Table 2.

Meta-analysis of clinical trials assessing the effect of age in DMT efficacy.

Authors (ref)	Aim	Included trials and patients	Main results
Signori et al. (130)	To identify patient subgroups with larger DMT effects.	6 RCT. 6,693 RRMS patients.	DMT efficacy was higher in younger than in older subjects* measured by reduction in ARR (p <0.001) and disability progression (p =0.017).
Weideman et al. (131)	To test whether DMT efficacy in inhibiting disability progression is independent of age.	38 RCT. More than 28,000 MS patients.	The efficacy DMTs on disability strongly decreased with advancing age (p =10−8). The regression predicted lack of efficacy beyond ≈53 years. Inclusion of baseline EDSS did not significantly improve the model. HeDMTs outperformed low-efficacy DMTs for patients <40.5 years.
Zhang et al. (132)	To investigate whether age impacts the efficacy of DMTs.	26 RCT. More than 28,000 RRMS patients.	The efficacy of DMTs on reducing ARR, new T2 lesions, and Gd+ lesions was not associated with age.

annualized relapse rate, ARR, EDSS, Expanded Disability Status Scale; DMT, disease-modifying treatment; HeDMT, high-efficacy disease-modifying treatment; leDMT, low-efficacy DMT; MS, multiple sclerosis; ref, reference; RRMS, relapsing-remitting multiple sclerosis; RCT, randomized controlled trial; *patients were grouped in two age groups (‘younger’ versus ‘older’) pooling the estimates collected in the groups as defined in each trial (cut-off point of 40 or 38 years)