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Published in: BMC Neurology 1/2017

Open Access 01-12-2017 | Research article

Reasons for discontinuation of subcutaneous interferon β-1a three times a week among patients with multiple sclerosis: a real-world cohort study

Authors: Meritxell Sabidó-Espin, Rick Munschauer

Published in: BMC Neurology | Issue 1/2017

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

Potential drivers of discontinuation change over time. Improved awareness of the drivers of discontinuation could lead to targeted interventions to improve adherence.
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Literature
1.
go back to reference Wingerchuk DM, Carter JL. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc. 2014;89:225–40.CrossRefPubMed Wingerchuk DM, Carter JL. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc. 2014;89:225–40.CrossRefPubMed
2.
go back to reference WHO. Adherence to long-term therapies: evidence for action. Geneva: WHO; 2003. WHO. Adherence to long-term therapies: evidence for action. Geneva: WHO; 2003.
3.
go back to reference 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 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
4.
go back to reference Steinberg SC, Faris RJ, Chang CF, Chan A, Tankersley MA. Impact of adherence to interferons in the treatment of multiple sclerosis: a non-experimental, retrospective, cohort study. Clin Drug Investig. 2010;30(2):89–100.CrossRefPubMed Steinberg SC, Faris RJ, Chang CF, Chan A, Tankersley MA. Impact of adherence to interferons in the treatment of multiple sclerosis: a non-experimental, retrospective, cohort study. Clin Drug Investig. 2010;30(2):89–100.CrossRefPubMed
5.
go back to reference Tan H, Yu J, Tabby D, Devries A, Singer J. Clinical and economic impact of a specialty care management program among patients with multiple sclerosis: a cohort study. Mult Scler. 2010;16(8):956–63.CrossRefPubMedPubMedCentral Tan H, Yu J, Tabby D, Devries A, Singer J. Clinical and economic impact of a specialty care management program among patients with multiple sclerosis: a cohort study. Mult Scler. 2010;16(8):956–63.CrossRefPubMedPubMedCentral
6.
go back to reference Treadaway K, Cutter G, Salter A, Lynch S, Simsarian J, Corboy J, Jeffery D, Cohen B, Mankowski K, Guarnaccia J, et al. Factors that influence adherence with disease-modifying therapy in MS. J Neurol. 2009;256(4):568–76.CrossRefPubMed Treadaway K, Cutter G, Salter A, Lynch S, Simsarian J, Corboy J, Jeffery D, Cohen B, Mankowski K, Guarnaccia J, et al. Factors that influence adherence with disease-modifying therapy in MS. J Neurol. 2009;256(4):568–76.CrossRefPubMed
7.
go back to reference Smith MY, Sabido-Espin M, Trochanov A, Samuelson M, Guedes S, Corvino FA, Richy FF. Postmarketing safety profile of subcutaneous interferon beta-1a given 3 times weekly: a retrospective administrative claims analysis. J Manag Care Spec Pharm. 2015;21(8):650–60.CrossRefPubMed Smith MY, Sabido-Espin M, Trochanov A, Samuelson M, Guedes S, Corvino FA, Richy FF. Postmarketing safety profile of subcutaneous interferon beta-1a given 3 times weekly: a retrospective administrative claims analysis. J Manag Care Spec Pharm. 2015;21(8):650–60.CrossRefPubMed
8.
go back to reference 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 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
9.
go back to reference Portaccio E, Amato MP. Improving compliance with interferon-beta therapy in patients with multiple sclerosis. CNS Drugs. 2009;23(6):453–62.CrossRefPubMed Portaccio E, Amato MP. Improving compliance with interferon-beta therapy in patients with multiple sclerosis. CNS Drugs. 2009;23(6):453–62.CrossRefPubMed
10.
11.
go back to reference 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 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
12.
go back to reference Chastek BJ, Oleen-Burkey M, Lopez-Bresnahan MV. Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims. J Med Econ. 2010;13(4):618–25.CrossRefPubMed Chastek BJ, Oleen-Burkey M, Lopez-Bresnahan MV. Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims. J Med Econ. 2010;13(4):618–25.CrossRefPubMed
13.
go back to reference Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–51.CrossRefPubMed Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–51.CrossRefPubMed
14.
go back to reference Steiner JF, Prochazka AV. The assessment of refill compliance using pharmacy records: methods, validity, and applications. J Clin Epidemiol. 1997;50(1):105–16.CrossRefPubMed Steiner JF, Prochazka AV. The assessment of refill compliance using pharmacy records: methods, validity, and applications. J Clin Epidemiol. 1997;50(1):105–16.CrossRefPubMed
15.
go back to reference Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, Wong PK. Medication compliance and persistence: terminology and definitions. Value Health. 2008;11(1):44–7.CrossRefPubMed Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, Wong PK. Medication compliance and persistence: terminology and definitions. Value Health. 2008;11(1):44–7.CrossRefPubMed
