Characterizing the High Disease Burden of Transthyretin Amyloidosis for Patients and Caregivers.

INTRODUCTION: Transthyretin amyloidosis (ATTR amyloidosis), whether manifesting as familial amyloid polyneuropathy (ATTR-PN) or cardiomyopathy (ATTR-CM), is a progressive, debilitating, and often fatal, rare disease requiring significant caregiver support. This study aims to better characterize the burden of disease for ATTR amyloidosis patients and caregivers. METHODS: Patients and caregivers in the USA and Spain were recruited through patient advocacy groups to complete a cross-sectional survey. Assessments included the 12-Item Short Form Health Survey, the Work Productivity and Activity Impairment Questionnaire, the Zarit Burden Interview, pain and symptom measures, health care resource use measures, and caregiving burden measures. RESULTS: Respondents included 60 ATTR amyloidosis patients and 32 caregivers. Patients registered scores up to two standard deviations below normal for physical health, impairment in quality of life, and reduced work productivity. Patients with liver transplant versus without liver transplant reported better overall outcomes, and those without liver transplant reported a greater impact on physical versus mental health. A high rate of health care utilization in the 3 months prior to the survey was reported by patients. Caregivers reported substantial burden, including poor mental health, work impairment, and much time spent providing care (mean 45.9 h/week). Work productivity was impacted for employed patients and caregivers. CONCLUSION: ATTR amyloidosis was associated with high levels of impairment in many domains, including physical health, quality of life, and reduced productivity. Providing care for ATTR amyloidosis patients is associated with a negative impact on the mental health of caregivers. These results highlight the substantial burden of ATTR amyloidosis for patients and caregivers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01604122. FUNDING: Pfizer.

The cost-effectiveness of growth hormone replacement therapy (Genotropin®) in hypopituitary adults in Sweden.

BACKGROUND: To evaluate the cost-effectiveness of growth hormone (GH) treatment (Genotropin®) compared with no GH treatment in adults with GH deficiency in a Swedish societal setting. METHODS: A Markov-type cost-utility simulation model was constructed and used to simulate, for men and women, morbidity and mortality for GH-treated and -untreated individuals over a 20-year period. The calculations were performed using current available prices concerning morbidity-related healthcare costs and costs for Genotropin®. All costs and treatment effects were discounted at 3%. Costs were expressed in Euro (1€ = 9.03 SEK). GH-treated Swedish patients (n = 434) were identified from the KIMS database (Pfizer International Metabolic Database) and untreated patients (n = 2135) from the Swedish Cancer Registry and the Hospital Discharge Registry. RESULTS: The results are reported as incremental cost per quality-adjusted life year (QALY) gained, including both direct and indirect costs for GH-treated versus untreated patients. The weighted sum of all subgroup incremental cost per QALY was €15,975 and €20,241 for men and women, respectively. Including indirect cost resulted in lower cost per QALY gained: €11,173 and €10,753 for men and women, respectively. Key drivers of the results were improvement in quality of life, increased survival, and intervention cost. CONCLUSIONS: The incremental cost per QALY gained is moderate when compared with informal thresholds applied in Sweden. The simulations suggest that GH-treatment is cost-effective for both men and women at the €55,371 (SEK 500,000 - the informal Swedish cost-effectiveness threshold) per QALY threshold.

Psychometric validation of the Visual Function Questionnaire-25 in patients with diabetic macular edema.

