ABSTRACT
Purpose: To report the incidence, clinical features, potential risk factors, and outcomes of intraocular inflammation (IOI) following brolucizumab in Indian eyes. Methods: All consecutive patients diagnosed with brolucizumab?induced IOI from 10 centers in eastern India between October 2020 and April 2022 were included. Results: Of 758 injections given during the study period across centers, 13 IOI events (1.7%) were recorded attributable to brolucizumab. The IOI occurred after the first dose in two eyes (15%) (median 45 days after brolucizumab), second dose in six eyes (46%) (median = 8.5 days), and third dose (39%) in the remaining five eyes (median 7 days). Reinjections of brolucizumab were administered at a median interval of 6 weeks (interquartile range = 4–10 weeks) in the 11 eyes, where IOI occurred after the second or third dose. Eyes that experienced IOI after the third dose had received a significantly greater number of previous antivascular endothelial growth factor injections (median = 8) compared to those who developed it after the first or second dose (median = 4) (P = 0.001). Anterior chamber cells were seen in almost all eyes (n = 11, 85%), while peripheral retinal hemorrhages were seen in two eyes, and one eye showed branch artery occlusion. Two?thirds of patients (n = 8, 62%) recovered with a combination of topical and oral steroids, while remaining recovered with topical steroids alone. Irreversible visual loss was not seen in any eye, and median vision recovered to pre?IOI levels by 3 months’ time point. Conclusion: Brolucizumab?induced IOI was relatively rare, occurring in 1.7% of eyes, was more common after the second or third injection, especially in those who required frequent reinjections every 6 weeks, and occurred earlier with increasing number of previous brolucizumab injections. Continued surveillance is necessary even after repeated doses of brolucizumab.
ABSTRACT
Purpose: The present study compares the efficacy, safety, and immunogenicity of Lupin’s biosimilar ranibizumab with that of Lucentis® in patients with neovascular age-related macular degeneration. Methods: This prospective, double-blind, multi-centric phase-III study was conducted across 19 centers in India. A total of 202 patients with neovascular age-related macular degeneration were randomized (1:1) to receive either Lupin’s biosimilar ranibizumab or Lucentis®, 0.5 mg, as an intravitreous injection once every month for 3 months. The primary efficacy endpoint was the proportion of patients who lost fewer than 15 letters from baseline in best-corrected visual acuity. The safety profile included assessment of adverse events, ophthalmic examination, physical and systemic examination, and vital parameters. The immunogenicity assessment was based on evaluation of anti-drug antibodies. Results: Overall, 174 patients (87 [86.14%] in each group) completed the study. The demographics and baseline characteristics were comparable between the treatment groups. The proportion of patients losing fewer than 15 letters from baseline best corrected visual acuity score in the study eye was comparable between two groups. The difference between Lupin’s ranibizumab and Lucentis® for the proportion of patients who lost fewer than 15 letters was within the predefined equivalence margin (intention-to-treat population: 1.0%; 95% confidence interval [CI], ?3.3% to 5.4% and per protocol population: 1.2%; 95% CI, ?3.2% to 6.4%). The incidence of treatment-emergent adverse events was comparable, and 11 (10.89%) patients in Lupin’s ranibizumab and 19 (18.81%) patients in Lucentis® group had at least one treatment-emergent adverse event. The immunogenicity incidence as assessed by proportion of patients with positive anti-drug antibodies was numerically lower in Lupin’s ranibizumab (4.95%) than Lucentis® (12.87%). Conclusion: Lupin’s biosimilar ranibizumab demonstrated therapeutic equivalence, desirable safety, and favorable immunogenicity profile compared to Lucentis
ABSTRACT
Purpose: To report the reasons for treatment discontinuation within 5 years in patients receiving intravitreal anti?vascular endothelial growth factor (anti?VEGF) therapy for neovascular age?related macular degeneration (nAMD). Methods: A retrospective case?notes review of patients commenced on anti?VEGF for nAMD who failed to complete 5 years of follow?up was undertaken. The reasons for treatment discontinuation, baseline age, baseline visual acuity (VA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and the VA change at the last follow?up were recorded. Age?specific all?cause mortality was calculated for deceased patients. Results: Of the 1177 patients, 551 patients (46.8%) failed to complete the 5?year follow?up. The reasons for treatment discontinuation were death (251), early discharge due to stable disease (110), further treatment deemed futile (100), failure to attend (15), ill health (14), patient choice (7), and transfer of care (1). In 53 patients, no reason was documented. The mean baseline age of those who completed the 5?year follow?up (77.4 ± 7.8 years, 95% confidence interval (CI): 76.8–77.9) was significantly lower than those who discontinued the treatment for any reason (82 ± 7.7 years, 95% CI: 81.4–82.6) (P < 0.0001). Survival analysis showed that baseline VA was not a factor in treatment discontinuation; however, visual stability (±5 letters from baseline) was associated with treatment continuation. The age?specific all?cause mortality in deceased patients was lower than that in the general population. Conclusion: At 5 years, only 53% of patients remained in active care, and death was the most common reason for treatment discontinuation. Lower baseline age and VA stability during therapy were associated with treatment continuation.
ABSTRACT
In order to study the structure-function relationship in the protein which is incorporated with p-nitro-L-phenylalanine,the method of MD(Molecular Dynamics) simulation was established and successfully used in the analysis of protein which contains p-nitro-L-phenylalanine.The force field of CHARMM can only stimulate protein with natural amino acid in NAMD.Compared with phenylalanine,p-nitro-L-phenylalanine just has one more group of nitro.If the parameter of group of nitro was defined,the protein containing p-nitro-L-phenylalanine can be simulated.CGenFF-paramchem was used to calculate the energy and topological structure of p-nitro-L-phenylalanine' s new bonds (r),angles (θ),dihendrals (φ) and improper angle (ψ).And then the new defined parameter and topology information was input into the related parameter files and topology files in CHARMM.On the basis of correct parameter,NAMD can successfully simulate the modified BAFF(B lymphocyte stimulator) which contains p-nitro-L-phenylalanine.The changes in structure indicated that there might be new B cell epitopes.The temperature distribution of each frame in the process of dynamics stimulation was in accord with normal distribution,which proved the defined force field parameters was feasible.The RMSD of whole protein solution systemis 2.5.Calculate each resides' RMSF in BAFF,the RMSF of p-nitro-L-phenylalanine's residue is 3.7,which is obviously higher than that of the other residues in β-pleated sheet,and close to the loop rings,indicate that there might be variation in the area of p-nitro-L-phenylalanine residue and might produce new comformational epitopes.The results of MD stimulation will guide the immunogenicity experiments of p-nitro-L-phenylalanine modified proteins.