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

Giovanni Ristori, Silvia Romano, Stefania Cannoni, Andrea Visconti, Emanuele Tinelli, Laura Mendozzi, Pietro Cecconi, Roberta Lanzillo, Mario Quarantelli, Carla Buttinelli, Claudio Gasperini, Marco Frontoni, Giulia Coarelli, Domenico Caputo, Vincenzo Bresciamorra, Nicola Vanacore, Carlo Pozzilli, Marco Salvetti

Research output: Contribution to journalArticle

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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 1 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).

Original languageEnglish
Pages (from-to)41-48
Number of pages8
JournalNeurology
Volume82
Issue number1
DOIs
Publication statusPublished - Jan 7 2014

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Confidence Intervals
Placebos
Gadolinium
Therapeutics
Interferons
Multiple Sclerosis
Odds Ratio
Magnetic Resonance Imaging
Lesion
Central Nervous System
Confidence Interval
Brain
Placebo
Therapy
Syndrome

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Ristori, G., Romano, S., Cannoni, S., Visconti, A., Tinelli, E., Mendozzi, L., ... Salvetti, M. (2014). Effects of Bacille Calmette-Guérin after the first demyelinating event in the CNS. Neurology, 82(1), 41-48. https://doi.org/10.1212/01.wnl.0000438216.93319.ab

Effects of Bacille Calmette-Guérin after the first demyelinating event in the CNS. / Ristori, Giovanni; Romano, Silvia; Cannoni, Stefania; Visconti, Andrea; Tinelli, Emanuele; Mendozzi, Laura; Cecconi, Pietro; Lanzillo, Roberta; Quarantelli, Mario; Buttinelli, Carla; Gasperini, Claudio; Frontoni, Marco; Coarelli, Giulia; Caputo, Domenico; Bresciamorra, Vincenzo; Vanacore, Nicola; Pozzilli, Carlo; Salvetti, Marco.

In: Neurology, Vol. 82, No. 1, 07.01.2014, p. 41-48.

Research output: Contribution to journalArticle

Ristori, G, Romano, S, Cannoni, S, Visconti, A, Tinelli, E, Mendozzi, L, Cecconi, P, Lanzillo, R, Quarantelli, M, Buttinelli, C, Gasperini, C, Frontoni, M, Coarelli, G, Caputo, D, Bresciamorra, V, Vanacore, N, Pozzilli, C & Salvetti, M 2014, 'Effects of Bacille Calmette-Guérin after the first demyelinating event in the CNS', Neurology, vol. 82, no. 1, pp. 41-48. https://doi.org/10.1212/01.wnl.0000438216.93319.ab
Ristori, Giovanni ; Romano, Silvia ; Cannoni, Stefania ; Visconti, Andrea ; Tinelli, Emanuele ; Mendozzi, Laura ; Cecconi, Pietro ; Lanzillo, Roberta ; Quarantelli, Mario ; Buttinelli, Carla ; Gasperini, Claudio ; Frontoni, Marco ; Coarelli, Giulia ; Caputo, Domenico ; Bresciamorra, Vincenzo ; Vanacore, Nicola ; Pozzilli, Carlo ; Salvetti, Marco. / Effects of Bacille Calmette-Guérin after the first demyelinating event in the CNS. In: Neurology. 2014 ; Vol. 82, No. 1. pp. 41-48.
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abstract = "Objective: To evaluate Bacille Calmette-Gu{\'e}rin (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 1 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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AU - Ristori, Giovanni

AU - Romano, Silvia

AU - Cannoni, Stefania

AU - Visconti, Andrea

AU - Tinelli, Emanuele

AU - Mendozzi, Laura

AU - Cecconi, Pietro

AU - Lanzillo, Roberta

AU - Quarantelli, Mario

AU - Buttinelli, Carla

AU - Gasperini, Claudio

AU - Frontoni, Marco

AU - Coarelli, Giulia

AU - Caputo, Domenico

AU - Bresciamorra, Vincenzo

AU - Vanacore, Nicola

AU - Pozzilli, Carlo

AU - Salvetti, Marco

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N2 - 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 1 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).

AB - 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 1 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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