Treating moderate-to-severe menopausal vasomotor symptoms with fezolinetant: analysis of responders using pooled data from two phase 3 studies (SKYLIGHT 1 and 2).

OBJECTIVES: The aims of the study were to further characterize the efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) due to menopause using responder analysis and to investigate whether efficacy, not adjusted for placebo, resulted in clinically meaningful within-patient change. METHODS: This prespecified analysis used pooled data from two phase 3, randomized, double-blind, placebo-controlled studies (SKYLIGHT 1 and 2). Responders were those experiencing ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. Responder analysis was performed for patient-reported outcome (PRO) measures to evaluate participants achieving a clinically meaningful within-patient change (not placebo adjusted) at week 4 and 12 versus baseline. Single responders were based on outcomes of VMS frequency, Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b Total Score, Menopause-Specific Quality of Life (MENQoL) Total Score, and MENQoL VMS Domain Score. Double and triple responder analyses combined VMS frequency plus one or more of the PRO. Patient Global Impression of Change VMS was deemed a suitable anchor measure for meaningful within-patient change in VMS frequency. RESULTS: A greater proportion of fezolinetant-treated versus placebo-treated participants had ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. A greater proportion of responders were observed in the fezolinetant groups versus placebo at week 12 in all four single responder analyses. In the double and triple responder analyses, odds ratios were supportive of a beneficial effect for both doses of fezolinetant versus placebo. CONCLUSIONS: Fezolinetant was associated with significantly higher within-patient clinically meaningful improvement in important PRO, including VMS frequency, PROMIS SD SF 8b Total Score, MENQoL Total Score, and MENQoL VMS Domain Score.

Fezolinetant impact on health-related quality of life for vasomotor symptoms due to the menopause: Pooled data from SKYLIGHT 1 and SKYLIGHT 2 randomised controlled trials.

OBJECTIVE: To assess the effect of fezolinetant treatment on health-related quality of life using pooled data from SKYLIGHT 1 and 2 studies. DESIGN: Prespecified pooled analysis. SETTING: USA, Canada, Europe; 2019-2021. POPULATION: 1022 women aged ≥40 to ≤65 years with moderate-to-severe vasomotor symptoms (VMS; minimum average seven hot flushes/day), seeking treatment for VMS. METHODS: Women were randomised to 12-week double-blind treatment with once-daily placebo or fezolinetant 30 or 45 mg. Completers entered a 40-week, active extension (those receiving fezolinetant continued that dose; those receiving placebo re-randomised to fezolinetant received 30 or 45 mg). MAIN OUTCOME MEASURES: Mean changes from baseline to weeks 4 and 12 on Menopause-Specific Quality of Life (MENQoL) total and domain scores, Work Productivity and Activity Impairment questionnaire specific to VMS (WPAI-VMS) domain scores, Patient Global Impression of Change in VMS (PGI-C VMS); percentages achieving PGI-C VMS of 'much better' (PGI-C VMS responders). Mean reduction was estimated using mixed model repeated measures analysis of covariance. RESULTS: Fezolinetant 45 mg mean reduction over placebo in MENQoL total score was -0.57 (95% confidence interval [CI] -0.75 to -0.39) at week 4 and -0.47 (95% CI -0.66 to -0.28) at week 12. Reductions were similar for 30 mg. MENQoL domain scores were also reduced and WPAI-VMS scores improved. Twice as many women receiving fezolinetant reported VMS were 'much better' than placebo based on PGI-C VMS assessment. CONCLUSIONS: Fezolinetant treatment was associated with improvement in overall QoL, measured by MENQoL, and work productivity, measured by WPAI-VMS. A high proportion receiving fezolinetant felt VMS were 'much better' based on PGI-C VMS responder analysis.

Prevalence and impact of vasomotor symptoms due to menopause among women in Brazil, Canada, Mexico, and Nordic Europe: a cross-sectional survey.

