A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration

Huixun Jia; Bing Lu; Yuanzhi Yuan; Fei Yuan; Lei Li; Yanping Song; Ao Rong; Minwen Zhou; Fenghua Wang; Xiaodong Sun

doi:10.3389/fmed.2022.852519

A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration

Front Med (Lausanne). 2022 Jun 20:9:852519. doi: 10.3389/fmed.2022.852519. eCollection 2022.

Authors

Huixun Jia^{1

2

3

4}, Bing Lu^{1

2

3}, Yuanzhi Yuan⁵, Fei Yuan⁵, Lei Li⁶, Yanping Song⁷, Ao Rong⁸, Minwen Zhou^{1

2

3}, Fenghua Wang^{1

2

3

4}, Xiaodong Sun^{1

2

3

4}

Affiliations

¹ National Clinical Research Center for Ophthalmic Diseases, Shanghai, China.
² Department of Ophthalmology, School of Medicine, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, Shanghai, China.
³ Shanghai Key Laboratory of Fundus Diseases, Shanghai, China.
⁴ Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.
⁵ Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, China.
⁶ Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China.
⁷ Department of Ophthalmology, Central Theater Command General Hospital, Wuhan, China.
⁸ Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

Purpose: To compare the efficacy and safety of conbercept using a treat-and-extend (T&E) regimen vs. a pro re nata (PRN) regimen in Chinese patients with neovascular age-related macular degeneration (nAMD).

Methods: This was a randomized, multicenter, non-inferiority study. After an initial loading phase of three consecutive monthly intravitreal injections of 0.5 mg Conbercept, the patients were treated to PRN or T&E regimen. The prespecified retreatment criteria was defined as a more than 5-letter decrease in BCVA from the previous visit or any evidence of new retinal hemorrhages, or the presence of any IRF and any SRF of more than 200 μm in height at the sub-foveal center. The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months, with a prespecified non-inferiority limit of -5 letters.

Results: From July 2016 through August 2018, 141 participants were allocated and treated (T&E, n = 69; PRN, n = 72). About one fifth of the overall participants were dropped out during the 12-month follow-up (28/141, 19.9%), and about one thirds of the overall participants were lost during the 24-month follow-up (51/141, 36%). At 2 years, mean BCVA letter improvement was + 4.0 in the T&E group vs. + 5.1 in the PRN group, and T&E regimen was not non-inferior to PRN regimen [difference, -1.169 letters; 95% confidence interval (CI): -6.864 ∼ 4.526]. Subgroup analyses also demonstrate the similar results in PCV patients, naive patients and no-naive patients. The mean decrease in central subfield thickness were 180 ± 165 μm in the T&E group and 247 ± 230 μm in the PRN group, respectively. The patients in the PRN group had required significantly fewer injections than those in the T&E group (12.4 vs. 14.6 injections, P = 0.041). The types and rates of adverse events were comparable in the two treatment groups.

Conclusion: These findings suggest that the T&E regimen was not non-inferior to the PRN regimen in patients with nAMD in terms of BCVA outcomes through 24 months.

Clinical trial registration: ClinicalTrials.gov, identifier NCT02802657.

Keywords: anti-VEGF; neovascular age-related macular degeneration; non-inferiority study; pro re nata; treat-and-extend.

Associated data

ClinicalTrials.gov/NCT02802657