Dataset Information

Cancer Incidence after Initiation of Antimuscarinic Medications for Overactive Bladder in the United Kingdom: Evidence for Protopathic Bias.

ABSTRACT:

Study objective

To estimate the incidence of 10 common cancers among patients treated with antimuscarinic medications for overactive bladder (AMOABs).

Design

Retrospective cohort study.

Data source

United Kingdom's Clinical Practice Research Datalink.

Patients

A total of 119,912 adults with no previous cancer diagnosis who were new users of AMOABs-darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium-between January 2004 and December 2012.

Measurements and main results

Sex-specific incidence rates per 1000 person-years and 95% confidence intervals (CIs) were estimated for each study cancer (bladder, breast, colorectal, lung, melanoma, non-Hodgkin lymphoma, pancreatic, prostate, renal, and uterine cancer) overall and stratified by time since cohort entry and by cumulative AMOAB dose. Among the 119,912 patients followed for 399,365 person-years, 4117 incident study cancers occurred. The incidence rate of prostate cancer was 14.2 (95% CI 12.9-15.5) in the year after cohort entry and decreased markedly thereafter. The incidence rate of bladder cancer was also higher in the year after cohort entry than subsequently (men: 5.5, 95% CI 4.8-6.4; women: 1.2, 95% CI 1.0-1.5). The incidence rates of both prostate and bladder cancer decreased with increasing cumulative dose of AMOAB. We observed no similar relations between incidence rates of other study cancers and time since cohort entry.

Conclusion

High incidence rates of bladder and prostate cancer soon after AMOAB initiation and a negative correlation between incidence and cumulative AMOAB dose suggest that protopathic bias is a more likely explanation for these findings than causality. (Protopathic bias in this context means patients' urinary symptoms prompted treatment with an AMOAB, but the symptoms were actually due to a cancer that was already present, although not yet diagnosed or not yet recorded.) To avoid unnecessary delays in the diagnosis of prostate and bladder cancer, physicians should consider these diseases in patients for whom treatment with AMOABs is indicated.

SUBMITTER: Kaye JA

PROVIDER: S-EPMC5518180 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cancer Incidence after Initiation of Antimuscarinic Medications for Overactive Bladder in the United Kingdom: Evidence for Protopathic Bias.

Kaye James A JA Margulis Andrea V AV Fortuny Joan J McQuay Lisa J LJ Plana Estel E Bartsch Jennifer L JL Bui Christine L CL Perez-Gutthann Susana S Arana Alejandro A

Pharmacotherapy 20170529 6

<h4>Study objective</h4>To estimate the incidence of 10 common cancers among patients treated with antimuscarinic medications for overactive bladder (AMOABs).<h4>Design</h4>Retrospective cohort study.<h4>Data source</h4>United Kingdom's Clinical Practice Research Datalink.<h4>Patients</h4>A total of 119,912 adults with no previous cancer diagnosis who were new users of AMOABs-darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium-between January 2004 and December 2012.<h4>M ...[more]

PMID: 28370075

Similar Datasets

Project description:ObjectivesThis study examined the incidence and predictors of antimuscarinic medication use including non-selective antimuscarinics among older adults with dementia and overactive bladder (OAB).MethodsThe study used a new-user cohort design involving older adults (≥65 years) with dementia and OAB based on 2013-2015 Medicare data. Antimuscarinics included non-selective (oxybutynin, tolterodine, trospium, fesoterodine) and selective (solifenacin, darifenacin) medications. Descriptive statistics and multivariable logistic regression models were used to determine the incidence and predictors of new antimuscarinic use including non-selective antimuscarinics, respectively.ResultsOf the 3.38 million Medicare beneficiaries with dementia, over one million (1.05) had OAB (31.03%). Of those, 287,612 (27.39%) were reported as prevalent antimuscarinics users. After applying continuous eligibility criteria, 21,848 (10.34%) incident antimuscarinic users were identified (77.6% non-selective; 22.4% selective). Most frequently reported antimuscarinics were oxybutynin (56.3%) and solifenacin (21.4%). Multivariable analysis revealed that patients ≥75 years, of black race, and those with schizophrenia, epilepsy, delirium, and Elixhauser's score were less likely to initiate antimuscarinics. Women, those with abnormal involuntary movements, bipolar disorder, gastroesophageal reflux disease, insomnia, irritable bowel syndrome, muscle spasm/low back pain, neuropathic pain, benign prostatic hyperplasia, falls/fractures, myasthenia gravis, narrow-angle glaucoma, Parkinson's disease, syncope, urinary tract infection and vulvovaginitis were more likely to initiate antimuscarinics. Further, patients with muscle spasms/low back pain, benign prostatic hyperplasia and those taking higher level anticholinergics had lower odds of receiving non-selective antimuscarinics, whereas white patients, black patients and those with schizophrenia and delirium were more likely to receive them.ConclusionsNearly one-third of dementia patients had OAB and over one-fourth of them used antimuscarinics. Majority of the incident users were prescribed non-selective antimuscarinics with several demographic and clinical factors contributing to their use. Given the high prevalence of OAB among dementia patients, there is a need to optimize their antimuscarinic use, considering their vulnerability for anticholinergic adverse effects.

