Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)

Objective- To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods- This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results- Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions- The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma

An evaluation of the safety and efficacy of bimatoprost for eyelash growth in pediatric subjects

Mark Borchert,1 Suzanne Bruce,2 David Wirta,3 Steven G Yoelin,4 Sungwook Lee,5 Cheri Mao,5 Amanda VanDenburgh5 1Children’s Hospital Los Angeles, Los Angeles, CA, USA; 2Suzanne Bruce and Associates, PA, Houston, TX, USA; 3David Wirta and Associates, Newport Beach, CA, USA; 4Medical Associates Inc., Newport Beach, CA, USA; 5Allergan plc, Irvine, CA, USA Purpose: Evaluate the safety and effectiveness of bimatoprost 0.03% for treatment of eyelash hypotrichosis in a pediatric population. Patients and methods: This multicenter, randomized, double-masked, parallel-group study was conducted at seven sites in the US and Brazil. Subjects with eyelash hypotrichosis caused by chemotherapy or alopecia areata (aged 5–17 years) or healthy adolescents aged 15–17 years were enrolled (N=71). Subjects applied bimatoprost 0.03% or vehicle to upper eyelid margins once nightly for 4 months and were followed for 1 month post-treatment. Eyelash prominence was assessed using the validated 4-grade Global Eyelash Assessment scale with photonumeric guide. Changes in eyelash length, thickness, and darkness were measured by digital image analysis. Safety was assessed by adverse events and ophthalmic observations. Results: Eyelash prominence improved in a significantly greater proportion of subjects treated with bimatoprost compared with vehicle at month 4 (70.8% versus 26.1%; P<0.001). This benefit was sustained at month 5 post-treatment assessment. Digital image analysis measures were significantly improved with bimatoprost. Significant treatment benefits with bimatoprost versus vehicle were evident among the healthy adolescents but not in the postchemotherapy or alopecia areata subgroups. The safety profile of bimatoprost was consistent with previous studies in adults. Conclusion: Bimatoprost was safe and well tolerated in pediatric subjects with eyelash hypotrichosis. In this study with limited sample size, subgroup analyses showed that treatment was effective in healthy adolescents with no concurrent contributing medical condition, but not in those with eyelash hypotrichosis due to chemotherapy or alopecia areata. Keywords: adolescent, child, hypotrichosis, Latisse&nbsp

Perceptions of heart failure symptoms, disease severity, treatment decision-making and side effects by patients and cardiologists: a multinational survey in a cardiology setting

Sara Bruce Wirta,1 Bogdan Balas,2 Catia C Proenca,3 Hollie Bailey,4 Zoe Phillips,4 James Jackson,4 Sarah Cotton4 1Real World Evidence, Cardio-Metabolic Franchise, Novartis Sweden, Stockholm, Sweden; 2Real World Evidence, Cardio-Metabolic Franchise, Novartis Pharma, Basel, Switzerland; 3Wellmera AG, Basel, Switzerland; 4Real World Research, Adelphi Real World, Bollington, UK Purpose: Explore the extent to which heart failure (HF) symptoms and side effects of HF treatment experienced by patients are recognized by cardiologists, and concordance between patient–cardiologist perceptions of HF severity and patients’ contributions to treatment decision-making. Methods: A multinational, cross-sectional survey of cardiologists and patients with HF was conducted. Patient-record forms (PRFs) were completed by cardiologists for consecutive consulting patients with HF, who completed a patient self-completion questionnaire (PSC). Responses from PRFs with an associated PSC were analyzed to compare patient- and cardiologist-reported occurrences of HF symptoms and treatment side effects, patient-perceived severity of HF and cardiologists’ perceived risk of death within 12 months, and patient input into treatment decisions. Concordance was calculated as the number of response agreements between PSCs and PRFs for total number of matched pairs. Over- or underreporting of symptoms and side effects by cardiologists relative to patient-reported occurrences were calculated. Results: Overall, 2,454 patient–cardiologist pairs were identified. High levels of concordance between matched pairs were observed for the occurrence of reported HF symptoms (93%), side effects (77%–98%) and degree of patient input into treatment decisions (74%); for perceived HF severity, concordance was 54%. Most symptoms (except dyspnea when active and fatigue/weakness, experienced by >50% of patients) were underreported by cardiologists. Of patients reporting to have been informed by their cardiologist that their HF was mild, 28% were perceived by their cardiologist to have a moderate–high/very high risk of death within 12 months. Treatment choice was not discussed with almost a third of patients. When discussed, 94% of patients (n=1,540) reported the cardiologist made the final decision. Cardiologists more often under- than overreported the occurrence of side effects reported by patients. Conclusion: Improved patient–cardiologist dialogue and shared decision-making is required for optimizing patient care and outcomes in HF. Keywords: patient influence, disease awareness, treatment decision-making, patient-reported outcomes, disease-specific program, real worl

