Medication persistence among people with multiple sclerosis in Slovenia treated with dimethyl fumarate

Abstract

Objective

Multiple sclerosis is a chronic, demyelinating inflammatory disease of the central nervous system. Medication persistence is defined as an interval between the initiation and last dose of the applied medication and presents a useful surrogate marker of a stable disease course. This observational study aimed to evaluate medication persistence and discontinuation reasons in Slovenian people with multiple sclerosis treated with dimethyl fumarate.

Methods

Our retrospective cohort study evaluated people with relapsing-remitting multiple sclerosis treated with dimethyl fumarate as an initial monotherapy or switched from injectable disease-modifying therapy medication between 2014 and 2021. Medication dispenses were extracted from the Slovenian National Institute of Public Health Outpatient Medication Database. The medication persistence criterion was based on the treatment gap. Patients exceeding a 60-day gap were considered nonpersistent. The median time to discontinuation was assessed using survival analyses. Considering discontinuation reasons, patients were further divided into safety and inefficacy groups. Due to the high probability of adverse effects, patients exceeding a 60-day gap were included in the safety group, but definite discontinuation reason remains unknown. The impact of covariates was evaluated by Cox regression.

Results

A total of 269 patients were included (183 women, mean age 37 years). During the 7-year follow-up period, 123 (45.7%) patients discontinued treatment. The median time to discontinuation was 5.6 years. After 1, 2, and 5 years of treatment, 84%, 77%, and 57% of patients were found to be persistent, respectively. All patients older than 30 years (p = 0.0013) and among them, those in the inefficacy group (p = 0.037) were more likely to be persistent.

Conclusions

The results of our study proved a high persistence rate among our patients. The most frequent discontinuation reason was gastrointestinal adverse effects. Medication persistence requires interventions in younger patients with an unstable disease course.

Keywords:

• Multiple sclerosis
• dimethyl fumarate
• Slovenia
• medication persistence

Transparency

 

Declaration of funding

This work was supported by the Slovenian Research Agency (Programme Group No. P1-0189, assigned to MK). The Slovenian Research Agency had no role in the design and conduct of the study; analysis and interpretation of data; preparation, approval, and submission of the manuscript for publication.

Declaration of financial/other relationships

MJ: None declared.

IL: received consultation and/or speaker fees from Novartis.

GBJ: participated as a clinical investigator and/or received consultation and/or speaker fees from: Biogen, Janssen, Lek, Merck, Novartis, Pliva/Teva, Roche, Sanofi Genzyme, and Swixx.

MK: Research contracts with Krka, Vizera, Clinres, and Phamalinea with the aim of statistical analysis and a grant from AstraZeneca as support to developments of sustainability and resilience of the healthcare system after the COVID-19 pandemic.

UR: participated as a clinical investigator and/or received consultation and/or speaker fees from: Bayer, Biogen, Sanofi Genzyme, Merck, Novartis, Pliva/Teva, and Roche.

A reviewer on this manuscript has disclosed that they have received reimbursement for developing educational presentations, educational and research grants, consultation fees, and/or travel stipends from Biogen Argentina and LATAM, Genzyme Argentina, Merck Argentina and LATAM, Roche Argentina and LATAM, Raffo, Novartis Argentina, AstraZeneca Argentina, Horizon therapeutics, LACTRIMS, Harvard Medical School (Postgraduate Medical Education), The Guthy-Jackson Charitable Foundation and The Sumaira Foundation. All peer reviewers on this manuscript have received an honorarium from CMRO for their review work.

Author contributions

All authors are accountable for all aspects of the work and made a contribution to the reported study, considering conception, study design, drafting, execution, acquisition of data, analysis, interpretation, revising or critically reviewing the article, and allowing the final approval of the published version in the journal to which the article has been submitted.

Acknowledgements

None.

Data availability statement

Data are available from the corresponding author on a reasonable request.

Patient and public involvement

Patients or the public were not directly involved in this study’s design, conduct, reporting, or dissemination plans.

Consent to participate

No informed consent was required for this database study because there were no direct contacts with the patients. All personal information was anonymized for the purpose of analysis.