Real-world persistence and adherence to oral antimuscarinics and mirabegron in patients with overactive bladder (OAB): a systematic literature review

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Abstract

Purpose

To evaluate persistence and adherence of oral pharmacotherapy used in the treatment of overactive bladder (OAB) in a real-world setting.

Materials and methods

Systematic literature searches of six electronic publication databases were performed to identify observational studies of patients with OAB treated with antimuscarinics and/or mirabegron. Studies obtaining persistence and adherence data from sources other than electronic prescription claims were excluded. Reference lists of identified studies and relevant systematic reviews were assessed to identify additional relevant studies.

Results

The search identified 3897 studies, of which 30 were included. Overall, persistence ranged from 5% to 47%. In studies reporting data for antimuscarinics and mirabegron (n=3), 1-year persistence was 12%–25% and 32%–38%, respectively. Median time to discontinuation was <5 months for antimuscarinics (except one study (6.5 months)) and 5.6–7.4 months for mirabegron. The proportion of patients adherent at 1 year varied between 15% and 44%. In studies reporting adherence for antimuscarinics and mirabegron, adherence was higher with mirabegron (mean medication possession ratio (MPR): 0.59 vs 0.41–0.53; mean proportion of days covered: 0.66 vs 0.55; and median MPR: 0.65 vs 0.19–0.49). Reported determinants of persistence and adherence included female (sex), older age group, use of extended-release formulation and treatment experience.

Conclusion

Most patients with OAB discontinued oral OAB pharmacotherapy and were non-adherent 1 year after treatment initiation. In general, mirabegron was associated with greater persistence and adherence compared with antimuscarinics. Combined with existing clinical trial evidence, this real-world review merits consideration of mirabegron for first-line pharmacological treatment among patients with OAB.

PROSPERO registration number

CRD42017059894.

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Most cited references 51

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Comparing Adherence and Persistence Across 6 Chronic Medication Classes

Jason Yeaw, Joshua S. Benner, John G. Walt … (2009)

BACKGROUND: The National Quality Forum recently endorsed the proportion of days covered (PDC)—a measure of medication adherence—as an indicator of quality in drug therapy management. OBJECTIVES: To inform initial efforts to improve the quality of drug therapy management, we compared PDC and persistence among new users of 6 commonly used chronic medication categories. METHODS: A retrospective analysis of pharmacy claims in a database of more than 64 million members enrolled in 100 health plans assessed persistence and adherence to drug therapy in 6 chronic conditions. Patients were included in the analysis if they initiated a prescription drug of interest in any of 6 drug classes—prostaglandin analogs, statins, bisphosphonates,oral antidiabetics, angiotensin II receptor blockers (ARBs), and overactive bladder (OAB) medications—between January 1 and December 31, 2005.The first claim for a drug of interest during this period was considered a patient’s index date. Patients were required to have a minimum of 12months of continuous enrollment both preceding and following their index date. New users of a treatment were identified by excluding patients who filled a prescription for any drug in the same class during the previous 12months and were followed for a minimum of 12 months. Nonpersistence was defined as discontinuation of the therapy class following an allowed gap between refills—30-, 60-, and 90-day refill gaps were used. Adherence was defined as a continuous measure of the proportion of days covered (PDC) during the 12-month post-index period. Logistic regression analyses predicted (a) nonpersistence during the 12-month post-index period and (b) adherence (PDC) of at least 80%, with drug class as the predictor variable of interest, controlling for demographic variables, insurance and plan type, history of hospitalization, Charlson comorbidity score,copayment for index medication, and number of medications at index. RESULTS: A total of 167,907 patients were identified across 6 cohorts.Using the 60-day gap, 6-month persistence rates were prostagl and in analogs 47%, statins 56%, bisphosphonates 56%, oral antidiabetics 66%,ARBs 63%, and OAB medications 28%. After the first 90 days of therapy,relative persistence was stable across cohorts, and rates declined consistently from 6 months post-index to study end. Logistic regression models showed that oral antidiabetic users had a 59%, 36%, 37%, and 79% decreased risk of nonpersistence in a 12-month follow-up period compared with patients taking prostaglandin analogs, statins, bisphosphonates, orOAB medications, respectively. Risk of nonpersistence decreased with increasing age. Mean (SD) 12-month adherence rates were: prostagl and in analogs 37% (26%), statins 61% (33%), bisphosphonates 60% (34%), oral antidiabetics 72% (32%), ARBs 66% (32%), and OAB medications 35%(32%). Logistic regression indicated that oral antidiabetic use was a significantpredictor of adherence (PDC) of at least 80% compared with other therapy classes. Adjusted odds ratios for oral antidiabetics were 17.60(95% confidence interval [CI]=15.38-20.14) versus prostaglandin analogs,2.06 (95% CI=1.99-2.12) versus statins, 1.92 (95% CI=1.83-2.02) versus bisphosphonates, 1.29 (95% CI=1.24-1.34) versus ARBs, and 5.77 (95%CI=5.38-6.19) versus OAB medications.

