Health-related Quality Of Life Benefits Research Articles

#443 LEVIL evaluates the impact of HDx on HR-QoL and symptoms, including durability-of-effect and variability

Abstract Background and Aims Current hemodialysis (HD), utilizing conventional high-flux dialyzers, is handicapped by clearance limitations (larger-sized uremic toxins), which contribute to poor health-related quality-of-life (HR-QoL) and symptom-burden. Recent international consensus and guideline-setting efforts have explicitly prioritized identification and management of symptoms and subjective experience, whilst also acknowledging the lack of tools available to fully appreciate and continuously monitor these challenges. This study aimed to utilize dynamic patient-reported-outcome-measurement tool (PROM), London Evaluation of Illness (LEVIL-developed in-house), to iteratively interrogate patient-experience and to confirm previously reported HR-QoL benefits of the use of expanded hemodialysis (HDx) using medium cut-off dialyzer (extending the spectrum of uremic toxins being addressed). Furthermore, this study aimed to extend appreciation of effects on patient subjective experience to include durability-of-effects, variability of symptom-measures and impact of HDx withdrawal. Methods We conducted a multi-centre interventional study in 47 patients established on conventional thrice weekly centre-based HD in Ontario, Canada. Study protocol was 15-months in length with five phases 1) one-month observation (high-flux-HD), 2) three-months HDx 3) two-month wash-out (high-flux-HD), 4) six-months HDx, 5) three-month wash-out (high-flux-HD). HR-QoL and symptom-burden were evaluated using LEVIL throughout study. Results HDx-therapy improved HR-QoL [p 0.0006 (19% from baseline)] and a variety of symptoms including general wellbeing [p 0.005 (23%)], energy [p 0.004 (33%)], sleep-quality [p 0.001 (33%)], pruritus [0.003 (30%)], pain [p 0.01 (19%)], restless leg syndrome [p 0.0006 (15%)], mood [p 0.02 (12%)], appetite [ p 0.03 (9%)], breathlessness [p 0.001 (9%)], and HD-recovery [p 0.004 (26%)]. Response was more pronounced in those with poorer HR-QoL and higher symptom-burden. Improvements were durable over time with continued use with less symptom-variability (range 10-35% improvement). Improvements diminished gradually with return to high-flux-HD. The drivers of poor HR-QoL were largely general-wellbeing, energy, sleep-quality, pruritus, and bodily pain. Conclusion Use of a dynamic PROM effectively allowed appreciation of HR-QoL burden in HD-patients. Use of HDx-therapy results in improved patient subjective outcomes that are durable and associated with significantly lower variation in important symptom-domains than patients experience with receiving conventional high-flux-HD.

Health-related quality of life with sacituzumab govitecan in HR+/HER2- metastatic breast cancer in the phase III TROPiCS-02 trial.

The TROPiCS-02 study (NCT03901339) demonstrated that sacituzumab govitecan (SG) has superior clinical outcomes over treatment of physician's choice (TPC) chemotherapy in patients with hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2-) metastatic breast cancer (mBC). Here, we present health-related quality of life (HRQoL) patient-reported outcome (PRO) findings from this study. Eligible adults with HR+/HER2- mBC who previously received a taxane, endocrine-based therapy, a CDK4/6 inhibitor, and 2-4 lines of chemotherapy were randomized 1:1 to receive SG or TPC until progression or unacceptable toxicity. PROs were assessed at baseline and on day 1 of each cycle, using the European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 (EORTC QLQ-C30), EQ-5D-5L, and PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE). Compared to TPC, overall least square mean change from baseline was significantly better for SG for physical functioning and dyspnea, but worse for diarrhea. Time to first clinically meaningful worsening or death was significantly longer for SG in global health status/quality of life, physical functioning, fatigue, emotional functioning, dyspnea, insomnia, and financial difficulties of the EORTC QLQ-C30 and the EQ-VAS, but longer for TPC in diarrhea. Few patients in both arms reported experiencing any worsening to level 3 or 4 treatment-related symptomatic events during treatment, as assessed by 16 PRO-CTCAE items, except for diarrhea frequency and amount of hair loss, which favored TPC. SG was associated with an HRQoL benefit in most symptoms and functioning, compared with TPC. This supports the favorable profile of SG as a treatment option for patients with pretreated HR+/HER2- mBC.

