Author: Marta S. Figueroa (Spain)
Co-authors: David Eichenbaum, David M. Brown, Arshad M. Khanani, Ian L McAllister, Augustinus Laude, Guru Prasad
Retinal fluid is an important biomarker of disease activity in neovascular age-related macular degeneration (nAMD). Resolving retinal fluid and maintaining a dry retina is a common clinical goal of anti-vascular endothelial growth factor (VEGF) therapy. Here we assess the impact of absolute retinal fluid-free duration and its association with visual and anatomic outcomes of nAMD patients in HAWK and HARRIER.
HAWK and HARRIER were two 96-week, Phase 3, prospective, randomized, double-masked, multicenter studies comparing efficacy and safety of brolucizumab 3 mg (HAWK only) and 6 mg with aflibercept 2 mg in eyes with nAMD.
In HAWK, patients were randomized 1:1:1 to brolucizumab 3 mg (n=358), brolucizumab 6 mg (n=360) or aflibercept 2 mg (n=360). In HARRIER, patients were randomized 1:1 to brolucizumab 6 mg (n=370) or aflibercept 2 mg (n=369). After three loading doses, brolucizumab patients received 12-weekly (q12w) dosing with an option to adjust to 8-weekly dosing (q8w) if disease activity (as identified by a masked investigator) was present; aflibercept was dosed q8w as per the label. 96-week data from the brolucizumab 6 mg and aflibercept 2 mg groups of the Phase III HAWK and HARRIER studies were pooled for the current treatment agnostic analysis. Patients were categorized based on the maximum consecutive number of months they remained fluid free after the anti-VEGF loading phase (from Week 12 to 96), with a fluid-free month (FFM) defined as the absence of sub-retinal fluid and intraretinal fluid. The categories were as follows: category 1: 0 FFMs (‘never dry’); category 2: 1‒3 FFMs; category 3: 4‒9 FFMs; category 4: 10‒21 FFMs (‘dry for a long period of time’); category 5: 22 FFMs (‘always dry’), with category 1 used as a reference for statistical comparison purposes.
At Week 96, patients in categories 4 and 5 had a least square mean (95% CI) best corrected visual acuity (BCVA) gain of 7.8 (4.5, 11.2) letters and 8.0 (4.3, 11.7) letters, respectively, compared with patients in category 1 (‘never dry’ [who gained 0.2 (-2.88, 3.30) letters from baseline]). At Week 96, the least square mean (95% CI) central subfield thickness (CSFT) of patients in categories 4 and 5 was -121.8 µm (-143.7, -99.8) and -127.8 µm (-152.2, -103.4) lower, respectively, compared with patients in category 1 (‘never dry’ [whose CSFT decreased by -86.2 µm (-106.0, -66.0] from baseline]).
In comparison with patients who were ‘never dry’ after anti-VEGF loading, nAMD patients in HAWK and HARRIER who were ‘always dry’ or ‘dry for a long period of time’ had better visual and anatomic outcomes at study end, and greater reduction of CSFT throughout. These findings suggest that longer absolute fluid-free periods have a positive impact on visual and anatomic outcomes in nAMD patients.
Novartis, Alcon, Bayer, Allergan, Roche, Zeiss