Publications by authors named "Jameel Nazir"

41 Publications

An Economic Comparison of Treatment Strategies with Anakinra in Systemic Juvenile Idiopathic Arthritis (sJIA).

Open Access Rheumatol 2021 10;13:257-266. Epub 2021 Sep 10.

Sobi, Stockholm, Sweden.

Introduction: Systemic juvenile idiopathic arthritis (sJIA) is a rare, complex autoinflammatory disease with substantial morbidity, often characterized by fever, rash, and muscle pain, amongst other symptoms. Biologic agents, such as anakinra, have been successfully used to treat patients internationally, but their usage in some regions is limited to patients that have failed to achieve clinically inactive disease with corticosteroids and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Use of anakinra early in the disease course leads to better clinical outcomes; however, longer-term costs for this treatment strategy have not been established. This study compares the economic implications of first-line versus later-line availability of anakinra for patients with sJIA.

Methods: Data for patients treated with first-line anakinra were identified from a single-center, prospective study and compared to a combination of published trial and economic evaluation information to facilitate a comparison to later-line anakinra (ie, following corticosteroids + csDMARDs). Costs were estimated for product acquisition and medical resource utilization (MRU), including planned outpatient visits and unplanned hospital admissions. Total costs over a 5-year horizon were compared.

Results: Total 5-year product acquisition cost for the first-line anakinra strategy was €24,021, and for later-line anakinra was €20,471. The corresponding MRU costs were €19,197 (first-line) versus €25,425 (later-line). Overall 5-year costs (product acquisition and MRU) were lower for the first-line strategy (€43,218 versus €45,896).

Conclusion: The use of anakinra for patients with sJIA in the first-line setting is efficacious to induce and sustain inactive disease, and the findings of this study show that this treatment strategy leads to cost savings through reduced medical expenditure.
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http://dx.doi.org/10.2147/OARRR.S325400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439981PMC
September 2021

Anticholinergic Burden and Associated Healthcare Resource Utilization in Older Adults with Overactive Bladder.

Drugs Aging 2021 Aug 13. Epub 2021 Aug 13.

Astellas Pharma Europe Ltd, Addlestone, UK.

Background: Bladder anticholinergics are the most widely used drugs to treat overactive bladder (OAB) but can contribute to cumulative anticholinergic burden, which may be associated with adverse outcomes.

Objective: This study aimed to evaluate the association between cumulative anticholinergic burden and healthcare resource utilization (HRU) and costs in older adults with OAB.

Materials And Methods: This was a retrospective, observational study that used data from the UK Clinical Practice Research Datalink (CPRD) GOLD database. Participants were aged ≥ 65 years with ≥ 3 years of continuous enrolment before and ≥ 2 years after the index date (date of OAB diagnosis or first prescription for any OAB drug between 1 April 2007 and 31 December 2015). The primary endpoint was the association between cumulative anticholinergic burden (assessed using the Anticholinergic Cognitive Burden [ACB] scale during the 3-year pre-index period) and HRU (GP consultations, specialist referrals, urological tests, hospital admissions) over the 2-year post-index period.

Results: Data from 23,561 adults were included in the analysis. Mean (SD) ACB scores in the pre- and post-index periods were 1.0 (1.1) and 2.4 (1.7), respectively; urological drugs contributed most (58.8%) to the latter. For the primary endpoint, higher pre-index ACB scores were associated with higher post-index HRU and costs. Mean (SD) ACB scores in the post-index period were 1.2 (1.3) and 2.5 (1.7) in those treated with mirabegron (beta-3 agonist) or bladder anticholinergics, respectively.

Limitations: The generalizability of the results outside the UK is unclear.

Conclusions: In older adults with OAB, higher anticholinergic burden before initiating OAB drugs is associated with higher HRU and costs. When making treatment decisions in older adults, consideration should be given to assessing the existing anticholinergic burden and using OAB treatments that do not add to this burden.
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http://dx.doi.org/10.1007/s40266-021-00884-0DOI Listing
August 2021

Efficacy of rFIXFc versus rIX-FP for the Treatment of Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PROLONG-9FP Trials.

J Blood Med 2021 14;12:613-621. Epub 2021 Jul 14.

Department of Internal Medicine, Hemophilia Treatment Centre, Vivantes Klinikum im Friedrichshain, Berlin, Germany.

Purpose: In patients with hemophilia B, treatment with extended half-life (EHL) recombinant factor IX allows for longer dosing intervals while providing equal or superior bleeding protection compared with standard half-life products. This enables flexible, individualized treatment schedules, which reduce the burden of prophylaxis and improve patient outcomes. This analysis compared the efficacy of recombinant factor IX Fc fusion protein (rFIXFc) and recombinant factor IX albumin fusion protein (rIX-FP), two EHL therapies approved for prophylaxis and treatment of bleeding in hemophilia B.

Patients And Methods: Matching-adjusted indirect treatment comparison (MAIC) was used to adjust the between-treatment differences in baseline characteristics. Individual patient data for rFIXFc (B-LONG) were matched to aggregated data for rIX-FP (PROLONG-9FP) followed by statistical comparison for estimated annualized bleeding rate (ABR) using a Poisson regression model with adjustment for over dispersion. Data were analyzed according to treatment regimen prior to study entry: prior prophylaxis (rFIXFc, n=48; rIX-FP, n=40) or prior episodic treatment (n=43 and n=19, respectively). Relative treatment effects are presented as incidence rate ratios (IRR) with 95% confidence intervals (CI).

Results: After adjustment for baseline characteristics, estimated ABR observed for rFIXFc and rIX-FP was not significantly different in patients on prior prophylaxis (1.87 versus 1.58; IRR 1.18, 95% CI 0.67-2.10) or prior episodic (2.25 versus 2.22; IRR 1.01 95% CI 0.40-2.57) regimens.

Conclusion: This MAIC analysis shows that the estimated ABR for rFIXFc-treated patients from B-LONG was similar to that of rIX-FP-treated patients from PROLONG-9FP and, therefore, indicates that the two EHL therapies provide similar efficacy when used as prophylaxis for patients with hemophilia B. Trough levels differ between the two products (1-3% [targeted] versus 20% [observed], respectively), suggesting that trough level is not a surrogate indicator when ABR is used as a criterion for clinical efficacy when comparing these FIX products in hemophilia B.
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http://dx.doi.org/10.2147/JBM.S312885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286734PMC
July 2021

Efficacy and Safety of Avatrombopag in Patients with Chronic Immune Thrombocytopenia: A Systematic Literature Review and Network Meta-Analysis.

Adv Ther 2021 06 1;38(6):3113-3128. Epub 2021 May 1.

National Research Institute of Oncology, Kraków, Poland.

Introduction: A network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with chronic immune thrombocytopenia (ITP) not responding adequately to corticosteroids.

Methods: A systematic search of publication and clinical trial databases was conducted to identify relevant randomized controlled trials (RCTs) and observational studies. Data from eligible studies were extracted and analyzed in a Bayesian framework using relative effect sizes vs placebo. Outcomes included durable platelet response; need for rescue therapy; reduction in use of concomitant ITP medication; incidence of any or World Health Organization (WHO) grade 2-4 bleeding events, and any adverse events. Results were reported as odds ratios or incidence rate ratios (IRR) with 95% credible intervals (CrIs).

Results: The NMA included seven phase 3 RCTs. Compared with placebo, avatrombopag was associated with statistically significant improvements in durable platelet response, reduction in use of concomitant ITP medication, and incidence of any bleeding events. Statistically significant differences vs placebo were also observed for durable platelet response and need for rescue therapy (eltrombopag, romiplostim, and fostamatinib); reduction in use of concomitant ITP medication (eltrombopag and romiplostim); incidence of any bleeding events (fostamatinib); and incidence of WHO grade 2-4 bleeding events (romiplostim and fostamatinib). No statistically significant differences were observed for any adverse events. Avatrombopag was associated with a statistically significant lower incidence of any bleeding events vs eltrombopag (IRR 0.38 [95% CrI 0.19, 0.75]) and romiplostim (IRR 0.38 [95% Crl 0.17, 0.86]); no other between-treatment differences were observed.

