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J. C. Javitt, G. Zlateva, S. Wolowacz, A. Pleil; Balancing Visual Acuity Benefits With Systemic Adverse Effects in Anti-VEGF Therapy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2106. doi: https://doi.org/.
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VEGF inhibitors offer unprecedented benefits to patients with age-related macular degeneration (AMD). However, concerns that pan-VEGF inhibitors may carry an increased risk of systemic complications have implications in assessing their risk/benefit ratio. We studied the potential quality of life tradeoff between selective and non-selective VEGF inhibition, incorporating the benefits of vision preservation and potential adverse consequences of stroke, as one such example.
Data from pivotal studies of two currently marketed therapies (ranibizumab and pegaptanib) were used to estimate the efficacy of non-selective vs. selective VEGF inhibition. Differences in quality-adjusted life years (QALYs) between treatments were estimated over 10 years. The disutility (QALYs lost) of stroke was estimated using published data. The population threshold risk ratio (RR) for stroke at which the QALYs gained through improved vision are offset by QALYs lost from stroke was estimated.
Pan-VEGF inhibition saves an esitmated 0.4 QALY’s per patient treated, compared with selective therapy. The incremental disutility for patients experiencing a stroke was estimated as 5.6 QALYs per occurrence. Analysis was performed to determine the theoretical increase in stroke risk at which the increased QALY benefit from improved vision would be offset. The literature suggests a baseline stroke incidence of 35/1000 over a two year treatment period. The threshold number of additional strokes in the population of treated patients at which the overall disutility of stroke in the population offsets the benefit of improved visual acuity was estimated as 1 in 13 patients treated (74/1000). Thus, a 3-fold increase in the incidence of stroke, associated with pan-VEGF inhibition (RR = 3.1) would negate the potential quality of life benefit associated with improved vision. This point estimate is sensitive to alternative assumptions regarding efficacy and safety.
The analysis suggests that increased risk of systemic complications has the potential to offset gains in quality of life associated with improved vision. Further multivariate modeling should consider what combined treatment strategies maximize the utility of treatment and minimize the disutility of adverse events and also the medical cost of therapy.
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