Burden of heart failure on patients from China: results from a cross-sectional survey

James DS Jackson,1 Sarah E Cotton,1 Sara Bruce Wirta,2 Catia C Proenca,3 Milun Zhang,4 Raquel Lahoz,5 Frederico J Calado5 1Real World Research, Adelphi Real World, Bollington, UK; 2Real World Evidence, Cardio-Metabolics Franchise, Novartis Sweden AB, Stockholm, Sweden; 3Wellmera AG, Basel, Switzerland; 4Health Economics and Outcomes Research and Access Strategy, Novartis Pharma China, Beijing, China; 5Real World Evidence, Cardio-Metabolics Franchise, Novartis Pharma AG, Basel, Switzerland Purpose: Little evidence exists on the burden that chronic heart failure (HF) poses specifically to patients in China. The objective of this study, therefore, was to describe the burden of HF on patients in China.Materials and methods: A cross-sectional survey of cardiologists and their patients with HF was conducted. Patient record forms were completed by 150 cardiologists for 10 consecutive patients. Patients for whom a patient record form was completed were invited to complete a patient questionnaire.Results: Most of the 933 patients (mean [SD] age 65.8 [10.2] years; 55% male; 80% retired) included in the study received care in tier 2 and 3 hospitals in large cities. Patients gave a median score of 4 on a scale from 1 (no disruption) to 10 (severe disruption) to describe how much HF disrupts their everyday life. Patients in paid employment (8%) missed 10% of work time and experienced 29% impairment in their ability to work due to HF in the previous week. All aspects of patients’ health-related quality of life (QoL) were negatively affected by their condition. Mean ± SD utility calculated by the 3-level 5-dimension EuroQol questionnaire was 0.8±0.2, and patients rated their health at 70.3 (11.5) on a 100 mm visual analog scale. Patients incurred costs associated with HF treatment, travel, and professional caregiving services.Conclusion: HF is associated with poor health-related QoL and considerable disruption in patients’ lives. Novel and improved therapies are needed to reduce the burden of HF on patients and the health care system. Keywords: patient burden, health-related quality of life, heart failure, survey, real-world&nbsp

Burden of heart failure on caregivers in China: results from a cross-sectional survey

James DS Jackson,1 Sarah E Cotton,1 Sara Bruce Wirta,2 Catia C Proenca,3 Milun Zhang,4 Raquel Lahoz,5 Frederico J Calado5 1Real World Research, Adelphi Real World, Bollington, Cheshire, UK; 2Real World Evidence Center of Excellence, Novartis Sweden AB, Stockholm, Sweden; 3Wellmera AG, Basel, Switzerland; 4Health Economics and Outcomes Research & Access Strategy, Novartis Pharma China, Beijing, China; 5Real World Evidence Center of Excellence, Novartis Pharma AG, Basel, Switzerland Purpose: Family and friends play a pivotal role in caring for patients with heart failure (HF); however, evidence of the impact of caregiving is limited. The objectives of this study were to describe the burden of caregiving on informal caregivers of patients with chronic HF in China.Materials and methods: A cross-sectional survey of cardiologists, their patients with HF, and those patients’ caregivers was conducted. Patient record forms were completed by 150 cardiologists for 10 consecutive patients. Caregivers of these patients were invited to complete a questionnaire.Results: Overall, 458 caregivers completed a questionnaire (mean ± standard deviation age 60.1±10.6 years; 60% female; 77% spouses; 74% retired). Caregivers spent a mean of 24.5 (16.9) hours caregiving per week, and a third reported a reduction in their social activity, time for themselves, or time for family. Caregivers in employment took several days off work in the past 3 months owing to caregiving, sometimes resulting in reduced income. Up to 79% of caregivers reported an impact on their physical or emotional well-being, and 57% reported deterioration in their objective health status. Inconsistencies stemming from differences in the three-level five-dimension EuroQol questionnaire and HF Caregiver Questionnaire were observed for the impact of caregiving on caregivers’ health-related quality of life. Conclusion: Assisting patients with HF is associated with caregiver burden. Addressing the needs of caregivers may help to promote their continued support and improve patient outcomes.Keywords: burden, caregiver, China, health-related quality of life, heart failure&nbsp