Conclusion: In this NMA, avatrombopag significantly increased the chance of achieving durable platelet response and reducing the use of concomitant ITP medication vs placebo, and significantly reduced the incidence of any bleeding events compared with placebo, eltrombopag, and romiplostim. The study aims to help guide clinicians managing patients with chronic ITP and insufficient response to previous treatment.
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http://dx.doi.org/10.1007/s12325-021-01752-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189936PMC
June 2021

Efficacy of rFVIIIFc versus Emicizumab for the Treatment of Patients with Hemophilia A without Inhibitors: Matching-Adjusted Indirect Comparison of A-LONG and HAVEN Trials.

J Blood Med 2021 25;12:115-122. Epub 2021 Feb 25.

The Bleeding and Clotting Disorders Institute, University of Illinois College of Medicine-Peoria, Peoria, IL, USA.

Purpose: Primary prophylaxis, using factor VIII replacement, is the recognized standard of care for severe hemophilia A. Recombinant factor VIII-Fc fusion protein (rFVIIIFc) and emicizumab, a humanized, bispecific antibody, are approved for routine prophylaxis of bleeding episodes in severe hemophilia A. These products have different mechanisms of action, methods of administration and treatment schedules. In the absence of head-to-head trials, indirect treatment comparisons can provide informative evidence on the relative efficacy of the two treatments. The aim of the study was to compare the approved dosing regimens for each product, rFVIIIFc individualized prophylaxis and emicizumab administered once every week (Q1W), every 2 weeks (Q2W) or every 4 weeks (Q4W), based on clinical trial evidence.

Patients And Methods: The comparison was conducted using matching-adjusted indirect comparison since clinical evidence did not form a connected network. Individual patient data for rFVIIIFc (A-LONG) were compared with data for emicizumab (HAVEN trial program) for mean annualized bleeding rate (ABR) and proportion of patients with zero bleeds. Safety data reported across the analyzed treatment arms were tabularized but not formally compared.

Results: After matching, no significant differences were observed between mean ABR for rFVIIIFc and emicizumab administered Q1W, Q2W or Q4W. The proportion of patients with zero bleeds was significantly higher with rFVIIIFc compared with emicizumab administered Q4W (51.2% versus 29.3%, respectively; odds ratio 2.53; 95% confidence interval 1.09-5.89); no significant differences noted when rFVIIIFc was compared with emicizumab administered Q1W or Q2W. The mean number of adverse events expressed per participant was 1.9 for individualized prophylaxis with rFVIIIFc and 3.7-4.0, 4.1 and 3.6 for emicizumab administered Q1W, Q2W or Q4W, respectively.

Conclusion: This indirect treatment comparison suggests that rFVIIIFc individualized prophylaxis is more efficacious than emicizumab Q4W, and at least as effective as more frequent emicizumab regimens, for the management of hemophilia A.
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http://dx.doi.org/10.2147/JBM.S288283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921628PMC
February 2021

Recombinant FVIIIFc Versus BAY 94-9027 for Treatment of Patients with Haemophilia A: Comparative Efficacy Using a Matching Adjusted Indirect Comparison.

Adv Ther 2021 02 30;38(2):1263-1274. Epub 2020 Dec 30.

Sobi, Stockholm, Sweden.

Introduction: Prophylaxis with recombinant factor VIII (rFVIII) is the current standard of care for haemophilia A. Several approaches have been used to extend the half-life of rFVIII to improve prophylaxis outcomes. An indirect comparison of pivotal clinical trial data was performed to evaluate the relative efficacy of two extended half-life therapies approved for the prophylactic treatment of haemophilia A: recombinant FVIII-IgG Fc domain fusion protein (rFVIIIFc) and pegylated rFVIII (BAY 94-9027).

Methods: Matching-adjusted indirect comparison (MAIC) was conducted to compare the rFVIIIFc individualised prophylaxis arm of the A-LONG phase III clinical trial (n = 117) and the BAY 94-9027 approved dosing regimens of the PROTECT VIII phase II/III study (n = 110). Following matching for baseline characteristics, mean annualised bleeding rate (ABR) and the proportion of patients with zero bleeds were compared for rFVIIIFc and BAY 94-9027. Additional supportive analyses comparing rFVIIIFc individualised prophylaxis and the individual prophylaxis regimens included in the PROTECT VIII group (twice weekly, and every 5 and 7 days [Q5D and Q7D]) were conducted.

Results: Mean ABR was lower in the rFVIIIFc individualised prophylaxis group versus the BAY 94-9027 pooled prophylaxis population (3.0 versus 4.9), providing a clinically relevant and statistically significant difference (mean difference [MD] - 1.9; 95% confidence interval [CI] - 3.5 to - 0.4). A statistically significant difference in ABR was also observed for rFVIIIFc compared with BAY 94-9027 Q7D (3.2 versus 6.4; MD - 3.3; 95% CI - 6.4 to - 0.2). The difference in the proportion of patients with zero bleeds between rFVIIIFc (46.5%) and BAY 94-9027 pooled prophylaxis population (38.2%) was not statistically significant (odds ratio 1.4; 95% CI 0.8 to 2.5).

Conclusions: This indirect treatment comparison indicates a statistically significant and clinically relevant difference in ABR favouring individualised prophylaxis with rFVIIIFc versus BAY 94-9027 prophylaxis. The proportion of patients with zero bleeds was numerically greater with rFVIIIFc treatment but did not achieve statistical significance.
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http://dx.doi.org/10.1007/s12325-020-01599-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889532PMC
February 2021

Qualitative Analysis of Factors Influencing Patient Persistence and Adherence to Prescribed Overactive Bladder Medication in UK Primary Care.

Adv Ther 2019 11 26;36(11):3110-3122. Epub 2019 Sep 26.

Manchester Metropolitan University, Manchester, UK.

Introduction: Pharmacotherapy for overactive bladder (OAB) is generally associated with low rates of persistence and adherence. This study was conducted to explore the patient journey in a UK primary care setting (experiences, perceptions, attitudes, and levels of engagement and expectations) and identify self-reported reasons for patient non-adherence and/or non-persistence to medications for OAB.

Methods: This was a qualitative, non-interventional study involving one-to-one semi-structured, face-to-face or phone interviews with individuals aged 40-80 years, diagnosed with OAB, and currently taking, or having taken, either antimuscarinic or β-adrenoceptor agonist medications within the last 12 months. Thematic analyses of interview transcripts identified themes surrounding the participants' experiences with OAB.

Results: A total of 20 interviews were conducted (face-to-face, n = 13; telephone, n = 7). Interviews from five men and 13 women (mean age 70 years) were included in the final analysis. The most common OAB symptoms reported included urgency, frequency, incontinence and nocturia. Several key themes of factors influencing persistence and/or adherence to prescribed OAB medication were identified: patients' attitude and condition adaptation behaviour; support with treatment; unmet efficacy/tolerability expectations; drug/condition hierarchy. Non-adherence and/or non-persistence to OAB medication was largely intentional, with patients balancing side effects against perceived clinical benefits. Perceived lack of efficacy was the primary reason for discontinuing treatment. Other factors cited included side effects of medication (either experienced or a fear of future effects), a general aversion to long-term medication taking, drug/condition hierarchy relative to other comorbidities, and limited healthcare professional (HCP) support/engagement. Patients expressed condition adaptation behaviours to help self-manage their condition.

Conclusion: Persistence and adherence to OAB medication may be suboptimal. HCPs might be able to improve persistence and adherence by fostering realistic treatment expectations and scheduling regular medication reviews. These measures may help optimise patient care and support more adherent behaviours, thus minimising the impact of undertreated OAB on patient quality of life.

