scholarly journals Safety and efficacy of Razumab™ (world’s first biosimilar ranibizumab) in wet age-related macular degeneration: a post-marketing, prospective ASSET study

Author(s):  
Shashikant Sharma ◽  
Vishali Gupta ◽  
Aniruddha Maiti ◽  
Sribhargava Natesh ◽  
Sandeep Saxena ◽  
...  

Abstract Background Razumab™ (world’s first biosimilar ranibizumab) is approved for several macular disorders including wet age-related macular degeneration (AMD). We evaluated the safety and efficacy of biosimilar ranibizumab in wet AMD. Methods This prospective, multicentre, rAnibizumab bioSimilar Safety Efficacy postmarkeTing (ASSET) study enrolled patients aged ≥ 50 years with wet AMD having best-corrected visual acuity (BCVA) between 20/40 and 20/320. The patients received intravitreal biosimilar ranibizumab 0.5 mg every 4 weeks for 24 weeks. Safety endpoints included the incidence of adverse events (AEs), serious AEs (SAEs), and immunoreactivity after 6 months. The efficacy endpoints were the proportion of patients who lose fewer than 15 letters, increase in BCVA, change in central retinal thickness (CRT), and change in Visual Function Questionnaire-25 (VFQ-25) score, from baseline to 24 weeks. Results Of the 126 enrolled patients, majority (95.24%) of the patients received all 6 doses of biosimilar ranibizumab (total 3 mg). Nineteen AEs were reported (n = 16; 12.7%); majority (78.9%) were mild. There were no serious AEs reported, except one AE of death which was unrelated to the study drug. None of the patients discontinued the study due to an AE. The most common ocular AE was increase in intraocular pressure (4 events) and non-ocular AE was pyrexia (5 events). A total of 7.9% (10/126) patients prior to dosing and 7.1% (9/126) patients post-treatment were positive for anti-ranibizumab antibodies. No AEs suggestive of immunogenicity were noted. At 24-weeks, 97.60% patients in the intent-to-treat (ITT) population (N = 125) and 97.41% patients in the per-protocol (PP) population (N = 116) lost < 15 letters from baseline visual acuity. In the ITT and PP populations, 31.20% and 32.76% patients, respectively, showed improved visual acuity by ≥ 15 letters. Significant improvements in BCVA (mean difference: 8.8, 9.2, p < 0.001 for ITT, PP) and VFQ-25 (8.5, 9.2, p < 0.001 for ITT, PP) were seen; CRT reduced significantly (125 µm, 119.3 µm, p < 0.001 for ITT, PP). Conclusion Razumab™ (world’s first biosimilar ranibizumab) was well-tolerated without new safety concerns and significantly improved visual acuity in wet AMD patients. Trial registration CTRI/2016/03/006739. Registered 18 March 2016—Prospectively registered, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=13141&EncHid=&userName=2016/03/006739

2019 ◽  
Vol 4 (1) ◽  
pp. e000109 ◽  
Author(s):  
Michel Weber ◽  
Laurent Velasque ◽  
Florence Coscas ◽  
Céline Faure ◽  
Isabelle Aubry ◽  
...  

Background/aimsTo monitor treatment-naïve patients with wet age-related macular degeneration (wet AMD) receiving intravitreal aflibercept (IVT-AFL) in France.MethodsRAINBOW (Real life use of intravitreal Aflibercept In FraNce - oBservatiOnal study in Wet age-related macular degeneration) is an ongoing, observational, retrospective and prospective 4-year study to assess visual (primary), anatomical and safety outcomes following IVT-AFL treatment in wet AMD patients. We report the interim 12-month outcomes in patients who have already been enrolled.ResultsSafety data were analysed from 586 patients (safety analysis set); and effectiveness data were analysed from 502 patients with at least one follow-up (full-analysis set) and from 353 patients with visual acuity data at baseline and month 12. The mean (SD) best-corrected visual acuity (BCVA) was 56.7 (18.2) letters and the mean (SD) central retinal thickness (CRT) was 395.6 (140.5)µm at baseline. Most patients (76.9%) received a loading dose (first three injections within 90 days). The mean (SD) number of IVT-AFL injections over 12 months was 6.0 (2.1) and 6.6 (1.8) (patients who received a loading dose). The mean (SD) change in BCVA was 5.5 (15.0) letters and 6.8 (14.5) letters (patients who received a loading dose) at month 12 (p<0.001 vs baseline). The mean (SD) CRT reduction was –108.7 (146.8)µm and –116.4 (150.4)µm (loading dose) at month 12 (p<0.001 vs baseline). Overall, 118 (20.1%) patients experienced at least one treatment-emergent adverse event (TEAE), 1.2% experienced ocular TEAEs and 3.9% experienced serious AEs.ConclusionThis 12-month interim analysis showed that IVT-AFL was associated with sustained improvements in a real-world setting. The RAINBOW results are consistent with the VIEW clinical studies.Trial registration numberNCT02279537 Pre-results.


