Predictors of patient-reported fatigue symptom severity in a nationwide multiple sclerosis cohort.

Background: Fatigue is a debilitating symptom of multiple sclerosis (MS), but its relation to sociodemographic and disease-related characteristics has not been investigated in larger studies. The objectives of this study were to evaluate predictors of self-reported fatigue in a Swedish nationwide register-based MS cohort.
Methods: Using a repeated cross-sectional design, we included 2,165 persons with relapsing- remitting and secondary progressive MS with one or multiple Fatigue Scale for Motor and Cognitive Functions (FSMC) scores, which was modelled using multivariable linear regressions for multiple predictors.
Results: Only associations to expanded disability status scale (EDSS) and Symbol Digit Modalities Test (SDMT) were considered clinically meaningful among MS-associated characteristics in our main model; compared to mild disability (EDSS 0-2.5), those with severe disability (EDSS ≥6) scored 17.6 (95% CI 13.1-22.2) FSMC points higher, while the difference was 10.7 (95% CI 8.0-13.4) points for the highest and lowest quartiles of SDMT. Differences between highest and lowest quartiles of health-related quality of life (HRQoL) instruments were even greater and considered clinically meaningful; EuroQoL Visual Analogue Scale (EQ-VAS) 31.9 (95% CI 29.9-33.8), Multiple Sclerosis Impact Scale (MSIS-29) psychological component 35.6 (95% CI 33.8-37.4) and MSIS-29 physical component 45.5 (95% CI 43.7-47.4).
Conclusion: Higher self-reported fatigue is associated with higher disability level and worse cognitive processing speed, while associations to other MS-associated characteristics including MS type, line of disease modifying therapy (DMT), MS duration, relapse and new cerebral lesions are weak. Furthermore, we found a strong correlation between high fatigue rating and lower ratings on health-related quality of life instruments.
Competing Interests: Declaration of Competing Interest Simon Englund declare that there is no conflict of interest; Marie Kierkegaard has received honoraria for lectures from Sanofi, Genzyme Roche and Novartis; Joachim Burman declare that there is no conflict of interest; Katharina Fink has received lecture honoraria from Biogen and Merck, has served on scientific advisory boards for Biogen, Roche, Merck and Alexion, has received a research grant from Amicus; Anna Fogdell-Hahn has received unrestricted funding from Biogen Idec, Pfizer, Orion Pharma and Celltrion, speaking honoraria from Merck, and consulting fee from Roche; Martin Gunnarsson declare that there is no conflict of interest; Jan Hillert has received honoraria for serving on advisory boards for Biogen, Celgene, Sanofi-Genzyme, Merck KGaA, Novartis and Sandoz and speaker's fees from Biogen, Novartis, Merck KGaA, Teva and Sanofi-Genzyme. He has served as P.I. for projects, or received unrestricted research support from, Biogen, Celgene, Merck KGaA, Novartis, Roche and Sanofi-Genzyme. His MS research was funded by the Swedish Research Council and the Swedish Brain foundation; Annette Langer-Gould receives grant support and awards from the Patient Centered Outcomes Research Institute and the National MS Society; she currently serves as a voting member on the California Technology Assessment Forum, a core program of the Institute for Clinical and Economic Review (ICER). She has received sponsored and reimbursed travel from ICER and the National Institutes of Health; Jan Lycke has received travel support and/or lecture honoraria from Biogen, BMS, Novartis, Sanofi, Roche and Alexion, has served on scientific advisory boards for Biogen, BMS, Novartis, Sanofi, Roche and Alexion, serves on the editorial board of the Acta Neurologica Scandinavica, and has received unconditional research grants from Biogen and Novartis. Petra Nilsson has received travel support from Bayer Schering Pharma, Merck Serono, Biogen and Genzyme a Sanofi Company, honoraria for lectures and advisory boards from Merck Serono and Genzyme a Sanofi Company, advisory boards for Novartis and Roche, lectures for Biogen and has received unrestricted grants from Biogen. Jonatan Salzer has received institutional fees from Mabion S.A. for serving as a consultant in a clinical trial. Anders Svenningsson declare that there is no conflict of interest; Johan Mellergård has received honoraria for Advisory boards for Sanofi Genzyme and Merck and lecture honoraria from Merck; Tomas Olsson has received honoraria for lectures/advisory boards, and unrestricted MS research grants from Biogen, Novartis, Sanofi, Merck and Roche; Elisa Longinetti declare that there is no conflict of interest; Thomas Frisell declare that there is no conflict of interest; Fredrik Piehl has received research grants from Janssen, Merck KGaA and UCB, and fees for serving on DMC in clinical trials with Chugai, Lundbeck and Roche, and preparation of expert witness statement for Novartis. There is no commercial entity relevant for potential conflicts.
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