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Health insurance-specific differences in persistence among women with breast cancer receiving endocrine therapy (Print)

Prof. Dr. re. medical habil. Karel Kostev MA / Prof. Dr. med. Matthias Kalder / Dr. med. Niklas Gremke

Breast cancer (BC) is the most common cancer among women in Germany, with around 69,000 new cases every year; 18,591 women died of BK in 2015 (Barnes et al., 2016). Approximately 70% of all newly diagnosed women with BK have a hormone receptor-positive tumor (HR+) who are eligible for primary adjuvant endocrine therapy (ET) with either tamoxifen (TAM) or an aromatase inhibitor (AI) (Franzoi et al., 2021) . Depending on the menopausal status, this standard therapy is taken daily for at least 5 years, significantly reduces the risk of BK recurrence and improves the overall survival of the patients (Waks & Winer, 2019, Font et al., 2022). Despite the proven effectiveness in preventing BK recurrence by 40%, approximately 50% of women take less than 80% of the prescribed dose. In addition, up to 50% of patients with BK discontinue their ET (Hadji et al., 2013; Moon et al., 2019; Peddie et al., 2021). It should be noted that both TAM and AI therapy can cause short- and long-term side effects in patients. These include hot flashes, myalgias and osteoporosis (Franzoi et al., 2021; Group et al., 2009). The occurrence of TAM- and AI-related side effects may therefore negatively impact a patient's persistence to ET. Persistence is defined as the continuation of drug use for the prescribed length of time (from initiation to discontinuation) while a patient adheres to the prescribed interval and dose of a dosing regimen (Cramer et al., 2008; Hadji et al., 2013). Recently, adherence to therapy and the persistence of ET in women with HR+ BK have been the subject of intense debate in the literature, since "non-adherence" to ET has been shown to be associated with an increased risk of disease recurrence (Font et al., 2019; Seneviratne et al ., 2015), for distant metastases (Blanchette et al., 2020; Lee et al., 2019) and for mortality (Inotai et al., 2021; Lao et al., 2019; Murphy et al., 2015). However, no study has yet investigated whether there is a connection between the health insurance company a woman has and her persistence in ET. The aim of this study was therefore to analyze persistence with TAM and AI and to show possible differences specific to health insurance companies.

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First publication date: 28.11.2022
Prof. Dr. rer. med. habil. Karel Kostev MAProf. Dr. re. medical habil. Karel Kostev MAProf. Dr. med. Matthias KalderProf. Dr. med. Matthias KalderDr. med. Niklas GremkeDr. med. Niklas Gremke

DOI

http://doi.org/10.24945/MVF.06.22.1866-0533.2467

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Abstract: Krankenkassenspezifische Unterschiede in der Persistenz bei Frauen mit Brustkrebs unter endokriner Therapie (Print)

The aim of this study was to analyze the persistence in women with breast cancer receiving endocrine therapy and to show possible differences specific to health insurance companies. The present retrospective cohort study was based on the IQVIA-LRx database. A total of 284,383 patients in 101 health insurance companies were available for the analyses. Of these, 269,214 women were insured in health insurance companies with a minimum number of 1,000 treated patients with breast cancer. Up to five years after the start of observation, only 51.9% of patients remained in treatment. The differences between patients insured by different health insurance companies were significant. The 5-year persistence rates ranged from 37% to 60%. In conclusion, persistence to all endocrine treatments in women with breast cancer is low and should be significantly increased. Further research is needed that can help understand health insurance differences in order to improve patient care in clinical practice.

Keywords (English)

breast cancer, claims, endocrine therapy, persistence

Literature


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Additional Information

Citation: Kostev, K., Kalder, M., Gremke, N.: “Health insurance-specific differences in persistence in women with breast cancer receiving endocrine therapy” in: “Monitor Health Care Research” (OnlineFirst on 06/22), pp. 79-82. http://doi.org/10.24945/MVF.06.22.1866-0533.2467

Plain Text

Health insurance-specific differences in persistence among women with breast cancer receiving endocrine therapy

Breast cancer (BC) is the most common cancer among women in Germany, with around 69,000 new cases every year; 18,591 women died of BK in 2015 (Barnes et al., 2016). Approximately 70% of all newly diagnosed women with BK have a hormone receptor-positive tumor (HR+) who are eligible for primary adjuvant endocrine therapy (ET) with either tamoxifen (TAM) or an aromatase inhibitor (AI) (Franzoi et al., 2021) . Depending on the menopausal status, this standard therapy is taken daily for at least 5 years, significantly reduces the risk of BK recurrence and improves the overall survival of the patients (Waks & Winer, 2019, Font et al., 2022). Despite the proven effectiveness in preventing BK recurrence by 40%, approximately 50% of women take less than 80% of the prescribed dose. In addition, up to 50% of patients with BK discontinue their ET (Hadji et al., 2013; Moon et al., 2019; Peddie et al., 2021). It should be noted that both TAM and AI therapy can cause short- and long-term side effects in patients. These include hot flashes, myalgias and osteoporosis (Franzoi et al., 2021; Group et al., 2009). The occurrence of TAM- and AI-related side effects may therefore negatively impact a patient's persistence to ET. Persistence is defined as the continuation of drug use for the prescribed length of time (from initiation to discontinuation) while a patient adheres to the prescribed interval and dose of a dosing regimen (Cramer et al., 2008; Hadji et al., 2013). Recently, adherence to therapy and the persistence of ET in women with HR+ BK have been the subject of intense debate in the literature, since "non-adherence" to ET has been shown to be associated with an increased risk of disease recurrence (Font et al., 2019; Seneviratne et al ., 2015), for distant metastases (Blanchette et al., 2020; Lee et al., 2019) and for mortality (Inotai et al., 2021; Lao et al., 2019; Murphy et al., 2015). However, no study has yet investigated whether there is a connection between the health insurance company a woman has and her persistence in ET. The aim of this study was therefore to analyze persistence with TAM and AI and to show possible differences specific to health insurance companies.

