Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis

Abstract

Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes.

Methods: Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors.

Results: Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4 months to 8 years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P = 0.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown.

Discussion: Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence.

Systematic review registration: PROSPERO CRD42020216205.

Keywords: Anti-VEGF; COVID-19; Intravitreal; Macular; Meta-analysis; Non-adherence; Non-persistence.

Fig. 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart. Illustrates the number of records identified, screened, and excluded at each stage

Fig. 2

Reasons for non-adherence and non-persistence provided by patients identified in this review. Findings are sorted by patient-led, treatment-led, and other factors as provided by WHO MAM Model. In total, 937/409,215 provided patient-led reasons, out of which treatment dissatisfaction (29.9%), financial burden (19.0%) and old age/co-comorbidities (15.5%) were the most commonly occurring reasons provided. *Old age and co-morbidities were given as a single percentage of 15.5% due to the fact that these were combined in several of the papers. Aside from patient-associated factors given, several studies included physician-associated factors and external factors such as patient death and transfer of care elsewhere

Fig. 3

Meta-analysis results. Prevalence of patient-led treatment non-persistence among the patients on anti-VEGF therapy and subgroup analysis within 1 year of non-persistence to the prescribed anti-VEGF therapy according to duration. The overall prevalence of non-persistence at this time point is 0.3 (i.e., 30%)