OBJECTIVE: This study investigated the prevalence and impact of moderate to severe vasomotor symptoms (VMS), related treatment patterns, and experiences in women. METHODS: The primary objective was to assess the prevalence of moderate to severe menopause-related VMS among postmenopausal women aged 40 to 65 years in Brazil, Canada, Mexico, and four Nordic European countries (Denmark, Finland, Norway, and Sweden) using an online survey. Secondary objectives assessed impact of VMS among perimenopausal and postmenopausal women with moderate to severe VMS using the Menopause-Specific Quality of Life questionnaire, Work Productivity and Activity Impairment questionnaire, Patient-Reported Outcomes Measurement Information System sleep disturbances assessment, and questions regarding treatment patterns and attitudes toward symptoms and available treatments. RESULTS: Among 12,268 postmenopausal women, the prevalence of moderate to severe VMS was about 15.6% and was highest in Brazil (36.2%) and lowest in Nordic Europe (11.6%). Secondary analyses, conducted among 2,176 perimenopausal and postmenopausal women, showed that VMS affected quality of life across all domains measured and impaired work activities by as much as 30%. Greater symptom severity negatively affected sleep. Many women sought medical advice, but most (1,238 [56.9%]) were not receiving treatment for their VMS. The majority (>70%) considered menopause to be a natural part of aging. Those treated with prescription hormone therapy and nonhormone medications reported some safety/efficacy concerns. CONCLUSIONS: Among women from seven countries, moderate to severe menopause-related VMS were widespread, varied by region, and largely impaired quality of life, productivity, and/or sleep.

A Retrospective Database Analysis to Investigate Treatment Patterns and Health Care Resource Utilisation in Patients who CYCLe AntiMuscarinics in ENgland (CYCLAMEN).

BACKGROUND: Patients with overactive bladder may cycle through different antimuscarinic medications even though there is limited evidence to support this approach. OBJECTIVE: To describe treatment patterns and the associated health care resource utilisation (HCRU) according to antimuscarinic cycling groups. DESIGN, SETTING, AND PARTICIPANTS: The CYCLe AntiMuscarinics in ENgland (CYCLAMEN) study was a retrospective observational investigation that used primary care records from the Clinical Practice Research Datalink GOLD database linked to Hospital Episode Statistics secondary care data. Eligible patients (≥18 yr) were prescribed their first antimuscarinic between January 2014 and December 2017. Patients were categorised into groups prescribed one, two, or three or more (groups 1-3) consecutive unique antimuscarinics over 18 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The HCRU rate and costs were calculated for the period of continuous antimuscarinic therapy (first antimuscarinic treatment episode) and the 18-mo follow-up period. Treatment sequence patterns were displayed using sunburst plots and Kaplan-Meier analysis was used to assess time on treatment. RESULTS AND LIMITATIONS: Overall, 35 369 patients were included, of whom 31 760 (89.8%) received one antimuscarinic (group 1), 3182 (9.0%) received two (group 2), and 427 (1.2%) received three or more (group 3). The most common initial antimuscarinics were solifenacin (13 628 patients, 42.9%) in group 1, and oxybutynin in group 2 (1267 patients, 39.8%) and group 3 (200 patients, 46.8%). The median duration of the first antimuscarinic treatment episode was 57 d and <20% of patients were receiving any antimuscarinic after 18 mo. The number of primary care visits and mean costs increased across groups. The reasons for cycling could not be identified in this study. CONCLUSIONS: Approximately 10% of patients underwent sequential cycling with two or more antimuscarinics. Furthermore, as the majority discontinued treatment within 18 mo, there is a need to improve the management of these patients in the clinical care setting. PATIENT SUMMARY: We investigated treatment patterns and health care use for patients with overactive bladder who were prescribed at least one antimuscarinic drug (AMD), which are drugs that reduce some of the impulses passing from the bladder to the brain. Around 10% of patients accessing primary health care in England received more than one sequential AMD. Most patients discontinued treatment, which may indicate inadequate management of their condition. Prescription of a higher number of AMDs was associated with higher health care costs.

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

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.