Health-related quality of life in trials with high rates of early censoring: Caution advised

Health-related quality-of-life (HRQoL) data are central to capturing the quality of patients’ life, while endpoints like overall survival (OS) focus on the quantity of life. When analyzing HRQoL data gathered from patients in a randomized trial, a key consideration is the completion rate – indicating the proportion of patients remaining in the trial and with completed questionnaires. When completion rates are disproportionately low in one treatment arm, one likely explanation is that patients who did not complete questionnaires suffered more from toxicities, negatively impacting their HRQoL. This is likely the case when low completion rates occur in the more toxic arm within a randomized trial. If the HRQoL analysis is run as a complete-case analysis – only considering patients without missing data – a decrement in HRQoL can be missed. Conversely, when completion rates are high, the HRQoL data are thought to be more reliable, and informative censoring is less likely. We describe why this reasoning can be inadequate. In trials where high and imbalanced rates of early censoring affect progression-free survival or OS endpoints, the completion rates only apply to the fraction of patients remaining in the trial. In those, HRQoL results should be considered with caution, and reasons for censoring in the primary time-to-event analyses should be explored before making definite conclusions about HRQoL. This is even more relevant in trials with non-inferiority design, where a benefit in HRQoL could be used as a justification to modify practice.

Application of restorative neurostimulation for chronic mechanical low back pain in an older population with 2-year follow up

IntroductionData on the Medicare-aged population show that older patients are major consumers of low back pain (LBP) interventions. An effective approach for patients with mechanical LBP that has been refractory...

Impacts of systemic treatments on health-related quality of life for patients with metastatic colorectal cancer: a systematic review and network meta-analysis

ObjectiveThere is limited evidence of comparative results among different treatments regarding impacts of Health-Related Quality of Life (HRQoL) for patients with metastatic colorectal cancer (mCRC). We aimed to compare efficacy of systemic treatments on HRQoL among patients with mCRC.MethodsWe collected randomized controlled trials (RCTs) reported in English up until July 2023, from databases including PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and prominent conference databases, for this Bayesian network meta-analysis. Phase 2 or 3 trials that evaluated at least two therapeutic regimens were included. Primary outcomes were short-term and long-term mean changes in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) scores. Secondary outcome was mean change in EQ-5D health utility scores. Mean differences (MDs) with 95% confidence intervals (CIs) were used as effect size. Subgroup analysis was performed based on whether patients received systemic treatments before. We conducted various sensitivity analyses, including differentiating between chemotherapy types, and analyzed patient cohorts with non-specified gene expression levels as well as those with target KRAS expression statuses. The current systematic review protocol was registered on PROSPERO (CRD42023453315 and CRD42023420498).ResultsImmunotherapy and targeted therapy significantly improved HRQoL over chemotherapy, with MDs of 9.27 (95% CI: 3.96 to 14.6) and 4.04 (95% CI: 0.11 to 7.94), respectively. Monotherapy significantly outperformed both combination therapy (MD 5.71, 95%CI 0.78 to 10.63) and no active treatment (MD 3.7, 95%CI 1.41 to 6.01) regarding GHS/QoL in the short-term. Combining targeted therapy with chemotherapy did not improve HRQoL. Focusing on HRQoL, cetuximab excelled when gene expression baselines were unspecified. Subgroup and sensitivity analyses upheld these robust findings, unaffected by model or patient baseline characteristics. Evidence from clinical trials without specific gene level data suggested that monotherapies, especially targeted therapies such as cetuximab, demonstrated superiority in HRQoL. For KRAS wild-type patients, no significant HRQoL differences emerged between chemotherapy, targeted therapy, or their combination..ConclusionsTargeted therapies and immunotherapy demonstrate superior HRQoL benefits, monotherapy such as cetuximab is associated with significant improvements as compared to combination therapy. However, tailoring these results to individual gene expression profiles requires more evidence.

Health-related quality of life with standard and curative therapies in thalassemia: A narrative literature review.

Health-related quality of life (HRQOL) is a patient-reported outcome that assesses the impact of a disease or illness on different domains of a patient's life. Different general and disease-specific measures can be used to evaluate HRQOL. This article aimed to summarize the evidence for HRQOL among patients with transfusion-dependent (TDT) and non-transfusion-dependent thalassemia (NTDT). We included HRQOL data related to standard therapy with blood transfusions, iron chelation, and/or luspatercept in TDT and NTDT, as well as curative therapies for TDT, including hematopoietic stem cell transplant (HSCT) and gene therapy. Patients with thalassemia had worse HRQOL scores compared to the general population, and chronic pain was seen to increase in frequency and severity over time with age. NTDT patients reported worse physical health and functioning, mental health, general health, and vitality than TDT patients. However, TDT patients reported worse pain, change in health, and social support than NTDT. Most therapies improved overall HRQOL among thalassemia patients. Deferasirox, an oral iron chelator, was associated with more HRQOL benefits compared to deferoxamine, an intravenous iron chelator. Luspatercept showed clinically meaningful improvement in physical functioning among TDT and NTDT. Furthermore, HSCT and gene therapy were associated with better physical, emotional, and mental domains scores.

