Search

Ocriplasmin is used to treat vitreomacular traction (VMT), with or without full-thickness macular hole (MH). We systematically reviewed the evidence on ocriplasmin's effect on vitreomacular adhesion resolution (VMAR), MH closure, vitrectomy, and best-corrected visual acuity (BCVA) and investigated the effect of baseline covariates on outcome. We applied individual participant data meta-analyses to the entire population and to subgroups defined by MH or epiretinal membrane (ERM) presence. Safety data were pooled and tabulated. Five randomized controlled trials (1,067 participants) were included. Six months after treatment, ocriplasmin achieved higher rates of VMAR and MH closure versus control, lowered vitrectomy odds, and increased the likelihood of a ≥10-letter BCVA increase. VMAR rates were lower when ERM, broad VMA (> 1500 µm), diabetic retinopathy, or pseudophakia were present and higher in younger participants, women, and eyes with MHs. Ocriplasmin-treated participants experienced more short-term visual impairment that was not predictive of final BCVA, as well as vitreous floaters, photopsia, photophobia, eye pain, blurred vision, and dyschromatopsia. The most common serious adverse events for ocriplasmin and control, respectively, were MH progression (22.5%, 17.3%), new MH (1.5%, 3.4%) and retinal detachment (0.8%, 1.2%). Ocriplasmin promotes VMAR and MH closure. Transient visual phenomena are not uncommon.

Purpose Effectiveness of ocriplasmin for vitreomacular traction (VMT) varies depending on the presence of common ocular conditions and patient selection criteria. We carried out a systematic literature review and meta‐analysis of ocriplasmin studies conducted in real‐world settings (RWS) and compared outcomes with those from randomized controlled trials (RCTs). Methods We included prospective and retrospective studies from RWS documenting effectiveness of ocriplasmin in patients with VMT with or without MH, and RCTs of ocriplasmin versus control. Key end‐points were vitreomacular adhesion resolution (VMAR), nonsurgical MH closure, need for vitrectomy and safety. We conducted meta‐regression on pooled results to evaluate effects of baseline covariates and study design on outcomes. Results Thirty RWS (2402 patients) and 5 RCTs (737 patients) were included epiretinal membrane (ERM) and broad VMA were more prevalent in RCTs. Primary VMAR, vitrectomy and MH closure rates were comparable between RWS and RCTs. Rates of nsVMAR were significantly higher in RWS than RCTs (odds ratio 1.66; 95% confidence interval [CI]: 1.18–2.34). nsVMAR rates were inversely associated with ERM prevalence (odds ratio 0.20; 95% CI: 0.08–0.51). Compared with the recent OASIS trial, RWS reported a higher incidence of new/worsening subretinal fluid cases and less photophobia, photopsia, vitreous floaters, electroretinogram abnormalities and MH progression. Conclusions Ocriplasmin was significantly more effective in achieving nsVMAR in RWS than in RCTs. Lower ERM prevalence in RWS was the single significant explanatory variable for this difference. Conclusions on ocriplasmin safety in RWS are limited due to inconsistent reporting.

Purpose The purpose of this analysis of patient-reported outcomes from the ELECT (Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment) trial (NCT00774930) was to explore the effect of lanreotide on symptoms of carcinoid syndrome. Specifically, this post hoc analysis was designed to identify the most important patient-reported outcomes for patients in ELECT. Methods The post hoc analysis of ELECT, a placebo-controlled study of lanreotide in patients with neuroendocrine tumors, evaluated patient-reported outcomes during the double-blind phase of the trial, specifically daily diarrhea and flushing symptoms, octreotide rescue use, and the EORTC QLQ-C30 and QLQ-GINET21 questionnaires at baseline and week 12. Principal component (PC) analysis was applied on baseline data to identify independent variable clusters and clinically meaningful summary measures that highly correlated to these PCs. From those, the minimum clinical important differences were derived so to perform a responder analysis. Results The three largest PCs captured 42.9% of the variation among baseline variables. The C30 summary score (C30-SS), diarrhea burden, and flushing burden were highly correlated with PC1, PC2, and PC3, respectively. Lanreotide patients were more likely to experience an improvement on the C30-SS (risk ratio [RR] 2.42; P=0.023), diarrhea burden (RR 2.85; P=0.005), and flushing burden (RR 1.39; P=0.31) compared to placebo patients. Lanreotide-treated patients have a higher probability of being a responder on at least one of the three domains of C30-SS, diarrhea burden, or flushing burden compared to placebo patients (RR 1.48; P=0.06). Conclusion The higher response rates in the diarrhea burden are consistent with the previously reported effects of lanreotide on octreotide rescue medication use, while the findings of a greater efficacy of lanreotide vs placebo in the quality-of-life domains represent a novel aspect in the benefits of lanreotide. Trial registration ClinicalTrials.gov identifier: NCT00774930.

