Ranibizumab treatment history as predictor of the switch-response to aflibercept: evidence for drug tolerance

PURPOSE: To investigate whether tolerance to the anti-VEGF drug, ranibizumab, develops after drug exposure and to determine whether the history of treatment with ranibizumab prior to refractoriness can predict the post-switching responses to aflibercept. METHODS: We retrospectively investigated neovascular age-related macular degeneration patients refractory to ranibizumab (intra- or subretinal fluid despite monthly injections for ≥6 months) who were switched to aflibercept and were followed up for at least 12 months on each of ranibizumab and aflibercept. Baseline characteristics and ranibizumab and aflibercept treatment history (number of injections during the first year and central retinal thickness [CRT]) were analyzed by univariate and multivariate correlation analyses. RESULTS: Ninety-eight eyes (88 patients, 70% females, mean age 77.5 years), including a high proportion of eyes with pigment epithelium detachment (63%), were treated with a mean of 26.2 injections during 36.8 months before switching to aflibercept. The number of ranibizumab injections required in the first year (p=0.0002) and the presence of pigment epithelium detachment (p=0.025) predicted the number of post-switching aflibercept injections required. The post-switching CRT change was predicted by the CRT increase from Month 3 to the switch time point (p<0.0001). Moreover, the CRT change correlated with the visual acuity benefit post-switching (p=0.038 and p=0.004, at 3 and 12 months post-switching, respectively). CONCLUSION: Ranibizumab treatment history before switching to aflibercept correlates with the post-switching response in terms of the number of drug injections needed and CRT. Thus, drug tolerance does indeed exist and this might help to identify switching candidates.