EE281 Predicted UK Health Care Associated Cost-Savings and Health-Related Quality of Life Benefits of Introducing a Digital Leakage Notification System for People Living with a Stoma

EE281 Predicted UK Health Care Associated Cost-Savings and Health-Related Quality of Life Benefits of Introducing a Digital Leakage Notification System for People Living with a Stoma

Health-Related Quality of Life in Adults with Hemophilia B after Receiving Gene Therapy with Fidanacogene Elaparvovec

Introduction : The burden of the management and clinical sequelae of hemophilia B (HB) negatively impacts health-related quality of life (HRQoL), including chronic pain and mental health. Fidanacogene elaparvovec (PF-06838435, formerly SPK-9001) is an adeno-associated virus-based gene therapy vector transferring the high activity variant of human factor IX (FIX), FIX-R338L, aimed at enabling endogenous FIX expression in individuals with hemophilia B. We present descriptive data on the impact on HRQoL for participants in the fidanacogene elaparvovec phase 1/2a study. Methods : Fifteen participants with moderately severe to severe hemophilia B (FIX activity ≤2%) received a single infusion of fidanacogene elaparvovec 5e11 vg/kg as part of a phase 1/2a study (NCT02484092). The study was 52 weeks in duration, after which participants were eligible to enroll in a long-term follow-up (LTFU) study for up to 5 years (NCT03307980). All 15 participants completed the phase 1/2a study and 14 subsequently enrolled in the LTFU study (1 participant declined participation). Participants in both studies completed patient-reported outcome (PRO) HRQoL assessments, including the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL), the visual analog scale of the EQ-5D (EQ-VAS), and the Change in Level of Activity questionnaire, every 6 months through Week 156 post infusion and then once annually during the LTFU study. The Haem-A-QoL questionnaire consists of 46 items pertaining to 10 domains to assess HRQoL, and domains scores and the Total Score ranging from 0-100 based on the individual items (high scores indicate high impairment in HRQoL). In the EQ-VAS, participants rate their current health state for endpoints of 100 (best imaginable health) to 0 (worst imaginable health). In the Change in Level of Activity questionnaire, participants assess whether they have been doing more/fewer/the same amount or intensity of physical activities in the past month. The data cutoff date was August 2, 2022. Results : For 14 participants (aged 20 to 63 years), the mean (SD) age at entry to the LTFU study was 42 (13.7) years, body mass index was 26.4 (4.4) kg/m 2, and 85.7% were White. Of the 14 participants, 13 had HRQoL data available through Week 156; beyond this time point, there were 10 or fewer participants with both post- and pre-vector infusion (baseline) values. For the Haem-A-QoL assessment, the mean (SD) Total Score at Week 156 (n=12) decreased by 15.2 (10.3) from pre-vector infusion, indicating an improvement in HRQoL ( Fig. 1). A 7-point reduction in the total score has been shown to be clinically meaningful in previous studies (Von Mackensen S et al, Haemophilia 2020;26:1019-30; Wyrwich KW et al, Haemophilia 2015;21:578-84). Of the 12 participants with data at Week 156, 8 had Total Score decreases of 7 or more at each visit through Week 156. Similarly, participant scores for each individual domain decreased over time (implying an improvement in HRQoL) from pre-vector infusion in all instances except for the Dealing with Hemophilia domain ( Fig. 1). Mean EQ-VAS scores were above mean baseline score and were consistently greater than baseline by 7 to 8 points during Year 2 onward, suggesting an improvement in overall health status. At Week 156, the EQ-VAS score increased from baseline by mean (SD) 7.2 (6.2): baseline 83.7 (7.3), n=13; Week 156 91.5 (5.4), n=12. An EQ-VAS score change of 7 points has been shown to be clinically meaningful (Pickard AS et al. Health Qual Life Outcomes 2007;21:5:70). Responses in the Change in Level of Activity questionnaire showed that a greater proportion of participants at each visit (n=12-14) reported doing the same or more intensive physical activities up to Week 156 than reported at baseline ( Fig. 2). No participant reported a reduction in the amount or intensity of physical activities at Week 156 (n=13) ( Fig. 2). Conclusion : HRQoL improvements after gene therapy are an indicator that fidanacogene elaparvovec can reduce the burden associated with hemophilia. PRO assessments will be a part of BENEGENE-2, an ongoing pivotal phase 3 study to demonstrate the efficacy of fidanacogene elaparvovec and will provide additional insights via the analyses of secondary endpoints into HRQoL benefits for participants with HB following gene therapy with fidanacogene elaparvovec.