BACKGROUND: Diabetic Macular Edema (DME) is a common cause of impaired vision and blindness amongst diabetics. If not detected and treated early, the resulting vision loss can lead to considerable health costs and decreased health-related quality of life (HRQoL). The aim of this study was to provide evidence of the psychometric properties of the National Eye Institute - Visual Functioning Questionnaire (VFQ-25) for use in a cohort of DME patients who participated in a clinical efficacy and safety trial of pegaptinib sodium (Macugen). METHODS: A phase 2/3 randomised, double masked trial evaluated pegaptanib injection versus sham injection in patients with DME. The analysis was conducted using baseline HRQoL data of the VFQ-25 and the EQ-5D, on a modified intent-to-treat sample of 235 patients. These measures were administered by a trained interviewer by telephone in all but one of the study countries, where face-to-face interviews were conducted in the clinic. The measures were completed in the week prior to baseline, and after 54 weeks of treatment. Distance visual acuity, measured according to the Early Treatment Diabetic Retinopathy Study (ETDRS), was assessed at all time points. Psychometric properties of the VFQ-25 assessed included domain structure, reliability, concurrent and construct validity, responsiveness. RESULTS: The VFQ-25 was found to consist of 11 domains slightly different than those proposed. Nevertheless, none of the eight established multi-item scales met the criterion for further splitting and the VFQ-25 was scored as in the developers' instructions. Internal consistency reliability was demonstrated for six out of the eight original multi-item scales, with Cronbach's alpha ranging from 0.58 (Distance Activities) to 0.85 (Vision Specific: Dependency). The VFQ-25 domains generally showed a low to moderate correlation with EQ-5D visual analogue scale (range 0.16-0.43) and with the visual acuity score (range 0.10-0.41). Construct validity was upheld with higher VFQ-25 scores for patients who saw more letters according to the ETDRS. Almost all scales were shown to be responsive with Guyatt's statistic ranging from 0.10 to 0.56 at 54 weeks. CONCLUSIONS: The VFQ-25 has evidence to support its validity and reliability for measuring HRQoL in DME. However, some operating characteristics of the instrument need further consideration and discussion in the case of DME patients. Further research is therefore warranted in this indication.

Long-term medical management of primary open-angle glaucoma and ocular hypertension in the UK: optimizing cost-effectiveness and clinic resources by minimizing therapy switches.

PURPOSE: The objective was to assess the long-term economic consequences of the medical management of glaucoma in the UK. METHODS: The economic evaluation was conducted using the results from a 10-year Markov model based around 3 key triggers for a switch in medical therapy for glaucoma, namely: lack of tolerance (using hyperemia as a proxy); intraocular pressure (IOP) not meeting treatment benchmark; and glaucoma progression. Clinical data from a comprehensive systematic literature review and meta-analysis were used. Direct costs associated with glaucoma treatment are considered (at 2008/9 prices) from the perspective of the UK NHS as payer (outpatient/secondary care setting). Using this model, the economic consequences of 3 prostaglandin-based treatment sequences were compared. RESULTS: Drug acquisition costs account for around 8% to 13% of the total cost of glaucoma and, if ophthalmologist visits are included, amount to approximately £0.80 to £0.90 per day of medical therapy. The total long-term costs of all prostaglandin strategies are similar because of a shift in resources: increased drug costs are offset by fewer clinic visits to instigate treatment switches, and by avoiding surgery or costs associated with managing low vision. Under the latanoprost-based strategy, patients would have longer intervals between the need to switch therapies, which is largely due to a reduction in hyperemia, seen as a proxy for tolerance. This leads to a delay in glaucoma progression of 12 to 13 months. For every 1000 clinic appointments, 719 patients can be managed for 1 year with a latanoprost-based strategy compared with 586 or 568 with a bimatoprost or travoprost-based strategy. CONCLUSIONS: Drug acquisition costs are not a key driver of the total cost of glaucoma management and the cost of medical therapy is offset by avoiding the cost of managing low vision. Economic models of glaucoma should include the long-term consequences of treatment as these will affect cost-effectiveness. This analysis supports the hypothesis that the economic and clinical benefits can be optimized by minimizing therapy switches.

Changes in vision- and health-related quality of life in patients with diabetic macular edema treated with pegaptanib sodium or sham.