Funding: Innovate UK and Astellas Pharma Europe Ltd (APEL).
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http://dx.doi.org/10.1007/s12325-019-01098-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822799PMC
November 2019

Quality of life in patients aged 65 years and older with overactive bladder treated with mirabegron across eight European countries: Secondary analysis of BELIEVE.

Int J Urol 2019 09 14;26(9):890-896. Epub 2019 Jul 14.

Department of Obstetrics and Gynaecology, University Hospitals, Plymouth, Devon, UK.

Objectives: To describe quality of life outcomes in patients with overactive bladder aged ≥65 years receiving mirabegron, a β3-adrenoreceptor agonist (BELIEVE).

Methods: BELIEVE was a European, prospective, non-interventional, real-world study of 848 patients with overactive bladder prescribed mirabegron in clinical practice. Overactive bladder questionnaire subscales were prespecified primary end-points, analyzed in the full analysis set (patients completing the questionnaire at baseline and ≥1 follow-up visit) and per protocol set (patients still taking mirabegron at 10-12 months) using accepted standards for minimally important differences (10 points).

Results: Nearly half of the patients in the full analysis set (380/796 [47.7%]) and per protocol set (224/452 [49.6%]) were aged ≥65 years. Similar proportions of patients aged ≥65 years (224/407; 55.0%) and <65 years (228/441; 51.7%) were taking mirabegron at 10-12 months. Mean symptom bother scores improved from baseline to month 10-12 in older patients (full analysis set 52.4 to 32.9; per protocol set 51.6 to 30.4) and younger patients (full analysis set 52.2 to 27.4; per protocol set 47.8 to 23.7). Proportions of older/younger patients with improvement in symptom bother were similar (full analysis set 52.1%/52.9%; per protocol set 70.1%/72.4%, respectively). Mean total quality of life scores improved in older patients (full analysis set 60.7-75.9; per protocol set 61.1-77.5) and younger patients (full analysis set 54.9 to 77.6; per protocol set 56.8 to 80.1). No unexpected safety issues were observed.

Conclusions: Patients aged ≥65 years receiving mirabegron in clinical practice reported clinically meaningful improvements in quality of life.
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http://dx.doi.org/10.1111/iju.14050DOI Listing
September 2019

The Last Year Before Graft Failure Negatively Impacts Economic Outcomes and is Associated With Greater Healthcare Resource Utilization Compared With Previous Years in the United Kingdom: Results of a Retrospective Observational Study.

Transplant Direct 2019 May 15;5(5):e443. Epub 2019 Apr 15.

Medical Affairs, Astellas Pharma Europe Ltd., Chertsey, Surrey, United Kingdom.

Background: Kidney and liver transplantation is the standard of care for end-stage renal or liver disease. However, long-term survival of kidney and liver grafts remain suboptimal. Our study aimed to understand the healthcare resources utilized and their associated costs in the years before graft failure.

Methods: Two noninterventional, retrospective, observational studies were conducted in cohorts of kidney or liver transplant patients. Once identified, patients were followed using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics databases from the date of transplantation to the date of the first graft failure. Total healthcare costs in the year before graft failure (primary endpoint) and during years 2-5 before graft failure (secondary endpoint) were collected.

Results: A total of 269 kidney and 81 liver transplant patients were analyzed. The mean total costs were highest for all resource components in the last year before graft failure, except for mean costs of immunosuppressive therapy per patient, which decreased slightly by index date (ie, graft failure). The mean total healthcare costs in the last year before graft failure were £8115 for kidney and £9988 for liver transplant patients and were significantly ( < 0.05) higher than years 2-5 before graft failure. Mean healthcare costs for years 2, 3, 4, and 5 before graft failure were £5925, £5575, £5469, and £5468, respectively, for kidney, and £6763, £7042, £6020, and £5651, respectively, for liver transplant patients.

Conclusions: Total healthcare costs in the last year before graft failure are substantial and statistically significantly higher than years 2-5 before graft failure, in both kidney and liver transplant patients. Our findings show the economic burden placed on healthcare services in the years before graft failure.
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http://dx.doi.org/10.1097/TXD.0000000000000884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511438PMC
May 2019

Drug utilization patterns and healthcare resource use and costs in patients with neurogenic bladder in the United Kingdom: A retrospective primary care database study.

Neurourol Urodyn 2019 06 28;38(5):1278-1289. Epub 2019 Mar 28.

School of Clinical Sciences, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.

Aim: To characterize patients with neurogenic bladder (NGB), their treatment patterns, healthcare resource utilization, and associated costs based on records from a primary care database in the United Kingdom.

Methods: This was a retrospective, descriptive, observational study of anonymized data from the Clinical Practice Research Datalink and Hospital Episode Statistics databases (selection period, 1 January 2004 to 31 December 2016). Adults with a definitive or probable diagnosis of NGB and ≥1 referral to a urologist were included.

Results: The study cohort included 3913 patients with definitive (n = 363) or probable (n = 3550) NGB. Patients had a mean of 8.6 (standard deviation [SD], 7.6) comorbidities, and mean Anticholinergic Cognitive Burden Scale score of 6.6 (SD, 5.9). During 12 months' follow-up, urinary tract infection (UTI) and urinary incontinence were the most common complications. Most patients (92.2%) received ≥1 prescription for an antimuscarinic agent or mirabegron, and 53.9% of patients received prescriptions for UTI-specific antibiotics. The mean number of visits to a general practitioner for any cause was 67.7 (SD, 42.6) per individual. Almost half (46.7%) of the study cohort visited a specialist during the 12-month follow-up period, and 11.0% had ≥1 hospital admission. Total mean per patient costs for healthcare resource utilization was £2395.

Conclusions: The burden of illness, healthcare resource needs, and associated costs among patients with NGB are considerable. Drug prescribing patterns are consistent with the symptoms and complications of NGB, although increased awareness of drugs with anticholinergic activity among prescribers may help to reduce the cumulative anticholinergic burden in this vulnerable population.
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http://dx.doi.org/10.1002/nau.23981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850049PMC
June 2019

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

BMJ Open 2018 11 21;8(11):e021889. Epub 2018 Nov 21.

Manchester Metropolitan University, Manchester, UK.

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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http://dx.doi.org/10.1136/bmjopen-2018-021889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252764PMC
November 2018

A retrospective study of treatment persistence and adherence to mirabegron versus antimuscarinics, for the treatment of overactive bladder in Spain.

BMC Urol 2018 Sep 4;18(1):76. Epub 2018 Sep 4.

Astellas Pharma S.A., Madrid, Spain.

Background: Persistence on-treatment with antimuscarinics in patients with overactive bladder (OAB) is reported to be sub-optimal. This retrospective, longitudinal, observational cohort study assessed treatment persistence with β-adrenoceptor agonists (i.e. mirabegron) and antimuscarinics, both classes of OAB pharmacotherapy, in patients with OAB in Spain.

Methods: Adults who received mirabegron or an antimuscarinic in routine clinical practice (1 June-31 October 2014), were identified from anonymised prescription data within the Spanish Cegedim Electronic Medical Records database. The primary endpoint, treatment persistence (time to treatment discontinuation [TTD] and the proportion of patients remaining on-treatment after 12 months), was unadjusted for potential confounders. Multivariate Cox regression models of persistence, adjusted for baseline characteristics, were used to compare differences in treatment groups. Adjusted subgroup analyses (target OAB drug, age, treatment status and sex) and sensitivity analyses (extending the time used to define treatment discontinuation from 30 days [base-case] to 45, 60 or 90 days without prescription renewal) were also performed.