Long-term outcomes of prophylaxis with a recombinant factor VIII Fc or recombinant factor IX Fc in patients with hemophilia previously treated on demand

BackgroundProphylactic factor replacement therapy is recommended over on-demand treatment for preserving long-term joint health in hemophilia. Extended half-life products, including efmoroctocog alfa/eftrenonacog alfa (recombinant factor VIII [FVIII]/FIX Fc fusion proteins; herein rFVIIIFc/rFIXFc), have the potential to reduce treatment burden with less frequent administration and improve bleed prevention. ObjectivesWe report post hoc data from patients with hemophilia A or B (HA/HB) who switched from prestudy on-demand FVIII/FIX to rFVIIIFc/rFIXFc prophylaxis at the start of A-LONG/B-LONG or start of/during ASPIRE/B-YOND phase 3 studies. MethodsPatients with ≥6 months rFVIIIFc/rFIXFc prophylaxis were enrolled. Treatment exposure, dosing, annualized bleeding rates, joint health, and health-related quality of life (HRQoL) outcomes were assessed. Results were also stratified by age. ResultsSixty-seven patients with HA and 50 with HB were analyzed; ≥60% were from regions outside Europe/North America, predominately those aged 12 to ‍25 years. No subjects returned to on-demand treatment postswitch.After switch to rFVIIIFc/rFIXFc prophylaxis, median annualized bleeding rates were reduced and sustained at low levels with stable factor usage across age groups (median treatment duration: 4.8/3.6 years). HRQoL outcomes improved for all ages; most pronounced changes were in the sports and leisure and physical health domains. After switch to rFVIIIFc prophylaxis, total modified Hemophilia Joint Health Score and joints with pain decreased in 64.6% and 29.2% of patients with HA. Insufficient data from patients with HB limited joint health evaluation of rFIXFc. ConclusionsFindings add to existing evidence and demonstrate the clinical and HRQoL benefits of switching patients from on-demand treatment to rFVIIIFc/rFIXFc prophylaxis.

Women achieve equivalent health-related quality of life benefits to men from attending cardiac rehabilitation: a matched case-control study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): SOLVE-CHD NHMRC Synergy Grant Background/Introduction Coronary heart disease (CHD) is the leading cause of death in women globally; and women have worse health outcomes from CHD than men, including poorer health-related quality of life (HRQL). Comprehensive cardiac rehabilitation (EBCR) has well-established benefit for patients with CHD in improving HRQL. These benefits have rarely been distinguished separately for women despite known differences to men. Purpose The aim of this study was to compare women and men’s HRQL outcomes after accounting for differences in age, partnership status and diagnosis. Methods A secondary analysis of a larger prospective observational study of CR outcomes using a matched case-control study of women and men. The sample included patients enrolled in four CR programs following admission for CHD (myocardial infarction [MI], percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]). Women were matched to men based on age (within 0-2 years), marital status (single, or partnered), and diagnosis (MI, PCI, or CABG). Sociodemographic data were collected from the participants and clinical information (diagnosis, comorbidities) from the medical record. HRQL was measured using the Short Form-12 Health Survey (SF-12). Results Thirty-seven matched women and men were included in this study at baseline, of whom 27 completed the study (72.9%). There were no significance differences in sociodemographic and clinical characteristics between men and women at baseline. Both women and men improved HRQL substantially from pre-post CR, with no significant differences in change scores in any domain between the sexes despite women having worse scores at baseline in Physical Functioning (mean score 41.59 vs 44.15), Bodily Pain (mean score 47.78 vs 48.71) and overall physical summary score (mean score 44.14 vs 45.29). Women had clinically meaningful improvements in Physical Functioning (MD 6.51, 95% CI 2.59-10.44) and Role Physical (MD 6.42, 95% CI 2.81-10.03), Mental Health (MD 4.35, 95% CI 2.05-6.66) and Bodily Pain (MD 4.97, 95% CI 1.36-8.60) and in the overall physical summary score (MD 5.67, 95% CI 1.98-9.38). Men achieved clinically meaningful improvements in the same domains as women plus Vitality (MD 5.11, 95% CI 0.87-9.36) and Social Function (MD 8.54, 95% CI 3.98-13.09). Conclusion(s) When matched to men for age, partnership status, and diagnosis, women achieve clinically meaningful and equivalent HRQL outcomes following CR. Women significantly improved in overall physical and mental health HRQL, as well as in the majority of HRQL domains. These findings could be used to strengthen advocacy in supporting women with CHD to participate and complete CR programs.