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Medication Adherence: Truth and Consequences.

Marie T Brown, Jennifer Bussell, Suparna Dutta … (2016)

Improving medication adherence may have a greater influence on the health of our population than in the discovery of any new therapy. Patients are nonadherent to their medicine 50% of the time. Although most physicians believe nonadherence is primarily due to lack of access or forgetfulness, nonadherence can often be an intentional choice made by the patient. Patient concealment of their medication-taking behavior is often motivated by emotions on the part of both provider and patient, leading to potentially dire consequences. A review of the literature highlights critical predictors of adherence including trust, communication and empathy, which are not easily measured by current administrative databases. Multifactorial solutions to improve medication adherence include efforts to improve patients' understanding of medication benefits, access and trust in their provider and health system. Improving providers' recognition and understanding of patients' beliefs, fears and values, as well as their own biases is also necessary to achieve increased medication adherence and population health.

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Patient-reported reasons for discontinuing overactive bladder medication.

Mohamed Hussein, Michael B Nichol, Jack Benner … (2010)

To evaluate patient-reported reasons for discontinuing antimuscarinic prescription medications for overactive bladder (OAB). A phase 1 screening survey was sent to a representative sample of 260 000 households in the USA to identify patients using antimuscarinic agents for OAB. A detailed phase-2 follow-up survey was sent to 6577 respondents with one or more antimuscarinic prescriptions for OAB in the 12 months before the phase 1 survey. The follow-up survey included questions about demographics, clinical characteristics, antimuscarinic use, beliefs about OAB, treatment expectations, OAB symptom bother, and pre-coded reasons for discontinuation. Patients who reported discontinuing one or more OAB medication during the 12 months before phase 2 were grouped by reason, using latent class analysis (LCA); the Lo-Mendell-Rubin likelihood statistical test was used to determine the number of classes. Conditional probabilities of reasons for discontinuation were calculated for each class. Multivariable logistic regression was used to assess the influence of demographic and clinical characteristics on class assignment. In all, 162 906 (63%) and 5392 (82%) useable responses were returned in phases 1 and 2, respectively; the demographics were similar in respondents and nonrespondents in both phases. In all, 1322 phase 2 respondents (24.5%) reported discontinuing one or more antimuscarinic drugs during the 12 months before phase 2. LCA identified two classes (Lo-Mendell-Rubin statistic, P = 0.01) based on reasons for discontinuation. Most respondents (89%) reported discontinuing OAB medication primarily due to unmet treatment expectations and/or tolerability; many respondents in this class switched to a new antimuscarinic agent. A smaller group (11%) indicated a general aversion to taking medication. Age, sex, race, income, and history of incontinence were not predictive of class assignment. Expectations about treatment efficacy and side-effects are the most important considerations in discontinuing OAB medications for most patients. Interventions to promote realistic expectations about treatment efficacy and side-effects might enhance adherence.

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Author and article information

Journal

Journal ID (nlm-ta): BMJ Open

Journal ID (iso-abbrev): BMJ Open

Journal ID (hwp): bmjopen

Journal ID (publisher-id): bmjopen

Title: BMJ Open

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2044-6055

Publication date Collection: 2018

Publication date (Electronic): 21 November 2018

Volume: 8

Issue: 11

Electronic Location Identifier: e021889

Affiliations

[1 ] Manchester Metropolitan University , Manchester, UK

[2 ] Astellas Pharma Europe Ltd , Chertsey, UK

[3 ] Astellas Pharma BV , Leiden, The Netherlands

Author notes

[Correspondence to ] Dr Gillian Yeowell; g.yeowell@ 123456mmu.ac.uk

Article

Publisher ID: bmjopen-2018-021889

DOI: 10.1136/bmjopen-2018-021889

PMC ID: 6252764

PubMed ID: 30467131

SO-VID: a6efa44d-8914-4658-b871-b93673da3f29

License:

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 25 January 2018

Date revision received : 12 September 2018

Date accepted : 25 September 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100007705, Astellas Pharma Global Development;

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ScienceOpen disciplines: Medicine

Keywords: overactive bladder,persistence,adherence,antimuscarinics,β3 adrenergic receptor agonists,systematic literature review

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ScienceOpen disciplines: Medicine

Keywords: overactive bladder, persistence, adherence, antimuscarinics, β3 adrenergic receptor agonists, systematic literature review

Real-world persistence and adherence to oral antimuscarinics and mirabegron in patients with overactive bladder (OAB): a systematic literature review

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Hematology and Oncology Discovery

Most cited references 51

Comparing Adherence and Persistence Across 6 Chronic Medication Classes

Medication Adherence: Truth and Consequences.

Patient-reported reasons for discontinuing overactive bladder medication.

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