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

Abstract

BackgroundContinuation 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.MethodsPatient 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.ResultsData 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).ConclusionsPotential drivers of discontinuation change over time. Improved awareness of the drivers of discontinuation could lead to targeted interventions to improve adherence.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-017-0831-4) contains supplementary material, which is available to authorized users.

Effectiveness, Healthcare Resource Utilization and Adherence to Subcutaneous Interferon Beta-1a According to Age in Patients With Multiple Sclerosis: A Cohort Study Using a US Claims Database

“…In keeping with the results of this study, in which 77.6–84.0% of patients were adherent to treatment over a median follow-up period of 6.0–7.2 months, are the results of an Italian population-based study that also reported high rates of adherence to interferons (>85%) ( 20 ). However, others studies have reported lower rates of adherence to IFN β-1a (48.3%) ( 21 ) and similarly with IFN β-1b (68.3%) ( 22 ). Yet, a systematic literature review of adherence to oral DMTs (dimethyl fumarate, fingolimod and teriflunomide) also found a high 1-year mean MPR of 83.3% (95% CI 74.5–92.1%) based on data from four studies ( 23 ).…”

<p>Interferon-Beta-Induced Headache in Patients with Multiple Sclerosis: Frequency and Characterization</p>

“…In our study, 29.39% (234/796) of patients developed de novo headaches within 4 weeks of initiation of IFN-β treatment. Interferon-beta pivotal trials [7][8][9][10][11] and post-market evidence 21,22 underestimated the prevalence of headaches as an adverse effect. In these studies, headaches were either not included among adverse events, 7,8 or may have been considered flu-like symptoms.…”

“…In these studies, headaches were either not included among adverse events, 7,8 or may have been considered flu-like symptoms. 13,15,22 However, headache is one of the most common adverse events associated with IFN-β treatment, [14][15][16] with a reported prevalence from 13.1% to 58% (Table 3). Smith et al 21 reported a more precise definition of headache incidence rates (IRs) per 100 person-years.…”

“…Moreover, headaches associated with IFN-β treatment were a significant reason for treatment withdrawal in a previous study. 7 Furthermore, headaches were included as a flu-like symptom in other trials, [22][23][24] but these studies did not specify which flu-like symptoms were responsible for withdrawal.…”

<p>Re-Evaluating the Use of IFN-β and Relapsing Multiple Sclerosis: Safety, Efficacy and Place in Therapy</p>

“…17 Sabido-Espin and Munschauer evaluated discontinuation rates using Market Scan Commercial and Medicare Supplemental healthcare claims databases, which revealed that in a cohort of 5956 patients treated with IFNβ, 36.9% discontinued at 1 year, and 55.8% discontinued by 3 years. 19 Mitigating adverse effects was considered especially important to foster patient compliance including thoroughly counseling patients on the benefit vs risk of the therapy, expected adverse effects, and that adverse effects tend to subside with longer duration of therapy. Additionally, the use of the "two-needle technique," an automated injection device, helped to decrease injection site reactions.…”