P94 Bimekizumab early treatment response translated into cumulative benefits in health-related quality of life in patients with moderate-to-severe plaque psoriasis: results from 2 years of the BE RADIANT phase IIIb trial

Abstract Speed of response is a key treatment goal for patients with psoriasis. This analysis aimed to assess how early clinical response translated into cumulative health-related quality of life (HRQoL) benefit in patients with moderate-to-severe plaque psoriasis over 2 years of bimekizumab (BKZ) treatment. Included patients from BE RADIANT were randomized to BKZ 320 mg every 4 weeks (Q4W), continued to receive Q4W dosing or switched to Q8W at week 16 and entered the open-label extension (OLE) at week 48 (receiving BKZ Q4W or Q8W; NCT03536884). The proportions of patients achieving Psoriasis Symptoms and Impacts Measure (P-SIM) 0 in itching, skin pain and scaling, and Dermatology Life Quality Index 0 or 1 (DLQI 0/1), were estimated using modified nonresponder imputation (mNRI); missing data were imputed via NRI for patients discontinuing due to the lack of efficacy or treatment-related adverse events and multiple imputation otherwise. Cumulative HRQoL and symptom benefit through to week 96 was estimated using the area under the curve (AUC0–96) by week 16 Psoriasis Area and Severity Index (PASI)-100 status (NRI), with week 16 and week 96 responses also reported. AUC0–96 was used to calculate the estimated number of days that each response was achieved. Of the 336 patients randomized to BKZ who entered the OLE, 216 achieved PASI 100 at week 16. Of these, 187/216 patients had already achieved PASI 100 at one or more visit(s) before week 16. Of the PASI-100 responders at week 16, 71.8%, 92.1%, 89.4% and 88.0% also achieved P-SIM 0 for itching, skin pain and scaling and DLQI 0/1, respectively, vs. 39.1%, 77.7%, 56.6% and 74.6% of nonresponders. Of the week 16 PASI-100 responders at week 96, 67.1%, 85.4%, 80.6% and 89.3% achieved P-SIM 0 for itching, skin pain and scaling and DLQI 0/1, respectively, vs. 55.6%, 77.7%, 63.7% and 80.8% of nonresponders. The total AUC0–96 for achievement of P-SIM 0 in itching, skin pain and scaling and DLQI 0/1 was greater for week 16 PASI-100 responders through 2 years, corresponding to a greater number of days achieving these outcomes vs. nonresponders (Table 1). A high proportion of patients achieved complete skin clearance at week 16, translating to a greater number of days achieving P-SIM 0 in itching, skin pain and scaling and DLQI 0/1 vs. week 16 PASI-100 nonresponders through 2 years of BKZ treatment.Table 1AUC0-96 by week 16 PASI-100 response over 2 years (mNRI)Week 16 PASI-100 responders (n = 216)Week 16 PASI-100 nonresponders (n = 120)P-SIM 0P-SIM 0ItchingSkin painScalingDLQI 0/1ItchingSkin painScalingDLQI 0/1AUC0–9666398504784982674918753957837584Days465595549579344528405531 Acknowledgment: Medical writing: Costello Medical. Funding sources: UCB Pharma.

PS14 Bimekizumab response up to 3 years in patients with moderate-to-severe plaque psoriasis who responded at week 16: post hoc results from the BE BRIGHT open-label extension trial

Abstract Treatment with the interleukin-17A/F inhibitor bimekizumab (BKZ) has demonstrated maintenance of efficacy and health-related quality of life (HRQoL) outcomes over 2 years. The objective of this analysis was to assess the long-term response in patients with moderate-to-severe plaque psoriasis who achieved Psoriasis Area and Severity Index (PASI) ≤ 2, a key treat-to-target outcome, after 16 weeks of BKZ treatment over 3 years. Patients who completed a 52- (BE VIVID) or 56-week (BE SURE and BE READY) phase III feeder study were eligible to enrol in the BE BRIGHT open-label extension (OLE) (NCT03370133, NCT03412747, NCT03410992 and NCT03598790). Upon OLE entry, patients received BKZ 320 mg Q4W or Q8W based on feeder study treatment and week 52/56 PASI 90 (≥ 90% improvement in PASI) response. Patients switched from BKZ Q4W to Q8W at OLE week 24 (based on investigator discretion and PASI 90 response), or OLE week 48/next scheduled visit (all patients). Achievement of body surface area (BSA) ≤ 1% and PASI 0 (all studies), and Dermatology Life Quality Index (DLQI)0/1 (BE SURE and BE READY only due to schedule differences) is reported among week 16 PASI ≤ 2 responders through year 1 (feeder study week 52/56) and year 3 (OLE week 96). Analysed patients were randomized to BKZ, received BKZ maintenance dosing from feeder study week 16 and entered the OLE, including a subset who received BKZ Q4W through to week 16 then continuous BKZ Q8W (Q4W/Q8W/Q8W). Missing data were imputed using modified nonresponder imputation (mNRI): patients who discontinued treatment due to lack of efficacy or treatment-related adverse events were considered nonresponders; multiple imputation was used for all other missing data. The week 16 responder rate is also reported (NRI). At baseline, 989 patients were randomized to BKZ; 87.8% (n = 868) achieved PASI ≤ 2 at week 16. Of these, 694 entered the OLE. Among week 16 PASI ≤ 2 responders (n = 694), 91.9% and 82.3% achieved BSA ≤ 1% and PASI 0 after year 1 (52 weeks), and 88.6% and 74.1% after year 3, respectively. Among week 16 PASI ≤ 2 responders (n = 445), 87.8% and 86.8% achieved DLQI 0/1 after year 1 (56 weeks) and year 3, respectively. Of the week 16 PASI ≤ 2 responders who received BKZ Q4W/Q8W/Q8W (n = 189), 95.2% and 87.6% achieved BSA ≤ 1% and PASI 0 after 1 year (52 weeks), and 93.4% and 79.7% after 3 years, respectively. Among the Q4W/Q8W/Q8W patients, 94.1% and 91.2% achieved DLQI 0/1 after year 1 (56 weeks) and year 3, respectively. The BKZ provided long-term efficacy and HRQoL benefits. Among week 16 PASI ≤ 2 responders, the vast majority sustained high levels of clinical and HRQoL responses through 3 years of BKZ treatment, including those who received BKZ Q4W/Q8W/Q8W. Funding: UCB Pharma. Medical writing: Costello Medical.

