Shifting the AMD Burden-Benefit Balance

Physicians now have the option of treating wet AMD patients with aflibercept administrations spaced at intervals beyond every 8 weeks in the first year (1). True, a loading period (three doses spaced four weeks apart) is still required, but the potential reduction in treatment burden nevertheless is significant. How does the evidence stack up for the risk-reward balance of this new regime? The most recent addition to the weight of data supporting treat and extend (T&E) aflibercept comes from the ALTAIR trial (see sidebar, “ALTAIR: Time for T&E”), an interventional study evaluating efficacy and safety of variable interval aflibercept administration in Japanese subjects with wet AMD.

Phase III trials of aflibercept showed that an eight-weekly dosing regime of aflibercept was associated with 96-week efficacy and safety outcomes similar to those of monthly ranibizumab (2, 3).  In brief, after an initial three doses spaced by intervals of a month, the ALTAIR treatment interval was extended to two months; subsequent intervals varied in the range 8–16 weeks, the interval being adjusted in two- or four-weekly increments on the basis of anatomic and visual measurements (see Table 1).

The trial results (see Table 2) indicate that both treatment arms enjoyed similar benefits with regard to visual and anatomical outcomes (4, 5, 6). Furthermore, improvements in visual acuity and retinal thickness were sustained through the 96-week follow-up, although there was a small numerical decline in BCVA letter score from week 52 in the second year (-1.4 letters in the two-week adjustment group and -2.3 letters in the four-week adjustment group). The proportions of patients who gained 15 letters or more from baseline to week 96 ranged from 28.5 percent to 31.7 percent, similar to the proportions that gained ≥15 letters from baseline at week 52 (range, 30.9 percent to 32.5 percent). Robust vision gains were achieved, with up to 60 percent of patients maintained at treatment intervals of ≥12 weeks and more than 40 percent of patients maintained at the maximum interval of 16 weeks by week 96.

What should ophthalmologists take home from this? The rapid and sustained improvements in visual acuity and central retinal thickness observed during the first year of treat-and-extend aflibercept were largely maintained during the second year – with both two- and four-week extensions. With regard to treatment burden, it is notable that injection frequency in the second year was substantially lower than that in the first 12 months of treatment. Overall, patients received an average of 10.4 injections through two years, with fewer than four injections given in the second year. Use of treat-and-extend dosing earlier in the first year of aflibercept treatment for wet AMD achieves excellent visual outcomes and, for many patients, may reduce the burden of treatment in terms of injection frequency and clinic visits.