Gail F. Schwartz

Adherence and Persistence with Glaucoma Therapy

Adherence and persistence with chronic therapies is crucial to prevent disease progression, such as in glaucoma. Patients report high rates of adherence, which are not supported by pharmacy claims analysis. This article reviews the literature regarding methods to assess adherence and persistence and the patient behaviors that pose challenges to proper treatment. Rates for persistence are generally below 50% at 1 year. Differentiating efficacy of eyedrops from lack of adherence presently confounds ophthalmic treatment. Additionally, as intraocular pressure (IOP) can appear controlled by short-term adherence, the physician can be fooled into believing the patients glaucoma is well-controlled. Likewise, when progressive worsening is noted despite good IOP control, it can be problematic whether the patients target pressure needs to be lowered or adherence needs to be improved. White-coat adherence is common, in which patient adherence rises sharply 1 week before the appointment with the physician, then declines rapidly following the appointment. White-coat adherence may make it difficult to assess IOP control over the longer term; cycling behavior with medication use is well-documented. Adherence and persistence rates differ by class of drug, with higher rates associated with prostaglandin use. We review findings from The Glaucoma Adherence and Persistency Study that identified behaviors associated with poor adherence. Greater physician awareness of adherence and persistence issues is necessary in order to help the patient become more adherent.

Objective assessment of compliance and persistence among patients treated for glaucoma and ocular hypertension: a systematic review.

Purpose This study summarizes findings from objective assessments of compliance (or adherence) and persistence with ocular hypotensive agents in patients with glaucoma and ocular hypertension. Design Systematic literature review. Methods A PubMed and reference list search was conducted across publication years 1970–2010, using these terms and variants: “compliance,” the equivalent term “adherence,” and “persistence” in patients with these conditions and therapies. Summaries of selected studies were stratified by measurement method (electronic monitor, prescription fills review, medical chart review). Measures of central tendency across studies were calculated for commonly-reported compliance or persistence measures. Results Fifty-eight articles met all inclusion/exclusion criteria: measurement of compliance–electronic monitoring (seven studies reported in 14 articles), measurement of compliance/ persistence–prescription records (36 studies in 38 articles), and measurement of persistence– medical chart review (six studies in six articles). From electronic monitoring, most therapy-experienced patients took medication consistently, but ≥20% met criteria for poor compliance. From prescription records, only 56% (range 37%–92%) of the days in the first therapy year could be dosed with the medication supply dispensed over this period. At 12 months from therapy start, only 31% (range 10%–68%) of new therapy users had not discontinued, and 40% (range 14%–67%) had not discontinued or changed the initial therapy. From medical chart review, only 67% (range 62%–78%) of patients remained persistent 12 months after starting therapy. Conclusions Evidence provided by this review suggests that poor compliance and persistence has been and remains a common problem for many glaucoma patients, and is especially problematic for patients new to therapy. The direction of empirical research should shift toward a greater emphasis on understanding of root causes and identification and testing of solutions for this problem.

Evaluation of eye drop administration technique in patients with glaucoma or ocular hypertension