Health-related quality of life (HRQoL) of risk-based patient subgroups with advanced renal cell cancer (aRCC) treated with nivolumab plus cabozantinib (NIVO+CABO) vs sunitinib (SUN) in the CheckMate 9ER trial.

4527 Background: In CheckMate 9ER, NIVO+CABO improved or maintained HRQoL vs SUN in previously untreated aRCC. We report an exploratory analysis of HRQoL in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk-based subgroups treated with NIVO+CABO vs SUN in CheckMate 9ER (minimum follow-up, 36.5 mo). Methods: Subgroups were stratified by IMDC categories of favorable (F) risk (score = 0) or intermediate/poor (I/P) risk (score = 1–6) at randomization. HRQoL was evaluated using Functional Assessment of Cancer Therapy–Kidney Symptom Index (FKSI-19). Changes from baseline (BL) through wk 151 were analyzed using mixed-model repeated measures (MMRM). Bother due to treatment side effects (FKSI-19 item GP5) was assessed using a generalized estimating equations model (response dichotomized as minimal [“not at all” or “a little bit”] vs notable [“somewhat,” “quite a bit,” or “very much”]). Cox proportional hazards (CPH) modeling was used to evaluate time to confirmed deterioration (TTCD). Results: Differences in least square means (LSM) for FKSI-19 scores through wk 151 indicated HRQoL benefit in the NIVO+CABO arm over the SUN arm for I/P-risk patients (n = 505) but not for F-risk patients (n = 146). In the I/P-risk subgroup, longitudinal analysis of FKSI-19 total scores indicated that HRQoL improved through wk 151 in the NIVO+CABO arm but decreased from BL in the SUN arm. HRQoL declined from BL through wk 151 in F-risk patients in the NIVO+CABO and SUN arms. Patients were less likely to be bothered by side effects of NIVO+CABO vs SUN regardless of risk (I/P-risk odds ratio [OR], 0.50; 95% CI, 0.34–0.75; F-risk OR, 0.51; 95% CI, 0.28–0.91). TTCD analysis of FKSI-19 scores of the I/P-risk subgroup indicated that the NIVO+CABO arm had lower deterioration risk than the SUN arm. For the F-risk subgroup, risk based on FKSI-19 total scores was similar for both treatment arms. Conclusions: Compared with SUN, NIVO+CABO improved or maintained HRQoL in I/P-risk patients and had less side effect bother in all subgroups. There were no significant differences between treatment arms for F-risk patients. Clinical trial information: NCT03141177 . [Table: see text]

Health-Related Quality of Life in Children With Unilateral Sensorineural Hearing Loss Following Cochlear Implantation.

Evaluate health-related quality of life (HR-QOL) benefits with cochlear implantation (CI) in children with unilateral sensorineural hearing loss (USNHL) versus bilateral sensorineural hearing loss (BSNHL). A cross-sectional survey of parents of children who underwent CI for USNHL and BSNHL. Tertiary care academic centers. The "Children with cochlear implants: parental perspectives" survey was administered. Parents rated responses on a 5-point Likert scale. Scores greater than 3.0 were considered favorable. Responses were recorded within 8 domains and groups were compared with respect to domain scores. Analysis of covariance models was used to compare groups while adjusting for age at implantation and duration of implant use. There were 31 patients with USNHL and 27 patients with BSNHL. The average age of implantation in BSNHL patients was 1.9 and 6.7 years for USNHL. Parents of all children answered favorably in all domains. When adjusted for age at implantation and duration of implant use, parents of BSNHL children responded significantly more favorably only in 2 domains. When comparing patients with older age or prolonged duration of hearing loss in the USNHL cohort, there were favorable responses in all domains with no significant differences between groups. There are HR-QOL benefits of CI in USNHL children; less pronounced favorable results were noted only in 2 domains when compared to BSNHL children. Benefits were noted with CI in USNHL children at an older age at implantation or prolonged duration of hearing loss. Therefore, these factors should not be absolute contraindications for CI in USNHL.

