and after IFX therapy.
Results: The overall clinical response assessed by EULAR response criteria was as follows: good response in 55%, including remission in 38%; moderate response in 18%; and no response (NOR) in 27%. The positivity of ANA (≥ 1:160) and anti-ds-DNA Abs significantly increased from 25% to 40% (P = 0.03) and from 3% to 26% (P < 0.001) after IFX, respectively. EULAR response differed significantly according to the ANA titer before IFX (P = 0.001), and the efficacy of IFX became worse as the ANA titer before starting IFX increased. Furthermore, the differences in the clinical response of the ANA titer before IFX ≤ 1:80 and ≥ 1:160 were significant (good, moderate, and no response were 66%, 9%, and 25% in ≤ 1:80 group versus 26%, 33%, 41% in ≥ 1:160 group, respectively; P < 0.001). In 13 patients whose ANA had increased after IFX, 10 showed NOR, only one showed a good response, and none reached remission. These clinical responses were significantly different from ANA no-change patients. In 21 patients with positive anti-ds-DNA Abs after IFX, 16 showed NOR, only two showed a good response, and none reached remission.
Conclusions: The present study suggests that the ANA titer before starting IFX predicts the clinical response to IFX. The increased titers of ANA or anti-ds-DNA Abs after IFX may be useful markers of NOR.
Introduction
Rheumatoid arthritis (RA) is a chronic, inflammatory disease with the potential to cause substantial joint damage and disability. Tumor necrosis factor (TNF)-α plays a central role in the pathogenesis of RA, as demonstrated by the clinical benefit of anti-TNF-α therapy. Infliximab (IFX), a chimeric anti-human TNF-α monoclonal antibody, has enabled great advances in the treatment strategy for RA, resulting in a paradigm shift of RA treatment. Although IFX therapy concomitant with methotrexate (MTX) is effective in the majority of RA patients, some patients have persistent active disease, and others lose efficacy after prolonged treatment. However, no useful clinical marker has been established to predict such nonresponse (NOR) to IFX.
The induction of antinuclear antibodies (ANAs) and anti-double stranded (ds)-DNA antibodies (Abs) during IFX therapy is a well-known phenomenon that has already been observed in earlier clinical trials. It has been reported that the induction of ANAs is independent of the IFX dose and is not modified by concomitant treatment with MTX, leflunomide, and corticosteroid. Furthermore, the production of ANA is not associated with the clinical response to IFX, and even when the development of anti-ds-DNA Abs is observed, onset of lupus-like symptoms is extremely rare. Thus, the significance of the development of such antibodies, including correlations of ANAs and anti-ds-DNA Abs with NOR in RA, has not yet been determined.
Recently, it was reported that the development of ANAs and anti-ds-DNA Abs with anti-TNF therapies may act as a marker of forthcoming treatment failure in patients with psoriasis. Conversely, as in RA patients, it has been reported that ANAs are a predictive factor of infusion reactions during IFX as well as without MTX. On the basis of these findings, the aims of this retrospective observational study were to examine the prevalence of positive ANAs and anti-ds-DNA Abs before and after IFX therapy in patients with RA, and to investigate whether the induction or increased titer of such Abs is associated with the clinical efficacy of IFX.