Purpose Vitreomacular traction (VMT) is a disease in which the vitreous exerts abnormally strong traction on the macula, the area of the eye responsible for detailed central vision. If this traction significantly distorts the macula then VMT can lead to troublesome distorted vision (metamorphopsia), sometimes occurring despite relatively preserved visual acuity. Ocriplasmin, administered as a single intravitreal injection, aims to release VMT and improve vision. While the effect of ocriplasmin on traction release and visual acuity is well characterized, the effect of symptoms like metamorphopsia is not. Methods A systematic review and synthesis of the literature on patient reported outcomes (PRO) in relation to the use of ocriplasmin for the treatment of VMT was undertaken using MED-LINE and Embase databases, and the Cochrane central register of controlled trials (CENTRAL). Results The review identified PRO data from 870 patients across three randomized controlled trials. The most commonly reported PROs were the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25), a broad measure of vision-related quality of life, and Visual Function Response (VFR), an outcome combining quality of life and visual acuity outcomes. Treatment with ocriplasmin produced significant patient benefit vs control (sham or placebo-injection). Ocriplasmin was associated with a higher proportion of patients experiencing a clinically meaningful improvement in visual functioning with a difference of 11.8% for VFQ-25 and 23.2% for VFR responder analyses, respectively. Conclusion Patients with VMT have material impairment in visual functioning and quality of life, relative to their reduction in visual acuity. Ocriplasmin results in a significant improvement in visual functioning. Future research could include the development of new PROs specific to VMT.

Purpose: To assess the effect of ocriplasmin on visual function response (VFR) measured using visual acuity (VA) and vision-related quality of life, and to quantify the association between release of vitreomacular adhesion (VMA) at day 28 and VFR.Methods: Prespecified analysis of secondary endpoints from a randomized controlled trial. Of 220 participants with symptomatic VMA/vitreomacular traction (VMT), including VMT associated with a macular hole up to 400 μm, 146 received a single intravitreal injection of 125 μg ocriplasmin and 74 a sham injection. Based on principal components analysis results, a VFR was defined as either a VA improvement of ≥2 lines or an improvement exceeding the minimal clinically important difference (MCID) in the composite or the mental health subscale scores of the Visual Function Questionnaire (VFQ-25). The MCID was estimated using the standard error of measurement approach. The main outcome measure was the VFR at month 6, with further assessments at months 12 and 24.Results: The MCID was estimated at 3.71 points for the VFQ-25 composite score and 10.71 for the VFQ-25 mental health subscale score. A VFR occurred in 51.0% of ocriplasmin versus 23.3% of sham participants (P = 0.0001). The VFR was maintained through months 12 and 24: 53.1% and 50.3% in ocriplasmin versus 21.9% and 20.5% in sham participants, respectively (P < 0.0001). Resolution of VMA at day 28 significantly increased the odds of a VFR at each assessment period.Conclusions: Treatment with ocriplasmin compared with sham resulted in a significant improvement in VFR. The 6-month treatment effect was sustained at months 12 and 24.

