Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR : A Randomized Controlled Trial

Masahito Ohji, Kanji Takahashi, Annabelle A Okada, Masato Kobayashi, Yoshimi Matsuda, Yasuhiro Terano, ALTAIR Investigators, Masahito Ohji, Tsukasa Hanemoto, Tatsushi Kaga, Takeya Kouno, Hirokuni Kitamei, Shinpei Sato, Kanji Takahashi, Ryoji Yanai, Eiichi Uchio, Kazunori Miyata, Yoshihiro Wakabayashi, Takatoshi Maeno, Tsutomu Yasukawa, Masayuki Horiguchi, Tetsuya Nishimura, Akiteru Kawahara, Yasuo Kurimoto, Kenichi Murai, Namie Kobayashi, Wataru Kimura, Eriko Matsushita, Tomohiro Iida, Kanako Yasuda, Yuji Kato, Masahiro Miura, Annabelle Ayame Okada, Ryusaburo Mori, Atsushi Sugiyama, Yasuo Ito, Daisaku Kimura, Kei Nakai, Chota Matsumoto, Shinobu Takeuchi, Kishiko Okoshi, Yoshihisa Nuno, Yohei Nomoto, Toshio Mori, Muneyasu Takeda, Noriko Yoshida, Mio Hosokawa, Kohei Sonoda, Masahito Ohji, Kanji Takahashi, Annabelle A Okada, Masato Kobayashi, Yoshimi Matsuda, Yasuhiro Terano, ALTAIR Investigators, Masahito Ohji, Tsukasa Hanemoto, Tatsushi Kaga, Takeya Kouno, Hirokuni Kitamei, Shinpei Sato, Kanji Takahashi, Ryoji Yanai, Eiichi Uchio, Kazunori Miyata, Yoshihiro Wakabayashi, Takatoshi Maeno, Tsutomu Yasukawa, Masayuki Horiguchi, Tetsuya Nishimura, Akiteru Kawahara, Yasuo Kurimoto, Kenichi Murai, Namie Kobayashi, Wataru Kimura, Eriko Matsushita, Tomohiro Iida, Kanako Yasuda, Yuji Kato, Masahiro Miura, Annabelle Ayame Okada, Ryusaburo Mori, Atsushi Sugiyama, Yasuo Ito, Daisaku Kimura, Kei Nakai, Chota Matsumoto, Shinobu Takeuchi, Kishiko Okoshi, Yoshihisa Nuno, Yohei Nomoto, Toshio Mori, Muneyasu Takeda, Noriko Yoshida, Mio Hosokawa, Kohei Sonoda

Abstract

Purpose: To evaluate efficacy and safety of intravitreal injections of aflibercept (IVT-AFL) treat-and-extend (T&E) dosing regimens in treatment-naïve patients with exudative age-related macular degeneration (AMD).

Methods: Adults aged at least 50 years old with exudative AMD and best-corrected visual acuity (BCVA) of 73-25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters were included. Patients received three monthly doses of IVT-AFL 2 mg. At week 16, patients were randomized 1:1 to IVT-AFL T&E with either 2- or 4-week adjustments. The primary endpoint was mean change in BCVA from baseline to week 52. Outcomes were assessed at weeks 52 and 96.

Results: Baseline characteristics were comparable between the groups (n = 123 each). Over 52 weeks, mean number of injections was 7.2 and 6.9 and mean last injection interval was 10.7 and 11.8 weeks, for the 2- and 4-week groups, respectively. From baseline, mean change in BCVA was + 9.0 and + 8.4 letters (week 52) and + 7.6 and + 6.1 letters (week 96); mean change in central retinal thickness was - 134.4 µm and - 126.1 µm (week 52) and - 130.5 µm and - 125.3 µm (week 96). Last injection interval before week 52 was at least 12 weeks in 42.3% and 49.6% of patients and 56.9% and 60.2% before week 96. Over 96 weeks, mean number of injections was 10.4 (both groups). The safety profile of IVT-AFL was consistent with previous reports.

Conclusions: IVT-AFL administered using two different T&E regimens for treatment-naïve exudative AMD improved functional and anatomic outcomes at week 52 and outcomes were maintained to week 96. Outcomes were similar between the 2- and 4-week groups.

Trial registration: ClinicalTrials.gov identifier, NCT02305238.

Keywords: Aflibercept; Anti-vascular endothelial growth factor agents; Exudative age-related macular degeneration; Ophthalmology; Treat-and-extend.

Figures

Fig. 1
Fig. 1
Patient disposition. *A total of eight patients were not randomized because of withdrawal by patient (n = 3), protocol violation (n = 2), physician decision (n = 1), logistic difficulties (n = 1), or no IVT-AFL injection (n = 1). 2W/4W 2-/4-week adjustment, AE adverse event, IVT-AFL intravitreal aflibercept
Fig. 2
Fig. 2
The last injection interval up to a Week 52 and b Week 96 (FAS)
Fig. 3
Fig. 3
Mean change in BCVA (ETDRS letter score) in IVT-AFL-2W and IVT-AFL-4W groups from baseline to week 96 (FAS). Last observation carried forward analysis. 2W/4W 2-/4-week adjustment, BCVA best-corrected visual acuity, CI confidence interval, ETDRS Early Treatment Diabetic Retinopathy Study, FAS full analysis set, IVT-AFL intravitreal aflibercept, LSM least squares mean
Fig. 4
Fig. 4
Mean change in central retinal thickness (µm) from baseline to week 96 (FAS). Last observation carried forward analysis. 2W/4W 2-/4-week adjustment, CI confidence interval, CRT central retinal thickness, IVT-AFL intravitreal aflibercept, LSM least squares mean

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