Table 3.
Summary of findings.
| Risk factor | Meta-analysis of all studies |
Effect size measure | Assessment of certainty (GRADE)a | |
|---|---|---|---|---|
| Effect size (95% CI) | P-value | |||
| Overall demographics | ||||
| Age | 1.45 (1.17, 1.79) | 0.001 | OR per 10 years | Moderateb |
| Male sex | 1.54 (1.31, 1.81) | < 0.001 | OR vs. female | High |
| Comorbidities | ||||
| Obesity | 1.87 (1.25, 2.80) | 0.002 | OR vs. non-obese) | Moderateb |
| Diabetes | 1.87 (1.46, 2.40) | < 0.001 | OR vs. non-diabetic | High |
| Pulmonary comorbidities | 1.50 (1.12, 2.01) | 0.007 | OR vs. no pulmonary comorbidities | High |
| Cardiovascular comorbidities | 1.96 (1.47, 2.60) | < 0.001 | OR vs. no CV comorbidities | High |
| Hypertension | 1.90 (1.30, 2.78) | 0.001 | OR vs. no HTN | Moderateb |
| Current/past Smoking | 0.98 (0.79, 1.22) | 0.845 | OR vs. never-smokers | High |
| MS characteristics | ||||
| Progressive MS | 3.74 (2.57, 5.46) | < 0.001 | OR vs. non-progressive MS | High |
| 3 < EDSS < 6 | 2.12 (1.38, 3.28) | 0.001 | OR vs. EDSS < 3 | Moderateb |
| EDSS > 6 | 3.48 (1.67, 7.24) | 0.001 | ||
| Disease duration | 3.93 (3.07, 4.80) | < 0.001 | Mean difference | Moderatec |
| Corticosteroid in past 2 months | 2.63 (1.78, 3.87) | < 0.001 | OR vs. no corticosteroid in past 2 months | Moderatec |
| DMTs | ||||
| Interferons | 0.37 (0.20, 0.67) | 0.001 | OR vs. no DMTs | High |
| Glatiramer | 0.78 (0.47, 1.32) | 0.358 | Moderated | |
| Teriflunomide | 0.66 (0.39, 1.12) | 0.125 | Moderatee | |
| Fumarate | 0.73 (0.50, 1.08) | 0.116 | Moderatee | |
| Fingolimod | 0.76 (0.50, 1.18) | 0.222 | Moderatee | |
| Anti-CD20 | 1.43 (1.10, 1.88) | 0.008 | High | |
| Natalizumab | 0.82 (0.54, 1.24) | 0.342 | Moderatee | |
| Alemtuzumab | 0.80 (0.25, 2.52) | 0.698 | Lowf | |
| Cladribine | 0.28 (0.05, 1.58) | 0.148 | Lowf | |
CI: confidence interval; OR: odds ratio; CV: cardiovascular; HTN: hypertension; MS: multiple sclerosis; EDSS: expanded disability status scale; DMT: disease-modifying therapy.
a
Based on a consensus reached by three independent reviewers (NS, ME, and MRM). The baseline certainty was considered as moderate, as the meta-analysis was performed on observational non-randomized studies, however, if the results from an adequate number of studies showed no sign of inconsistency, imprecision, and risk of missing results, the certainty was upgraded to high.
b
Due to inconsistency.
c
Due to limited number of studies.
d
Due to imprecision and risk of missing results.
e
Due to imprecision.
f
Due to imprecision and limited number of studies.