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A. R. Levy, S. M. Szabo, A. Davie, G. Zlateva, A. M. Pleil, A. Briggs; Estimating Net Health Benefits (NHB) of Vascular Endothelial Growth Factor (VEGF) Inhibitors for Neovascular Age-Related Macular Degeneration (NV-AMD). Invest. Ophthalmol. Vis. Sci. 2008;49(13):5572.
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To estimate the NHB of intravitreal VEGF inhibitors indicated for patients with NV-AMD with differing baseline risks for cardiovascular and hemorrhagic events.
A decision-analytic risk-benefit model with a 10-year time horizon was developed to jointly assess the intended and unintended effects of pegaptanib and ranibizumab. Input data were abstracted from the results of published randomized trials of active treatment versus usual care. Intended effects of treatment were quantified using the change in visual acuity (VA) over 1 year. It was assumed that the treatment benefit observed in the first year (intention-to-treat) was retained after year 1. Unintended effects included Anti-Platelet Trialists’ Collaborative events (APTC: non-fatal myocardial infarction, stroke, or death from unknown or vascular cause) or severe non-ocular hemorrhage (NOH). Utilities for intended and unintended effects were combined using a multiplicative model. To estimate NHB in populations at differing underlying risks of adverse drug reactions, sensitivity and threshold analyses were undertaken for different risks of cardiovascular events and NOH.
Ranibizumab treatment in the ANCHOR/MARINA trials was associated with relative risks (RR; compared to usual care) of 1.5 (loss of <3 lines of VA), 2.2 (APTC events) and 5.5 (NOH). Pegaptanib treatment in the VISION Study was associated with RRs (compared to usual care) of 1.2 (loss of <3 lines of VA), 1.5 (APTC events) and 0.8 (NOH). In a cohort of NV-AMD patients aged 75 years, the estimated NHB for ranibizumab- and pegaptanib-treated patients were both 4.3 quality-adjusted life years (QALYs). As the increased risk of NOH increased to 5%, the decline in benefit in ranibizumab-treated patients was greater than for pegaptanib-treated patients (to 3.6 vs. 4.1 QALYs, respectively). All findings were based on point estimates only, and do not take into account estimate uncertainty.
As it quantitatively incorporates both intended and unintended effects, estimating NHB is more informative than combining estimates of efficacy with an unstructured incorporation of adverse event rates. While both pegaptanib and ranibizumab show positive NHB for NV-AMD, this model demonstrates that an individual’s underlying risk of non-ocular hemorrhage may be an important consideration when selecting treatment.
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