Visual benefit versus visual gain: What is the effect of baseline covariants in the treatment arm relative to the control arm? A pooled analysis of ANCHOR and MARINA

Background: This study aimed to elucidate visual benefits of ranibizumab in patients with neovascular age-related macular degeneration (nAMD) compared with control arms and identify factors affecting response. Methods: This is a post-hoc pooled analysis of two phase III studies, ANCHOR and MARINA, of ranibizumab for the treatment of nAMD. ANCHOR included 83 international sites. MARINA included 96 sites in the USA. Analysis included patients (control, n=323; ranibizumab, n=332) with nAMD and a baseline best-corrected visual acuity (BCVA) of ≥35-<85 letters. Results: Patients receiving ranibizumab achieved an adjusted mean BCVA superiority of 18.9 and 21.2 letters over 12 and 24 months, respectively, compared with control. Ranibizumab treatment, higher baseline BCVA, lower age and smaller lesion size were positively associated with the ability to achieve BCVA >69 letters. Patients with the highest baseline BCVA had lowest BCVA gains. Ranibizumab treatment, lower baseline BCVA, lower age and smaller lesion size were identified as significant predictors of BCVA gain from baseline at month 24 (all p<0.0001). However, the difference in mean BCVA gains at month 24 between treatment and control groups was similar for all baseline BCVA subgroups (≥35-<55 letters, 21.9 letters; ≥55-<70 letters, 25.2 letters; ≥70-<85 letters, 19.3 letters). Conclusions: Higher baseline BCVA is associated with lower BCVA gains but a greater likelihood of achieving good final BCVA >69 letters due to smaller gains needed to achieve response. Visual benefits, including maintenance of visual acuity (VA), final VA achieved and relative gain compared with natural disease progression, should be considered when assessing treatment response in nAMD.