2019 ◽  
Vol 3 (6) ◽  
pp. 438-444
Author(s):  
Eliot R. Dow ◽  
Jennifer O. Adeghate ◽  
Peter G. Coombs ◽  
Mrinali Gupta Patel ◽  
Donald J. D’Amico ◽  
...  

Purpose: This article assesses anatomical and visual outcomes after intravitreal antivascular endothelial growth factor (anti-VEGF) treatment in fellow eyes with wet age-related macular degeneration (AMD). Methods: A retrospective chart review was conducted of 349 patients diagnosed with wet AMD between 2005 and 2017 at a single academic institution. Initial diagnosis of unilateral wet AMD and a minimum follow-up time of 1 year after diagnosis were required for inclusion. Individuals were excluded if the initial diagnosis of wet AMD was made at an outside institution, if they had received prior treatment at another institution, or if they had bilateral wet AMD at the time of inclusion. Best-corrected visual acuity, optical coherence tomography (OCT) parameters, and frequency and type of intravitreal anti-VEGF injections were recorded. MedCalc Statistical Software version 17.6 (MedCalc Software) and GraphPad Software (GraphPad Software, Inc) were used for statistical analysis. Results: Of the 349 patients with wet AMD, 192 were included in the study (55%). Of these, 47 (24.5%) developed wet AMD in the fellow eye. The average time to second-eye conversion was 2.6 years, with fellow-eye conversion more likely to occur after 2 years of unilateral disease. On average, patients received 2.16 fewer injections per year in the fellow eye compared with the initially diagnosed eye ( P = .03), and fellow eyes tended to have better OCT results after 12 months of treatment. In addition, compared with ranibizumab and bevacizumab, aflibercept injections appeared to improve visual acuity both in initially diagnosed and fellow eyes. Conclusions: Exudative AMD in the fellow eye has a decreased treatment burden and better visual outcomes compared with the initial eye, which may be attributed to more frequent surveillance and early diagnosis.


Author(s):  
Daniel Caballe-Fontanet ◽  
Cristina Alvarez-Peregrina ◽  
Neus Busquet-Duran ◽  
Eduard Pedemonte-Sarrias ◽  
Miguel Angel Sanchez-Tena

Background: Age-related macular degeneration (AMD) is a disease with an increasing incidence due to the general aging of the population that decreases the patient’s quality of life. This work aims to study whether selective cut optical filters improve the AMD patient’s quality of life. Methods: Prospective and longitudinal study in 79 patients. Visual acuity, contrast sensitivity, and the line differences in the Colenbrander test were measured. Patients answered The National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25), which measures the quality of life related to vision before and after using cut optical filters. Results: There was an improvement of 5.99 points (3.7–8.3) in NEI VFQ-25 after wearing filters. This improvement was 4.0 points for 450-nm filters and 12.7 points for 511-nm filters. For patients with visual acuity (VA) < 0.25, results of NEI VFQ-25 increased by 10.11 points (1.19–19.02) and for patients with late AMDs, results increased by 5.33 points (1.31–9.35). Conclusions: Selective filters improve the quality of life of patients with AMD. The success rate in the fitting of filters is better for those with VA lower than 0.25 and those with late or advanced AMD.


2013 ◽  
Vol 6 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Natalya Viktorovna Chistyakova ◽  
Yuriy Sergeevich Astakhov ◽  
Nikita Yuryevich Dal