Patient-reported outcomes in metastatic renal cell carcinoma trials using combinations versus sunitinib as first-line treatment.

Over the past 5 years, several new immunotherapy treatments have been tested for metastatic renal cell carcinoma (mRCC). Clinical trials assessing combinations of different immunotherapies, or of an immunotherapy with a tyrosine kinase inhibitor (TKI), have reported improved clinical outcomes compared with the standard of care - that is, treatments using TKIs alone. However, to understand the holistic impact of new treatments on patients, physicians must also consider effects on health-related quality of life (HRQoL). As patient-reported outcome measures (PROMs) on HRQoL are often treated as a secondary outcome in clinical trials, their collection and reporting are non-standardized and, therefore, difficult to compare and interpret. However, results from six clinical trials indicate that two immunotherapy treatments overwhelmingly outperform sunitinib in HRQoL measurements: nivolumab plus cabozantinib (CheckMate 9ER) and atezolizumab plus bevacizumab (IMmotion151). An additional two treatments generally outperform sunitinib: nivolumab plus ipilimumab (CheckMate 214) and lenvatinib plus pembrolizumab (CLEAR). Of three studies that reported no difference from sunitinib, two suffered design flaws that might have obscured HRQoL benefits (JAVELIN Renal 101and KEYNOTE-426). To ensure future HRQoL data are of the highest quality and comparable across trials, future studies should adopt best practices for the design, analysis and reporting of PROMs.

HTA90 Use of General Population Utilities in NICE Highly Specialised Technology Appraisals of Treatments With the Potential to Restore Normal Physiology

Rare diseases can have a considerable impact on patients’ health-related quality of life (HRQoL). The National Institute for Health and Care Excellence’s (NICE) Highly Specialised Technologies (HST) process evaluates treatments indicated for very rare diseases. For interventions that have the potential to restore normal physiology in rare disease sufferers, capturing long-term impact on HRQoL in economic evaluations may be particularly challenging, due to sparsity of data. The aim of this study is to explore how long-term HRQoL benefit was modelled in NICE HSTs of treatments that could restore patient health to near that of the general population.

Systematic Review and Network Meta-analysis of Neurostimulation for Painful Diabetic Neuropathy.

Different waveforms of spinal cord stimulation (SCS) have now been evaluated for the management of painful diabetic neuropathy (PDN). However, no direct or indirect comparison between SCS waveforms has been performed to date. To conduct a systematic review and network meta-analysis to evaluate the effectiveness of SCS for PDN. MEDLINE, CENTRAL, Embase, and WikiStim were searched from inception until December 2021. Randomized controlled trials (RCTs) of SCS for PDN were included. Pain intensity, proportion of patients achieving at least a 50% reduction in pain intensity, and health-related quality of life (HRQoL) data were extracted. Significant reductions in pain intensity were observed for low-frequency SCS (LF-SCS) (mean difference [MD] -3.13 [95% CI -4.19 to -2.08], moderate certainty) and high-frequency SCS (HF-SCS) (MD -5.20 [95% CI -5.77 to -4.63], moderate certainty) compared with conventional medical management (CMM) alone. There was a significantly greater reduction in pain intensity on HF-SCS compared with LF-SCS (MD -2.07 [95% CI -3.26 to -0.87], moderate certainty). Significant differences were observed for LF-SCS and HF-SCS compared with CMM for the outcomes proportion of patients with at least 50% pain reduction and HRQoL (very low to moderate certainty). No significant differences were observed between LF-SCS and HF-SCS (very low to moderate certainty). Limited number of RCTs and no head-to-head RCTs conducted. Our findings confirm the pain relief and HRQoL benefits of the addition of SCS to CMM for patients with PDN. However, in the absence of head-to-head RCT evidence, the relative benefits of HF-SCS compared with LF-SCS for patients with PDN remain uncertain.