Results: Overall, 1798 patients received mirabegron (N = 1169) or an antimuscarinic (N = 629); the mean age was 66.42 years. Median TTD was longer for mirabegron versus antimuscarinics (90 vs 56 days) and a higher proportion of patients who received mirabegron were persistent after 12 months (20.2% vs 10.2%); multivariate analyses indicated significantly greater persistence with mirabegron versus antimuscarinics (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.37-1.70; p < 0.001). Significant differences were also observed in subgroup analyses of mirabegron versus individual antimuscarinics (median TTD: 90 vs [range] 28-60 days; HR range: 1.21-2.17; p ≤ 0.013) and in all other subgroups assessed (p < 0.001). Sensitivity analysis showed that the median TTD for mirabegron increased by up to 31 days, and was significantly longer versus antimuscarinics across all adjusted periods (HR range: 1.43-1.53; all p < 0.001).

Conclusions: Patients with OAB in Spain who received mirabegron experienced longer persistence on-treatment than those who received antimuscarinics and the proportion of patients persistent on-treatment at 12 months with mirabegron was two-times higher versus antimuscarinics. These data may provide strategic insights for clinicians and policy makers involved in the management of OAB.
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http://dx.doi.org/10.1186/s12894-018-0390-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122705PMC
September 2018

A critical appraisal of the principal guidelines for neurogenic lower urinary tract dysfunction using the AGREE II instrument.

Neurourol Urodyn 2018 11 30;37(8):2945-2950. Epub 2018 Jul 30.

Faculty of Health, Department of Health Professions, Manchester Metropolitan University, Manchester, United Kingdom.

Aims: The process of identifying research questions, synthesizing and interpreting evidence, and weight given to health economics differs between the clinical guidelines (CGs) for neurogenic lower urinary tract dysfunction (NLUTD). Consequently, the quality also varies which can have implications for clinical practice.

Methods: We used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument to assess the quality of the National Institute for Health and Care Excellent (NICE), European Association of Urology (EAU), and the International Consultations on Incontinence (ICI) CGs on neurogenic bladder.

Results: The NICE CGs were deemed to be of the highest quality (overall score of 92%). NICE were the only guidelines to systematically incorporate cost-effectiveness research into their recommendations. The EAU CGs received an overall score of 83% and the ICI CGs achieved the lowest overall score (75%). The highest scoring domain among all the CGs was scope purpose (86%) and the lowest scoring domain was applicability (69%). All guidelines were recommended for use (mostly with some modifications).

Conclusions: All CGs had their inherent advantages and disadvantages, though all were still deemed to be of high quality. Incorporating cost-effectiveness research would be near impossible for guidelines with a broad-country remit. Incorporating the AGREE II instrument in the development of CGs and better collaboration between the ICI, NICE, and EAU could improve the quality, and consistency between NLUTD CGs and ultimately improve health outcomes for this important patient group.
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http://dx.doi.org/10.1002/nau.23775DOI Listing
November 2018

Efficacy and Tolerability of Mirabegron Compared with Antimuscarinic Monotherapy or Combination Therapies for Overactive Bladder: A Systematic Review and Network Meta-analysis.

Eur Urol 2018 09 23;74(3):324-333. Epub 2018 Apr 23.

Royal Hallamshire Hospital, Sheffield, UK.

Background: Mirabegron is an established treatment alternative to antimuscarinic therapy for patients with overactive bladder (OAB), as shown by efficacy and tolerability data from phase III trials.

Objective: To assess efficacy and tolerability of mirabegron 50mg versus antimuscarinic monotherapies and combination therapies.

Design, Setting, And Participants: Systematic literature review and network meta-analysis of randomised controlled trials (2000-2017) assessing eligible treatments for OAB.

Outcome Measurements And Statistical Analysis: Efficacy assessments included micturition frequency, urgency urinary incontinence, dry rate, and 50% reduction in incontinence. Tolerability assessments included dry mouth, constipation, blurred vision, and hypertension.

Results And Limitations: A total of 64 studies (n=46 666) were included in the network meta-analysis. Mirabegron 50mg was significantly more efficacious than placebo for all efficacy endpoints. Comparable overall efficacy was observed for mirabegron 50mg versus most active treatments, but solifenacin 10mg monotherapy and solifenacin 5mg plus mirabegron 25 or 50mg in combination were more efficacious for some/all outcomes. Mirabegron 50mg was significantly better tolerated regarding dry mouth, constipation, and urinary retention than 21/22, 9/20, and 7/10 active comparators, respectively; similar overall tolerability was observed between mirabegron 50mg and all treatments (including placebo) for the remaining endpoints. Limitations of the study included between-trial variations in the definition of certain endpoints and heterogeneity of the available data (eg, number of studies and patients assessed) for comparator treatments across different endpoints.

Conclusions: The relief of key OAB symptoms produced by mirabegron 50mg is significantly better than placebo, and similar to a range of common antimuscarinics, with the benefit of significantly fewer bothersome anticholinergic side effects such as dry mouth. Combination treatment of solifenacin 5mg plus mirabegron 25 or 50mg appears to provide an efficacy benefit compared with mirabegron 50mg, with the expected side effects of individual antimuscarinics.

Patient Summary: This study assessed the efficacy and tolerability of different drug treatments for OAB. Mirabegron 50mg was as effective as antimuscarinic therapy, with fewer common, bothersome side effects such as dry mouth, constipation, and urinary retention. Combination treatment of solifenacin 5mg plus mirabegron 25 or 50mg was more effective than mirabegron 50mg alone, but with more anticholinergic side effects.
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http://dx.doi.org/10.1016/j.eururo.2018.03.020DOI Listing
September 2018

Cost-effectiveness of solifenacin compared with oral antimuscarinic agents for the treatment of patients with overactive bladder in the UK.

J Mark Access Health Policy 2018 20;6(1):1438721. Epub 2018 Mar 20.

Medical Affairs Department, Astellas Pharma Europe Ltd, Chertsey, UK.

To evaluate the cost-effectiveness of solifenacin 5 mg/day versus other oral antimuscarinic agents used for overactive bladder (OAB) from a UK National Health Service (NHS) perspective. In a Markov model, hypothetical patients received solifenacin 5 mg/day or a comparator antimuscarinic, after which they could switch to an alternative antimuscarinic. The model estimated incremental cost-effectiveness ratios (ICER), expressed as cost per quality-adjusted life year (QALY) over a 5-year period. Solifenacin 5 mg/day was the dominant treatment strategy (i.e., less costly and more effective) versus tolterodine extended-release (ER) 4 mg/day, fesoterodine 4 and 8 mg/day, oxybutynin ER 10 mg/day and solifenacin 10 mg/day, and was cost-effective (i.e., ICERs below the £30,000 per QALY threshold generally applied in the NHS) versus oxybutynin immediate release (IR) 10 mg/day, tolterodine IR 4 mg/day and trospium chloride 60 mg/day. The probability of solifenacin 5 mg/day being dominant/cost-effective at a willingness-to-pay threshold of £30,000 per QALY was 57-98%. Solifenacin 5 mg/day appears to be a cost-effective strategy for the treatment of OAB over a 5-year timeframe compared with other oral antimuscarinic agents in the UK. These findings are important for decision-makers considering the economic implications of selecting treatments for OAB.
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http://dx.doi.org/10.1080/20016689.2018.1438721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907635PMC
March 2018

Economic Impact of Mirabegron Versus Antimuscarinics for the Treatment of Overactive Bladder in the UK.

Pharmacoecon Open 2017 Mar;1(1):25-36

Geriatric Medicine, University of Alberta, Edmonton, AB, Canada.

Purpose: Our objective was to estimate the economic outcomes of using mirabegron versus antimuscarinics in the treatment of patients with overactive bladder (OAB) from a societal perspective in the UK.

Materials And Methods: A Markov model was developed using Microsoft Excel. The time horizon and cycle length are 12 and 1 months, respectively; and the hypothetical cohort size 100 patients. Antimuscarinic comparators are fesoterodine, oxybutynin extended release (ER) and immediate release (IR), solifenacin, tolterodine ER/IR, trospium ER/IR, darifenacin and flavoxate. Model inputs included real-world treatment patterns data, healthcare resource use (e.g. clinic visits) and direct and indirect costs (e.g. drug acquisition and productivity loss). Model outputs included patient disposition, healthcare resource use, drug acquisition costs and other treatment-related costs over a 1-year time horizon. A one-way sensitivity analysis was performed to determine the key drivers of the model.