Design: prospective non-randomized experimental longitudinal cohort study. The aim of the study: to evaluate the visual acuity after phacoemulsification in patients with the “wet” form of age-related macular degeneration, treated by intravitreal angiogenesis inhibitor injections. Materials: 48 patients (48 eyes) with the “wet” form of AMD, treated by intravitreal angiogenesis inhibitor injections, and incipient cataract. All eyes in the study had a diagnosis of “wet” AMD and underwent cataract surgery. They were followed for a minimum of two years after the cataract surgery. The mean age of patients was 78.16 ± 5 years. There were 36 female (75 %) and 12 male (25 %) patients. Results: All patients were retrospectively divided into two groups. Group No. 1 consisted of 23 patients — operated within a year of the diagnosis of “wet” AMD, and group No. 2 which consisted of 25 patients who had a diagnosis of “wet” AMD for longer than one year prior to the cataract surgery. The mean preoperative visual acuity in the 1st group was 0.16 ± 0.07 (median 0.15), and in patients of group 2 — 0.23 ± 0.06 (median 0,2). Mean visual acuity immediately before surgery in the 1st group was 0.13 ± 0.04 (median 0.09), in the 2nd group — 0.12 ± 0.04 (median 0,08). After surgery, in the 1st group, mean visual acuity was — 0.28 ± 0.08 (median 0.25), in the 2nd group —0.18 ± 0.07 (median 0,15). The difference between the two groups was statistically significant, p < 0.01, t-test. Statistically significant visual acuity increase after surgery was registered in both groups and was preserved after one and two years, when compared to the data before surgery: for the 1st group — 0.13 and 0.1; for the 2nd group — 0,1 and 0.07, respectively (p < 0,01, Wilcoxon criterion). Conclusions: Phacoemulsification is reasonable for eyes with the “wet” form of age-related macular degeneration. Patients with shorter “wet” AMD duration obtain a higher visual acuity increase after cataract surgery. Statistically significant visual acuity increase after surgery is preserved in the majority of patients during next 2 years of follow-up.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kaushal Sharma ◽  
Priya Battu ◽  
Ramandeep Singh ◽  
Suresh Kumar Sharma ◽  
Akshay Anand

AbstractAge-related macular degeneration (AMD) is a devastating retinal disease that results in irreversible vision loss in the aged population. The complex genetic nature and degree of genetic penetrance require a redefinition of the current therapeutic strategy for AMD. We aimed to investigate the role of modifiers for current anti-VEGF therapy especially for non-responder AMD patients. We recruited 78 wet AMD cases (out of 278 AMD patients) with their socio-demographic and treatment regimen. Serum protein levels were estimated by ELISA in AMD patients. Data pertaining to the number of anti-VEGF injections given (in 1 year) along with clinical images (FFA and OCT) of AMD patients were also included. Visual acuity data (logMAR) for 46 wet AMD cases out of a total of 78 patients were also retrieved to examine the response of anti-VEGF injections in wet AMD cases. Lipid metabolizing genes (LIPC and APOE) have been identified as chief biomarkers for anti-VEGF response in AMD patients. Both genotypes ‘CC’ and ‘GC’ of LIPC have found to be associated with a number of anti-VEGF injections in AMD patients which could influence the expression of B3GALTL,HTRA1, IER3, LIPC and SLC16A8 proteins in patients bearing both genotypes as compared to reference genotype. Elevated levels of APOE were also observed in group 2 wet AMD patients as compared to group 1 suggesting the significance of APOE levels in anti-VEGF response. The genotype of B3GALTL has also been shown to have a significant association with the number of anti-VEGF injections. Moreover, visual acuity of group 1 (≤ 4 anti-VEGF injections/year) AMD patients was found significantly improved after 3 doses of anti-VEGF injections and maintained longitudinally as compared to groups 2 and 3. Lipid metabolising genes may impact the outcome of anti-VEGF AMD treatment.


Author(s):  
George W. Rozakis ◽  
Brian A. Bakke

The objective of the Hormones, Oxidative stress, Methylation, Inflammation and Gene expression (HOMING) trial was to assess the efficacy of personalized bio identical hormone, dietary supplement and nutritional care plans on dry and wet Age-related Macular Degeneration (AMD) outcomes.  We evaluated 220 Age-related Macular Degeneration (AMD) patients that followed a personalized clinical care plan for up to 9 months.   The care plans consisted of bio identical hormones, dietary supplements and nutrition recommendations with the objective to improve lab and clinical measurements linked to oxidative stress, inflammation and gene expression.  Serum concentrations of CRP, HbA1c and homocysteine responded favorably to the HOMING protocol with full program compliance. Sixty percent (42/70) of wet AMD patients reported improvement in visual acuity and/or a reduction in the frequency of anti-VEGF injections during the study period.  Forty eight percent (44/92) of dry AMD patients reported improvement in visual acuity during the study period.  Nine percent (4/45) patients reported improvement in visual acuity in the dry AMD control group and no (0/13) wet AMD patients in the control group reported improvement.  Six percent (4/70) of wet AMD patients reported that their vision declined and/or that their F frequency increased during the study period.  Five percent (4/92) of dry AMD patients reported that their vision was worse.  Keywords:  Bio identical Hormones, Oxidative stress, Methylation, Inflammation, Gene Expression, Nutrition and AMD.


