The effect of disease modifying therapies on fatigue in multiple sclerosis

Samantha Cruz Rivera; Olalekan Lee Aiyegbusi; Daniela Piani Meier; Achille Dunne; Danielle E Harlow; Christian Henke; Paul Kamudoni; Melanie J Calvert

doi:10.1016/j.msard.2023.105065

The effect of disease modifying therapies on fatigue in multiple sclerosis

Mult Scler Relat Disord. 2023 Nov:79:105065. doi: 10.1016/j.msard.2023.105065. Epub 2023 Oct 10.

Authors

Samantha Cruz Rivera¹, Olalekan Lee Aiyegbusi², Daniela Piani Meier³, Achille Dunne⁴, Danielle E Harlow⁵, Christian Henke⁴, Paul Kamudoni⁴, Melanie J Calvert⁶

Affiliations

¹ Centre for Patient Reported Outcomes Research, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, UK; Birmingham Health Partners Centre for Regulatory Science and Innovation, University of Birmingham, Birmingham, UK. Electronic address: s.rivera@bham.ac.uk.
² Centre for Patient Reported Outcomes Research, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, UK; Birmingham Health Partners Centre for Regulatory Science and Innovation, University of Birmingham, Birmingham, UK; National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, UK; NIHR Applied Research Collaboration (ARC) West Midlands, University of Birmingham, Birmingham, UK; NIHR Blood and Transplant Research Unit (BTRU) in Precision Transplant and Cellular Therapeutics, University of Birmingham, UK.
³ Ares Trading SA, Eysins, An affiliate of Merck KGaA, Switzerland.
⁴ Merck KGaA, Darmstadt, Germany.
⁵ EMD Serono, Billerica, Massachusetts, US.
⁶ Centre for Patient Reported Outcomes Research, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, UK; Birmingham Health Partners Centre for Regulatory Science and Innovation, University of Birmingham, Birmingham, UK; National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, UK; NIHR Applied Research Collaboration (ARC) West Midlands, University of Birmingham, Birmingham, UK; NIHR Blood and Transplant Research Unit (BTRU) in Precision Transplant and Cellular Therapeutics, University of Birmingham, UK; UK SPINE, University of Birmingham, Birmingham, UK; Health Data Research, Birmingham, UK.

PMID: 37839365
DOI: 10.1016/j.msard.2023.105065

Abstract

Introduction: Fatigue is one of the most common and debilitating symptoms in people with multiple sclerosis (PwMS). Disease-modifying therapies (DMTs) are currently the gold standard in the treatment of MS and their effectiveness has been assessed through randomized clinical trials (RCTs). However, there is limited evidence on the impact of DMTs on fatigue in (PwMS). We conducted a systematic review to 1) understand whether fatigue is included as an outcome in MS trials of DMTs; 2) determine the effects on fatigue of treating MS with DMTs and 3) assess the quality of MS trials including fatigue as an outcome.

Methods: Two independent researchers systematically searched MEDLINE, EMBASE and ClinicalTrials.gov from 1993 to January 2023 for RCTs that measured fatigue as an outcome. Adherence to reporting standards was assessed with the Consolidated Standards of Reporting Trials (CONSORT)-Patient-Reported Outcomes (PRO), while the risk of bias (RoB) was assessed with the RoB 2 tool by the Cochrane Handbook for Systematic Reviews of Interventions. The systematic review protocol was registered in PROSPERO (CRD42022383321).

Results: The search strategy identified 130 RCTs of DMTs of which 7 (5%) assessed fatigue as an outcome. Of the 7 trials, only two presented statistically significant results. In addition, the reporting of fatigue among RCTs was suboptimal with a mean adherence to the CONSORT-PRO Statement of 36% across all trials. Of the 7 trials included, four were assessed as 'high' RoB..

Conclusions: Fatigue has a major impact on PwMS yet there is limited trial-based evidence on the impact of DMTs on fatigue. Assessment of fatigue as an outcome is underrepresented in trials of DMTs and the reporting of PRO trial data is suboptimal. Thus, it is imperative that MS researchers conduct RCTs that include fatigue as an outcome, to support clinicians and people with MS (PwMS) to consider the impact of the different DMTs on fatigue.

Keywords: Disease-modifying therapies (DMTs); Fatigue; Patient-reported outcomes (PROs).

Publication types

Review
Systematic Review

MeSH terms

Fatigue / drug therapy
Fatigue / etiology
Humans
Multiple Sclerosis* / complications
Multiple Sclerosis* / therapy
Patient Reported Outcome Measures
Reference Standards
Systematic Reviews as Topic