Results: In a hypothetical cohort of 100 patients, total annual costs per patient were lower with mirabegron than with all antimuscarinics (£1270.84 vs. 1321.71-1607.48). Healthcare resource use was lower with mirabegron than with all antimuscarinics (115 vs. 119-123 general practitioner visits; 173 vs. 178-185 specialist visits and 0.0042 vs. 0.0050-0.0060 surgical operations) and fewer work hours were lost (4017 vs. 5114-6990 [all per 100 patients]). Sensitivity analysis showed the model was sensitive to persistence and switching rates, although the impact on the overall results was minimal.

Conclusions: In the UK, using mirabegron to treat OAB may improve persistence and lead to reductions in switching treatment, healthcare resource utilization, productivity costs, and overall treatment costs versus antimuscarinics.
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http://dx.doi.org/10.1007/s41669-017-0011-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689035PMC
March 2017

Comparative efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents in overactive bladder: A systematic literature review and network meta-analysis.

Neurourol Urodyn 2018 03 15;37(3):986-996. Epub 2017 Nov 15.

Astellas Pharma Europe Ltd., Chertsey, Surrey, United Kingdom.

Aims: To compare efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents for the treatment of overactive bladder (OAB).

Methods: Literature searches of MEDLINE, Embase, and the Cochrane Library were undertaken to identify randomized controlled trials in OAB (2000-2015) for antimuscarinic agents. A network meta-analysis (NMA) was performed to estimate efficacy and tolerability outcomes for solifenacin 5 mg/day relative to other antimuscarinics.

Results: The NMA included 53 eligible trials (published, n = 48; unpublished on search date, n = 5). Solifenacin 5 mg/day was significantly more effective than tolterodine 4 mg/day for reducing incontinence and urgency urinary incontinence (UUI) episodes, but significantly less effective than solifenacin 10 mg/day for micturition; no other statistically significant differences were noted for efficacy. Solifenacin 5 mg/day had a statistically significant lower risk of dry mouth compared with darifenacin 15 mg/day, fesoterodine 8 mg/day, oxybutynin extended-release 10 mg/day, oxybutynin immediate-release (IR) 9-15 mg/day, tolterodine IR 4 mg/day, propiverine 20 mg/day, and solifenacin 10 mg/day. There were no significant differences between solifenacin 5 mg/day and other antimuscarinics for risk of blurred vision, or for 11 of 17 active comparators for risk of constipation.

Conclusions: This NMA suggests that the efficacy of solifenacin 5 mg/day is at least similar to other common antimuscarinics across the spectrum of OAB symptoms analyzed, and is more effective than tolterodine 4 mg/day in reducing incontinence and UUI episodes. Solifenacin 5 mg/day has a lower risk of dry mouth compared with several agents.
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http://dx.doi.org/10.1002/nau.23413DOI Listing
March 2018

Persistence and adherence with mirabegron vs antimuscarinics in overactive bladder: Retrospective analysis of a UK General Practice prescription database.

Int J Clin Pract 2017 Oct 14;71(10). Epub 2017 Sep 14.

Astellas Pharma Ltd, Chertsey, UK.

Introduction And Objectives: Persistence with antimuscarinic (AM) drugs prescribed for overactive bladder (OAB) is poor. This study aimed to compare persistence and adherence with the beta-3-adrenoceptor agonist mirabegron (MIR) vs AMs over 12 months.

Patients And Methods: This retrospective cohort analysis included patients aged ≥18 years who were prescribed MIR, or any AM. A 12-month look-back was used to assess inclusion eligibility. The primary end-point was persistence, defined as time to first discontinuation of index drug, during 1 year follow-up. The secondary end-point was adherence, estimated by medication possession ratio (MPR).

Results: Inclusion criteria were met by 6189 patients. Those prescribed AMs were mostly treatment-naïve (range 72.9%-95.3%) vs 54.4% of MIR patients. There was greater persistence with MIR vs AM. The median number of days on therapy with MIR was 101, vs 27-56 for AMs. Patients receiving AMs were significantly more likely to discontinue than those receiving MIR (hazard ratio [HR] range 1.24-2.05, P < .01 for each AM vs MIR. In treatment-naïve patients, HRs ranged from 1.25 (solifenacin, P = .012) to 2.07 (oxybutynin IR, P < .001). In treatment-experienced patients, they ranged from 1.10 (fesoterodine, P = NS) to 2.12 (oxybutynin IR, P < .001). Adherence was greater with MIR (mean MPR 48.4%) than with AMs (range 27.6%-40.4%, P < .001). Treatment-experienced patients were significantly less likely to discontinue treatment (HR 0.87, P = .006).

Discussion And Conclusion: MIR was associated with a significantly longer time to discontinuation, greater persistence and better adherence than AMs. However, there was a steep decline in persistence with all drugs after 1 month. This is unlikely to be wholly explained by anticholinergic adverse events, as it was also seen with MIR. The lower proportion of MIR patients who were treatment-naive reflects current prescribing guidelines whereby MIR is prescribed after an initial generic AM trial. The study was limited by the small number of MIR patients. Study identifier: ISN 178-MA-3059.
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http://dx.doi.org/10.1111/ijcp.12996DOI Listing
October 2017

The Best of Both Worlds: An Example Mixed Methods Approach to Understand Men's Preferences for the Treatment of Lower Urinary Tract Symptoms.

Patient 2018 02;11(1):55-67

Health Economics Research Unit, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UK.

Background: Discrete choice experiments (DCEs) are widely used to quantify individuals' preferences for healthcare. Guidelines recommend the design of DCEs should be informed by qualitative research. However, only a few studies go beyond guidelines by fully presenting qualitative and quantitative research jointly together in a mixed methods approach (MMA).

Objectives: Using an example study about men's preferences for medical treatment of lower urinary tract symptoms (LUTS), we demonstrate how qualitative research can complement DCEs to gain a rich understanding of individuals' preferences.

Methods: We were the first to combine online discussion groups (ODGs) with an online DCE. A thematic analysis of the ODGs and a conceptual map provided insights into men's quality of life (QoL) with LUTS and relevant treatment attitudes. This was used to design the DCE. Men's willingness to pay (WTP) for these attributes was estimated. Findings from ODGs and DCE were compared to understand WTP and preference heterogeneity.

Key Findings: Men mostly valued medicine that reduced urgency and night-time frequencies of urination but avoided sexual side effects. We find heterogeneity in the effect of sexual side effects on men's preferences. The ODGs suggest this is because several men may be sexually inactive due to their age, being widowed or having comorbidities. The ODGs also raised concern about men's awareness of LUTS.

Conclusion: We argue that the insights gained into men's preferences for treatment and how LUTS affects men's QoL could not have been obtained by either the qualitative research or the DCE alone.
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http://dx.doi.org/10.1007/s40271-017-0263-7DOI Listing
February 2018

Assessing Preference-Based Outcome Measures for Overactive Bladder: An Evaluation of Patient-Reported Outcome Data from the BESIDE Clinical Trial.

Patient 2017 Dec;10(6):677-686

The Office of Health Economics, Southside, 7th Floor, 105 Victoria Street, London, SW1E 6QT, UK.

Objectives: The aim of this study was to compare outcomes using two preference-based measures of health status (EQ-5D-5L and OAB-5D) in patients with overactive bladder (OAB) treated with solifenacin plus mirabegron or solifenacin monotherapy in the BESIDE trial.