Background Chronic hepatitis B (CHB) is an important health concern, but there are few studies describing its management in different countries. This prospective, longitudinal, non-interventional study aimed to assess differences in CHB management in five European countries (Germany, France, Poland, Romania and Turkey). Methods Data were collected from CHB patients’ records between 2008 and 2010. Patients were stratified by treatment status at baseline (treated or untreated). The primary objective was to estimate the probability of a CHB management modification (treatment initiation or change) among patients from each country during a 2-year follow-up. Results A total of 1,267 patients were included (567 treated, 700 untreated). Baseline characteristics between countries and treatment status groups were broadly comparable. Most patients had an alanine aminotransferase measurement in the 12 months prior to baseline; proportions of patients with an HBV DNA assessment varied by country and treatment status. The Kaplan–Meier-estimated probability of any treatment modification ranged from 9.4% (Turkey) to 30.1% (Poland) at 12 months and 10.0% (Turkey) to 40.0% (Poland) at 24 months. Modifications were more common in treated than untreated patients. The most frequently reported reasons for modifying treatment were HBV-DNA-related. The majority of treated patients were treated with monotherapy; however, choice of therapy differed between countries. Conclusions This is the first longitudinal study describing CHB management in European countries. Differences were observed in treatment and monitoring between countries, but alanine aminotransferase and HBV DNA levels consistently emerged as key tests in the management of CHB in all five countries.

PURPOSE: To assess the effect of an intravitreal ocriplasmin injection on visual function, measured using visual acuity (VA) and vision-related quality of life.METHODS: Post hoc analysis of prespecified secondary end-points in two multicentre, randomized, double-masked, phase 3 clinical trials. A total of 652 participants with symptomatic vitreomacular adhesion were enrolled, of whom 464 received a single intravitreal injection of 125 μg ocriplasmin and 188 received a single intravitreal placebo injection. Based on principal components analysis results, visual function response (VFR) was defined as either a VA improvement of ≥2 lines; or an improvement in the composite score of the National Eye Institute Visual Function Questionnaire (VFQ-25) exceeding the minimal clinically important difference (MCID), estimated using the standard error of measurement approach; or an improvement in the VFQ-25 driving subscale score exceeding the MCID. The main outcome measure was VFR at 6 months.RESULTS: A VFR occurred in 55.1% of the ocriplasmin group versus 34.2% of the placebo injection group (p < 0.0001). This comprised 23.7% versus 11.2% (p = 0.0003) with a ≥ 2-line VA improvement, 35.9% versus 22.7% (p = 0.0016) for the VFQ-25 composite score, and 10.2% versus 6.2% (p = 0.1697) for the driving subscale.CONCLUSION: Ocriplasmin produces a clinically meaningful visual function benefit.

Background : If left untreated, vitreomacular traction (VMT) will infrequently improve through spontaneous resolution of vitreomacular adhesion (VMA), and patients remain at risk of further deterioration in vision. The mainstay of treatment for VMT is vitrectomy, an invasive procedure that carries the risk of rare but serious complications and further vision loss. As such, a ‘watch and wait’ approach is often adopted before this surgical intervention is performed. Ocriplasmin (microplasmin) is a potential alternative treatment for patients with symptomatic VMA/VMT that may remove the requirement for vitrectomy. Objective : The purpose of this study was to evaluate the cost-effectiveness of ocriplasmin for the treatment of VMT in comparison to standard of care. Study design : A cohort-based computer simulation model was developed, capturing three mutually exclusive subgroups: 1) VMT without epiretinal membrane (ERM) or full thickness macular hole (FTMH), 2) VMT with ERM but no FTMH, and 3) VMT with FTMH. Transition probabilities between health states, utilities, and resource utilisation were estimated based on clinical trial results, the literature, and expert opinion. The cost per quality-adjusted life year (QALY) gained was estimated over a lifetime, using UK unit costs and utilities associated with visual acuity, adverse events, metamorphopsia, and surgical interventions. Setting : Analyses were conducted from a UK payer perspective. Population : Transition probabilities for the model were primarily estimated from patient-level data from the combined Phase 3 MIVI-TRUST trials in patients with symptomatic VMA/VMT, including when associated with a FTMH ≤400 µm. Intervention : Ocriplasmin (microplasmin) is a one-time intravitreal injection designed specifically to release the abnormal traction between the macula and the vitreous and thereby treat VMT, as well as macular hole with persistent vitreous attachment. Main outcome measure : The main outcome measure of the economic evaluation was cost per QALY. Results : In all subgroups, ocriplasmin management generated more QALYs: 1) VMT without ERM or FTMH (0.105, (0.036, 0.191)); 2) VMT with ERM but no FTMH (0.041, (0.011, 0.131)); and 3) VMT with FTMH (0.053, (−0.002, 0.113)). The initial treatment costs were partially offset by later savings and net costs were estimated at £1,901 (£1,325, £2,474), £2,491 (£1,067, £2,511), and £1,912 (£1,233, £2,506), respectively. Costs per QALY were estimated at £18,056 (£8,241, £64,874), £61,059 (£8,269, £168,664), and £36,250 (−£144,788, £290,338), respectively. Short-term efficacy parameters were found to be key drivers of results. Conclusion : Ocriplasmin is most cost-effective in VMT patients without either ERM or FTMH. Keywords: anatomical outcomes; economic evaluation; quality adjusted life year; United Kingdom; vitrectomy; PPV; symptomatic vitreomacular adhesion (Published: 23 June 2016) Citation: Journal of Market Access & Health Policy 2016, 4: 31472 - http://dx.doi.org/10.3402/jmahp.v4.31472

Hepatitis C virus (HCV) affects 170 million patients worldwide and is the leading cause of liver cirrhosis and hepatocellular carcinoma. The aim of the current study is to examine the burden of HCV in the European Union (EU) from a patient perspective.Using data from the 2010 EU National Health and Wellness Survey, patients who reported a diagnosis of HCV (n=332) were compared with a propensity-score-matched non-HCV control group (n=332) on measures of quality of life (using the SF-12v2), work productivity, and healthcare resource utilization in the past 6 months. All analyses applied sampling weights to project to the respective country populations.Projected prevalence estimates of HCV were 0.59% in France, 0.44% in Germany, 1.42% in Italy, 0.82% in Spain, and 0.35% in the UK. HCV patients reported significantly lower levels of emotional role limitations (means=66.4 vs. 70.6, P=0.040), physical functioning (means=63.8 vs. 71.9, P=0.001), general health (means=48.3 vs. 54.4, P=0.004), bodily pain (means=64.3 vs. 70.8, P=0.002), and physical component summary scores (means=42.9 vs. 45.3, P=0.002) than the matched controls. Patients with HCV also reported significantly higher levels of presenteeism (means=27.1 vs. 21.0%, P=0.044) and a greater number of physician visits in the past 6 months (means=9.9 vs. 6.7, P0.001).Using a population-based survey methodology and a propensity-score matching analysis, these results add to the literature by documenting the significant effect that HCV has on a variety of both humanistic and economic outcomes in the EU.

Introduction: We aimed to quantify patients‘ and physicians’ preferences for therapeutic trade-offs involving the efficacy, side-effect risks, and evidence uncertainty in chronic hepatitis B (CHB) treatments. Materials and Methods: Physicians who treat CHB patients and adult patients with a self-reported physician diagnosis of CHB completed a web-enabled, discrete-choice experiment survey in Turkey. Both patients and physicians answered 12 treatment-choice questions. Each question required evaluating a pair of hypothetical CHB medication profiles defined by the years the medicine has been studied (weight of evidence), probability that the patient’s viral load remains undetectable for five years with possible reversal of disease progression (efficacy), five-year treatment-related risks of a fracture and renal insufficiency, and monthly medication cost. Logit models were used to estimate preference weights for all attribute levels and the profile preference scores for three current CHB treatments. A choice format conjoint analysis was used. Results: 159 physicians and 117 patients completed the survey. Patients and physicians had discordant views on the relative importance of CHB treatment attributes. Patients ranked weight of evidence and efficacy as the most important attributes, while physicians ranked efficacy and risk of renal insufficiency as the most important attributes. Both groups preferred a CHB medication profile characterized by potent efficacy and low side-effect risk versus a medication profile characterized by a potent efficacy and moderate side-effect risk profile (p> 0.05). Both medication profiles were preferred over a CHB medication with poor efficacy and low side-effect risk profile (p> 0.05 for patients and p< 0.05 for physicians). Conclusion: This is the first study to quantify patients’ and physicians’ preferences for CHB treatments in Turkey. Discordance between physicians’ and patients’ preferences can be explained by asymmetric knowledge and information regarding the importance of weight of evidence and efficacy versus side-effect risks. This fact highlights the need for reflection of physician and patient perspectives on regulatory and reimbursement decisions.

This longitudinal non-interventional study aims to describe the demographics data disease characteristics and clinical management of a cross-sectional CHB patient population in Poland treated in regional medical centers.[corrected] Between March 2008 and December 2010 we observed patients with HBV related liver disease from 5 medical centers in Poland, both sexes,18 years old. At baseline, we used a case report form to extract data from patient charts, comprising: sociodemographic data; disease characteristics, HBeAg/ antiHBeAg status, genotype HBV; co-morbidities; viral load, liver biopsy and ALT levels in previous 12 months; treatment history in previous 12 months; current CHB treatment; changes in disease characteristics and CHB management; time from diagnosis to the therapy and resource utilization and any reasons for termination of follow-up. Written informed consent was obtained from all participantsThe analysis population included 253 patients (94 treated and 159 non-treated at baseline) mostly male (69.1 vs. 56.6). Patients in treated group compared with untreated group were: significantly older (mean 42.6 vs. 37.5 years respectively, p0.001), observed longer since diagnosis(3.9 vs.2.9 years), with higher rate of HBeAg(+)(42.6% vs.5.1%), lower ALT activity, and higher VL HBV DNA PCR. Of the 53% of treated patients, the most frequently prescribed anti-HBV drugs were: Lamivudine (53%), Entecavir (23.7%), Pegylated IFN-alfa2a (23.7%), Adefovir (11.1%). During 24 months of follow-up in treated group 13(36.1%) patients underwent a treatment switch to another nucleosi(-ti)de analogue, in one (2.8%) patient another analogue was added, and in 25 (69.4%)patients the therapy was stopped. The proportion of all patients treated with monotherapy at the end of follow-up was 99.4%, unfortunately mostly with Lamivudine-49.3%.1. Despite the several methodological limitations usually associated with this type of observation, the collected data does characterize the demographics of polish patients chronically infected with HBV well, provides some insights into the determinants of treatment initiation and the clinical management of patients in real-word settings. 2. These results indicate that in clinical practice in 5 medical non-academic centers in Poland, European guidelines regarding the qualification to HBV treatment were followed, but there were discrepancies between the initial treatment decisions in real-life current clinical practice and guideline recommendations

The aim of this study was to estimate the cost-effectiveness of atazanavir/ritonavir (atazanavir/r) versus lopinavir/ritonavir (lopinavir/r) in treatment-naïve human immunodeficiency virus-1 (HIV-1) patients in Sweden for whom efavirenz is not suitable.A Markov model was developed to predict the lifetime outcomes of atazanavir/r and lopinavir/r in terms of quality-adjusted life years (QALYs) and total costs. The model was structured to focus on treatment lines--how patients progress from first- to second-, and then to third-line treatment. Model inputs were derived directly from clinical trials, such as the CASTLE study (a 96-week head-to-head trial in first-line therapy), and from the Framingham risk-equation. The analysis was conducted from a payer perspective and included extensive scenario and probabilistic sensitivity analyses.The model predicted atazanavir/r to save 0.16 (95% confidence interval (CI) 0.00 to 0.33) QALYs and reduce total costs by -202,896 SEK (95% CI -332,156 to -81,644 SEK) over a lifetime horizon. Probabilistic sensitivity analyses showed that atazanavir/r had a 100% probability to be cost-effective at a willingness to pay of 200,000 SEK per QALY.The results indicate that atazanavir/r is cost-saving and more effective compared to lopinavir/r for patients who have previously not been exposed to antiretroviral drugs in Sweden.

The study calculates inpatient costs generated at the University Hospital in Antwerp (Belgium) and outpatient costs generated at the Institute of Tropical Medicine or at the University Hospital of 213 seropositive patients without AIDS and of 48 AIDS patients, for the year 1991. Outpatient drug use other than Zidovudine was excluded. An HIV + patient has an average annual total billing cost of 2062 ECU, 43% of which is spent in hospital, 29% on Zidovudine and 28% for follow-up at the Institute of Tropical Medicine. The average cost of care for an AIDS patient is 5.5 times higher and amounts to 11 277 ECU—hospitalisation costs (8349 ECU) and costs of Zidovudine (2031 ECU) are much higher. Costs vary with the severity of illness. In comparison to 1987, costs decreased due to lower drug prices and reduced hospitalisations. Life time costs of a seropositive patient are estimated at about 35 000 ECU, based on cost calculations per CD4-class for a follow-up period from 1991 to 1993.