2014 ◽  
Vol 7 (4) ◽  
pp. 27-32
Author(s):  
Yuriy Sergeyevich Astakhov ◽  
Nikita Yur’yevich Dal’ ◽  
Natal’ya Viktorovna Chistyakova

Many patients with wet age-related macular degeneration (AMD) also have a cataract in the same eye. Because there is a theoretical risk of progression of the degenerative processes in the macular area after surgical lens removal, this raises some ethical, clinical and economical questions for ophthalmologists. The purpose of the study was to compare the course of wet AMD in eyes with incipient cataract and the course in eyes after surgical cataract removal. Materials and methods: 135 eyes with wet AMD, 48 eyes - treated group - were subjects to phacoemulsification during the study, 87 eyes - control group - with incipient cataract without indications for surgery. Regular visits every 1.5 months during 2 years of follow-up with visual acuity testing, central retinal thickness analysis by optical coherence tomography (OCT). Anti-VEGF injections were performed according to a PRN regimen. Results: there was no statistically significant difference in visual acuity, central retinal thickness, intravitreal injection frequency between both groups during the study period. Conclusions: No influence of phacoemulsification on the wet AMD course was found.


2020 ◽  
Vol 7 (2) ◽  
pp. 18
Author(s):  
Xiaohong Sheng ◽  
Xiangyang Xin ◽  
Liming Wang ◽  
Yan Sun ◽  
Xiaohua Li

Objective: To observe the clinical efficacy of ranibizumab combined with triamcinolone acetonide on wet age-related macular degeneration (AMD) and explore the effect of this method on the levels of IL-1, IL-2, IL-6 and IL-8.Methods: Prospective study was conducted in this research. 86 cases of patients with wet AMD (102 eyes) admitted in Baogang Hospital of Inner Mongolia from November 2017 to October 2018 were chosen and randomly divided into the ranibizumab group (43 cases, 50 eyes) and the combination group (43 cases, 52 eyes). The ranibizumab group of patients were given intravitreal injection of ranibizumab, and the combination group was additionally given triamcinolone acetonide on the basis of the ranibizumab group. The intraocular pressure values of the two groups before treatment, in 2 weeks, 1 month and 3 months after treatment were compared. The central macular thickness (CMT) and visual acuity of the two groups before treatment as well as in 1 month, 3 months and 6 months after treatment were compared. The levels of IL-1, IL-2, IL-6 and IL-8 in the serum were compared between the two groups before treatment and in 1 month after treatment. The incidences of complications during treatment in the two groups were recorded and compared. The data were analyzed by use of t-test, repeated measures ANOVA and χ2 test.Results: There were no statistically significant differences in intraocular pressure value between the two groups (Fgroups = 1.275, p = .496; Ftime = 1.810, p = .211; Finteraction = 1.772, p = .335). There were no statistically significant differences in CMT and visual acuity before treatment between the two groups (t = 0.042, p = .967; t = 0.720, p = .473). In one month, three months and six months after treatment, CMT in the combined group was lower than that in the ranibizumab group (t = 2.086, p = .039; t = 3.398, p = .001; t = 2.987, p = .004), and the visual acuity of the combined group was higher than that of the ranibizumab group (t = 3.265, p = .001; t = 2.217, p = .029; t = 2.519, p = .013). CMT showed a decreasing tendency (tbefore treatment vs. t1 month after treatment = 6.210, 4.218, p < .001; t1 month after treatment vs. t3months after treatment = 16.772, 15.865, p < .001; t3 months after treatment vs. t6 months after treatment = 4.472, 4.848, p < .001) and the visual acuity showed an increasing trend (tbefore treatment vs. t1 month after treatment = 4.527, 8.395, p < .001; t1 month after treatment vs. t3 months after treatment = 5.369, 5.349, p < .001; t3 months after treatment vs. t6 months after treatment = 3.335, 3.730, p < .001) with the time going by in the two groups. Compared with the indicators before treatment, the levels of IL-1_, IL-6 and IL-8 in the serum in 1 month after treatment were lower in both two groups (tcombination group = 10.544, 32.169, 33.156, all p < .001; tranibizumab group = 8.996, 25.687, 30.754, all p < .001), and these indicators in the combination group were lower than those in the ranibizumab group (t = 2.894, p = .005; t = 5.997, p < .001; t = 3.934, p < .001). Compared with the indicators before treatment, the levels of IL-2 in the serum in 3 months after treatment in the two groups were higher (t = 20.067, 9.091, all < .001), and the indicator in the combination group was higher than that in the ranibizumab group (t = 7.705, p < .001). There were no statistically significant differences in the incidences of bleeding, intraocular foreign body sensation and transient high IOP and the total incidence of complications between the two groups (correction χ2 = 0.001, p = .972; correction χ2 = 0.221, p = .638; Fisher’s exact test p = .116; correction χ2 = 0.004, p = .951).Conclusions: Intravitreal injection of ranibizumab combined with triamcinolone acetonide can effectively improve the visual function of wet AMD, reduce CMT and the levels of IL-1, IL-6 and IL-8 in the serum, increase the level of IL-2 in the serum and relieve the degree of inflammatory responses. 


