Clinical trial evidence of quality-of-life effects of disease-modifying therapies for multiple sclerosis: a systematic analysis

Abstract

Background: Increasingly, patients, clinicians, and regulators call for more evidence on the impact of innovative medicines on quality of life (QoL). We assessed the effects of disease-modifying therapies (DMTs) on QoL in people with multiple sclerosis (PwMS).

Methods: Randomized trials assessing approved DMTs in PwMS with results for at least one outcome referred to as "quality of life" were searched in PubMed and ClinicalTrials.gov.

Results: We identified 38 trials published between 1999 and 2023 with a median of 531 participants (interquartile range (IQR) 202 to 941; total 23,225). The evaluated DMTs were mostly interferon-beta (n = 10; 26%), fingolimod (n = 7; 18%), natalizumab (n = 5; 13%), and glatiramer acetate (n = 4; 11%). The 38 trials used 18 different QoL instruments, with up to 11 QoL subscale measures per trial (median 2; IQR 1-3). QoL was never the single primary outcome. We identified quantitative QoL results in 24 trials (63%), and narrative statements in 15 trials (39%). In 16 trials (42%), at least one of the multiple QoL results was statistically significant. The effect sizes of the significant quantitative QoL results were large (median Cohen's d 1.02; IQR 0.3-1.7; median Hedges' g 1.01; IQR 0.3-1.69) and ranged between d 0.14 and 2.91.

Conclusions: Certain DMTs have the potential to positively impact QoL of PwMS, and the assessment and reporting of QoL is suboptimal with a multitude of diverse instruments being used. There is an urgent need that design and reporting of clinical trials reflect the critical importance of QoL for PwMS.

Keywords: (MeSH): Multiple sclerosis; Patient-reported outcome measures; Quality of life; Randomized controlled trial; Systematic review.

Fig. 1

Distribution of p values (116 QoL results from 30 trials). Note: The 116 QoL results come from 89 quantitative results and 27 reported as p values alone. Abbreviations: DMT disease-modifying therapy, EQ-5D European Quality of Life Dimensions, FAMS Functional Assessment of Multiple Sclerosis, GHQ VAS General Health Questionnaire Visual Analog Scale, HAQUAMS Hamburg Quality of Life Questionnaire for Multiple Sclerosis, MSIS Multiple Sclerosis Impact Scale, MSQLI Multiple Sclerosis Quality of Life Inventory, MSQOL Multiple Sclerosis Quality of Life, MSTCQ Multiple Sclerosis Treatment Concerns Questionnaire, MusiQoL Multiple Sclerosis International Quality of Life, n number, NEI-VFQ National Eye Institute Visual Functioning Questionnaire, QoL quality of life, SF Short Form