Discontinuation of dimethyl fumarate in multiple sclerosis - a nationwide study

Malte Roar; Amalie Rhode Høgh Nielsen; Jonas Munksgaard Berg; Georgi Sirakov; Morten Stilund; Jakob Schäfer; Rikke Ratzer; Jette Frederiksen; Nasrin Asgari; Said Nasim Ashna; Henrik Boye Jensen; Matthias Kant; Ásta Theódorsdóttir; Zsolt Illes; Finn Sellebjerg; Melinda Magyari; Louise Mose Schlosser; Hilde Nordborg; Stig Wergeland; Tobias Sejbaek

doi:10.1016/j.msard.2023.105127

Discontinuation of dimethyl fumarate in multiple sclerosis - a nationwide study

Malte Roar, Amalie Rhode Høgh Nielsen, Jonas Munksgaard Berg, Georgi Sirakov, Morten Stilund, Jakob Schäfer, Rikke Ratzer, Jette Frederiksen, Nasrin Asgari, Said Nasim Ashna, Henrik Boye Jensen, Matthias Kant, Ásta Theódorsdóttir, Zsolt Illes, Finn Sellebjerg, Melinda Magyari, Louise Mose Schlosser, Hilde Nordborg, Stig Wergeland, Tobias Sejbaek^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Background: Adherence is a prerequisite for the efficacy of any drug, and previous studies have shown that non-adherence is associated with disease activity and increased health care cost in multiple sclerosis (MS). The aim of this study was to investigate rates and reasons for discontinuation of dimethyl fumarate (DMF) among people with MS on a national level and differences between clinics in Denmark. Methods: This was a nationwide, registry and population study of patients treated with DMF. We calculated standard residuals (SR) demonstrate differences between clinics. For survival analysis regarding discontinuation rates and discontinuation due to specific AEs we used log-rank test Cox-proportional hazards and plotted Kaplan-Meier graphics. Results: We included 2,448 people with MS, treated with DMF from 2013 to 2020. Average treatment duration was 26 months (5,382 treatment years). 49.2 % of patients who initiated treatment with DMF (n = 1205) were continuously treated. Reasons for discontinuation were adverse events (54.5 %, n = 656), active disease (26.1 %, n = 315), pregnancy (9.4 %, n = 113) or other reasons (13.2 %, n = 159). We compared SR to the mean regarding reasons for discontinuation and found significant differences between sites regarding gastrointestinal adverse events, flushing and lymphopenia. Discontinuation due to all adverse events, flushing and lymphopenia were more frequent in female than male patients. Conclusion: In this population-based study, we found major differences between the MS clinics in rates and reason for discontinuation of DMF. Our results suggest that management strategies during DMF treatment can reduce discontinuation rates.

Original language	English
Article number	105127
Journal	Multiple Sclerosis and Related Disorders
Volume	80
ISSN	2211-0348
DOIs	https://doi.org/10.1016/j.msard.2023.105127
Publication status	Published - Dec 2023

Keywords

Adherence
Adverse events
Dimethyl fumarate
Discontinuation
Multiple sclerosis
Nationwide registry
Humans
Male
Dimethyl Fumarate/adverse effects
Multiple Sclerosis, Relapsing-Remitting/drug therapy
Lymphopenia/chemically induced
Multiple Sclerosis/drug therapy
Immunosuppressive Agents/adverse effects
Female

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10.1016/j.msard.2023.105127

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Roar, M., Nielsen, A. R. H., Berg, J. M., Sirakov, G., Stilund, M., Schäfer, J., Ratzer, R., Frederiksen, J., Asgari, N., Ashna, S. N., Jensen, H. B., Kant, M., Theódorsdóttir, Á., Illes, Z., Sellebjerg, F., Magyari, M., Schlosser, L. M., Nordborg, H., Wergeland, S., & Sejbaek, T. (2023). Discontinuation of dimethyl fumarate in multiple sclerosis - a nationwide study. Multiple Sclerosis and Related Disorders, 80, Article 105127. https://doi.org/10.1016/j.msard.2023.105127