31085 Bimekizumab early treatment response translates into cumulative benefits in health-related quality of life in patients with moderate to severe plaque psoriasis: Pooled results from three multicenter, randomized, double-blinded phase 3 trials

Introduction: Speed of clinical response is an important treatment goal for patients with plaque psoriasis. We examined how early clinical response translated into cumulative health-related quality of life (HRQoL) benefits in patients with moderate to severe plaque psoriasis treated with bimekizumab (BKZ) over 1 year. Methods: Data were pooled for patients randomized to BKZ 320 mg every 4 weeks (wks)(Q4W) in BE SURE, BE READY, and BE RADIANT. Through Wks16–48, data were combined for both BKZ maintenance doses (BKZ 320 mg Q4W and Q8W). The proportions of patients achieving DLQI0/1 (no effect of skin disease on patient’s life) are reported at Wk4 by PASI90 status; cumulative HRQoL benefits through 48 wks were estimated using total area under the curve (AUC0–48) for patients achieving DLQI0/1 by Wk4 PASI90 status. Missing data were imputed as nonresponse (NRI). Results: At Wk4, 352/880 (40.0%) patients achieved PASI90. 57.4% of Wk4 PASI90 responders achieved DLQI0/1, compared with 40.5% of Wk4 PASI90 nonresponders. Total AUC0–48 for achievement of DLQI0/1 was greater in Wk4 PASI90 responders vs Wk4 PASI90 nonresponders: 3664 vs 3263. Patients who achieved PASI90 at Wk4 achieved DLQI0/1 for a greater number of days throughout the 48-wk trial compared with patients who did not achieve PASI90 at Wk4: 256 vs 228 days. Conclusions: BKZ demonstrated fast skin clearance. Early treatment response on BKZ translated into cumulative benefits in HRQoL: Wk4 PASI90 responders achieved DLQI0/1 for a greater number of days during the 48-wk trial than Wk4 PASI90 nonresponders.

1553O Health-related quality of life (HRQoL) in the phase III TROPiCS-02 trial of sacituzumab govitecan (SG) vs chemotherapy in HR+/HER2- metastatic breast cancer (MBC)

The antibody-drug conjugate SG comprises an anti-Trop-2 antibody coupled to SN-38 via a hydrolyzable linker. In the ongoing randomized TROPiCS-02 trial, SG is being evaluated vs single-agent chemotherapy treatment of physician’s choice (TPC) after CDK 4/6 inhibitor, endocrine therapy, and at least 2 chemotherapies in HR+/HER2- MBC setting. Here we assess the impact of SG on HRQoL in TROPiCS-02. Patients (pts) with locally determined HR+/HER2- MBC following (2-4 prior chemotherapies) for metastatic disease, were randomized to receive SG (10 mg/kg IV on days 1 and 8 of a 21-day treatment [Tx] cycle) or TPC (capecitabine, eribulin, gemcitabine, or vinorelbine). HRQoL was assessed at baseline (BL), day 1 of each Tx cycle (CxDx) and at end of treatment visit using the EORTC QLQ-C30. The analysis included all pts with valid HRQoL assessments at BL and ≥1 post-BL visit. Linear mixed-effect models for repeated measures were used to estimate differences in overall least-square mean changes from BL between Tx arms, using on-Tx data up to C11D1 (n ≥25 in both arms). The analysis included 446 pts (236 SG, 210 TPC; median age 56 y). The EORTC QLQ-C30 completion rate was ≥85% up to C13D1 in both Tx arms. Mean HRQoL scores at BL were generally similar for SG and TPC. The SG arm showed a trend of improvement in most HRQoL domains. A significantly greater improvement in physical functioning and dyspnea was observed for SG vs TPC and greater worsening in diarrhea (table).Table: 1553OEORTC QLQ-C30 least-square mean change from baselineSG vs TPC (95% CI)Global health status/QoL2.4 (-0.7, 5.5)FunctioningPhysical3.9 (0.9, 6.9)Role3.1 (-1.2, 7.4)Emotional0.9 (-2.4, 4.3)Cognitive-0.2 (-3.3, 2.9)Social0.8 (-3.2, 4.7)Summary Score0.6 (-1.8, 3.1)SymptomsFatigue-3.3 (-7.1, 0.5)Pain-1.6 (-5.5, 2.3)Nausea/Vomiting1.4 (-0.9, 3.8)Dyspnea-4.3 (-8.5, -0.1)Insomnia-3.7 (-8.1, 0.8)Appetite Loss-3.3 (-7.3, 0.8)Constipation-1.0 (-5.5, 3.4)Diarrhea10.4 (6.3, 14.5)Financial Difficulties0.9 (-2.5, 4.2)Positive value represents improvement for functioning and worsening for symptoms.SG, sacituzumab govitecan; TPC, treatment of physician’s choice. Open table in a new tab SG, sacituzumab govitecan; TPC, treatment of physician’s choice. Despite the association with worsening diarrhea, SG demonstrated an overall HRQoL benefit in heavily-pretreated patients with HR+/HER2- MBC.

Effects of a home-based Radio-Taiso exercise programme on health-related quality of life in older adults with frailty: protocol for an assessor-blind randomised controlled trial

IntroductionFew clinical trials have examined the effects of home-based exercise programmes on health-related quality of life (HR-QoL) in older adults with frailty. Radio-Taiso is the most famous exercise programme in...