Post Marketing Surveillance of Treatments of Wet Age-related Macular Degeneration

Abstract

Background: Currently the recommended treatment for all eyes with wet age-related macular degeneration (AMD) with neovascularization affecting the centre of the macula (the vast majority) consists of regular intravitreal injections of vascular endothelial growth factor inhibitors VEGF). The global cost for this indication alone amounts to billions of dollars and other indications, e.g. diabetic retinopathy and retinal vein occlusion have emerged. Given the heavy treatment load and expense of treatment, it will be important to identify how quality of life issues affect patients’ willingness and ability to undergo ongoing treatment, since these will affect the long-term outcomes of intervention. Also, it is now apparent that many eyes can be treated less frequently, some may even be able to discontinue therapy altogether. Hence there is a need to carry out studies that will provide objective evidence that will establish the optimal dosing regimen for individual eyes. Aims: This study was divided into two components with a common theme of optimizing the dosing regimen. The first component was aimed at estimating the risk of recurrence of choroidal neovascularisation in eyes with neovascular AMD in which treatment was discontinued after they had not required intravitreal anti­VEGF injection for more than three months and to define the baseline variables, including the type and size of the neovascular lesion, that predict risk of recurrent disease. The second component of the study was aimed at identifying the reasons for anti-VEGF treatment discontinuation in patients with neovascular AMD. Methods: This was a retrospective review of observational study data (Fight Retinal Blindness! Project) of a single Australian private practice. Patients in whom treatment with intravitreal ranibizumab or bevacizumab was discontinued for more than 3 months during a 3-year period from March 2006 to April 2009 were included in the analysis for the first part of the study. Patients who discontinued treatment during a six-year period from March 2006 to June 2012 were included in the analysis for the second part of the study Results: Of 115 eyes of 103 patients in which treatment was discontinued, 105 (91%) eyes developed reactivation of their choroidal neovascular lesion with a significant decline in the mean visual acuity from 58.2 letters at the time of last injection to 50.2 letters at the time of recurrence (P < 0.001, paired t test). Median time to reactivation was 33.1 weeks (95% CI: 28.1 to 40.9) after stopping treatment. Subgroup analysis based on the angiographic type and size of the lesion did not identify any characteristics that predicted the time to reactivation (P = 0.47 and 0.26 respectively, log-rank test). Of 248 patients that commenced treatment during the six-year period, 105 (42.3 %) had discontinued by June 2012. Reasons for discontinuation were available for 102/105 (97.1%) patients. In 9 (3.6%) of the entire cohort, the doctor stopped the treatment as the lesion became inactive and in 27 (10.9%) patients further treatment was thought to be futile. Twenty six (10.5%) patients declined further treatment with 2 (0.8%) due to excessive treatment visits, 2 (0.8%) for difficulty in attending, 2 (0.8%) due to the expense, 3 (1.2%) due to pain/discomfort, 6 (2.4%) thought treatment was not beneficial and 11 (4.4%) had other more severe medical conditions. In 40 (16.1%) patients treatment was discontinued for other reasons such as patient moving to another region in 27 (10.9%) and death in 11 (4.4%). Conclusion: This study indicates that there is a high risk of recurrence after suspending intravitreal VEGF inhibitors for neovascular AMD, even if the lesion has been inactive for 3 months. Careful, indefinite follow up of all patients who appear to have been successfully treated is necessary to detect recurrence early. The burden of intravitreal anti-VEGF injections was a reason for treatment discontinuation in only a small minority of patients.