A systematic review of modifiable risk factors in the progression of multiple sclerosis.
BACKGROUND
The presenting symptoms and rate of progression of multiple sclerosis (MS) are very heterogeneous. The diverse clinical manifestations and the clinical course of the disease may vary with modifiable risk factors.


OBJECTIVE
To systematically review modifiable risk factors and exposures associated with MS progression.


METHODS
We searched six databases till March 2015, reference-mined reviews, and consulted with experts (PROSPERO 2015:CRD42015016461). Two reviewers screened and extracted data. We used random meta-analysis models and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the quality of evidence.


RESULTS
In total, 59 studies met inclusion criteria. Lower vitamin D levels were associated with higher Expanded Disability Status Scale (EDSS) scores ( r = -0.22; confidence interval (CI) = -0.32, -0.12; 11 studies; I2= 66%), smokers had an increased risk of MS progression (hazard ratio (HR) = 1.55; CI = 1.10, 2.19; I2= 72%; seven studies), and there was no association of MS progression with the use of epidural analgesics during childbirth delivery (three studies). There was insufficient evidence to draw conclusions for 11 risk factors due to conflicting results or use of different predictor and outcome measures.


CONCLUSIONS
MS progression was consistently associated with low vitamin D levels, and smoking was associated with a more rapid decline in MS disability. Studies used a variety of methods, predictors, and outcomes making it difficult to draw conclusions. Future studies should focus on prospective assessments.
Southern California Evidence-based Practice Center, RAND Corporation, Santa Monica, CA, USA.
Susanne
S
Hempel
Specialty Care Services, U.S. Department of Veterans Affairs, Washington, DC, USA/Department of Neurology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Glenn D
GD
Graham
Southern California Evidence-based Practice Center, RAND Corporation, Santa Monica, CA, USA.
Ning
N
Fu
Evidence-based Synthesis Program (ESP) Center, West Los Angeles VA Medical Center, Los Angeles, CA, USA.
Elena
E
Estrada
Evidence-based Synthesis Program (ESP) Center, West Los Angeles VA Medical Center, Los Angeles, CA, USA.
Annie Y
AY
Chen
Evidence-based Synthesis Program (ESP) Center, West Los Angeles VA Medical Center, Los Angeles, CA, USA.
Isomi
I
Miake-Lye
Southern California Evidence-based Practice Center, RAND Corporation, Santa Monica, CA, USA.
Jeremy N V
JN
Miles
Southern California Evidence-based Practice Center, RAND Corporation, Santa Monica, CA, USA.
Roberta
R
Shanman
Southern California Evidence-based Practice Center, RAND Corporation, Santa Monica, CA USA/Evidence-based Synthesis Program (ESP) Center, West Los Angeles VA Medical Center, Los Angeles, CA, USA.
Paul G
PG
Shekelle
Evidence-based Synthesis Program (ESP) Center, West Los Angeles VA Medical Center, Los Angeles, CA, USA.
Jessica M
JM
Beroes
Multiple Sclerosis Centers of Excellence-East, U.S. Department of Veterans Affairs, Washington, DC, USA/Department of Neurology, School of Medicine, Georgetown University, Washington, DC, USA.
Mitchell T
MT
Wallin
D018450:Disease Progression; D006801:Humans; D009103:Multiple Sclerosis / Q000150:complications* / Q000378:metabolism; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014807:Vitamin D / Q000378:metabolism*
D014807:Vitamin D
Multiple sclerosis; multiple sclerosis progression; prognostic study; risk factors; systematic review