16.
go back to reference Bruce JM, Lynch SG. Multiple sclerosis: MS treatment adherence--how to keep patients on medication? Nat Rev Neurol. 2011;7(8):421–2.CrossRefPubMed Bruce JM, Lynch SG. Multiple sclerosis: MS treatment adherence--how to keep patients on medication? Nat Rev Neurol. 2011;7(8):421–2.CrossRefPubMed
17.
go back to reference Hansen K, Schussel K, Kieble M, Werning J, Schulz M, Friis R, Pohlau D, Schmitz N, Kugler J. Adherence to disease modifying drugs among patients with multiple sclerosis in Germany: a retrospective cohort study. PLoS One. 2015;10(7):e0133279.CrossRefPubMedPubMedCentral Hansen K, Schussel K, Kieble M, Werning J, Schulz M, Friis R, Pohlau D, Schmitz N, Kugler J. Adherence to disease modifying drugs among patients with multiple sclerosis in Germany: a retrospective cohort study. PLoS One. 2015;10(7):e0133279.CrossRefPubMedPubMedCentral
18.
go back to reference Wong J, Gomes T, Mamdani M, Manno M, O’Connor PW. Adherence to multiple sclerosis disease-modifying therapies in Ontario is low. Can J Neurol Sci. 2011;38(3):429–33.CrossRefPubMed Wong J, Gomes T, Mamdani M, Manno M, O’Connor PW. Adherence to multiple sclerosis disease-modifying therapies in Ontario is low. Can J Neurol Sci. 2011;38(3):429–33.CrossRefPubMed
19.
go back to reference 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 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
20.
go back to reference Gobbi C, Zecca C, Linnebank M, Muller S, You X, Meier R, Borter E, Traber M. Swiss analysis of multiple sclerosis: a multicenter, non-interventional, retrospective cohort study of disease-modifying therapies. Eur Neurol. 2013;70(1–2):35–41.CrossRefPubMed Gobbi C, Zecca C, Linnebank M, Muller S, You X, Meier R, Borter E, Traber M. Swiss analysis of multiple sclerosis: a multicenter, non-interventional, retrospective cohort study of disease-modifying therapies. Eur Neurol. 2013;70(1–2):35–41.CrossRefPubMed
21.
go back to reference Remington G, Rodriguez Y, Logan D, Williamson C, Treadaway K. Facilitating medication adherence in patients with multiple sclerosis. Int J MS Care. 2013;15(1):36–45.CrossRefPubMedPubMedCentral Remington G, Rodriguez Y, Logan D, Williamson C, Treadaway K. Facilitating medication adherence in patients with multiple sclerosis. Int J MS Care. 2013;15(1):36–45.CrossRefPubMedPubMedCentral
22.
go back to reference Evans C, Tam J, Kingwell E, Oger J, University of British Columbia MSCN, Tremlett H. Long-term persistence with the immunomodulatory drugs for multiple sclerosis: a retrospective database study. Clin Ther. 2012;34(2):341–50.CrossRefPubMed Evans C, Tam J, Kingwell E, Oger J, University of British Columbia MSCN, Tremlett H. Long-term persistence with the immunomodulatory drugs for multiple sclerosis: a retrospective database study. Clin Ther. 2012;34(2):341–50.CrossRefPubMed
23.
go back to reference Wallin MT, Wilken JA, Turner AP, Williams RM, Kane R. Depression and multiple sclerosis: review of a lethal combination. J Rehabil Res Dev. 2006;43(1):45.CrossRefPubMed Wallin MT, Wilken JA, Turner AP, Williams RM, Kane R. Depression and multiple sclerosis: review of a lethal combination. J Rehabil Res Dev. 2006;43(1):45.CrossRefPubMed
24.
go back to reference Marrie RA, Reingold S, Cohen J, Stuve O, Trojano M, Sorensen PS, Cutter G, Reider N. The incidence and prevalence of psychiatric disorders in multiple sclerosis: a systematic review. Mult Scler. 2015;21(3):305–17.CrossRefPubMedPubMedCentral Marrie RA, Reingold S, Cohen J, Stuve O, Trojano M, Sorensen PS, Cutter G, Reider N. The incidence and prevalence of psychiatric disorders in multiple sclerosis: a systematic review. Mult Scler. 2015;21(3):305–17.CrossRefPubMedPubMedCentral
26.
go back to reference Tarrants M, Oleen-Burkey M, Castelli-Haley J, Lage MJ. The impact of comorbid depression on adherence to therapy for multiple sclerosis. Mult Scler Int. 2011;2011:271321.PubMedPubMedCentral Tarrants M, Oleen-Burkey M, Castelli-Haley J, Lage MJ. The impact of comorbid depression on adherence to therapy for multiple sclerosis. Mult Scler Int. 2011;2011:271321.PubMedPubMedCentral
27.
go back to reference Govindappa K, Sathish J, Park K, Kirkham J, Pirmohamed M. Development of interferon beta-neutralising antibodies in multiple sclerosis--a systematic review and meta-analysis. Eur J Clin Pharmacol. 2015;71(11):1287–98.CrossRefPubMed Govindappa K, Sathish J, Park K, Kirkham J, Pirmohamed M. Development of interferon beta-neutralising antibodies in multiple sclerosis--a systematic review and meta-analysis. Eur J Clin Pharmacol. 2015;71(11):1287–98.CrossRefPubMed
Metadata
Title
Reasons for discontinuation of subcutaneous interferon β-1a three times a week among patients with multiple sclerosis: a real-world cohort study
Authors
Meritxell Sabidó-Espin
Rick Munschauer
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2017
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-017-0831-4

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