Abstract Objective: To evaluate eye drop administration by patients at multiple visits in the setting of a randomized controlled trial. Study design and methods: Patients with glaucoma or ocular hypertension were randomized to 12 weeks of treatment with topical ocular hypotensive medication in a multicenter, investigator-masked trial. At baseline, patients were given a questionnaire for self-assessment of difficulty with drop administration. At baseline and 12 weeks, patients demonstrated drop instillation using a bottle of artificial tears. Main outcome measures: Patient self-assessment of difficulty with drop administration and observed patient difficulty with drop administration, defined as bottle touching eye/adnexa, drop missing the ocular surface, or administering more than 1 drop. Results: Of 164 enrolled patients, 50% had previously been treated with ocular hypotensive medication for ≥3 years. Only 11.4% of patients reported difficulty with eye drop administration at study entry. At baseline, 18.2% of patients touched their eye/adnexa with the bottle and 10.3% missed the eye. At 12 weeks, 18.5% and 8.6% of patients, respectively, had similar difficulties. Overall, difficulty with drop instillation was observed in 42.1% of patients. Difficulty at both visits was seen in 35.3% of patients who reported difficulty at entry and in 17.2% of patients who denied difficulty. The relative risk of demonstrating difficulty at either visit was 2.0 times greater for patients who self-reported difficulty at study entry (P = 0.004). The relative risk of demonstrating difficulty at week 12 was 3.8 times greater for patients with observed difficulty at baseline (P < 0.001). Limitations of the study design included self-administration of drops to the eye of the patient’s choice and observation in an office setting. Conclusions: Patients with experience instilling topical glaucoma medications continue to have difficulties with eye drop administration, including patients who do not self-report difficulty. The risk of difficulty with eye drop administration is increased in patients who self-report difficulty and in patients who have been previously observed to have difficulty. Clinical trial registry number: NCT01253902.

Hyperemia-Associated Costs of Medication Changes in Glaucoma Patients Treated Initially With Prostaglandin Analogs

AIMS To develop a model to estimate and compare the cost of changing therapy due to hyperemia in glaucoma patients treated initially either with latanoprost, bimatoprost, or travoprost monotherapy. METHODS Data collected from the HealthCore Integrated Research Database, as part of the Glaucoma Adherence and Persistency Study (GAPS), were used to populate the model. Patients with a documented diagnosis of glaucoma who were newly treated (no ocular hypotensive medication and no glaucoma-related procedure during 6 months before first prescription) with latanoprost, bimatoprost, or travoprost monotherapy were identified. The time horizon for the base-case model was the duration of chart abstraction (mean = 4.1 years); a 3-month model also was developed. Physician-reported rates of hyperemia were obtained from chart reviews of 300 patients. Transition rates reflected events related to reports of hyperemia where a physician-driven change (switch or discontinuation) in therapy was documented. The per-patient direct cost (2008) due to hyperemia-driven change in therapy was calculated as the sum of the cost of the initial prescription plus the cost of the office visit where the patient was evaluated and the decision to change therapy was made. Costs were stratified by whether patients were hyperemia free or discontinued the initial therapy due to hyperemia. RESULTS From the sample of 13,977 newly treated patients, 8,743 patients were started on a prostaglandin monotherapy only. Of these, 5,726 received latanoprost, 1,633 were treated with bimatoprost, and 1,384 received travoprost index monotherapy. Across all treatment groups, costs among hyperemia-free patients were US

Adherence and Persistence with Glaucoma Therapy: Brimonidine/Timolol versus Dorzolamide/Timolol and Various Two-Bottle Combinations

73.67 versus US

Patient adherence and persistence with topical ocular hypotensive therapy in real-world practice: a comparison of bimatoprost 0.01% and travoprost Z 0.004% ophthalmic solutions

140.02 for those who discontinued the initial prostaglandin due to hyperemia. Per-patient costs were lowest in the group treated initially with latanoprost. For the base-case model, with latanoprost as the reference, total per-patient incremental costs due to hyperemia-driven change in therapy were US

Comparison of adherence and persistence with bimatoprost 0.01% versus bimatoprost 0.03% topical ophthalmic solutions

5.92 for bimatoprost and US

An adherence based cost–consequence model comparing bimatoprost 0.01% to bimatoprost 0.03%

5.43 for travoprost. Results were not highly sensitive to increases either in the incidence of hyperemia among latanoprost-treated patients or in the cost of latanoprost. CONCLUSIONS Hyperemia results in increased overall costs in patients treated with latanoprost, bimatoprost, and travoprost. Treatment with latanoprost is associated with lower hyperemia-related costs than treatment with bimatoprost or travoprost.

