ABSTRACT
PURPOSE: To evaluate 2-year efficacy, durability, and safety of faricimab in the TENAYA Japan subgroup and pooled global TENAYA/LUCERNE cohort of patients with neovascular age-related macular degeneration (nAMD). METHODS: Subgroup analysis of TENAYA/LUCERNE (NCT03823287/NCT03823300): phase III, multicentre, randomised, active comparator-controlled, double-masked, non-inferiority trials. Treatment-naïve patients aged ≥ 50 years with nAMD were randomised (1:1) to intravitreal faricimab (6.0 mg up to every 16 weeks [Q16W] after 4 initial Q4W doses) or aflibercept (2.0 mg Q8W after 3 initial Q4W doses). Outcomes were assessed through year 2 for the TENAYA Japan subgroup (N = 133) and global pooled TENAYA/LUCERNE cohort (N = 1329). RESULTS: Vision and anatomic improvements achieved with faricimab at year 1 were maintained over 2 years and were generally comparable between the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Adjusted mean best-corrected visual acuity (BCVA) change from baseline at year 2 for the TENAYA Japan subgroup and global pooled TENAYA/LUCERNE cohort was +7.1 (3.7-10.5) and +4.4 (3.2-5.5) letters in the faricimab arm, respectively, and +5.2 (1.9-8.6) and +4.3 (3.1-5.4) letters in the aflibercept arm, respectively. At week 112, the proportion of faricimab-treated patients on Q16W dosing was 61.0% and 63.1% in the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Faricimab was well tolerated through year 2. CONCLUSION: Year 2 TENAYA Japan subgroup findings for faricimab were generally consistent with the pooled global TENAYA/LUCERNE results in patients with nAMD. Vision and anatomical benefits with faricimab were similar to those with aflibercept but with fewer injections.
Subject(s)
Angiogenesis Inhibitors , Intravitreal Injections , Receptors, Vascular Endothelial Growth Factor , Visual Acuity , Wet Macular Degeneration , Humans , Male , Double-Blind Method , Female , Japan/epidemiology , Wet Macular Degeneration/drug therapy , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/physiopathology , Treatment Outcome , Middle Aged , Aged , Follow-Up Studies , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Tomography, Optical Coherence , Recombinant Fusion Proteins/administration & dosage , Time Factors , Dose-Response Relationship, Drug , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Drug Administration Schedule , Fluorescein AngiographyABSTRACT
PURPOSE: To evaluate the 1-year efficacy, durability, and safety of faricimab versus aflibercept in patients with neovascular age-related macular degeneration (nAMD) enrolled in the Japan subgroup of the TENAYA trial. STUDY DESIGN: TENAYA (NCT03823287) was a global, phase 3, multicenter, randomized, active comparator-controlled, double-masked, noninferiority, parallel-group, 112-week trial. After completion of global enrollment, additional patients were enrolled in the Japan extension of TENAYA. METHODS: Treatment-naïve patients aged ≥ 50 years with nAMD were randomized (1:1) to intravitreal faricimab 6 mg up to every 16 weeks (Q16W) after 4 initial Q4W doses based on disease activity at weeks 20 and 24 or aflibercept 2 mg Q8W after 3 initial Q4W doses. Primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48. Anatomical/durability outcomes were assessed. RESULTS: Overall, 133 patients were included in the TENAYA Japan subgroup analysis (faricimab, n = 66; aflibercept, n = 67). The adjusted mean (95% confidence interval) BCVA changes were + 7.1 (4.6â9.7) and + 7.7 (5.2â10.1) letters in the faricimab and aflibercept treatment groups, respectively. At week 48, 66.1%, 22.6%, and 11.3% of patients in the faricimab group were on Q16W, Q12W, Q8W and dosing intervals, respectively. Ocular adverse event rates were similar between treatment groups (faricimab, n = 14 [21.2%] versus aflibercept, n = 17 [25.4%]). CONCLUSION: The TENAYA Japan subgroup analysis showed that faricimab up to Q16W had sustained efficacy with an acceptable safety profile. These findings are consistent with the global TENAYA and LUCERNE findings.
Subject(s)
Macular Degeneration , Wet Macular Degeneration , Humans , Angiogenesis Inhibitors , Japan/epidemiology , Visual Acuity , Intravitreal Injections , Receptors, Vascular Endothelial Growth Factor , Macular Degeneration/drug therapy , Recombinant Fusion Proteins , Treatment Outcome , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/drug therapyABSTRACT
PURPOSE: To evaluate efficacy, durability, and safety of faricimab in Japanese patients with diabetic macular edema (DME). STUDY DESIGN: Subgroup analysis of 2 global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 trials (YOSEMITE, NCT03622580; RHINE, NCT03622593). METHODS: Patients with DME were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W through week 100. Primary endpoint was best-corrected visual acuity (BCVA) change from baseline at 1 year, averaged over weeks 48, 52, and 56. This is the first time 1-year outcomes between Japanese patients (only enrolled into YOSEMITE) and the pooled YOSEMITE/RHINE cohort (N = 1891) have been compared. RESULTS: The YOSEMITE Japan subgroup included 60 patients randomized to faricimab Q8W (n = 21), faricimab PTI (n = 19), or aflibercept Q8W (n = 20). Consistent with global results, the adjusted mean (95.04% confidence interval) BCVA change at 1 year in the Japan subgroup was comparable with faricimab Q8W (+11.1 [7.6-14.6] letters), faricimab PTI (+8.1 [4.4-11.7] letters), and aflibercept Q8W (+6.9 [3.3-10.5] letters). At week 52, 13 (72%) patients in the faricimab PTI arm achieved ≥ Q12W dosing, including 7 (39%) patients receiving Q16W dosing. Anatomic improvements with faricimab were generally consistent between the Japan subgroup and pooled YOSEMITE/RHINE cohort. Faricimab was well tolerated; no new or unexpected safety signals were identified. CONCLUSION: Consistent with global results, faricimab up to Q16W offered durable vision gains and improved anatomic and disease-specific outcomes among Japanese patients with DME.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Humans , Angiogenesis Inhibitors/therapeutic use , Diabetes Mellitus/chemically induced , Diabetes Mellitus/drug therapy , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/drug therapy , East Asian People , Intravitreal Injections , Japan/epidemiology , Macular Edema/diagnosis , Macular Edema/drug therapy , Macular Edema/etiology , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins/adverse effects , Treatment Outcome , Visual AcuityABSTRACT
Diazinon is an organophosphorus (OP) insecticide and is widely used not only in agriculture but also homes and garden in Japan. Diazinon has been reported to increase TNF-α production in rat serum and brain, suggesting that it can modify the proinflammatory response. In this study, we investigated the effects of diazinon on macrophage functions, such as cytokine production, reactive oxygen species (ROS) generation, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expressions, cell-surface molecule expressions, and phagocytosis in RAW264.7 cells. In RAW264.7 cells, diazinon induced the production of TNF-α and IL-6. Diazinon induced ROS generation and the expressions of COX-2, iNOS, and cell-surface molecules CD40, CD86, and MHC class II, but reduced phagocytic activity in RAW264.7 cells. ERK and p38, but not JNK and p65 were involved in diazinon-induced IL-6 expression in RAW264.7 cells. We also examined these proinflammatory responses in bone marrow-derived macrophages (BMDM) and bronchoalveolar lavage fluid (BALF) cells. These results suggested that diazinon can activate macrophages and enhance inflammatory responses.