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Health Technology Assessment... May 2008To assess the clinical effectiveness and cost-effectiveness of ranibizumab and pegaptanib for subfoveal choroidal neovascularisation (CNV) associated with wet... (Review)
Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of ranibizumab and pegaptanib for subfoveal choroidal neovascularisation (CNV) associated with wet age-related macular degeneration (AMD).
DATA SOURCES
Electronic databases were searched from inception to September 2006. Experts in the field were consulted and manufacturers' submissions were examined.
REVIEW METHODS
The quality of included studies was assessed using standard methods and the clinical effectiveness data were synthesised through a narrative review with full tabulation of results. A model was developed to estimate the cost-effectiveness of ranibizumab and of pegaptanib (separately), compared with current practice or best supportive care, from the perspective of the NHS and Personal Social Services. Two time horizons were adopted for each model. The first adopted time horizons determined by the available trial data. The second analysis extrapolated effects of treatment beyond the clinical trials, adopting a time horizon of 10 years.
RESULTS
The combined analysis of two randomised controlled trials (RCTs) of pegaptanib [0.3 mg (licensed dose), 1.0 mg and 3.0 mg] versus sham injection in patients with all lesion types was reported by three publications (the VISION study). Three published RCTs of ranibizumab were identified (MARINA, ANCHOR, FOCUS), and an additional unpublished RCT was provided by the manufacturer (PIER). Significantly more patients lost less than 15 letters of visual acuity at 12 months when taking pegaptanib (0.3 mg: 70% of patients; 1.0 mg: 71% of patients; 3.0 mg: 65% of patients) or ranibizumab (0.3 mg: 94.3-94.5%; 0.5 mg: 94.6-96.4%) than sham injection patients (55% versus pegaptanib and 62.2% versus ranibizumab) or, in the case of ranibizumab, photodynamic therapy (PDT) (64.3%). The proportion of patients gaining 15 letters or more (a clinically important outcome having a significant impact on quality of life) was statistically significantly greater in the pegaptanib group for doses of 0.3 and 1.0 mg but not for 3.0 mg, and for all ranibizumab groups compared to the sham injection groups or PDT. This was also statistically significant for patients receiving 0.5 mg ranibizumab plus PDT compared with PDT plus sham injection. Pegaptanib patients lost statistically significantly fewer letters after 12 months of treatment than the sham group [mean letters lost: 7.5 (0.3 mg), 6.5 (1.0 mg) or 10 (3.0 mg) vs 14.5 (sham)]. In the MARINA and ANCHOR trials, ranibizumab patients gained letters of visual acuity at 12 months whereas patients with sham injection or PDT lost about 10 letters (p<0.001) and in the PIER study, ranibizumab patients lost significantly fewer than the sham injection group. Significantly fewer patients receiving pegaptanib or ranibizumab deteriorated to legal blindness compared with the control groups. Adverse events were common for both pegaptanib andranibizumab but most were mild to moderate. Drug costs for 1 year of treatment were estimated as 4626 pounds for pegaptanib and 9134 pounds for ranibizumab. Non-drug costs accounted for an additional 2614 pounds for pegaptanib and 3120 pounds for ranibizumab. Further costs are associated with the management of injection-related adverse events, from 1200 pounds to 2100 pounds. For pegaptanib compared with usual care, the incremental cost-effectiveness ratio (ICER) ranged from 163,603 pounds for the 2-year model to 30,986 pounds for the 10-year model. Similarly, the ICERs for ranibizumab for patients with minimally classic and occult no classic lesions, compared with usual care, ranged from 152,464 pounds for the 2-year model to 25,098 pounds for the 10-year model.
CONCLUSIONS
Patients with AMD of any lesion type benefit from treatment with pegaptanib or ranibizumab on measures of visual acuity when compared with sham injection and/or PDT. Patients who continued treatment with either drug appeared to maintain benefits after 2 years of follow-up. When comparing pegaptanib and ranibizumab, the evidence was less clear due to the lack of direct comparison through head-to-head trials and the lack of opportunity for indirect statistical comparison due to heterogeneity. The cost-effectiveness analysis showed that the two drugs offered additional benefit over the comparators of usual care and PDT but at increased cost. Future research should encompass trials to compare pegaptanib with ranibizumab and bevacizumab, and to investigate the role of verteporfin PDT in combination with these drugs. Studies are also needed to assess adverse events outside the proposed RCTs, to consider the optimal dosing regimes of these drugs and the benefits of re-treatment after initial treatment, and to review costing in more detail. Health state utilities and their relationship with visual acuity and contrast sensitivity, the relationship between duration of vision loss and the quality of life and functional impact of vision loss, behavioural studies of those genetically at risk are other topics requiring further research.
Topics: Age Factors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Aptamers, Nucleotide; Choroidal Neovascularization; Contrast Sensitivity; Cost-Benefit Analysis; Drug Costs; Humans; Macular Degeneration; Randomized Controlled Trials as Topic; Ranibizumab; Visual Acuity
PubMed: 18462575
DOI: 10.3310/hta12160 -
The Cochrane Database of Systematic... Apr 2008Age-related macular degeneration (AMD) is a common cause of severe vision loss in people 55 years and older. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Age-related macular degeneration (AMD) is a common cause of severe vision loss in people 55 years and older.
OBJECTIVES
The objective of this review was to investigate the effects of anti-VEGF (vascular endothelial growth factor) modalities for treating neovascular AMD.
