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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 + 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).
GLOSSARY
- BCG=
- Bacille Calmette-Guérin;
- CDMS=
- clinically definite multiple sclerosis;
- CI=
- confidence interval;
- CIS=
- clinically isolated syndrome;
- CSE=
- conventional spin-echo;
- DMT=
- disease-modifying therapy;
- EDSS=
- Expanded Disability Status Scale;
- Gd=
- gadolinium;
- IFN=
- interferon;
- MS=
- multiple sclerosis;
- RR=
- relative risk;
- T1W=
- T1-weighted;
- T2W=
- T2-weighted;
- TE=
- echo time;
- TR=
- repetition time
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 15
Supplemental data at www.neurology.org
- Received December 27, 2012.
- Accepted in final form August 28, 2013.
- © 2013 American Academy of Neurology
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