Patient persistency with topical ocular hypotensive therapy in a managed care population

Purpose: Patients with glaucoma often require multiple topical medications to reach target intraocular pressure. This database analysis examined persistence and adherence in patients’ prescribed fixed-combination brimonidine/ timolol, fixed-combination dorzolamide/timolol, or various commonly used two-bottle combinations. Participants: Glaucoma patients (ICD-9 code: 365.xx; n=7883) from the Source Healthcare Analytics Source®; Lx database with an index prescription for fixed-combination brimonidine/timolol, fixed-combination dorzolamide/timolol, or various commonly used two-bottle combinations during the 6-month qualifying period (January 2008–June 2008), but not the 12 months before, were included. Methods: In this retrospective prescription database analysis, adherence and persistence for fixedcombination brimonidine/timolol were compared to fixed-combination dorzolamide/timolol and various commonly used two-bottle combinations. The two-bottle arms were: β-blocker+brimonidine; β-blocker+carbonic anhydrase inhibitor; β-blocker+prostaglandin analogue; carbonic anhydrase inhibitor+brimonidine; carbonic anhydrase inhibitor+prostaglandin analogue; and prostaglandin analogue+brimonidine. Main outcome measures: Persistence for brimonidine/timolol was compared with each of the comparators using Kaplan-Meier survival analysis for 12 months after the index prescription. Adherence was assessed using the medication possession ratio. Results: Kaplan-Meier analyses found that a significantly greater proportion of patients remained on treatment with brimonidine/timolol (34.9%) compared with each of the other treatments (13.4%–20.8%; p<0.0001) at the end of the study period. In addition, the 12-month medication possession ratio was significantly higher for brimonidine/ timolol (42.7%) than for each of the two-bottle arms (23.3%–34.9%; p<0.0001 for all comparisons). The medication possession ratio for brimonidine/timolol was also slightly, but significantly, higher than that for dorzolamide/timolol (40.6%; p=0.0208). Conclusions: Persistence and adherence are higher with a fixed-combination single bottle of brimonidine/timolol than with fixed-combination dorzolamide/timolol and commonly used two-bottle combinations.

Persistency with latanoprost or timolol in primary open-angle glaucoma suspects

Background Effective control of intraocular pressure is predicated upon patient compliance with pharmacotherapy. We compared patient adherence and persistence with two new ocular hypotensive formulations, using real-world utilization data. Methods This observational cohort study employed pharmacy claims data from the Source® Lx (Wolters Kluwer Pharma Solutions) database. Patients with an initial (index) prescription for topical bimatoprost 0.01% or travoprost Z (April to June 2011) and no claim for ophthalmic prostaglandin or prostamide analogs within the previous 18 months were identified. Treatment adherence was expressed as proportion of days covered with study medication during the first 365 days after the index prescription. Treatment persistence with study medication was assessed over the first 12 months using Kaplan–Meier survival analyses, allowing a maximum 30-day gap for prescription refill. Treatment status was determined monthly over this period. Results A total of 12,985 patients were assessed for treatment adherence, and 10,470 for treatment persistence. Adherence was better with bimatoprost 0.01% than with travoprost Z (mean proportion of days covered 0.540 versus [vs] 0.486, P<0.001), and more patients showed high adherence (proportion of days covered >0.80) with bimatoprost 0.01% than travoprost Z (29.1% vs 22.3%, P<0.001). Continuous 12-month persistence was higher with bimatoprost 0.01% than with travoprost Z (29.5% vs 24.2%, P<0.001). At month 12, more patients were on treatment with bimatoprost 0.01% than travoprost Z (48.8% vs 45.7%, P<0.01). Similar findings were demonstrated in cohorts of ocular hypotensive treatment-naïve patients, branded latanoprost switchers, and older patients (age ≥65 years), and after inclusion of patient characteristics as covariates. Conclusion For patients with glaucoma or ocular hypertension, bimatoprost 0.01% offers compliance advantages over travoprost Z.