@article{d3dfe342213d4d47babf197892a2526c,

title = "Discontinuation of dimethyl fumarate in multiple sclerosis - a nationwide study",

abstract = "Background: Adherence is a prerequisite for the efficacy of any drug, and previous studies have shown that non-adherence is associated with disease activity and increased health care cost in multiple sclerosis (MS). The aim of this study was to investigate rates and reasons for discontinuation of dimethyl fumarate (DMF) among people with MS on a national level and differences between clinics in Denmark. Methods: This was a nationwide, registry and population study of patients treated with DMF. We calculated standard residuals (SR) demonstrate differences between clinics. For survival analysis regarding discontinuation rates and discontinuation due to specific AEs we used log-rank test Cox-proportional hazards and plotted Kaplan-Meier graphics. Results: We included 2,448 people with MS, treated with DMF from 2013 to 2020. Average treatment duration was 26 months (5,382 treatment years). 49.2 % of patients who initiated treatment with DMF (n = 1205) were continuously treated. Reasons for discontinuation were adverse events (54.5 %, n = 656), active disease (26.1 %, n = 315), pregnancy (9.4 %, n = 113) or other reasons (13.2 %, n = 159). We compared SR to the mean regarding reasons for discontinuation and found significant differences between sites regarding gastrointestinal adverse events, flushing and lymphopenia. Discontinuation due to all adverse events, flushing and lymphopenia were more frequent in female than male patients. Conclusion: In this population-based study, we found major differences between the MS clinics in rates and reason for discontinuation of DMF. Our results suggest that management strategies during DMF treatment can reduce discontinuation rates.",

keywords = "Adherence, Adverse events, Dimethyl fumarate, Discontinuation, Multiple sclerosis, Nationwide registry, Humans, Male, Dimethyl Fumarate/adverse effects, Multiple Sclerosis, Relapsing-Remitting/drug therapy, Lymphopenia/chemically induced, Multiple Sclerosis/drug therapy, Immunosuppressive Agents/adverse effects, Female",

author = "Malte Roar and Nielsen, {Amalie Rhode H{\o}gh} and Berg, {Jonas Munksgaard} and Georgi Sirakov and Morten Stilund and Jakob Sch{\"a}fer and Rikke Ratzer and Jette Frederiksen and Nasrin Asgari and Ashna, {Said Nasim} and Jensen, {Henrik Boye} and Matthias Kant and {\'A}sta The{\'o}dorsd{\'o}ttir and Zsolt Illes and Finn Sellebjerg and Melinda Magyari and Schlosser, {Louise Mose} and Hilde Nordborg and Stig Wergeland and Tobias Sejbaek",

year = "2023",

month = dec,

doi = "10.1016/j.msard.2023.105127",

language = "English",

volume = "80",

journal = "Multiple Sclerosis and Related Disorders",

issn = "2211-0348",

publisher = "Elsevier BV",

}

Roar, M, Nielsen, ARH, Berg, JM, Sirakov, G, Stilund, M, Schäfer, J, Ratzer, R, Frederiksen, J, Asgari, N, Ashna, SN, Jensen, HB, Kant, M, Theódorsdóttir, Á, Illes, Z, Sellebjerg, F, Magyari, M, Schlosser, LM, Nordborg, H, Wergeland, S & Sejbaek, T 2023, 'Discontinuation of dimethyl fumarate in multiple sclerosis - a nationwide study', Multiple Sclerosis and Related Disorders, vol. 80, 105127. https://doi.org/10.1016/j.msard.2023.105127

Discontinuation of dimethyl fumarate in multiple sclerosis - a nationwide study. / Roar, Malte; Nielsen, Amalie Rhode Høgh; Berg, Jonas Munksgaard et al.
In: Multiple Sclerosis and Related Disorders, Vol. 80, 105127, 12.2023.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Discontinuation of dimethyl fumarate in multiple sclerosis - a nationwide study

