Background/Purpose: Chronic progressive neurological manifestations in Behcet’s disease (BD) is characterized by progressive deterioration leading to disability either with or without a history of previous attacks, thus called chronic progressive neuro-Behcet’s disease (CPNBD). Although high doses of steroids, including steroid pulse therapy, cyclophosphamide and azathioprine have been anecdotally used in the treatment of CPNBD, the prognosis of the patients treated with such drugs have been usually miserable. Notably, methotrexate has been found effective for CPNBD in a prospective open trial with a small number of patients. However, its influences on the long-term outcome in a larger population remain unclear. The present study was designed to explore the effects of various treatment regimens, including methotrexate, on the prognosis of patients with CPNBD.

Methods: Thirty-seven patients, who met the international classification criteria for BD, and developed chronic progressive manifestations of NBD after 1988, were followed up until October 2013. The effects of various treatment regimens on prevention of death or severe disability of bedridden state were examined by Kaplan-Meier analysis and Cox’s proportional hazard model.

Results: In 37 patients with CPNBD, 28 patients (75.7%) received methotrexate. Among the 28 patients with methotrexate, no patients died and only 5 patients progressed to disability with bedridden state. By contrast, among the 9 patients without methotrexate, 5 patients died and 3 patients progressed to the bedridden state. Thus, methotrexate significantly improved the survival of patients with CPNBD (HR 0.0507, 95% CI: 0.0077-0.334, p=0.020 as calculated by Mantel-Cox test) (figure), but any of steroid pulse, azathioprine or cyclophosphamide did not. Methotrexate also significantly reduced the proportion of the patients who were progressed into the bedridden state or death (HR 0.0694, 95% CI: 0.0047-0.7327, p=0.0258 as determined by multivariate analysis in Cox proportional hazard model).

Conclusion: These results indicate that methotrexate, but not high doses of steroids, azathioprine or cyclophosphamide, is effective to prevent the progression of CPNBD. Thus, it is recommended that methotrexate should be started as soon as possible the diagnosis of CPNBD is made.

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