Care pathways and treatment patterns for patients with heart failure in China: results from a cross-sectional survey

James DS Jackson,1 Sarah E Cotton,1 Sara Bruce Wirta,2 Catia C Proenca,3 Milun Zhang,4 Raquel Lahoz,5 Bogdan Balas,5 Frederico J Calado5 1Real World Research, Adelphi Real World, Bollington, UK; 2Real World Evidence, Cardio-Metabolic Franchise, Novartis Sweden AB, Stockholm, Sweden; 3Wellmera AG, Basel, Switzerland; 4Health Economics and Outcomes Research, Novartis Pharma China, Beijing, China; 5Medical Affairs, Cardio-Metabolic Franchise, Novartis Pharma AG, Basel, Switzerland Purpose: The objective of this study was to describe the clinical care pathways, management and treatment patterns, and hospitalizations for patients with heart failure (HF) in China. Subjects and methods: A cross-sectional survey of cardiologists and their patients with HF was conducted. Patient record forms were completed by 150 cardiologists for 10 consecutive patients. Patients for whom a patient record form was completed were invited to complete a patient self-completion questionnaire. Results: Most of the 1,500 patients (mean [SD] age 66 [10] years; 55% male) included in the study received care in tier-2 and -3 hospitals in large cities. Cardiologists were responsible for initial consultation, diagnosis, and treatment of patients with HF. The use of guideline-recommended diagnostics was high. However, guideline-recommended double- and triple-combination therapy was received by only 51% and 18% of patients, respectively. In total, 20% of patients with HF reported that they were not consulted on the choice of therapy. Concordance was high (≥80%) between matched cardiologist and patient pairs for the occurrence of side effects, while cardiologists more often under- than overreported the occurrence of side effects of treatment reported by patients. Conclusion: The management of HF was predominantly overseen by cardiologists. The use of diagnostic tests was high, but the use of guideline-recommended treatment was low in this population. Improved communication between patients and cardiologists is essential to optimize treatment decision making and to increase awareness of treatment side effects. Keywords: heart failure, disease management, patient preference, treatment satisfaction, real-world evidenc

Early insights into the characteristics and evolution of clinical parameters in a cohort of patients prescribed sacubitril/valsartan in Germany

<p><b>Objectives</b>: This study aimed to provide early insights into sacubitril/valsartan (sac/val) prescription patterns and the demographic and clinical characteristics of patients prescribed sac/val in primary care and cardiology settings in Germany.</p> <p><b>Methods</b>: The study used electronic medical records from the German IMS® Disease Analyzer database. Patients with ≥1 prescription for sac/val during 1 January–31 December 2016 (<i>n</i> = 1643) were identified and followed up for ≤12 months from first prescription. Patients with ≥1 heart failure (HF) diagnosis during the study period, ≥1 additional HF diagnosis in the full history of the database, and ≥1 prescription for an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and a β-blocker during the study period, without a prescription for sac/val (<i>n</i> = 25,264), were included as a reference cohort. Changes in clinical parameters in the 12 months before and after sac/val initiation were investigated and compared with those from the PARADIGM-HF study.</p> <p><b>Results</b>: The characteristics of patients prescribed sac/val more closely resembled those of patients enrolled in PARADIGM-HF (e.g. younger age, higher proportion of men than women, lower systolic blood pressure) than patients in the reference cohort. Most patients were initiated on the lowest dose of sac/val irrespective of clinical setting. Significant decreases (<i>p</i> < 0.001) in NT-proBNP and glycated haemoglobin levels were observed following sac/val initiation.</p> <p><b>Conclusions:</b> Patients prescribed sac/val had similar baseline demographics and clinical characteristics to those from PARADIGM-HF, and most patients were initiated on the lowest dose. Changes in clinical parameters before and after initiation mirrored findings from the PARADIGM-HF study.</p