AU - Roar, Malte

AU - Nielsen, Amalie Rhode Høgh

AU - Berg, Jonas Munksgaard

AU - Sirakov, Georgi

AU - Stilund, Morten

AU - Schäfer, Jakob

AU - Ratzer, Rikke

AU - Frederiksen, Jette

AU - Asgari, Nasrin

AU - Ashna, Said Nasim

AU - Jensen, Henrik Boye

AU - Kant, Matthias

AU - Theódorsdóttir, Ásta

AU - Illes, Zsolt

AU - Sellebjerg, Finn

AU - Magyari, Melinda

AU - Schlosser, Louise Mose

AU - Nordborg, Hilde

AU - Wergeland, Stig

AU - Sejbaek, Tobias

PY - 2023/12

Y1 - 2023/12

N2 - Background: Adherence is a prerequisite for the efficacy of any drug, and previous studies have shown that non-adherence is associated with disease activity and increased health care cost in multiple sclerosis (MS). The aim of this study was to investigate rates and reasons for discontinuation of dimethyl fumarate (DMF) among people with MS on a national level and differences between clinics in Denmark. Methods: This was a nationwide, registry and population study of patients treated with DMF. We calculated standard residuals (SR) demonstrate differences between clinics. For survival analysis regarding discontinuation rates and discontinuation due to specific AEs we used log-rank test Cox-proportional hazards and plotted Kaplan-Meier graphics. Results: We included 2,448 people with MS, treated with DMF from 2013 to 2020. Average treatment duration was 26 months (5,382 treatment years). 49.2 % of patients who initiated treatment with DMF (n = 1205) were continuously treated. Reasons for discontinuation were adverse events (54.5 %, n = 656), active disease (26.1 %, n = 315), pregnancy (9.4 %, n = 113) or other reasons (13.2 %, n = 159). We compared SR to the mean regarding reasons for discontinuation and found significant differences between sites regarding gastrointestinal adverse events, flushing and lymphopenia. Discontinuation due to all adverse events, flushing and lymphopenia were more frequent in female than male patients. Conclusion: In this population-based study, we found major differences between the MS clinics in rates and reason for discontinuation of DMF. Our results suggest that management strategies during DMF treatment can reduce discontinuation rates.

AB - Background: Adherence is a prerequisite for the efficacy of any drug, and previous studies have shown that non-adherence is associated with disease activity and increased health care cost in multiple sclerosis (MS). The aim of this study was to investigate rates and reasons for discontinuation of dimethyl fumarate (DMF) among people with MS on a national level and differences between clinics in Denmark. Methods: This was a nationwide, registry and population study of patients treated with DMF. We calculated standard residuals (SR) demonstrate differences between clinics. For survival analysis regarding discontinuation rates and discontinuation due to specific AEs we used log-rank test Cox-proportional hazards and plotted Kaplan-Meier graphics. Results: We included 2,448 people with MS, treated with DMF from 2013 to 2020. Average treatment duration was 26 months (5,382 treatment years). 49.2 % of patients who initiated treatment with DMF (n = 1205) were continuously treated. Reasons for discontinuation were adverse events (54.5 %, n = 656), active disease (26.1 %, n = 315), pregnancy (9.4 %, n = 113) or other reasons (13.2 %, n = 159). We compared SR to the mean regarding reasons for discontinuation and found significant differences between sites regarding gastrointestinal adverse events, flushing and lymphopenia. Discontinuation due to all adverse events, flushing and lymphopenia were more frequent in female than male patients. Conclusion: In this population-based study, we found major differences between the MS clinics in rates and reason for discontinuation of DMF. Our results suggest that management strategies during DMF treatment can reduce discontinuation rates.

KW - Adherence

KW - Adverse events

KW - Dimethyl fumarate

KW - Discontinuation

KW - Multiple sclerosis

KW - Nationwide registry

KW - Humans

KW - Male

KW - Dimethyl Fumarate/adverse effects

KW - Multiple Sclerosis, Relapsing-Remitting/drug therapy

KW - Lymphopenia/chemically induced

KW - Multiple Sclerosis/drug therapy

KW - Immunosuppressive Agents/adverse effects

KW - Female

UR - http://www.scopus.com/inward/record.url?scp=85176426387&partnerID=8YFLogxK

U2 - 10.1016/j.msard.2023.105127

DO - 10.1016/j.msard.2023.105127

M3 - Journal article

C2 - 37956521

AN - SCOPUS:85176426387

SN - 2211-0348

VL - 80

JO - Multiple Sclerosis and Related Disorders

JF - Multiple Sclerosis and Related Disorders

M1 - 105127

ER -

Discontinuation of dimethyl fumarate in multiple sclerosis - a nationwide study

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Keywords

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