Project description:IntroductionAlthough antimuscarinics form the first-line therapy in overactive bladder (OAB), little is known regarding antimuscarinic discontinuation among OAB patients in nursing homes. This study examined treatment patterns and predictors of antimuscarinic discontinuation among long-term nursing home (LTNH) residents with OAB.MethodsThe study cohort included LTNH residents (defined as residents staying ≥ 101 consecutive days) from the Minimum Data Set linked 2013-2015 Medicare claims data. Patients with OAB were defined by OAB-related claims and medication codes. Treatment patterns and discontinuation (medication gap ≥ 30 days) were characterized by examining OAB-specific antimuscarinics prescribed during LTNH stays. The Andersen Behavioral Model was used to identify predisposing, enabling and need factors that predict discontinuation. Kaplan-Meier curves and multivariable Cox proportional hazards regression model were used to assess the unadjusted and adjusted times to discontinuation, respectively, among different antimuscarinics.ResultsThe mean age of the study cohort (n = 11,012) was 81.6 years (± 8.5), 74.6% were female, and 89.8% were non-Hispanic White. The mean duration of nursing home stay was 530.1 (± 268.4) days. The most commonly prescribed OAB-specific antimuscarinic was oxybutynin (69.8%). Overall, 66.5% of the study cohort discontinued the index antimuscarinic. Multivariable Cox PH regression analysis revealed that compared to LTNH residents who initiated treatment with oxybutynin, treatment discontinuation was lower with solifenacin or fesoterodin and discontinuation was more frequent when treatment was initiated with tolterodine, darifenacin or trospium compared with oxybutynin. In addition, several need factors (comorbidities, medication use and anticholinergic burden, etc.) were associated with antimuscarinic discontinuation.ConclusionAbout two-thirds of LTNH residents with OAB discontinued their index antimuscarinic during their nursing home stay. There was significant variation in discontinuation based on the index antimuscarinic agent with lowest risk of discontiuation with solifenacin and fesoterodin. Concerted efforts to optimize antimuscarinic use are needed to improve the management of OAB in nursing homes.

Project description:ObjectivesThe aim of this study was to evaluate the cost effectiveness of mirabegron relative to two antimuscarinics, oxybutynin extended release (ER) and tolterodine ER, in patients with overactive bladder (OAB) from the perspective of a third-party payer in Colombia.MethodsA Markov model simulated the therapeutic management, disease course, and complications in hypothetical cohorts of OAB patients over a 5-year period. The model predicted costs and three outcomes: quality-adjusted life-years (QALYs), micturition state improvement (MSI), and incontinence state improvement (ISI). In each 1-month cycle, patients could transition between different health states reflecting symptom severity. Transition probabilities were estimated from a published mirabegron trial and mixed treatment comparison. Other inputs such as treatment discontinuation based on treatment-specific rates of persistence, resource use and costs, anticholinergic burden, comorbidity treatment, and drug acquisition were obtained from Società Italiana Scienze Mediche, Instituto de Seguros Sociales Tariff Manual, published literature, and expert opinion. Deterministic and probabilistic sensitivity analyses were conducted. Costs are presented in 2017 Colombia Pesos (COP).ResultsMirabegron was cost effective for all outcome measures at a willingness-to-pay threshold of 124,919,725 COP, which is three times the per capita gross domestic product (GDP). Using QALYs as the measure of effect, mirabegron had an incremental cost-effectiveness ratio (ICER) of 85,802,036 COP/QALY (26,365 USD/QALY) and 66,360,134 COP/QALY (20,384 USD/QALY) versus oxybutynin and tolterodine, respectively. Probabilistic sensitivity analyses showed that mirabegron was cost effective in 99.5% and 100% of simulations compared with oxybutynin and tolterodine, respectively. Using MSI and ISI as the measure of effects yielded ICERs below one GDP.ConclusionsMirabegron is a cost effective alternative to oxybutynin and tolterodine from the perspective of a third-party payer in Colombia.

Project description:BACKGROUND:Despite several new medications being Food and Drug Administration-approved for overactive bladder (OAB) and new prescription drug payment programs, there are limited population-based data regarding OAB medication use among older adults. OBJECTIVES:To examine: (1) impacts of new medications and $4 generic programs on time trends for OAB-related medication dispensing for older adults in the United States; (2) differences by age and sex; and (3) temporal changes in OAB-related medication payments. METHODS:Using Truven Health Analytics' Medicare Supplemental Database (2000-2015), we analyzed OAB-related medication claims for 9,477,061 Medigap beneficiaries age 65-104. We estimated dispensing rates (per 1000 person-months), assessed dispensing trends using interrupted time-series methods, compared dispensing rates by age and sex, and summarized payment trends. RESULTS:From 2000 to 2015, 771,609 individuals filled 13,863,998 OAB-related prescriptions. During 2000-2007, 3 new extended-release medications became available (tolterodine, darifenacin, solifenacin), leading to increases in overall OAB-related dispensing rates by 19.1 (99% confidence interval, 17.0-21.2), a 92% increase since 2000; overall rates remained stable during 2008-2015. By 2015, the most common medications were oxybutynin (38%), solifenacin (20%), tolterodine (19%), and mirabegron (12%). Dispensing rates peaked at age 90 (rate, 53.4; 99% confidence interval, 53.1-53.7). Women had higher rates than men at all ages (average ratewomen-ratemen, 22.0). The gap between upper and lower percentiles of medication payments widened between 2008-2015; by 2015, 25% of reimbursed dispensed prescriptions had total payments exceeding $250. CONCLUSIONS:Medication-specific dispensing rates for OAB changed when new alternatives became available. Recent changes in utilization and cost of OAB medications have implications for clinical guidelines, pharmacoepidemiologic studies, and payment policies.

Dataset Information

Cancer Incidence after Initiation of Antimuscarinic Medications for Overactive Bladder in the United Kingdom: Evidence for Protopathic Bias.

Study objective

Design

Data source

Patients

Measurements and main results

Conclusion

Publications

Cancer Incidence after Initiation of Antimuscarinic Medications for Overactive Bladder in the United Kingdom: Evidence for Protopathic Bias.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets