Author: Usha Chakravarthy (United Kingdom)
Co-authors: Steven Blotner, Shamika Gune, Merce Morral, Carl Regillo
Purpose
To evaluate changes in retinal thickness in participants enrolled in the Archway phase 3 trial, which compared continuous intravitreal delivery of ranibizumab using the Port Delivery System (PDS; an investigational device) against intravitreal injections of ranibizumab given monthly for neovascular age-related macular degeneration (nAMD). We analyzed the frequency of clinically significant alterations in retinal thickness (fluctuations) and association with visual acuity by study arm.
Setting/Venue
Archway (NCT03677934) was a phase 3, randomized, active treatment–controlled trial for the treatment of nAMD, conducted at 77 study locations in the United States.
Methods
Archway compared the PDS with ranibizumab 100 mg/mL with fixed 24-week refill-exchanges (PDS Q24W) versus intravitreal ranibizumab 0.5 mg every 4 weeks (monthly ranibizumab) in nAMD. At enrollment, before randomization, participants had received a mean of 5 anti–vascular endothelial growth factor (VEGF) injections. This post hoc analysis was confined to participants with ≥ 7 study visits with evaluable optical coherence tomography (OCT) images over 40 weeks and best-corrected visual acuity (BCVA) measurements at baseline and week 40. Central subfield thickness (CST) was measured from the internal limiting membrane to Bruch’s membrane. A fluctuation in retinal thickness was defined as a change in CST ≥ 50 µm in either direction. A fluctuation score was calculated using the cumulative changes in µm of CST measurements over 40 weeks; changes less than 50 µm were considered clinically insignificant and not included. Associations between CST fluctuations and vision outcomes at week 40 were analyzed.
Results
Analyses included 243 PDS Q24W and 163 monthly ranibizumab patients. Through week 40, 78.2% and 79.1% of patients in the PDS Q24W and monthly ranibizumab arms, respectively, did not experience any CST fluctuations ≥ 50 µm. In patients who experienced CST fluctuations ≥ 50 µm, the mean (95% CI) number of fluctuations through week 40 was 1.8 (1.5, 2.1) in the PDS Q24W arm and 2.3 (1.7, 2.9) in the monthly ranibizumab arm; the cumulative mean CST change through week 40 was 181.2 µm and 232.7 µm in the PDS Q24W and monthly ranibizumab arms, respectively. Mean (95% CI) BCVA change from baseline at week 40 in PDS Q24W versus monthly ranibizumab patients, respectively, was –1.6 (–3.6, 0.3) versus –1.0 (–3.4, 1.4) letters in patients who experienced CST fluctuations ≥ 50 µm through week 40 and +1.1 (0.0, 2.1) versus +1.0 (–0.2, 2.3) letters in patients who did not experience any CST fluctuations ≥ 50 µm through week 40.
Conlusions
In this study of retinal thickness fluctuations during the maintenance phase of anti-VEGF treatment, numerically fewer clinically significant fluctuation events were observed in the PDS Q24W arm compared with the monthly ranibizumab arm. This was accompanied by numerically reduced CST change in the PDS Q24W arm. However, these differences in CST did not result in clinically significant differences in visual acuity in the 2 arms. Further characterization of the approximately one-fifth of participants who experienced clinically significant fluctuations may yield valuable OCT biomarkers of responsiveness to anti-VEGF therapy.
Financial Disclosure
Usha Chakravarthy is a visiting Professor at F. Hoffmann-La Roche; consultant of and received speaker fees from Apellis, Alimera, Bohringer Ingelheim, Iveric Bio, Novartis, and Roche; and member of the data monitoring committee for Bayer and Gyroscope. Steven Blotner and Shamika Gune are employees of Genentech, Inc. Merce Morral is an employee of F. Hoffmann-La Roche. Carl Regillo is a consultant/advisor for Adverum Biotechnologies, Allergan, Chengdu Kanghong Pharmaceutical Group, Clearside Biomedical, EyePoint Pharmaceuticals, Genentech, Inc., Iveric Bio, Graybug Vision, Kodiak Sciences, Lineage Cell Therapeutics, Merck, NGM Biopharmaceuticals, Notal Vision, Novartis, RegenxBio, Takeda, and Zeiss
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