AIMS: Autoantibodies against hexokinase 1 (HK1) were recently proposed to be associated with diabetic macular edema (DME). We hypothesized that anti-HK1 autoantibodies can be used as DME markers and to predict DME onset. MATERIALS AND METHODS: Serum from patients with 1) DME, 2) diabetes mellitus (DM), 3) allergies or autoimmunities, and 4) control subjects was tested for anti-HK1 and anti-hexokinase 2 (HK2) autoantibodies by immunoblotting. Patients with DM were prospectively followed for up to nine years, and the association of anti-HK1 antibodies with new-onset DME was evaluated. The vitreous humor was also tested for autoantibodies. RESULTS: Among patients with DME, 32 % were positive for anti-HK1 autoantibodies (42 % of those with underlying type 1 DM and 31 % of those with underlying type 2 DM), and 12 % were positive for anti-HK2 autoantibodies, with only partial overlap of these two groups of patients. Anti-HK1 positive were also 7 % of patients with DM, 6 % of patients with allergies and autoimmunities, and 3 % of control subjects. The latter three groups were anti-HK2 negative. Only one of seven patients with DM who were initially anti-HK1 positive developed DME. CONCLUSIONS: Anti-HK1 autoantibodies can be used as DME markers but fail to predict DME onset.

• MeSH
• autoprotilátky * krev   imunologie   MeSH
• biologické markery krev   MeSH
• diabetes mellitus 1. typu imunologie   komplikace   krev   MeSH
• diabetes mellitus 2. typu imunologie   komplikace   krev   MeSH
• diabetická retinopatie * imunologie   krev   MeSH
• dospělí MeSH
• hexokinasa * imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makulární edém * imunologie   krev   MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

IMPORTANCE: Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy. OBJECTIVE: To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD). DESIGN, SETTING, AND PARTICIPANTS: This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up. INTERVENTION: Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56. MAIN OUTCOMES AND MEASURES: The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity. RESULTS: The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 μm vs AFL, -115.7 μm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04450329.

• MeSH
• biosimilární léčivé přípravky * škodlivé účinky   MeSH
• inhibitory angiogeneze škodlivé účinky   MeSH
• injekce intravitreální MeSH
• lidé MeSH
• makulární degenerace * farmakoterapie   MeSH
• ranibizumab terapeutické užití   MeSH
• receptory vaskulárního endoteliálního růstového faktoru terapeutické užití   MeSH
• rekombinantní fúzní proteiny škodlivé účinky   MeSH
• senioři MeSH
• vlhká makulární degenerace * diagnóza   farmakoterapie   chemicky indukované   MeSH
• výsledek terapie MeSH
• zraková ostrost MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Importance: Neovascular age-related macular degeneration is the leading cause of blindness in individuals 50 years or older. The availability of a ranibizumab biosimilar product (SB11) may facilitate access to an effective alternative to this treatment. Objective: To demonstrate equivalence of efficacy, similar safety, and similar immunogenicity of SB11 compared with the reference ranibizumab. Design, Setting, and Participants: This randomized, double-masked, parallel-group phase 3 equivalence study was conducted in 75 centers in 9 countries from March 14, 2018, to December 9, 2019, among 705 participants 50 years or older with neovascular age-related macular degeneration with active subfoveal choroidal neovascularization lesions. Analysis was performed on an intent-to-treat basis. Interventions: Intravitreous injection of SB11 or ranibizumab, 0.5 mg, every 4 weeks through week 48. Main Outcomes and Measures: Preplanned interim analysis after all participants completed the week 24 assessment of primary efficacy end points at week 8 for change from baseline in best-corrected visual acuity (BCVA) and week 4 for central subfield thickness (CST), with predefined equivalence margins for adjusted treatment differences of -3 letters to 3 letters for BCVA and -36 μm to 36 μm for CST. Results: Baseline and disease characteristics among 705 randomized participants (403 women [57.2%]; mean [SD] age, 74.1 [8.5] years) were comparable between treatment groups (SB11, 351; ranibizumab, 354). Least-squares mean (SE) changes in BCVA from baseline at week 8 were 6.2 (0.5) letters in the SB11 group vs 7.0 (0.5) letters in the ranibizumab group, with an adjusted treatment difference of -0.8 letter (90% CI, -1.8 to 0.2 letters). Least-squares mean (SE) changes in CST from baseline at week 4 were -108 (5) μm in the SB11 group vs -100 (5) μm in the ranibizumab group, with an adjusted treatment difference of -8 μm (95% CI, -19 to 3 μm). Incidences of treatment-emergent adverse events (231 of 350 [66.0%] vs 237 of 354 [66.9%]), including serious treatment-emergent adverse events (44 of 350 [12.6%] vs 44 of 354 [12.4%]) and treatment-emergent adverse events leading to study drug discontinuation (8 of 350 [2.3%] vs 5 of 354 [1.4%]), were similar in the SB11 and ranibizumab groups. Immunogenicity was low, with a cumulative incidence of antidrug antibodies up to week 24 of 3.0% (10 of 330) in the SB11 group and 3.1% (10 of 327) in the ranibizumab group. Conclusions and Relevance: These findings of equivalent efficacy and similar safety and immunogenicity profiles compared with ranibizumab support the use of SB11 for patients with neovascular age-related macular degeneration. Trial Registration: ClinicalTrials.gov Identifier: NCT03150589.

• MeSH
• biosimilární léčivé přípravky škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• časové faktory MeSH
• dvojitá slepá metoda MeSH
• inhibitory angiogeneze škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• injekce intravitreální MeSH
• lidé středního věku MeSH
• lidé MeSH
• makulární degenerace diagnóza   farmakoterapie   patofyziologie   MeSH
• neovaskularizace choroidey diagnóza   farmakoterapie   patofyziologie   MeSH
• obnova funkce MeSH
• ranibizumab škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• terapeutická ekvivalence MeSH
• vaskulární endoteliální růstový faktor A antagonisté a inhibitory   MeSH
• výsledek terapie MeSH
• zrak účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH