ObjectiveCompare the efficacy of ranibizumab, aflibercept, laser, and sham in the first-line treatment of diabetic macular edema (DME) to inform technology assessments such as those conducted by the UK National Institute for Health and Care Excellence (NICE).Data sourcesMEDLINE, Embase, Cochrane Library, congress abstracts, ClinicalTrials.gov registry and Novartis data on file.Inclusion criteriaStudies reporting 6- or 12-month results of randomized controlled trials (RCTs) evaluating at least two of ranibizumab 0.5 mg pro re nata, aflibercept 2.0 mg bi-monthly, laser photocoagulation or sham. Study quality was assessed based on likelihood of bias in selection, attrition, detection and performance.Outcome measureImprovement in best-corrected visual acuity (BCVA) measured as the proportion of patients gaining ≥10 letters on the Early Treatment Diabetic Retinopathy Study scale. The outcome was chosen following acceptance by NICE of a Markov model with 10-letter health states in the assessment of ranibizumab for DME.Meta-analysisBayesian network meta-analyses with fixed and random effects adjusted for differences in baseline BCVA or central retinal thickness.ResultsThe analysis included 1,978 patients from eight RCTs. The random effects model adjusting for baseline BCVA was the best model based on total residual. The efficacy of ranibizumab was numerically, but not statistically, superior to aflibercept (odds ratio [OR] 1.59; 95% credible interval [CrI], 0.61–5.37). Ranibizumab and aflibercept were statistically superior to laser monotherapy with ORs of 5.50 (2.73–13.16) and 3.45 (1.62–6.84) respectively. The probability that ranibizumab is the most efficacious treatment was 73% compared with 14% for aflibercept, 12% for ranibizumab plus laser, and 0% for laser.LimitationsThree of the eight RCTs included are not yet published. The models did not adjust for all potential effect modifiers.ConclusionRanibizumab was non-significantly superior to aflibercept and both anti-VEGF therapies had statistically superior efficacy to laser.

BackgroundRanibizumab and aflibercept are alternative anti-vascular endothelial growth factor agents approved for the treatment of visual impairment (VI) due to diabetic macular edema (DME).ObjectiveTo estimate, from a UK healthcare perspective, the cost-effectiveness of ranibizumab 0.5 mg pro re nata (PRN) and ranibizumab 0.5 mg treat and extend (T&E) compared with aflibercept 2 mg every 8 weeks after five initial monthly doses (2q8) in the treatment of VI due to DME.MethodsA Markov model previously reviewed by the National Institute for Health and Care Excellence was used to simulate the long-term outcomes and costs of treating DME. Health states were defined by increments of ten letters in best-corrected visual acuity (BCVA), with a 3-month cycle length. Patients could gain (or lose) a maximum of two health states between cycles. A 3-year treatment time frame and a lifetime horizon were used. Future costs and health outcomes were discounted at 3.5% per annum. Patient baseline characteristics and the efficacy of ranibizumab PRN were derived using data from the RESTORE study. The relative efficacies of ranibizumab PRN, ranibizumab T&E, and aflibercept were assessed with a network meta-analysis. Different utilities were assigned based on BCVA and whether the treated eye was the better- or the worse-seeing eye. Sensitivity analyses tested the robustness of the model.ResultsLifetime costs per patient of treating DME were £20,019 for ranibizumab PRN, £22,930 for ranibizumab T&E, and £25,859 for aflibercept 2q8. Ranibizumab was dominant over aflibercept, with an incremental gain of 0.05 quality-adjusted life-years (QALYs) and cost savings of £5,841 (PRN) and £2,930 (T&E) compared with aflibercept. Ranibizumab PRN and ranibizumab T&E had 79% and 67% probability, respectively, of being cost-effective relative to aflibercept at a willingness-to-pay threshold of £20,000/QALY. When assuming the higher end of PRN injection frequency (15.9 over 3 years), the cost savings associated with ranibizumab were £3,969.ConclusionFrom a UK healthcare perspective, ranibizumab provides greater health gains with lower overall costs than aflibercept in patients with VI due to DME.

