Cost-effectiveness of ranibizumab and bevacizumab for age-related macular degeneration: 2-year findings from the IVAN randomised trial

Abstract

Objective: To assess the incremental cost and cost-effectiveness of continuous and discontinuous regimens of bevacizumab (Avastin) and ranibizumab (Lucentis) for neovascular age-related macular degeneration (nAMD) from a UK National Health Service (NHS) perspective.

Design: A within-trial cost-utility analysis with a 2-year time horizon, based on a multicentre factorial, non-inferiority randomised controlled trial.

Setting: 23 hospital ophthalmology clinics.

Participants: 610 patients aged ≥50 years with untreated nAMD in the study eye.

Interventions: 0.5 mg ranibizumab or 1.25 mg bevacizumab given continuously (monthly) or discontinuously (as-needed) for 2 years.

Main outcome measures: Quality-adjusted life-years (QALYs).

Results: Total 2-year costs ranged from £3002/patient ($4700; 95% CI £2601 to £3403) for discontinuous bevacizumab to £18 590/patient ($29 106; 95% CI £18 258 to £18 922) for continuous ranibizumab. Ranibizumab was significantly more costly than bevacizumab for both continuous (+£14 989/patient ($23 468); 95% CI £14 522 to £15 456; p<0.001) and discontinuous treatment (+£8498 ($13 305); 95% CI £7700 to £9295; p<0.001), with negligible difference in QALYs. Continuous ranibizumab would only be cost-effective compared with continuous bevacizumab if the NHS were willing to pay £3.5 million ($5.5 million) per additional QALY gained. Patients receiving continuous bevacizumab accrued higher total costs (+£599 ($938); 95% CI £91 to £1107; p=0.021) than those receiving discontinuous bevacizumab, but also accrued non-significantly more QALYs (+0.020; 95% CI -0.032 to 0.071; p=0.452). Continuous bevacizumab therefore cost £30 220 ($47 316) per QALY gained versus discontinuous bevacizumab. However, bootstrapping demonstrated that if the NHS is willing to pay £20 000/QALY gained, there is a 37% chance that continuous bevacizumab is cost-effective versus discontinuous bevacizumab.

Conclusions: Ranibizumab is not cost-effective compared with bevacizumab, being substantially more costly and producing little or no QALY gain. Discontinuous bevacizumab is likely to be the most cost-effective of the four treatment strategies evaluated in this UK trial, although there is a 37% chance that continuous bevacizumab is cost-effective.

Trial registration number: ISRCTN92166560.

Keywords: Neovascular age-related macular degeneration (AMD); cost-effectiveness; cost-minimisation analysis; cost-utility analysis; trial-based economic evaluation; vascular endothelial growth factor (VEGF) inhibitors.

Figure 1

Schematic illustrating the assumptions made about the frequency of injection and monitoring consultations within the costing analysis. The consultations required by patients on discontinuous treatment will depend on when they met treatment failure criteria; patient 2 met the retreatment criteria at visits 0, 7 and 11. ✓ Relevant consultation cost was applied. ? The cost of fundus fluorescein angiography (FFA) was applied if clinically indicated: for discontinuous patients, this was applied whenever the patient had FFA in the trial; for continuous patients, the proportion of patients having FFA was based on estimated use in routine clinical practice. X No consultation cost was applied as the participant missed the visit.

Figure 2

Cost-effectiveness acceptability curve showing the probability that each treatment is the most cost-effective strategy evaluated in the UK Inhibition of VEGF in Age-related choroidal Neovascularisation trial at a range of ceiling ratios. For example, at a ceiling ratio of £20 000/quality-adjusted life-year (QALY) gained (shown by the vertical dashed line), there is a 63% probability that discontinuous bevacizumab is best and a 37% probability that continuous bevacizumab is best, while the probability that either ranibizumab treatment regimen is best is approximately 0% (total=100%).

Figure 3

Effect of sensitivity analyses on total net benefits for each of the four treatment arms, assuming a £20 000/quality-adjusted life-year (QALY) ceiling ratio. Treatments that are more cost-effective have higher net benefits; the treatment furthest to the right is therefore most cost-effective, while the treatment furthest to the left is the least cost-effective. Error bars represent 95% CIs. In the analysis ‘doubling SAE impact’, both the medication/medical service use cost and the impact of serious adverse events (SAEs) on QALYs were doubled. The ‘best case’ analysis simultaneously changed several assumptions in favour of ranibizumab: 50% discount off the ranibizumab list price; assuming that 15.9% of bevacizumab (as occurred in the trial) but no ranibizumab is wasted; assuming that bevacizumab costs £100 per dose; and including medical service use costs associated with expected and unexpected adverse events (AEs) and SAEs.