The online version of this article (doi:10.1186/s12883-017-0831-4) contains supplementary material, which is available to authorized users.
Continuation of interferon (IFN) β-based therapies is important for maximum treatment effectiveness in patients with multiple sclerosis (MS); however, few real-world data are available on discontinuation from IFN β. The aim of this cohort analysis was to estimate real-world discontinuation rates up to 3 years among MS patients in the United States taking subcutaneous (sc) IFN β-1a three times a week (tiw) and to identify whether the factors associated with discontinuation change over time.
Patient data were pooled from the MarketScan© Commercial and Medicare Supplemental healthcare claims databases. Patients with ≥1 multiple sclerosis diagnosis who were sc IFN β-1a tiw naïve, had ≥1 year of continuous eligibility before treatment, and ≥1 prescription were followed from first prescription (index date) until date of discontinuation, switch, or end of observation. Treatment status was analysed at exactly 1, 2 or 3 years after index. Multivariable models were used to identify drivers of discontinuation.
Data from 5956 patients were included; 2862 patients (48.1%) discontinued therapy. Discontinuation rates were 36.9% (1 year), 49.5% (2 years) and 55.8% (3 years). A greater proportion of discontinuing patients had poor adherence (<80% [94.0%] versus ≥80% [51.7%]) or were taking additional medication at follow-up versus the overall population. Factors independently associated with discontinuation irrespective of time on therapy were increasing number of magnetic resonance imaging scans (1 year adjusted odds ratio 1.45, 95% confidence interval 1.26–1.67; 2 years 1.18, 1.06–1.32; 3 years 1.20, 1.07–1.34) and adherence <80% versus ≥80% (1 year 180.95, 135.84–241.03; 2 years 135.80, 100.10–184.23; 3 years 174.89, 115.27–265.38). Factors associated only with early discontinuation (at 1 year) were ≥3 sets of laboratory investigations versus none (2.54, 1.20–5.38), and anxiolytic use at follow-up (1.40, 1.06–1.82). Factors associated only with later discontinuation (at 2 years and/or at 3 years) were antidepressant use at follow-up (2 years 1.46, 1.10–1.94) and greater number of relapses (2 years 1.60, 1.11–2.30; 3 years 2.31, 1.27–4.22).
Potential drivers of discontinuation change over time. Improved awareness of the drivers of discontinuation could lead to targeted interventions to improve adherence.
Additional file 1: Table S1. Health care resource usage of patients with multiple sclerosis initiating subcutaneous interferon β-1a, three times weekly by discontinuation status. Table S2. Crude odds ratios of factors associated with discontinuation of subcutaneous interferon β-1a, three times weekly, at 1, 2, and 3 years, respectively. Table S3. Adjusted odds ratios of factors associated with discontinuation of subcutaneous interferon β-1a, three times weekly, at 1, 2, and 3 years, respectively, with adherence removed from the model. (DOCX 36 kb)12883_2017_831_MOESM1_ESM.docx
WHO. Adherence to long-term therapies: evidence for action. Geneva: WHO; 2003.
Kappos L, Kuhle J, Multanen J, Kremenchutzky M, Verdun di Cantogno E, Cornelisse P, Lehr L, Casset-Semanaz F, Issard D, Uitdehaag BM. Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15. J Neurol Neurosurg Psychiatry. 2015;86(11):1202–7. CrossRefPubMedPubMedCentral
Zhornitsky S, Greenfield J, Koch MW, Patten SB, Harris C, Wall W, Alikhani K, Burton J, Busche K, Costello F, et al. Long-term persistence with injectable therapy in relapsing-remitting multiple sclerosis: an 18-year observational cohort study. PLoS One. 2015;10(4):e0123824. CrossRefPubMedPubMedCentral
Ollendorf DA, Jilinskaia E, Oleen-Burkey M. Clinical and economic impact of glatiramer acetate versus beta interferon therapy among patients with multiple sclerosis in a managed care population. J Manag Care Pharm. 2002;8(6):469–76. PubMed
Hupperts R, Ghazi-Visser L, Martins Silva A, Arvanitis M, Kuusisto H, Marhardt K, Vlaikidis N. The STAR Study: a real-world, international, observational study of the safety and tolerability of, and adherence to, serum-free subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis. Clin Ther. 2014;36(12):1946–57. CrossRefPubMed
Yao S. FDA approves new multiple sclerosis treatment: Tecfidera [Press release]. Retrieved from: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm345528.htm. Accessed 18 Jan 2016.
Biogen Idec. Biogen Idec total revenues increased 32% to $1.8 billion in the third quarter; company raise 2013 financial guidance [Press release]. Retrieved from http://media.biogen.com/press-release/investor-relations/biogen-idec-total-revenues-increased-32-18-billion-third-quarter-co. Accessed 18 Jan 2016. [ http://media.biogen.com/press-release/investor-relations/biogen-idec-total-revenues-increased-32-18-billion-third-quarter-co].
- Reasons for discontinuation of subcutaneous interferon β-1a three times a week among patients with multiple sclerosis: a real-world cohort study
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