Real-world efficacy and safety of dividing aflibercept into three syringes in the treatment of wet age-related macular degeneration.

Abstract

Aflibercept, bevacizumab and ranibizumab are vascular endothelial growth factor inhibitors used for the treatment of wet age-related macular degeneration (wet AMD). Aflibercept and ranibizumab are registered for intraocular use whereas off-label bevacizumab is widely used due to its affordability. As use of aflibercept and ranibizumab induces significantly higher treatment costs compared to off-label bevacizumab, Finnish Choosing Wisely recommendation suggests avoiding expensive drugs as first-line therapy as studies have demonstrated similar effectiveness and safety of AMD drugs (Tuuminen et al. 2019). In Finland, the National Council for Choices in Health Care acknowledges treatment of wet AMD with intravitreal bevacizumab in the publicly funded health care (Tuuminen et al. 2017). When costs of one disease increase more than overall costs in the tax-funded health care system, it is crucial to search means to improve cost-effectiveness of care to be able to ensure required care for all eye diseases. Oslo University Eye Clinic has introduced a practice, where the drug from aflibercept-vial is divided into three prefilled syringes. Using low dead-space syringes, each prefilled syringe contains 0.05 ml aflibercept (Sivertsen et al. 2018). Tays Eye Centre followed by implementing the same policy since October 2016. Safety of compounding aflibercept into prefilled syringes has been shown in few previous studies (Cao et al. 2017; Forooghian et al. 2017). To evaluate real life safety and efficacy of this policy, data from wet AMD eyes treated with aflibercept between September 2015 and October 2017 in Tampere Eye Centre were collected from the electronic medical records. Eyes were divided into two groups: Group 1 treated during 1 September 2015–31 August 2016, and Group 2 during 1 November 2016–31 October 2017. To consider bias, eyes from Group 1 were excluded from Group 2. One eye per patient was included in the analysis (the first eye diagnosed with wet AMD). Data were analysed with spss version 25 (IBM® Statistics SPSS; Armonk, NY, USA) using Mann–Whitney U-test and Pearson Chi square for comparisons. In Group 1, all patients were treated with aflibercept drawn from a vial just prior to the injections. In Group 2, most eyes (mean 86 ± 9%) received aflibercept injections from prefilled syringes, generated by the university hospital pharmacy implementing a validated process. At the beginning of transition period, in November 2016 the divided aflibercept accounted 70% of aflibercept injections and increased to 100% by October 2017. A total of 144 eyes with at least one aflibercept injection were identified in Group 1 and 145 eyes in Group 2. The mean follow-up in both groups was 11 ± 1 months. Numbers of the aflibercept injections administered were 411 and 434 in Groups 1 and 2, respectively. Time from wet AMD diagnosis to the beginning of the study follow-up period was different between the groups (30 versus 25 months, p = 0.01). There were no significant differences between mean visual acuities (Fig. 1A), number of total intravitreal injections (IVIs) given (5 ± 2 versus 6 ± 2 IVIs, p = 0.1), or total number of aflibercept injections given (3 ± 2 IVIs in both groups, p = 0.7). We found similar results in a subgroup analysis with eyes receiving aflibercept injections only (Fig. 1A). No endophthalmitis or other serious adverse effects were observed after aflibercept injections in any group. Our 1-year real-world data indicate that divided aflibercept into prefilled syringes seems to be safe and does not affect the effectiveness of aflibercept but reduces drug related cost significantly (Fig. 1B). The total AMD drug costs of Tays Eye Centre in 2008–2017 were 2.9 million euros. If the most expensive available AMD drug had been used for all patients, the cost would have been 23 million euros which represents a huge cost saving.