Antinuclear antibodies associated with reduced effects of infliximab treatment in Behçet's disease

1. Daiju Iwata¹
2. Kenichi Namba¹
3. Kazuomi Mizuuchi¹
4. Nobuyoshi Kitaichi²
5. Shigeaki Ohno³
6. Susumu Ishida¹

¹Department of Ophthalmology Hokkaido University Graduate School of Medicine
²Department of Ophthalmology Health Sciences University of Hokkaido
³Department of Ocular inflammation and Immunology Hokkaido University Graduate School of Medicine

Purpose
Infliximab, an anti-TNF-alpha monoclonal antibody has been used for the treatment of refractory intraocular inflammation of Behçet's disease, with excellent clinical effects in Japan. However, some patients showed less response to infliximab in the course of the treatment. Recently, we found developing antinuclear antibodies (ANA) in these patients. In this study we investigated the association of developing ANA with reduced effects of infliximab treatment.

Methods
Seventeen patients with Behçet's disease who had been treated over 1 year with infliximab were the subjects. 13 were males and 4 were females. Their blood results and clinical histories were obtained from medical records. The titers of ANA were calculated and results were classified as positive (ANA≧80) or negative (ANA≦40).

Results
Three patients (17.6%) had already showed positive ANA before the induction of infliximab, and 8 patients (57.1%) had newly developed positive ANA during the treatment. The development of ANA was observed after 6 months of the treatment with infliximab and gradually increased. Though ANA titers had achieved over 640 in some patients, no patients showed lupus symptoms. All of 4 patients (23.5%) who showed ocular inflammatory attacks after 6months of infliximab treatment were ANA positive. On the other hand, all of 6 patients (35.3%) with negative ANA had showed no ocular attacks.

Conclusions
This study suggests that the development of ANA during infliximab treatment may act as a predictable marker of forthcoming recurrent ocular attacks. Large-scale prospective studies are required to assess the importance of this observation.