Background/Aims Prospective data on switching anti-vascular endothelial growth factors in patients with neovascular age-related macular degeneration (nAMD) who have previously shown no/partial response are limited. This prospective study assessed the effect of switching from aflibercept to ranibizumab on anatomical and functional outcomes in patients with persistent/recurrent disease activity.
Methods SAFARI (NCT02161575) was a 6-month, prospective, single-arm study conducted in the UK and Germany. Patients, meeting strict eligibility criteria for one of two subgroups (primary treatment failure or suboptimal treatment response), received 3 monthly intravitreal ranibizumab injections (0.5 mg). Thereafter, ranibizumab was administered pro re nata at monthly visits. The primary endpoint was change from baseline (CfB) to day 90 in central subfield retinal thickness (CSRT). Best-corrected visual acuity (BCVA) and retinal morphology parameters were assessed.
Results One hundred patients were enrolled (primary treatment failure, 1; suboptimal treatment response, 99). In the overall population, there was a significant CfB in median CSRT of −30.75 µm (95% CI −59.50,–20.50; p<0.0001) to day 90. Improvements were also observed in other quantitative and qualitative optical coherence tomography parameters. In Early Treatment Diabetic Retinopathy Study letters assessed by category, 55% and 59% of patients gained 0–≥15 letters versus baseline at day 90 and day 180, respectively. However, mean improvements in BCVA (CfB) to each time point were small (≤2 letters). No new safety signals were identified.
Conclusion Switching from aflibercept to ranibizumab led to a significant improvement in CSRT, with ~60% experiencing stabilised/improved BCVA. Therefore, patients with nAMD who have shown a suboptimal response to aflibercept may benefit from switching to ranibizumab.
- clinical trial
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Contributors Substantial contributions to study conception and design as members of the study steering committee: RPG, IP, NE, FG, FGH, SS-V; substantial contributions to analysis and interpretation of the data: RPG, IP, NE, FG, FGH, SS-V, KB, BJLB, SD, HE, SG, DFG, RH, AL, NP, PP, CS, ST, DV, GW, MAW, AW, RZ, FI, FA; drafting the article or revising it critically for important intellectual content: RPG, IP, NE, FG, FGH, SS-V, KB, BJLB, SD, HE, SG, DFG, RH, AL, NP, PP, CS, ST, DV, GW, MAW, AW, RZ, FI, FA; final approval of the version of the article to be published: RPG, IP, NE, FG, FGH, SS-V, KB, BJLB, SD, HE, SG, DFG, RH, AL, NP, PP, CS, ST, DV, GW, MAW, AW, RHZ, FI, FA.
Funding Funding for this study was provided by Novartis Pharmaceuticals UK Limited.
Competing interests RPG: consultancy, educational grants and institutional research grants for Novartis and Bayer; IP: speakers’ fees, consulting fees and travel support from Novartis and Bayer; NE: grant/research support from Novartis and Bayer; speakers’ honoraria from: Novartis, Bayer, Allergan and Heidelberg Engineering; Advisory board member for: Novartis, Bayer, Allergan, Bausch and Lomb, Alimera Sciences and Roche; consultancy fees from Bayer; FG: consultant for Novartis and Bayer; advisory board member for Novartis and Bayer; speakers’ fees and research support from Bayer; FGH: financial support from: Acucela, Allergan, Bayer, Bioeq, CenterVue, Hoffmann-La Roche/Genentech, Heidelberg Engineering, Novartis, and Zeiss; Consultant for Acucela, Alcon, Bayer, Boehringer-Ingelheim, Hoffmann-La Roche/Genentech, Grayburg Vision, Heidelberg Engineering, Lin Bioscience, Novartis, Stealth Biotherapeutics, and Zeiss; SS-V: financial support from: Acucela, Alcon/Novartis, Allergan, Bayer, Bioeq/Formycon, Carl Zeiss MedicTec, CenterVue, Hoffman-La Roche/Genentech, Heidelberg Engineering, Katairo and Optos; consultant for: Alcon/Novartis, Bioeq/Formycon and Galimedix Therapeutics; recipient of gifts, honoraria, travel reimbursement, patent royalties and/or any other financial compensation from: Alcon/Novartis, Allergan, Bayer, Carl Zeiss MedicTec and Hoffmann-La Roche/Genentech; KB: travel grants and speakers’ fees from: Novartis, Bayer, Alimera, Topcon and Heidelberg Engineering; research grants from Novartis and Bayer; BJLB: advisory board and international conference attendance sponsored by Novartis and Bayer; SD: principal investigator on trials sponsored by: Novartis, Bayer, Roche, and Ely Lilly; speakers’ honoraria from: Novartis, Bayer, Roche and/or Eli Lilly; conference and travel support from Novartis and Eli Lilly; consultant for Hakko Kyowa and Circadian Therapeutics; grant/research support from Novartis; HE: travel grants and speakers’ fees from Novartis; advisory board member for Novartis; SG: speakers’ fees from Hoffman-La Roche and Novartis; advisory board member for, and travel grants from Bayer; DFG: travel grants from Novartis and Bayer; speakers’ fees from Novartis; RH: research support and travel grants from, and advisory board member for Novartis, Bayer, Allergan, and Ellex; AL: travel support to attend educational meetings from Bayer; NP: grant support and travel grants from Novartis and Bayer; PP: none declared; CS: speakers’ fees, consulting fees, conference and travel support from Novartis and Bayer; ST: travel grant and conference registration from Bayer; DV: travel grants from Novartis, Bayer and Allergan; Advisory board member for: Allergan, Novartis, Bayer, Alcon and Polyphotonix; investigator on clinical trials sponsored or funded by: Novartis, Bayer, Hoffmann-La Roche and Allergan; Speakers’ fees from Bayer and Novartis; GW: advisory board member for, and support to attend conferences from Novartis and Bayer; MAW: travel grants from Novartis, Bayer and Allergan; recipient of grant to develop medical education material on ophthalmology; AW: consulting fees from Novartis and Bayer; speakers’ fees from Novartis; advisory board member for Novartis; travel grants from Bayer; research support from Novartis and Bayer; RHZ: none declared; FI: employee of Novartis Pharmaceuticals UK Ltd; FA: employee of Novartis Pharmaceuticals UK Ltd.
Patient consent for publication Not required
Ethics approval This study was conducted in accordance with the current version of the applicable regulatory and International Conference on Harmonisation-Good Clinical Practice requirements, the ethical principles that have their origin in the principles of the Declaration of Helsinki, and the local laws of the countries involved.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Analysed data has been publically disclosed at clintrials.gov study number NCT02161575 and on the Novartis clinical trials portal at: https://www.novctrd.com/CtrdWeb/home.nov. For more details on the Novartis Position on Data Sharing and the eligibility criteria/process for patient-level data and clinical documents please go to www.clinicalstudydatarequest.com.
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