A systematic review of the effects of modifiable risk factor interventions on the progression of multiple sclerosis.
BACKGROUND
Several risk factors are associated with multiple sclerosis (MS) progression and may be amenable to intervention.


OBJECTIVE
To systematically review the evidence for interventions targeting risk factors for MS progression.


METHODS
We searched six databases and existing reviews till March 2015 and consulted with experts to identify randomized controlled trials (RCTs) of interventions targeting MS risk factors (PROSPERO 2015:CRD42015016461).


RESULTS
In total, 37 RCTs met inclusion criteria. Expanded Disability Status Scale (EDSS) scores after exercise interventions did not differ compared with untreated controls (standardized mean differences (SMDs): 0.02; confidence interval (CI): -0.40, 0.44; I2: 0%; seven RCTs; very low quality of evidence (QoE)). Dietary interventions did not show a statistically significant effect on the relative risk (RR) of progression (RR: 0.86; CI: 0.67, 1.05; I2: 0%; four RCTs; moderate QoE) compared to placebo. EDSS scores after vitamin D supplementation were not significantly different from placebo (SMD: -0.15; CI: -0.33, 0.02; I2: 0%; five RCTs; very low QoE).


CONCLUSIONS
We did not identify any risk factor interventions with significant effects on MS progression, but the overall QoE was limited. More adequately powered trials are needed on vitamin D supplementation, long-term exercise, and smoking cessation.
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
D000818:Animals; D002986:Clinical Trials as Topic; D019587:Dietary Supplements; D018450:Disease Progression; D015444:Exercise / Q000502:physiology*; D006801:Humans; D009103:Multiple Sclerosis / Q000209:etiology*; D012307:Risk Factors
MS progression; Multiple sclerosis; randomized controlled trial; risk factors; systematic review