Methods: Patients with OAB who remained incontinent after 4 weeks' treatment with solifenacin 5 mg were randomized 1:1:1 to combination treatment (solifenacin 5 mg plus mirabegron [25 mg for the first 4 weeks/50 mg for the last 8 weeks]), solifenacin 5 mg, or solifenacin 10 mg. EQ-5D-5L and OAB-q were administered at baseline, weeks 4, 8, 12, and end of treatment (EoT). OAB-5D scores were derived from OAB-q results. Responder analysis was carried out using several definitions of minimally important difference.

Results: A total of 2054 patients received one or more doses of study treatment (combination, n = 694; solifenacin 5 mg, n = 684; solifenacin 10 mg, n = 676). EQ-5D-5L Index mean score changes (from baseline to EoT) were greater with combination (0.059) than with solifenacin 5 mg (0.040) and 10 mg (0.044) monotherapy, but the differences were not statistically significant. A significantly greater improvement was observed for combination on OAB-5D (0.107 vs 0.085 for 5 mg, and 0.087 for 10 mg; p ≤ 0.01). The dimensions most improved overall were anxiety/depression, pain/discomfort, and usual activities on EQ-5D-5L, and urge, urine loss, and coping on OAB-5D. The proportion of responders was significantly greater with combination compared with monotherapy using OAB-5D only.

Conclusions: Improvements were observed in all study arms on both the EQ-5D-5L and OAB-5D, although only the OAB-5D showed a statistically significant benefit for combination versus solifenacin monotherapy. Combining generic and condition-specific preference-based health status measures allowed for assessment of dimensions that were particularly relevant to this patient population, while permitting comparison with outcomes from other studies, treatments, and populations via EQ-5D.
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http://dx.doi.org/10.1007/s40271-017-0262-8DOI Listing
December 2017

A retrospective study of treatment persistence and adherence to α-blocker plus antimuscarinic combination therapies, in men with LUTS/BPH in the Netherlands.

BMC Urol 2017 May 22;17(1):36. Epub 2017 May 22.

Astellas Pharma Europe Ltd, Chertsey, UK.

Background: To assess treatment persistence and adherence in men ≥45 years of age with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), using prescription records from the Netherlands IMS Lifelink™ LRx database.

Methods: In this retrospective, observational cohort study, we identified men who received combination therapy with an α-blocker plus an antimuscarinic (e.g. solifenacin or tolterodine) between 1 November 2013 and 31 October 2014. Treatment could be received as a fixed-dose combination (FDC) tablet or as two drugs administered together (concomitant therapy), if both combination drugs were prescribed within 30 days. The primary objective was to assess treatment persistence, defined as the time from initiation of combination therapy until first discontinuation of the FDC or at least one of the drugs given concomitantly (i.e. ≥30 days without prescription renewal). Subgroup and sensitivity analyses were conducted to assess persistence by antimuscarinic agent, and with different gap lengths used to define discontinuation (45, 60 and 90 days), respectively.

Results: A total of 1891 men received an α-blocker plus an antimuscarinic (FDC, N = 665; concomitant therapy, N = 1226). Median time to discontinuation was significantly longer with FDC versus concomitant therapy (414 vs. 112 days; adjusted hazard ratio [HR] 2.04, 95% confidence interval 1.77, 2.35; p < 0.0001). Persistence at 12 months (51.3% vs. 29.9%) was also significantly greater with FDC compared with concomitant therapy. Assessment of antimuscarinic subgroups showed that median time to discontinuation was longest with solifenacin combinations (214 days) compared with other antimuscarinic combinations (range, 47-164 days; adjusted HR range, 1.27-1.77, p = 0.037). No observable impact on treatment persistence was found by adjusting the gaps used to define discontinuation.

Discussion: This study of real-world evidence of men with LUTS/BPH treated with α-blocker plus antimuscarinic combination therapy in the Netherlands showed that treatment persistence was significantly greater in those who received a FDC tablet compared with combination therapy given concomitantly. The study also shows that treatment persistence was extended in men who received combination therapy containing solifenacin compared with other antimuscarinics.

Conclusions: Overall, these findings may be useful for prescribers, as improved persistence on-treatment may translate into improved outcomes for men with LUTS/BPH. Further study is warranted to establish the key drivers of persistence in men receiving combination therapy for LUTS/BPH.
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http://dx.doi.org/10.1186/s12894-017-0226-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440896PMC
May 2017

Cost-effectiveness of mirabegron compared to tolterodine ER 4 mg for overactive bladder in Canada.

Can Urol Assoc J 2017 Mar-Apr;11(3-4):123-130

Astellas Pharma Europe B.V., Leiden, The Netherlands.

Introduction: This analysis compared the cost-effectiveness of once-daily regimens of mirabegron 50 mg and generic tolterodine ER 4 mg in a hypothetical cohort of previously treated patients with overactive bladder (OAB) in Canada.

Methods: A Markov model was developed to represent different health states according to OAB symptoms (frequency, incontinence), presence/absence of adverse events (AEs; dry mouth, constipation, blurred vision), and treatment status (on-treatment, discontinue treatment, restart previous treatment). The time horizon used was one year, with monthly transitions between health states. The model was populated using data from a phase 3, placebo-controlled trial of mirabegron that included tolterodine as an active comparator (SCORPIO), as well as other published literature and expert opinion. Cost-effectiveness was calculated from Canadian public payer (based on Quebec list prices) and societal perspectives.

Results: The incremental one-year cost per patient for mirabegron over tolterodine was $182 CAD and $157 CAD from the payer and societal perspectives, respectively. The incremental quality-adjusted life year (QALY) gain for mirabegron was 0.0066 when using EQ-5D health-state utilities. Mirabegron was cost-effective compared with tolterodine, from both payer and societal perspectives, and remained cost-effective vs. tolterodine across the majority of sensitivity analyses. The model was based on limited clinical trial evidence supplemented with expert opinion and assumptions; a select number of OAB symptoms, AEs, and direct and indirect medical costs associated with OAB; and a timeframe of only one year.

Conclusions: From the payer and societal perspectives, the health economic model indicates that in Canada, mirabegron is a cost-effective treatment strategy compared with tolterodine, leading to improved health outcomes (QALYs) at an acceptable incremental cost.
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http://dx.doi.org/10.5489/cuaj.4114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434500PMC
May 2017

Clinical and economic impact of mirabegron compared with antimuscarinics for the treatment of overactive bladder in Canada.

J Med Econ 2017 Jun 12;20(6):614-622. Epub 2017 Mar 12.

g University of Alberta , Edmonton , Canada.

Background: The β-adrenoceptor agonist, mirabegron, and antimuscarinic agents provide similar efficacy for the treatment of overactive bladder (OAB), but mirabegron appears to be associated with better persistence, perhaps due to an absence of anticholinergic side-effects. This study estimated the expected costs associated with the management of OAB in Canada from a societal perspective by utilizing real-world evidence.

Methods: An economic model with monthly cycles and a 1-year time horizon was developed to depict a treatment pathway for a hypothetical cohort of 100 patients with OAB. At model entry, patients receive mirabegron or an antimuscarinic. Patients who do not persist may switch treatment, undergo a minimally invasive procedure, or remain symptomatic (uncontrolled). The model includes direct costs (e.g. physician visits) and indirect costs (e.g. lost productivity). A one-way univariate sensitivity analysis assessed a ±20% variation in each of the key model inputs.

Results: At 1 year, a greater proportion of patients persisted on treatment with mirabegron compared with antimuscarinics (33% vs 15-23%), and a smaller proportion switched treatment (17% vs 20-22%). The number of healthcare visits (292 vs 299-304), pads used (74,098 vs 77,878-81,669), and work hours lost (4,497 vs 5,372-6,249) were all lower for mirabegron vs antimuscarinics. The estimated total annual cost of treatment per patient with mirabegron was $2,127.46 Canadian dollars (CAD) ($5.82 CAD/day) compared with $2,150.20-$2,496.69 CAD ($5.89-$6.84 CAD/day) for antimuscarinics. The one-way sensitivity analysis indicated the results are robust.

