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Neurology. 2014 Jan 7;82(1):41-8. doi: 10.1212/01.wnl.0000438216.93319.ab. Epub 2013 Dec 4.

Effects of Bacille Calmette-Guerin after the first demyelinating event in the CNS.

Author information

1
From the Center for Experimental Neurological Therapies (G.R., S.R., S.C., A.V., C.B., G.C., M.S.), S. Andrea Hospital-site, Neurosciences, Mental Health, and Sensory Organs (NESMOS) Department and Department of Neurology and Psychiatry (E.T., M.F., C.P.), "Sapienza" University of Rome, Department of Neurological Sciences (C.G.), Azienda Ospedaliera S Camillo-Forlanini, Rome; MSCenter (L.M., D.C.) and Neuroradiology Unit (P.C.), Fondazione don Carlo Gnocchi, IRCCS, Milan; Department of Neurological Sciences (R.L., V.B.), Federico II University, and Biostructure and Bioimaging Institute (M.Q.), CNR, Naples; and National Centre of Epidemiology (N.V.), National Institute of Health, Rome, Italy.

Abstract

OBJECTIVE:

To evaluate Bacille Calmette-Guérin (BCG) effects after clinically isolated syndromes (CIS).

METHODS:

In a double-blind, placebo-controlled trial, participants were randomly assigned to receive BCG or placebo and monitored monthly with brain MRI (6 scans). Both groups then entered a preplanned phase with IM interferon-β-1a for 12 months. From month 18 onward, the patients took the disease-modifying therapies (DMTs) that their neurologist considered indicated in an open-label extension phase lasting up to 60 months.

RESULTS:

Of 82 randomized subjects, 73 completed the study (33 vaccinated and 40 placebo). During the initial 6 months, the number of cumulative lesions was significantly lower in vaccinated people. The relative risks were 0.541 (95% confidence interval [CI] 0.308-0.956; p = 0.03) for gadolinium-enhancing lesions (the primary endpoint), 0.364 (95% CI 0.207-0.639; p = 0.001) for new and enlarging T2-hyperintense lesions, and 0.149 (95% CI 0.046-0.416; p = 0.001) for new T1-hypointense lesions. The number of total T1-hypointense lesions was lower in the BCG group at months 6, 12, and 18: mean changes from baseline were -0.09 ± 0.72 vs 0.75 ± 1.81 (p = 0.01), 0.0 ± 0.83 vs 0.88 ± 2.21 (p = 0.08), and -0.21 ± 1.03 vs 1.00 ± 2.49 (p = 0.02). After 60 months, the cumulative probability of clinically definite multiple sclerosis was lower in the BCG + DMT arm (hazard ratio = 0.52, 95% CI 0.27-0.99; p < 0.05), and more vaccinated people remained DMT-free (odds ratio = 0.20, 95% CI 0.04-0.93; p = 0.04).

CONCLUSIONS:

Early BCG may benefit CIS and affect its long-term course.

CLASSIFICATION OF EVIDENCE:

BCG, as compared to placebo, was associated with significantly reduced development of gadolinium-enhancing lesions in people with CIS for a 6-month period before starting immunomodulating therapy (Class I evidence).

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