Defining Nonadherence and Nonpersistence to Anti–Vascular Endothelial Growth Factor Therapies in Neovascular Age-Related Macular Degeneration

Abstract

IMPORTANCEPoor adherence or persistence to treatment can be a barrier to optimizing clinical practice (real-world) outcomes to intravitreal injection therapy in patients with neovascular age-related macular degeneration (nAMD). Currently, there is a lack of consensus on the definition and classification of adherence specific to this context. OBJECTIVE To describe the development and validation of terminology on patient nonadherence and nonpersistence to anti-vascular endothelial growth factor therapy.DESIGN, SETTING, AND PARTICIPANTS Following a systematic review of currently used terminology in the literature, a subcommittee panel of retinal experts developed a set of definitions and classification for validation. Definitions were restricted to use in patients with nAMD requiring intravitreal anti-vascular endothelial growth factor therapy. Validation by the full nAMD Barometer Leadership Coalition was established using a modified Delphi approach, with predetermined mean scores of 7.5 or more signifying consensus. Subsequent endorsement of the definitions was provided from a second set of retinal experts, with more than 50% members agreeing or strongly agreeing with all definitions.MAIN OUTCOMES AND MEASURES Development of consensus definitions for the terms adherence and persistence and a classification system for the factors associated with treatment nonadherence or nonpersistence in patients with nAMD.RESULTS Nonadherence was defined as missing 2 or more treatment or monitoring visits over a period of 12 months, with a visit considered missed if it exceeded more than 2 weeks from the recommended date. Nonpersistence was defined by nonattendance or an appointment not scheduled within the last 6 months. The additional terms planned discontinuation and transfer of care were also established. Reasons for treatment nonadherence and nonpersistence were classified into 6 dimensions: (1) patient associated, (2) condition associated, (3) therapy associated, (4) health system and health care team associated, (5) social/economic, and (6) other, with subcategories specific to treatment for nAMD.CONCLUSIONS AND RELEVANCE This classification system provides a framework for assessing treatment nonadherence and nonpersistence over time and across different health settings in the treatment of nAMD with current intravitreal anti-vascular endothelial growth factor treatments. This may have additional importance, given the potential association of the coronavirus pandemic on adherence to treatment in patients with nAMD.

Drivers of and Barriers to Adherence to Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema Treatment Management Plans: A Multi-National Qualitative Study

“…For instance, in recent work, a definition of non-adherence and non-persistence was developed by a group of retinal experts, who classified reasons for treatment non-adherence/non-persistence in nAMD patients requiring IVT anti-VEGF therapy. 31 This could provide a framework for future assessments in this group of patients.…”

Intravitreal Aflibercept Therapy and Treatment Outcomes of Eyes with Neovascular Age-Related Macular Degeneration in a Real-Life Setting: A Five-Year Follow-Up Investigation

“…Another limitation was the definition of nonpersistence as nonattendance to any treatment or monitoring visit for 6 months. This was partly owed to long treatment intervals of up to 16 weeks; thus, a cut-off after 4 months would be too short [ 8 ]. To address all these challenges, future investigations could determine their nonattendance cut-off depending on the treatment protocol and/or the patients’ individual treatment interval.…”

“…The functional and anatomical outcomes of eyes that were persistent to intravitreal aflibercept therapy (persistent group) were compared to the outcomes of eyes that were nonpersistent to therapy for at least 6 months during their individual observation period (the nonpersistent group). As suggested by Okada et al, we defined nonpersistence as not attending any scheduled treatment or monitoring visit for any reasons for at least 6 months within the observational period [ 8 ]. Patients who were scheduled beyond 6 months for the follow-up were not considered as nonpersistent.…”

A model to quantify the influence of treatment patterns and optimize outcomes in nAMD

“…Randomized controlled trials (RCT) showed that individualized PRN and T&E are not inferior to fixed treatment regimens but mitigate treatment burden for the patient 8 – 10 . However, the average number of intravitreal injections applied by PRN or T&E in real-world setting is consistently lower than in RCTs due to multifactorial reasons including the patient, physician, treatment center set up and logistical factors 11 – 15 . Concurrently, VA gains observed in real-world settings stay below those observed in RCT.…”