Background Central nervous system involvement in Behçet’s disease (neuro- Behçet’s disease [NB]) includes acute type and chronic progressive type, which may ultimately lead to the deterioration of the patients’ personality (1). Previous studies showed that infliximab (IFX) prevented the progression of chronic progressive NB along with marked reduction of cerebrospinal fluid (CSF) IL-6 levels in a 14-week open trial (2). However, the long-term efficacy and safety of IFX therapy for chronic progressive NB remains unclear.

Objectives We performed a further follow-up survey of the 5 patients who had completed the 14-week trial of IFX therapy, for as long as 6 years.

Methods Five patients (all males who were HLA-B51 positive; mean age at enrollment: 35.8±7.2 years [±SD]) with any of psychosis, dementia, urinary incontinence, or cerebellar ataxia who had been inadequately responded to methotrexate (MTX) and enrolled in the previous 14-week open trial of IFX therapy, were followed-up with regard to the clinical responses, brain magnetic resonance imaging (MRI) scans, CSF IL-6 levels and adverse events for up to 6 years.

Results In 1 of the 5 patients, IFX was withdrawn without any increase in the dose of MTX after the 14-week trial, in whom CSF IL-6 levels remained below 20 pg/ml throughout the course without exacerbation of the manifestation and brainstem atrophy on MRI scans. In another patient complicated by refractory posterior uveitis, IFX was continued every 8 weeks with CSF IL-6 levels below 20 pg/ml throughout the course without exacerbation of the neurological manifestations. In the other 3 patients, IFX was stopped after 4-9 additional infusions following the 14-week trial. However, after 3-6 months IFX was resumed along with increasing the dose of MTX in all the 3 patients due to marked elevation of CSF IL-6 levels became elevated. IFX could be discontinued after 9 infusions in 1 of the 3 patients, showing no exacerbation of the neurological manifestation nor elevation of CSF IL-6 over 20 pg/ml until now, whereas IFX was continued every 6 weeks in the remaining 2 of the 3 patients, in whom CSF IL-6 levels were not decreased below 20 pg/ml with significant progression of the neurological manifestations and brainstem atrophy on MRI scans. Mild adverse effects occurred in 2 patients during the follow-up study, including transient headache and subclinical pneumocystis pneumonia, which was resolved by using trimethoprim-sulfamethoxazole.

Conclusions These results indicate that IFX has a beneficial effect in the treatment of chronic progressive NB by reducing CSF IL-6 levels. However, there is a subset of patients who do not respond adequately to IFX. Further study is needed in order to establish an effective treatment regimen for such intractable chronic progressive NB.

1. Hirohata S. et al., Behçet’s disease. Arthritis Res Ther 2003, 5:139-146

2. Kikuchi H. et al., Effect of infliximab in progressive neuro-Behçet’s syndrome. J Neurol Sci 2008, 272:99-105

Disclosure of Interest None Declared