Authors' objectives:

The objective of this report is to assess the impact of the pharmaceutical management of neovascular age-related macular degeneration by answering the following research questions:
• What is the clinical evidence on the relative effectiveness of pegaptanib, bevacizumab, ranibizumab, triamcinolone, anecortave acetate, or placebo (either alone or in combination)
versus V-PDT in neovascular AMD?
• What is the relative cost-effectiveness of the various forms of pharmaceutical management of neovascular AMD?
• What is the evidence regarding the timing for the initiation of therapy for the comparisons listed above?
• What is the evidence regarding re-treatment with a different regimen in persons who did not have satisfactory clinical response to a particular regimen?

Authors' results and conclusions: Ranibizumab showed statistically significant improvement in visual acuity [in terms of loss of less than 15 letters or gain of at least 15 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale] relative to V-PDT. Compared with V-PDT, ranibizumab improved vision by an increase of 4.9 to 11.3 letters on the ETDRS scale on average at 12 months post-treatment. Other vision outcomes involving vision loss also favoured ranibizumab over V-PDT. When examining lesion characteristics, ranibizumab-treated eyes showed a smaller increase in lesion size over V-PDT as well as an increase in lesion shrinkage over V-PDT. The only trial that compared anecortave acetate and V-PDT showed that both failed to improve visual acuity in patients. With the exception of the FOCUS trial, no RCTs compared the efficacy and safety of combination anti-vascular endothelial growth factor (anti-VEGF) therapies versus V-PDT. Although long-term studies are lacking, current studies suggest that ranibizumab is well tolerated concerning systemic adverse events. Local adverse events that were compared with V-PDT included post-injection increases in intraocular pressure and cataract formation, endophthalmitis, retinal detachment, retinal tears, and vitreous hemorrhages. Regarding the quality of the nine RCTs included for review, the mean Jadad score was 2.89, of a maximum of five.

Authors' recommendations: The review of clinical evidence found that, with the exception of trials comparing ranibizumab with V-PDT, there was a significant lack of trials comparing the other anti-VEGF agents in general. There is only one RCT that looked at the efficacy and safety of anecortave acetate compared with V-PDT. However, although results have shown seemingly effective visual acuity improvement with bevacizumab, this was based only on three poor quality RCTs. Whether generalizations from ranibizumab to bevacizumab can be made is not clear from the evidence identified. Six non-RCT studies suggest the combination therapies analyzed are effective. These combination therapies are typically a combination of V-PDT and anti-VEGF therapies. However, inferences regarding relative efficacy cannot be made from these study designs. Conclusions drawn by these studies need to be confirmed by results of future larger-scale randomized controlled trials.Overall, the efficacy of anti-VEGF therapies over V-PDT is well supported by RCTs. What remains unclear is whether combination therapy (and which combinations) are superior or merely equal to monotherapy. Furthermore the efficacy of one anti-VEGF agent compared with another is also unclear and this has very important practical and economic implications. The scant nature of the evidence does not allow us to draw conclusions regarding optimal timing of initiation of therapy and re-treatment.Between V-PDT, pegaptanib, and ranibizumab, only ranibizumab demonstrated a reversal of the degenerative process for neovascular CNV, on average. The primary economic evaluation found that the premium for using ranibizumab would not be considered cost-effective using a willingness-topay threshold of $50,000. A 3.5% reduction in the price of ranibizumab would be required to achieve that. Alternately, this might be achieved by reducing the frequency of treatment below that used in the clinical trials. However evidence for the impact this might have on effectiveness is lacking. Using bevacizumab as a substitute for ranibizumab could be more effective and less costly than either VPDT or pegaptanib. However, currently there is limited clinical trial evidence on the efficacy and safety of bevacizumab in the treatment of AMD.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.cadth.ca/index.php/en/hta/reports-publications/search/publication/813

Year Published: 2008

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Canadian Agency for Drugs and Technologies in Health

Contact Address: 600-865 Carling Avenue, Ottawa, ON K1S 5S8 Canada. Tel: +1 613 226 2553; Fax: +1 613 226 5392;

Contact Name: requests@cadth.ca

Contact Email: requests@cadth.ca

Copyright: Canadian Agency for Drugs and Technologies in Health (CADTH)