ABSTRACT
Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of lifelong anti-VEGF injections with drugs like aflibercept, brolucizumab, ranibizumab and bevacizumab. However, the burden imposed on patients is a major deterrent for continual therapy and recovery. Faricimab, a bispecific antibody, blocking both VEGF-A and Ang-2 molecules, produces a comparable functional and anatomical results, with less injections, significantly reducing patient burden. Visual acuity, safety, adverse effects, and anatomical outcomes are discussed in the pivotal clinical trials (YOSEMITE/RHINE and TENAYA/LUCERNE), and early data from real-world studies (TRUCKEE, TAHOE, FARWIDE-DME, FARETINA and others). In YOSEMITE and RHINE, faricimab demonstrated non-inferior vision gains, better anatomical outcomes compared to aflibercept every 8 weeks. Faricimab in the personalized treatment interval (PTI), after week 96, achieved 12-week interval in 78.1% of the patients and 16-week interval in 62.3%. TENAYA and LUCERNE reported comparable best corrected visual acuity (BCVA) improvement and better anatomic outcomes during head-to-head phase, parallel to aflibercept, at its 8-week treatment schedule. Faricimab in the PTI regimen, after week 96 achieved 12-week interval in 77.8% of the patients and 16-week interval in 63.1%. Safety of faricimab has been comparable to aflibercept in these pivotal trials. Real-world data supports the data from the pivotal studies regarding the efficacy and safety profile of faricimab in heterogenous real world patient population. Moreover, in previously treated patients, it also demonstrated a faster fluid resolution, good safety profile. Considering faricimab has demonstrated anatomic and durability benefit in the treatment of nAMD and DME, additional data from ongoing extension clinical trials, AVONELLE-X and RHONE-X will help understand longer term outcomes for patients treated with faricimab as well as patients switching from aflibercept to faricimab after finishing the pivotal trials. Longer term data from the real-world studies will also continue to contribute to our understanding of long-term efficacy, safety and durability in the real world patient population.
ABSTRACT
The agrammatic or nonfluent variant of Primary Progressive Aphasia (nfvPPA) is a form of Frontotemporal Dementia (FTD) that is characterized by progressive language dysfunction, poor sentence construction, and low verbal fluency. Individuals with nfvPPA have intact insight into their decline, which may manifest as frustration and hopelessness, and show signs of impulsivity and disinhibition. Little is known about suicide risk in this patient population. Here we describe a case of an 84 year-old male with nfvPPA who, over the course of his care, experienced a decline in language and motoric functioning which coincided with increasing irritability and impulsivity. Despite this significant decline, he denied depressive symptoms or showed any suicidal tendencies, and he seemed to be looking forward to future events. His suicide, committed with a handgun during what appeared to be a rather innocuous trip to the garage, came as a significant shock to his spouse, family, and his clinical care team. To our knowledge, this is the first reported case of completed suicide in a patient with the nfvPPA subtype of FTD. Though this patient demonstrated demographic risk factors for suicide (advanced age, retired military veteran with easy access to firearms) there is a lack of data regarding how FTD may have contributed. Retained insight especially seems to be a risk factor for suicide across all forms of dementia. Impulsivity may be key when considering suicidality amongst FTD patients. Additionally, this case demonstrates the importance of addressing gun safety as there are few guidelines around gun ownership in this patient population.