SEARCH STRATEGY
We searched CENTRAL, MEDLINE, EMBASE and LILACS. We handsearched ARVO abstracts for 2006, 2007 for ongoing trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs).
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. We contacted trial authors for additional data. We summarized outcomes as relative risks (RR), number needed to treat (NNT) and weighted mean differences.
MAIN RESULTS
We included five RCTs of good methodological quality. All five trials were conducted by pharmaceutical companies. An intention-to-treat analysis using the last observation carried forward method was done in most trials. Two trials compared pegaptanib versus sham. One trial compared ranibizumab versus sham, another compared ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and the final trial compared ranibizumab plus verteporfin PDT versus verteporfin PDT alone. Fewer patients treated with pegaptanib lost 15 or more letters of visual acuity at one year follow-up compared to sham (pooled relative risk (RR) 0.71; 95% confidence interval (CI) 0.61 to 0.84). The NNT was 6.67 (95% CI 4.35 to 14.28) for 0.3 mg pegaptanib, 6.25 (95% CI 4.17 to 12.5) for 1 mg pegaptanib and 14.28 (95% CI 6.67 to 100) for 3 mg pegaptanib. In a trial of ranibizumab versus sham, RR for loss of 15 or more letters visual acuity at one year was 0.14 (95% CI 0.1 to 0.22) in favour of ranibizumab. The NNT was 3.13 (95% CI 2.56 to 3.84) for 0.3 mg ranibizumab and 3.13 (95% CI 2.56 to 3.84) for 0.5 mg ranibizumab. In a trial of ranibizumab versus verteporfin PDT, RR for loss of 15 or more letters at one year was 0.13 (95% CI 0.07 to 0.23) favouring ranibizumab. The NNT was 3.33 (95% CI 2.56 to 4.76) for 0.3 mg ranibizumab and 3.12 (95% CI 2.43 to 4.17) for 0.5 mg ranibizumab. In another trial of combined ranibizumab plus verteporfin PDT versus verteporfin PDT, RR for loss of 15 or more letters at one year favoured combined therapy (RR 0.3 (95% CI 0.15 to 0.60). The NNT was 4.35 (95% CI 2.78 to 11.11). Pooled RR for gain of 15 or more letters visual acuity at one year was 5.81 (95% CI 3.29 to 10.26) for ranibizumab versus sham, 6.79 (95% CI 3.41 to 13.54) for ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and 4.44 (95% CI 1.40 to 14.08) for ranibizumab plus verteporfin PDT versus verteporfin PDT. Frequency of endophthalmitis in included studies was between 0.7% to 4.7% with ranibizumab and 1.3% with pegaptanib. Improvement in vision-specific quality of life was reported for both treatments.
AUTHORS' CONCLUSIONS
Pegaptanib and ranibizumab reduce the risk of visual acuity loss in patients with neovascular AMD. Ranibizumab causes gains in visual acuity in many eyes. Quality of life and cost will be important for treatment decisions. Other agents blocking VEGF are being tested in ongoing trials.
Topics: Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Aptamers, Nucleotide; Choroidal Neovascularization; Humans; Macular Degeneration; Middle Aged; Porphyrins; Randomized Controlled Trials as Topic; Ranibizumab; Vascular Endothelial Growth Factor A; Verteporfin
PubMed: 18425911
DOI: 10.1002/14651858.CD005139.pub2 -
The British Journal of Ophthalmology Sep 2007To assess the clinical effectiveness of pegaptanib sodium and ranibizumab for neovascular age-related macular degeneration (AMD). (Review)
Review
AIMS
To assess the clinical effectiveness of pegaptanib sodium and ranibizumab for neovascular age-related macular degeneration (AMD).
METHODS
A systematic review of randomised controlled trials (RCTs) identified through searching 12 electronic databases, bibliographies and consultation with experts and manufacturers. RCTs were eligible if they assessed the effects of pegaptanib or ranibizumab with best supportive care, sham injection or photodynamic therapy (PDT) on patients with subfoveal choroidal neovascularisation associated with wet AMD and examined outcomes including visual acuity and adverse events.
RESULTS
Three RCTs of ranibizumab (MARINA, ANCHOR, FOCUS) and two of pegaptanib (VISION study) met the inclusion criteria. The RCTs included patients with different lesion types. The studies showed statistically significant benefit on different measures of visual acuity for patients receiving pegaptanib, ranibizumab or ranibizumab with PDT compared to control (sham injection, PDT or sham injection with PDT) after 12 months. These differences appeared to be clinically significant. Although adverse events were common among those receiving pegaptanib or ranibizumab, they were considered mild to moderate in nature. Meta-analysis of ranibizumab trials and indirect comparison of the two drugs were not possible due to differences in the study populations' lesion types. However, results from the RCTs of ranibizumab tended to show a greater effect on visual acuity than results from the RCT of pegaptanib.
CONCLUSIONS
Pegaptanib and ranibizumab appear to slow or stop the progression of neovascular AMD. Uncertainty remains over the relative benefits of pegaptanib compared with ranibizumab and other unlicensed drugs (eg, Avastin), due to the nature of the evidence. Head-to-head RCTs and economic evaluations comparing these alternatives are needed.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Aptamers, Nucleotide; Choroidal Neovascularization; Disease Progression; Humans; Macular Degeneration; Randomized Controlled Trials as Topic; Ranibizumab; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 17475698
DOI: 10.1136/bjo.2007.118562