Author: Focke Ziemssen (Germany)
Co-authors: Robert P. Finger, Albrecht Lommatzsch, Joachim Wachtlin, Ulrike Bauer-Steinhusen, Tobias Machewitz, Christine Rech
There are gaps in understanding causes of non-adherence (NA) to anti-vascular endothelial growth factor (VEGF) therapy and subsequent undertreatment in patients with neovascular age-related macular degeneration (nAMD). The aim of the ANDROMEDA study is to assess treatment adherence over a period of 24 months during intravitreal aflibercept (IVT-AFL) therapy for nAMD, and to identify the impact of patient- and/or physician-related factors on adherence.
ANDROMEDA (NCT03714308) is a 24-month, prospective, observational cohort study in treatment-naïve as well as pre-treated patients with nAMD receiving IVT-AFL injections across 41 centers in Germany. All treatment decisions, including the decision to treat with IVT-AFL, were made by the treating physician.
A 4-month interim analysis was performed for the total study cohort as well as for treatment-naïve and pre-treated patients. The date of data cut-off for the 4-month analysis was May 31, 2021. Primary endpoints are the time to first occurrence of NA, defined as relevant deviation from on-label use of IVT-AFL, and reasons for missing a scheduled injection visit asked directly in telephone interviews. Secondary endpoints include best-corrected visual acuity (BCVA), health-related and vision-related quality of life, treatment satisfaction, and patient-reported barriers to adherence. Health-related and vision-related quality of life, treatment satisfaction, and treatment adherence barriers were assessed via telephone interviews using the 5-level EuroQol 5-Dimension (EQ-5D-5L) health questionnaire, the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25), the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ), and the Patient Questionnaire for Longitudinal Assessment of Adherence Factors to Intravitreal (anti-vascular endothelial growth factor therapy) Therapy (LAF-IVT). Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for time to first occurrence of NA for defined baseline risk factors, which was visualized using Kaplan–Meier plots.
Of a total of 554 patients enrolled in the study, 511 were valid for analysis of study endpoints. BCVA of naïve patients (58.6 ±18.55, n=224) was worse than that of pretreated patients (IVT-AFL pretreated 66.8 ±15.34, n=118; other pretreatment 64.8 ±15.78, n=169) and increased after 4 months to 63.3 ±17.47 in the naïve patient group and 66.8 ±15.34 and 64.8 ±15.78 in IVT-AFL pretreated and other pretreatment group respectively. Telephone interviews were documented for 91.2% of the total cohort at baseline and 89.2% at 4 months. The EQ-5D-5L and NEI-VFQ-25 scores were 0.8 (±0.20) and 79.2 (±13.32) at baseline and 0.8 (±0.23) and 79.7 (±13.72) at 4 months, respectively. The mean (± SD) MacTSQ (first applied at 4 months) score was 59.7 (±9.89). During the first 4 months, 45 (8.8%) patients reported missed injection visits in the LAF-IVT questionnaire. Patients reported "other diseases" as the most common reason (n=26, 57.8%) for a missed injection appointment during this observation period. The COVID-19 pandemic coincided to varying degrees with the enrolment and/or observation of 85% of the study population.
NAMD patients showed a high rate of non-adherence, even higher than anticipated before start of the study.Thus, not only the successful recruitment of comparable groups with and without IVT-AFL pretreatment promises insights into which phenomena are actually vs. patient perceived to be relevant for off-label treatment intervals. Pertinent risk factors will be identified in the analysis of the 12- and 24-month data and furthermore the impact of the COVID-19 pandemic on treatment adherence will be considered.
F Ziemssen: Consulting: Allergan/Abbvie, Alimera, Bayer Healthcare, Boehringer-Ingelheim, Roche/Genentech, Novartis, NovoNordisk, MSD, Oxurion, Lecture fees: Allergan/Abbvie, Bayer Healthcare, CME Heallth, Novartis, ODOS, Roche R. Finger: Consulting: Bayer, Novartis, Roche/Genentech, Zeiss Meditech, Inositec, ProQR, Opthea, Alimera, Allergan; Funding: Novartis, Bayer, CentreVue, Zeiss Meditech, Heidelberg Engineering, Biogen, Alimera A. Lommatzsch: Lecture fees: Novartis, Bayer Vital GmbH, Pharm Allergan, Zeiss; Consulting: Novartis, Bayer Vital GmbH, C. Rech: Emplyee of Bayer Vital GmbH, T. Machewitz: Employee of Bayer Vital GmbH, U. Bauer-Steinhusen: employee Bayer Vital GmbH F.G.Holz: Consultating and funding: Genentech/Roche, Bayer, Boehringer-Ingelheim, Novartis, Allergan, Heidelberg Engineering, Kanghong; Consulting: Apellis, LIN Bioscience; Funding: Nightstar, Centervue, Optos, Acucela, Alcon; Advisory Boards: Acucela, Allergan, Avalanche, Bayer, Genentech, Heidelberg Engineering, Johnson & Johnson, LinBioscience, Novartis, Ophthotech, Roche, Oxurion.
Additional Co-author: 7. Christine Rech - employee Bayer Vital GmbH 8. Frank G. Holz: Department of Ophthalmology, University of Bonn, Germany