Conclusions: Improved persistence observed in routine clinical practice with mirabegron appears to translate into benefits of reduced healthcare resource use, and lower direct and indirect costs of treatment compared with antimuscarinics. Overall, these data suggest that mirabegron may offer clinical and economic benefits for the management of patients with OAB in Canada.
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http://dx.doi.org/10.1080/13696998.2017.1294595DOI Listing
June 2017

Persistence and Adherence with Mirabegron versus Antimuscarinic Agents in Patients with Overactive Bladder: A Retrospective Observational Study in UK Clinical Practice.

Eur Urol 2017 09 11;72(3):389-399. Epub 2017 Feb 11.

Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

Background: Persistence with antimuscarinic therapy in overactive bladder (OAB) is poor, but may be different for mirabegron, a β-adrenoceptor agonist with a different adverse event profile.

Objective: To compare persistence and adherence with mirabegron versus tolterodine extended release (ER) and other antimuscarinics in routine clinical practice over a 12-mo period.

Design, Setting, And Participants: Retrospective, longitudinal, observational study of anonymised data from the UK Clinical Practice Research Datalink GOLD database. Eligibility: age ≥18 yr, ≥1 prescription for target OAB drug (between May 1, 2013 and June 29, 2014), and 12-mo continuous enrolment before and after the index prescription date.

Interventions: Mirabegron, darifenacin, fesoterodine, flavoxate, oxybutynin ER or immediate-release (IR), propiverine, solifenacin, tolterodine ER or IR, and trospium chloride.

Outcome Measurements And Statistical Analysis: The primary endpoint was persistence (time to discontinuation). Secondary endpoints included 12-mo persistence rates and adherence (assessed using medication possession ratio, MPR). Cox proportional-hazards regression models and logistic regression models adjusted for potential confounding factors were used to compare cohorts. Analyses were repeated after 1:1 matching.

Results And Limitations: The study population included 21996 eligible patients. In the unmatched analysis, the median time-to-discontinuation was significantly longer for mirabegron (169 d, interquartile range [IQR] 41-not reached) compared to tolterodine ER (56 d, IQR 28-254; adjusted hazard ratio [HR] 1.55, 95% confidence interval 1.41-1.71; p<0.0001) and other antimuscarinics (range 30-78 d; adjusted HR range 1.24-2.26, p<0.0001 for all comparisons). The 12-mo persistence rates and MPR were also significantly greater with mirabegron than with all the antimuscarinics. Limitations include the retrospective design, use of prescription records to estimate outcomes, and inability to capture reasons for discontinuation.

Conclusions: Persistence and adherence were statistically significantly greater with mirabegron than with tolterodine ER and other antimuscarinics prescribed for OAB in the UK.

Patient Summary: This study assessed persistence and adherence (or compliance) with medications prescribed for OAB in a large UK population. We found that patients prescribed mirabegron remained on treatment for longer and showed greater adherence than those prescribed traditional antimuscarinics.
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http://dx.doi.org/10.1016/j.eururo.2017.01.037DOI Listing
September 2017

Men's preferences for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia: a discrete choice experiment.

Patient Prefer Adherence 2016 24;10:2407-2417. Epub 2016 Nov 24.

Health Economics Research Unit, University of Aberdeen, Aberdeen, UK.

Objective: To explore and quantify men's preferences and willingness to pay (WTP) for attributes of medications for lower urinary tract symptoms associated with benign prostatic hyperplasia using a discrete choice experiment.

Subjects And Methods: Men in the UK aged ≥45 years with moderate-to-severe lower urinary tract symptoms/benign prostatic hyperplasia (based on self-reported International Prostate Symptom Score ≥8) were recruited. An online discrete choice experiment survey was administered. Eligible men were asked to consider different medication scenarios and select their preferred medication according to seven attributes: daytime and nighttime (nocturia) urinary frequency, urinary urgency, sexual and nonsexual side effects, number of tablets/day, and cost/month. A mixed-logit model was used to estimate preferences and WTP for medication attributes.

Results: In all, 247 men completed the survey. Men were willing to trade-off symptom improvements and treatment side effects. Men preferred medications that reduced urinary urgency and reduced day- and nighttime urinary frequency. Men preferred medications without side effects (base-case level), but did not care about the number of tablets per day. WTP for symptomatic improvement was £25.33/month for reduced urgency (urge incontinence to mild urgency), and £6.65/month and £1.39/month for each unit reduction in night- and daytime urination frequency, respectively. The sexual and nonsexual side effects reduced WTP by up to £30.07/month. There was significant heterogeneity in preferences for most attributes, except for reduced urinary urgency from urge incontinence to mild urgency and no fluid during ejaculation (dry orgasm).

Conclusion: To compensate for side effects, a medicine for lower urinary tract symptoms/benign prostatic hyperplasia must provide a combination of benefits, such as reduced urgency of urination plus reduced nighttime and/or reduced daytime urination.
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http://dx.doi.org/10.2147/PPA.S112161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125770PMC
November 2016

Using EQ-5D-3L and OAB-5D to assess changes in the health-related quality of life of men with lower urinary tract symptoms associated with benign prostatic hyperplasia.

Qual Life Res 2017 05 28;26(5):1187-1195. Epub 2016 Nov 28.

Astellas Pharma Europe Ltd., Astellas Medical Affairs, EMEA, HEOR, Chertsey, UK.

Objectives: To assess changes in the health status of men with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) using the EQ-5D-3L and OAB-5D instruments and to evaluate the sensitivity of the instruments.

Methods: Data were available from a large randomised phase III trial of men with moderate-to-severe storage and voiding LUTS/BPH (NEPTUNE). Men received a fixed-dose combination of solifenacin 6 mg plus oral controlled absorption system (OCAS™) formulation of tamsulosin (TOCAS, 0.4 mg), TOCAS monotherapy or placebo and completed the EQ-5D-3L and OAB-5D at baseline and weeks 4, 8 and 12. Analysis of covariance was used to estimate changes in EQ-5D-3L Index, EQ-VAS and OAB-5D. Changes in dimension level were summarised using the Paretian Classification of Health Change (PCHC).

Results: Improved health-related quality of life from baseline was seen in all treatment arms on EQ-5D-3L and OAB-5D at week 12, although only OAB-5D showed statistically significant differences between active treatment and placebo, both on the index score and using the PCHC approach. Effect sizes in the active treatment groups were large (>0.8) on OAB-5D but small (≈0.2) on EQ-5D-3L. EQ-5D-3L showed a very high ceiling effect (45% of men reported full health at baseline) and a substantial proportion of these men reported improvements at week 12 in several dimensions of OAB-5D.

Conclusions: A large ceiling effect on EQ-5D-3L substantially limited its sensitivity in this population. OAB-5D proved more sensitive to changes in health status and could be considered a complement to ED-5D-3L as a source of utilities for health economic modelling.
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http://dx.doi.org/10.1007/s11136-016-1460-xDOI Listing
May 2017

Mirabegron as Add-On Treatment to Solifenacin in Patients with Incontinent Overactive Bladder and an Inadequate Response to Solifenacin Monotherapy: Responder Analyses and Patient-Reported Outcomes from the BESIDE Study [corrected].

J Urol 2016 09 8;196(3):809-18. Epub 2016 Apr 8.

University of Bristol and Bristol Urological Institute, Bristol, United Kingdom.

Purpose: We investigated improvements in overactive bladder and patient reported outcomes in patients with overactive bladder and refractory incontinence treated with mirabegron 50 mg plus solifenacin 5 mg vs solifenacin 5 or 10 mg.