scores were compared to corresponding 10 year ACM predictions from the CDM. Base case (BC) analyses applied UKPDS-68 risk equations (UK68-RE) for CV risk and mortality. Two sets of sensitivity analyses were conducted using UK68-RE for CV risk but mortality tracked individually per complication event (non combined mortality approach) (SA1) and UKPDS-82 risk equations (UK82-RE) applied for CV risk and mortality (SA2). Results: Across all age and co-morbidity states, CDM simulations demonstrated the closest match to CCI-scores in SA1 with an R 2 -statistic of 0.877. This compared to R 2 -statistics of 0.757, and 0.851 for BC and SA2, respectively. BC and SA2 analyses noteworthy underestimated ACM risk in analyses with increased co-morbitity level by 68% (BC) and 49% (SA2) vs. 17% (SA1) in (MI+S+HF) and 44% (BC) and 36% (SA2) vs. 3% (SA1) in (MI+S+HF+RF). ConClusions: The CDM demonstrated a closer match to CCI mortality scores (vs. outcome studies) with a trend to underestimate ACM. This trend increased with baseline age and (only BC and SA2) co-morbidity level.objeCtives: Multivariate functions can be used to predict individual risk for cardiovascular (CVD) events and also to estimate baseline risk in economic models. We present a comparison of deterministic versus stochastic risk predictions using Framingham's [D'Agostino 2008] and REACH's [Wilson 2012] functions. Stochastic risk prediction accounts for patient-level heterogeneity, but involves a number of issues including increased complexity, data requirements, need for assumptions and computational burden. To our knowledge, this topic has not been studied in the CVD setting. Methods: D'Agostino 2008 and Wilson 2012 modeled primary (PE) and recurrent event (RE) risks, respectively. Both studies considered fatal and non-fatal aggregate CVD events and estimated a Cox Proportional Hazards (CPH) multivariate risk function. In the deterministic prediction, the means of the risk factors were used to predict the population's risk directly from the functions. In the stochastic prediction, individual patient profiles (n= 10,000) were generated using Monte Carlo simulation. Individual risks were then estimated from the functions and averaged to compute the population's risk. Multinomomial distributions were assumed for discrete variables (e.g. diabetes, number of vascular beds) and normal or log-normal distributions were assumed for continuous variables depending on skewness (e.g. age, total cholesterol). Probability distributions were parameterized based on the risk factors descriptives reported in the original references. Simulations were performed with and without considering dependence of risk factors. Results: Due to the nonlinearity of the CPH function, the stochastic prediction yielded 23% (PE) and 17% (RE) higher risks than the deterministic approach (14% and 10%, respectively, if age was kept constant). Differences between prediction approaches are even higher if the estimated correlation structure of risk factors is accounted for. ConClusions: When compared to th...

A179according to Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores. METHODS: All patients who stayed on the same active treatment for 52 weeks were included. Active treatments were subcutaneous secukinumab 300 mg (n= 568) or 150 mg (n= 570) at weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks, and subcutaneous etanercept 50 mg twice weekly for 12 weeks and then once weekly (n= 323). Total AUCs over the 52-week period by percentage of PASI-75/90/100 and DLQI-0/1 (no impact on patient quality of life) responders-measuring overall controlled disease time-were determined using all responder numbers at all scheduled visits. RESULTS: Total AUCs for patients who received secukinumab 300 and 150 mg, and etanercept, respectively, were: 3857.8, 3286.9, and 2628.1 (PASI-75); 3017.7, 2212.2, and 1531.8 (PASI-90); 1677.0, 978.9, and 452.5 (PASI-100); and 3029.8, 2492.2, and 1991.4 (DLQI-0/1). Total AUC ratios for secukinumab 300 and 150 mg, respectively, vs etanercept were 1.47 and 1.25 (PASI-75); 1.97 and 1.44 (PASI-90); 3.71 and 2.16 (PASI-100); and 1.52 and 1.25 (DLQI-0/1). Total AUC ratios for secukinumab 300 vs 150 mg were 1.17 (PASI-75), 1.36 (PASI-90), 1.71 (PASI-100), and 1.22 (DLQI-0/1). CONCLUSIONS: In patients with moderate-severe plaque psoriasis, greater AUCs by PASI-75/90/100 and DLQI-0/1 responders were achieved with secukinumab 300 mg, followed by secukinumab 150 mg and etanercept. This analysis suggests that secukinumab 300 mg resulted in the best overall disease control over time.OBJECTIVES: Assessment of how therapies achieve cumulative disease control over time is critical. In two phase III, 52-week trials (ERASURE and FIXTURE), secukinumab-a human, anti-interleukin-17A, monoclonal antibody-was an effective treatment for moderate-severe chronic plaque psoriasis. Pooled analysis of these trials was performed to explore the cumulative efficacy of secukinumab by assessing area-under-the-curve (AUC) of percentage of treatment responders

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