>> The present retrospective cohort study was based on the IQVIA-LRx database (Richter et al., 2015). This database includes around 80 % prescriptions reimbursed by statutory health insurance companies in Germany. The data is available at the patient level and includes information on the patient's age and gender. All patient information is completely anonymized by the data provider in accordance with data protection laws. Each available prescription includes full product information and date of issue. The database does not contain any diagnoses or laboratory values.
This retrospective cohort study includes women with a first prescription of TAM or AI between January 2016 and December 2020 (index date). The outcome of the study was the persistence rate five years after the index date. Each patient was followed for up to 60 months (standard duration for ET) from the index date until TAM and AI therapy was discontinued or discontinued. Treatment discontinuation was defined as at least 180 days without therapy. If patients switched from TAM to AI or vice versa within 180 days of discontinuing the respective therapy, they were still classified as persistent.
Kaplan-Meier analyzes were performed to show persistence for TAM and AI depending on health insurance provider. Only health insurance companies with at least 1,000 BK patients were considered. In this study, the health insurance companies were treated anonymously. P values <0.01 were considered statistically significant. Analyzes were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA).
Results
A total of 284,383 patients from 101 health insurance companies were available for the analyses. Of these, 269,214 women were insured in health insurance companies with at least 1,000 BK patients treated. The mean age was 69.0 (standard deviation: 12.3) years. The majority of patients (74.5%) were treated by gynecologists.
Up to five years after the index date, only 51.9% patients remained on treatment. The differences between patients insured by different health insurance companies were significant. The 5-year persistence rates ranged from 37% to 60%. (Fig. 1). Figure 2 shows the very low correlation between (correlation coefficient 0.06) the persistence rate and the average age of patients per health insurance company.

discussion

The present study examined the persistence of ET with TAM or AI treatment up to five years after the index date. Only half of the patients remained on ET at the end of the fifth year of treatment when treatment discontinuation was defined as at least 180 days without therapy. This result is confirmed by the current literature. In studies where patients were treated with TAM, treatment discontinuation ranged from 31% to 60% at the end of the fifth year (Owusu et al., 2008; van Herk-Sukel et al., 2010). In studies analyzing both TAM and AI treatment, discontinuation rates after five years of treatment ranged from 32% to 73% (Guth et al., 2008; Guth et al., 2011; Murphy et al., 2012). In this study, however, it should be mentioned that the highest possible persistence rate was measured here, since the actual medication intake of the patients could not be controlled and it has already been sufficiently published that around 50 % of the patients do not take the medication as prescribed (Brown & Bussell, 2011). In addition, different definitions of the treatment gap (between 45 and 180 days) and persistence itself make it difficult to compare studies on ET persistence (Peddie et al., 2021).
One of the reasons for the early discontinuation of therapy could be due to the occurrence of ET-related side effects that affect the quality of life of the patients. It has been published in the literature that early discontinuation of ET is associated with new hot flashes. Early discontinuation of ET also results in a dramatic increase in BK recurrence compared to women who complete recommended treatment (Collin et al., 2021; Kemp et al., 2014).
The most important result of this study is the persistence differences between patients who are insured by different health insurance companies.
A first hypothesis concerns the possible differences between the age structure of insured women in different health insurance companies and the known influence of age on persistence. Hershman et al. reported that In a large population-based study, women younger than 40 years of age were at highest risk of having an abortion. He et al. described that patients with BK in the age groups < 40 years and ≥ 65 years had the highest risk of discontinuation. A variety of factors related to fertility, the occurrence of more serious side effects when starting ET treatment, body image concerns, etc. may make young women with BC a vulnerable group at higher risk of recurrence if treatment is discontinued (He et al., 2015; Hershman et al., 2010; Llarena et al., 2015; Sella & Chodick, 2020).
However, in our study there was no correlation between persistence and the age of the patients in relation to the health insurance company.
A second hypothesis would be that the women insured by different health insurance companies are regionally distributed differently. As a result, they are treated by different doctors. In 2014, Kostev et al. showed that breast cancer patients treated in a practice with poor compliance had an almost 60 % higher risk of treatment discontinuation than in a practice with good compliance (Kostev et al., 2014 ). This hypothesis is supported by another study that showed that breast cancer patients enrolled in a disease management program were less likely to discontinue therapy (Jacob et al., 2015).
Consequently, it seems important that the health insurance companies motivate the doctors of their treated insured persons to strive for good compliance among their patients.  
In conclusion, persistence to all endocrine treatments in women with breast cancer is low and should be significantly increased. Further research is needed that can help understand health insurance differences in order to improve patient care in clinical practice.
Several limitations of the present study should be mentioned. First, the LRx prescription database does not contain information about diagnoses and TNM status, so stratification by cancer stage and analysis of co-diagnoses is not possible. Second, mortality data and information on the occurrence of adverse events were not available to evaluate the reasons for loss to follow-up. As a result, loss to follow-up may be related to death, change of health insurance provider, or change of residence, rather than just discontinuation of treatment. However, these potential limitations must be considered in relation to the strengths of this study, which include the large number of patients, the long observation period and the nationally representative data on drug prescriptions as well as the health insurance-specific analyzes. <<
Author's statement
Karel Kostev is an employee at IQVIA Germany in Frankfurt am Main. Matthias Kalder and Niklas Gremke contributed to the analysis of the data and the interpretation of the results free of charge. The authors declare that there are no conflicts of interest

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