Materials And Methods: Patients with overactive bladder who were incontinent despite 4 weeks of single-blind daily solifenacin 5 mg were randomized 1:1:1 to a double-blind daily combination of mirabegron 50 mg/solifenacin 5 mg, or solifenacin 5 or 10 mg for 12 weeks. The mirabegron dose was increased from 25 to 50 mg after week 4. Symptom bother, health related quality of life and patient perception of bladder condition were assessed by OAB-q (Overactive Bladder Questionnaire) and the PPBC (Patient Perception of Bladder Condition) questionnaire, respectively. Responder rates were based on a 50% reduction in daily incontinence, zero incontinence episodes and fewer than 8 micturitions per 24 hours with minimal important differences in OAB-q and PPBC.

Results: Overall 2,174 patients with a median age of 59 years were randomized, including 727 to the combination, 728 to solifenacin 5 mg and 719 to solifenacin 10 mg. Symptom bother, total health related quality of life and its subscales (coping, concern and social), and PPBC were significantly improved with combination vs solifenacin monotherapy (p <0.05). The odds of achieving clinically meaningful improvements in incontinence, micturition frequency, symptom bother, health related quality of life and PPBC were significantly higher for combination than solifenacin monotherapy. The odds of becoming continent was 47% and 28% higher for combination vs solifenacin 5 and 10 mg (OR 1.47, 95% CI 1.17-1.84, p = 0.001 and OR 1.28; 95% CI 1.02-1.61, p = 0.033, respectively).

Conclusions: Significantly more patients on the combination achieved clinically meaningful improvements in incontinence and micturition frequency. Improvements were accompanied by similar improvements in PPBC, symptom bother and health related quality of life.
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http://dx.doi.org/10.1016/j.juro.2016.03.174DOI Listing
September 2016

A cost-effectiveness and budget impact analysis of first-line fidaxomicin for patients with Clostridium difficile infection (CDI) in Germany.

Infection 2016 Oct 9;44(5):599-606. Epub 2016 Apr 9.

Astellas EMEA, Chertsey, UK.

Purpose: Clostridium difficile infection (CDI) represents a significant economic healthcare burden, especially the cost of recurrent disease. Fidaxomicin produced significantly lower recurrence rates and higher sustained cure rates in clinical trials. We evaluated the cost-effectiveness and budget impact of fidaxomicin compared with vancomycin in Germany in the first-line treatment of patient subgroups with CDI at increased risk of recurrence.

Methods: A semi-Markov model was used to compare the cost-effectiveness and budget impact of fidaxomicin vs. vancomycin from a payer perspective in Germany. The model cycle length was 10 days. The time horizon was 1 year. Model inputs were probability of clinical cure, 30-day probability of recurrence, and 30-day attributable mortality based on evidence from two randomized controlled trials comparing fidaxomicin and vancomycin in patients with CDI. Cost-effectiveness outcomes were cost per quality-adjusted life year gained, cost per bed-day saved, and cost per recurrence avoided.

Results: Despite higher drug acquisition costs, fidaxomicin was dominant in the cancer subgroup (less costly and more effective) and cost-effective in the other subgroups, with incremental cost-effectiveness ratios vs. vancomycin ranging from €26,900 to €44,500. Hospitalization costs of the first-line treatment of CDI with fidaxomicin vs. vancomycin were lower in every patient subgroup, resulting in budget impacts ranging from -€1325 (in patients ≥65 years) to -€2438 (in cancer patients). Reductions in the cost of treating recurrence with fidaxomicin ranged from -€574.32 per patient in those receiving concomitant antibiotics to -€1500.68 per patient in renally impaired patients.

Conclusions: In patient subgroups with CDI at increased recurrence risk, fidaxomicin was cost-effective vs. vancomycin, and less costly and more effective in patients with cancer.
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http://dx.doi.org/10.1007/s15010-016-0894-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042976PMC
October 2016

Cost-Effectiveness of Mirabegron Compared with Antimuscarinic Agents for the Treatment of Adults with Overactive Bladder in the United Kingdom.

Value Health 2015 Sep 9;18(6):783-90. Epub 2015 Sep 9.

Creativ-Ceutical SARL, Saint Honoré, Paris, France.

Background: Mirabegron, a first-in-class selective oral β3-adrenoceptor agonist, has similar efficacy to most antimuscarinic agents and a lower incidence of dry mouth in patients with overactive bladder (OAB).

Objectives: To evaluate the cost-effectiveness of mirabegron 50 mg compared with oral antimuscarinic agents in adults with OAB from a UK National Health Service perspective.

Methods: A Markov model including health states for symptom severity, treatment status, and adverse events was developed. Cycle length was 1 month, and the time horizon was 5 years. Antimuscarinic comparators were tolterodine extended release, solifenacin, fesoterodine, oxybutynin extended release and immediate release (IR), darifenacin, and trospium chloride modified release. Transition probabilities for symptom severity levels and adverse events were estimated from a mirabegron trial and a mixed treatment comparison. Estimates for other inputs were obtained from published literature or expert opinion. Quality-adjusted life-years (QALYs) and total health care costs, including costs of drug acquisition, physician visits, incontinence pad use, and botox injections, were modeled. Deterministic and probabilistic sensitivity analyses were performed.

Results: Base-case incremental cost-effectiveness ratios ranged from £367 (vs. solifenacin 10 mg) to £15,593 (vs. oxybutynin IR 10 mg) per QALY gained. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of £20,000/QALY gained, the probability of mirabegron 50 mg being cost-effective ranged from 70.2% versus oxybutynin IR 10 mg to 97.8% versus darifenacin 15 mg. A limitation of our analysis is the uncertainty due to the lack of direct comparisons of mirabegron with other agents; a mixed treatment comparison using rigorous methodology provided the data for the analysis, but the studies involved showed heterogeneity.

Conclusions: Mirabegron 50 mg appears to be cost-effective compared with standard oral antimuscarinic agents for the treatment of adults with OAB from a UK National Health Service perspective.
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http://dx.doi.org/10.1016/j.jval.2015.05.011DOI Listing
September 2015

Patient-reported outcomes with the β -adrenoceptor agonist mirabegron in a phase III trial in patients with overactive bladder.

Neurourol Urodyn 2016 11 19;35(8):987-994. Epub 2015 Aug 19.

Astellas Pharma Global Development EU, Leiden, the Netherlands.

Aims: To assess patient-reported outcomes (PROs) in patients with overactive bladder (OAB) receiving the novel β -adrenoceptor agonist mirabegron.

Methods: Data from a randomised, double-blind, controlled phase III trial in 1,987 patients aged ≥18 years with OAB symptoms for ≥3 months were analysed. Patients received placebo, mirabegron 50 or 100 mg/day, or tolterodine extended release (ER) 4 mg orally once daily for 12 weeks after a 2-week placebo run-in. Prespecified analysis of PROs (changes in OAB Questionnaire [OAB-q], Patient Perception of Bladder Condition [PPBC], and Work Productivity and Activity Impairment: Specific Health Problem [WPAI-SHP] instrument) in patients treated with mirabegron 50 mg/day, tolterodine ER 4 mg/day or placebo is reported. Post-hoc analyses of OAB-q, PPBC and the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) in patients who were incontinent at baseline are also reported.

Results: Significant improvements over placebo in OAB-q coping and concern from baseline to final visit were observed with mirabegron 50 mg/day. No significant improvements in these parameters were observed with tolterodine ER 4 mg/day. Mirabegron 50 mg/day significantly increased the proportion of patients showing a PPBC improvement over placebo. Mirabegron 50 mg/day also produced greater improvements in WPAI-SHP presenteeism and greater reductions in absenteeism and overall work impairment than placebo or tolterodine ER 4 mg/day. The impact of mirabegron 50 mg/day treatment on PROs in the incontinent population appears to be greater than that in the overall OAB population.

Conclusions: At the approved dose of 50 mg/day, mirabegron significantly improves OAB patients' perception of disease and quality of life, independent of whether they are incontinent at baseline. Neurourol. Urodynam. 35:987-994, 2016. © 2015 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/nau.22844DOI Listing
November 2016
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