Author(s):  
O.Y. Kuznetsova ◽  
◽  
D.V. Peregudov ◽  
D.V. Levina ◽  
A.Y. Novikova. ◽  
...  

Purpose. To evaluate the efficiency of Aflibercept in patients with various vas-cular and neovascular diseases of the retina. Material and methods. 43 patients (55 eyes) with various ophthalmic patholo-gies were treated: wet form of age-related macular degeneration of the retina (AMD), myopic CNV, diabetic macular edema (DME) and macular edema due to occlusion of the retinal veins. Among them, 17 (39.5%) men and 26 (60.5%) women aged 38 to 84 years (62±1.9 years). All patients underwent a compre-hensive ophthalmological examination. A total of 158 intravitreal injections (IVI) of Aflibercept were performed. The observation period was 6 months. The efficiency of treatment was assessed according to the data of visual acuity, OCT, as well as subjective feelings and changes in the area of central scotoma. Results. Visual acuity among all patients after three loading injections increased by an average of 2.8 lines. Subjective improvement in visual functions was noted in 38 (89%) patients. The greatest increase in visual functions was observed in the exudative form of wet AMD, which manifests itself mainly in the form of detachment and / or edema of the neuroepithelium. The smallest in-crease in visual acuity was observed in patients with exudative-hemorrhagic form of wet AMD with detachment of the pigmented epithelium and neuroepi-thelium, as well as in myopic CNV. Over the next three months after the course of loading injections, visual acuity increased by an average of 5-7%. The thick-ness of the retina in the fovea decreased by an average of 156.8 ± 52 µm (from 45 to 290 µm), while the greatest decrease in the thickness was observed in pa-tients with DMO and exudative form of wet AMD, manifested as detachment of neuro- and pigmented epithelium, and the least expressed was in myopic CNV. Conclusion. The use of IVV Aflibercept is effective in various vascular and ne-ovascular diseases of the retina. The highest functional result is observed in pa-tients with an exudative form of wet AMD, manifested by detachment and / or edema of the neuroepithelium. Key words: аflibercept, intravitreal injection, vascular endothelial growth fac-tor, age-related macular degeneration, macular edema.


2014 ◽  
Vol 7 (4) ◽  
pp. 13-21
Author(s):  
Yuriy Sergeyevich Astakhov ◽  
Gassan Basharovich Shaar ◽  
Nikita Yur’yevich Dal’

Purpose. To study the effects of vitrectomy on the course of wet age-related macular degeneration (AMD). Materials and methods. 99 patients (99 eyes) with wet AMD associated with vitreo-macular adhesion or posterior hyaloid traction were included in the study. During the first 6 months, all patients received anti-VEGF treatment according to a PRN regimen. Then, they were divided into two groups: in 45 patients vitrectomy was performed and 54 patients did not receive surgical treatment. The follow-up period duration was one year. Results. At the beginning of the study, visual acuity was 0.27 ± 0.17 in the control group, and 0.17 ± 0.15 in the treatment group. Most prominent differences in visual acuity between the two groups were observed during the first 6 months (visual acuity in the treatment group before surgery was 0.12 ± 0.1) (p < 0.01 and p < 0.001), at the same time during the following 6 follow-up months, this difference decreased (p < 0.05 and p < 0.01). 1 year from the study start, visual acuity in the control group was 0.24 ± 0.17, and 0.17 ± 0.13 in the treatment one. Conclusions. Vitrectomy surgery in patients with wet AMD in association with vitreo-macular adhesion or posterior hyaloid traction does not exacerbate the disease course, stabilizes visual functions and improves the quality of life.


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