Aflibercept treatment for patients with exudative age-related macular degeneration who were incomplete responders to multiple ranibizumab injections (TURF trial)

Abstract

AimTo determine the efficacy of 2.0 mg aflibercept in the management of patients with recalcitrant exudative age-related macular degeneration (AMD).MethodsIn this prospective, open-label, single-arm clinical trial, patients were seen monthly and given mandatory 2.0 mg aflibercept at baseline, months 1, 2 and 4. Pro re nata (PRN) retreatment at months 3 and 5 was performed upon evidence of disease on spectral domain-optical coherence tomography (SD-OCT). End point at month 6: mean change in Early Treatment Diabetic Retinopathy Study best corrected visual acuity (ETDRS BCVA) and central subfield thickness (CST), mean number of aflibercept injections, percentage of PRN injections required, patients with no fluid on SD-OCT and patients losing >15 letters.ResultsAt baseline, 46 patients with a mean of 42 prior antivascular endothelial growth factor-A (anti-VEGF) intravitreal treatments had a mean of 74.2 letters (Snellen equivalent 20/32) and mean CST of 347 µm. ETDRS letters remained stable throughout the trial; at month 6, mean BCVA change was +0.2 letters (range −10 to +13, p=0.71). Anatomically, mean CST improved significantly from baseline at each study visit including −23.6 µm at month 1 and −27.3 µm at month 6 (p=0.018). Seventy-one of 90 (79%) possible PRN injections were required and a mean of 5.6 aflibercept injections out of the maximum six were administered. Ten of 45 (22%) patients had no retinal fluid on SD-OCT at month 6. No patient lost >15 letters.ConclusionsAflibercept 2.0 mg treatment maintained mean visual acuity improvements previously achieved with high-dose 2.0-mg ranibizumab injections in recalcitrant wet AMD patients. Aflibercept 2.0 mg treatment led to significant anatomic improvement and was required monthly in most patients.Clinical Trials RegistrationFDA IND#12462. NCT 01543568.Trial DetailsIND 12462, NCT 01543568 http://clinicaltrials.gov/show/NCT01543568.

Aflibercept in persistent neovascular AMD: comparison of different treatment strategies in switching therapy

“…22 At present the dilemma of when and how to change medications after their efficacy has diminished has not been addressed. [23][24][25][26] Aflibercept is the last anti-VEGF drug that has been approved for the treatment of naive CNV associated with AMD, based on the efficacy demonstrated in the VIEW trials. 8,9 In recent studies, it has been considered as a treatment option for patients presenting with persistent/ resistant nAMD or with high recurrence rate.…”

“…8,9 In recent studies, it has been considered as a treatment option for patients presenting with persistent/ resistant nAMD or with high recurrence rate. [9][10][11][12][13][14][15][16][17][18][19][20][23][24][25][26] Moreover, aflibercept has also been used as alternative treatment in patients treated successfully with ranibizumab or bevacizumab. 19 Additional activity of aflibercept may rely on higher binding affinity to VEGF-A and the ability to target VEGF-B and PlGF.…”

Transitioning to intravitreal aflibercept following a previous treat-and-extend dosing regimen in neovascular age-related macular degeneration: 24-month results

“…[4][5][6] We examined nAMD patients transitioned to aflibercept who were previously treated with a 'treat-and-extend' protocol with either ranibizumab or bevacizumab (Avastin, Genentech, South San Francisco, CA, USA), and could not be extended exudation-free beyond an 8-week interval.…”

Non-Responders to Intravitreal Ranibizumab in Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

“…Previous studies investigating the effects of the pharmacological conversion between ranibizumab, aflibercept and bevacizumab on the functional and morphological effects on CNV associated with AMD turned out not always to be reproducible [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]. …”

“…However, in common clinical practice the benefits of anti-VEGF therapy with IVRI are minimal in the case of some patients, and treatment can actually be shifted to different anti-VEGF molecules [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18]. The timely identification of patients non-responsive to ranibizumab is therefore essential in order to avoid overtreatment with an ineffective drug and the risk of progressive and irreversible retinal damage.…”