PURPOSE: To compare vision function and self-reported quality of life (QoL) in patients with diabetic macular edema (DME) treated with intravitreous pegaptanib 0.3 mg or sham injection. METHODS: This randomized (1:1), controlled, multicenter trial included subjects with DME (center point thickness on OCT, ≥ 250 µm) and visual acuity (VA) ≤ 65 letters and ≥ 35 letters. In year 1, pegaptanib or sham was administered every 6 weeks with focal/grid photocoagulation at investigator discretion after week 18. Subjects received injections as often as every 6 weeks per pre-specified criteria in year 2. Primary efficacy endpoint: proportion gaining ≥10 letters of VA from baseline to week 54. Change in QoL from baseline to weeks 54 and 102 was assessed with the 25-item National Eye Institute-Visual Function Questionnaire (NEI-VFQ 25) and the EQ-5D. RESULTS: One hundred thirty-three pegaptanib- and 127 sham-treated subjects were in the year 1 intent-to-treat population. From baseline to week 54, ≥ 10 letter gains seen in 49 (36.8%) pegaptanib- and 25 (19.7%) sham-treated subjects (odds ratio [95% CI]: 2.38 [1.32-4.30]; P = 0.0047). At 2 years, the VA trend favored pegaptanib. The NEI-VFQ 25 domains of Near Vision, Distance Vision, and Social Functioning (week 54) and Distance Vision, Social Functioning, Mental Health, and Composite Score (week 102) demonstrated clinically meaningful (>5-point between-group difference) and statistically significant (P < 0.05) benefits favoring pegaptanib. No significant difference in the mean change in generic EQ-5D-weighted utility scores was seen. CONCLUSIONS: The VA improvement from pegaptanib treatment versus sham is reflected by improved vision-related QoL as reported by the DME patient (ClinicalTrials.gov number, NCT00605280).

A phase 2/3, multicenter, randomized, double-masked, 2-year trial of pegaptanib sodium for the treatment of diabetic macular edema.

PURPOSE: To confirm the safety and compare the efficacy of intravitreal pegaptanib sodium 0.3 mg versus sham injections in subjects with diabetic macular edema (DME) involving the center of the macula associated with vision loss not due to ischemia. DESIGN: Randomized (1:1), sham-controlled, multicenter, parallel-group trial. PARTICIPANTS: Subjects with DME. INTERVENTION: Subjects received pegaptanib 0.3 mg or sham injections every 6 weeks in year 1 (total = 9 injections) and could receive focal/grid photocoagulation beginning at week 18. During year 2, subjects received injections as often as every 6 weeks per prespecified criteria. MAIN OUTCOME MEASURES: The primary efficacy endpoint was the proportion gaining ≥ 10 letters of visual acuity (VA) from baseline to year 1. Safety was monitored throughout. RESULTS: In all, 260 (pegaptanib, n = 133; sham, n = 127) and 207 (pegaptanib, n = 107; sham, n = 100) subjects were included in years 1 and 2 intent-to-treat analyses, respectively. A total of 49 of the 133 (36.8%) subjects from the pegaptanib group and 25 of the 127 (19.7%) from the sham group experienced a VA improvement of ≥ 10 letters at week 54 compared with baseline (odds ratio [OR], 2.38; 95% confidence interval, 1.32-4.30; P = 0.0047). For pegaptanib-treated subjects, change in mean VA from baseline by visit was superior (P<0.05) to sham at weeks 6, 24, 30, 36, 42, 54, 78, 84, 90, 96, and 102. At week 102, pegaptanib-treated subjects gained, on average, 6.1 letters versus 1.3 letters for sham (P<0.01). Fewer pegaptanib- than sham-treated subjects received focal/grid laser treatment (week 54, 31/133 [23.3%] vs 53/127 [41.7%], respectively, P = 0.002; week 102, 27/107 [25.2%] vs 45/100 [45.0%], respectively, P = 0.003). The pegaptanib treatment group showed significantly better results on the National Eye Institute-Visual Functioning Questionnaire than sham for subscales important in this population. Pegaptanib was well tolerated; the frequencies of discontinuations, adverse events, treatment-related adverse events, and serious adverse events were comparable in the pegaptanib and sham groups. CONCLUSIONS: Patients with DME derive clinical benefit from treatment with the selective vascular endothelial growth factor antagonist pegaptanib 0.3 mg. These findings indicate that intravitreal pegaptanib is effective in the treatment of DME and, taken together with prior study data, support a positive safety profile in this population. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.