Predictors of Nonadherence to Topical Intraocular Pressure Reduction Medications Among Medicare Members: A Claims-Based Retrospective Cohort Study.

BACKGROUND: Reported adherence rates with ocular hypotensive medications typically range from 51% to 56% over the first year of therapy. As intraocular pressure (IOP) reduction slows the progression of vision loss from glaucoma, early identification of nonadherent members is crucial to effective disease management. OBJECTIVES: To (a) identify member characteristics and other factors related to nonadherence with topical IOP-lowering medications available in administrative claims data and (b) create a predictive model incorporating these variables. METHODS: This retrospective cohort study analyzed data from Humana's administrative claims database. The study cohort included members aged 65-89 years enrolled in a Medicare Advantage Prescription Drug plan (MAPD; medical and pharmacy benefits), with > 1 topical IOP-lowering medication claims between January 2011 and September 2012 and a minimum of 24 months of continuous enrollment-12 months before and 12 months after the initial (index) prescription claim for a topical IOP-lowering medication. Adherence was defined as the proportion of days covered (PDC) with drug supply (calculated from the number of drops per bottle and dose) over the first year after the index prescription. Members with PDC > 0.80 were considered adherent, while members with PDC < 0.80 were considered nonadherent. Multivariable stepwise logistic regression with backward elimination was used to construct a predictive model for the likelihood of nonadherence (PDC < 0.80). The model was developed using 28 input variables*#x2013;10 variables were retained in the final model. RESULTS: 73,256 MAPD members were included in this study; most (69%) of these members were continuing topical IOP-lowering medication users. The proportion of patients adherent (PDC > 0.80) to IOP-lowering medications was 51%. The study sample was split, using a 2:1 ratio, into a development sample (n = 48,840 members) and a validation sample (n=24,416 members). The model performed equally well in the development sample and the validation sample (area under the curve = 0.71 for development and validation sets), making it appear robust in this Medicare population. In the final predictive model, characteristics increasing the likelihood (P < 0.01) of nonadherence to IOP-lowering medication within the MAPD population included index IOP prescription filled through mail order, higher medical costs during the pre-index period, being a new IOP-lowering medication user, and being male. Characteristics that lowered the likelihood of nonadherence included advanced age, higher pharmacy costs during the pre-index period, receiving a low-income subsidy, residing in the South, and a previous diagnosis of open-angle glaucoma or history of glaucoma surgery. CONCLUSIONS: Nonadherence to topical IOP-lowering medication can be predicted with 10 commonly available demographic, clinical, and treatment-related variables generally available in administrative claims data for an MAPD population. Given that this predictive model was constructed using these generally available data, it could potentially be replicated by other health plans for use in predicting nonadherence to topical IOP-lowering medications among MAPD plan members. This predictive model can be used to identify members that are likely to be nonadherent in order to target interventions intended to improve ocular hypotensive medication adherence. DISCLOSURES: Funding for this study was contributed by Allergan. Comprehensive Health Insights was contracted by Allergan to conduct this study. Sheer, Bunniran, and Uribe are employed by Comprehensive Health Insights/Humana and own stock in Humana. Fiscella, Chandwani, and Patel are employed by Allergan. Study concept and design were contributed by Sheer, Fiscella, and Patel, along with Bunniran and Uribe. Sheer and Bunniran took the lead in data collection, and data interpretation was performed by Bunniran and Uribe, along with the other authors. The manuscript was written and revised by Sheer, Bunniran, Chandwani, and Uribe, with assistance from Fiscella and Patel.

Understanding dry eye disease: a managed care perspective.

Dry eye disease (DED) is a multifactorial disorder that results in eye discomfort, visual disturbance, and often ocular surface damage. This supplement to The American Journal of Managed Care discusses the prevalence of DED and the economic burden associated with DED. The etiology and pathophysiology of DED will also be discussed, including disease progression and impact on the patient's quality of life. With greater understanding of the pathophysiology of DED, there are numerous available therapies/strategies for the management of the disorder, ranging from artificial tear substitutes, anti-inflammatory agents, secretagogues, punctal plugs, and systemic immunosuppressives, to surgery. This activity will aim to provide managed healthcare professionals with an understanding of when and how to use these different strategies to reduce morbidity and prevent complications.

An adaptable HPLC method for the analysis of frequently used antibiotics in ocular samples.

Four different antibiotics, delivered individually to rabbit eyes via hydrophilic intraocular lenses soaked in the drug solution prior to implantation, were measured in aqueous and vitreous humor samples from the eyes. To meet this analytical need, we developed a sensitive, high performance liquid chromatographic (HPLC) method for measuring the concentrations of moxifloxacin, gatifloxacin, linezolid, and cefuroxime in the ocular tissue. Separations were carried out on a LichroSpher RP-18 column, maintained at room temperature. The fluoroquinolones were eluted with a mobile phase consisting of 20% acetonitrile, in 0.1% trifluoroacetic acid (pH 3.0) with 30 mM tetrabutylammonium chloride. Linezolid and cefuroxime were eluted with 25% acetonitrile in 25 mM Na acetate buffer, pH 5.0. All elutions were isocratic. With ultraviolet detection, the lower limit of quantitation (LLOQ) for these compounds approached 1 ng (on-column injection). By using fluorescence detection, the LLOQ for the fluoroquinolones improved to 200 pg. The overall accuracy of the method was >or=90%. With minor modifications, the method was optimized for each of the agents, and the resulting analytical sensitivity made the method suitable for clinical investigations of the ocular penetration of these drugs.

Cost of illness of glaucoma: a critical and systematic review.

Cost-of-illness studies determine the total financial burden of a disease by considering direct and indirect costs, including medication, diagnostics and surgery. Studies of resource use and costs associated with primary open-angle glaucoma have used varying methodologies. Most have focused on consumption of healthcare resources at various stages of disease to anticipate costs. The direct costs associated with the disease often continue to increase as glaucoma progresses from the earliest to most advanced stages. Determinations of the costs associated with glaucoma progression and prevention should also incorporate the chance of patient non-compliance with treatment. Since glaucoma severity most often correlates with increased costs, minimizing or halting visual field loss and increasing patient treatment compliance may all contribute to a reduction in the overall economic burden of glaucoma.

Third- and fourth-generation fluoroquinolones: retrospective comparison of endophthalmitis after cataract surgery performed over 10 years.

PURPOSE: To determine differences in endophthalmitis rates with prophylactic use of third- versus fourth-generation fluoroquinolones in cataract surgery. SETTING: University hospitals. METHODS: This retrospective cross-sectional (prevalence) study looked at patients who had phacoemulsification at a university eye center over a 10-year period. A nosocomial infectious reporting database was used to report endophthalmitis occurrences. The following were performed: a retrospective analysis of prospectively collected data to establish endophthalmitis rates, a prevalence analysis of the postoperative quinolone antibiotic prescribed, and a comparative analysis of endophthalmitis rate versus postoperative quinolone prescribed for all reported endophthalmitis cases. The main outcome measure was occurrence of endophthalmitis after cataract surgery. RESULTS: From January 1997 to December 2007, 29276 patients had phacoemulsification cataract surgery. Forty cases of postoperative bacterial endophthalmitis were reported. The endophthalmitis rate from January 1997 to August 2003 associated with use of third-generation fluoroquinolones (ciprofloxacin, ofloxacin) was 0.197% (33/16710). The rate from September 2003 to December 2007 associated with fourth-generation fluoroquinolones (gatifloxacin, moxifloxacin) was 0.056% (7/12566). The difference between third- and fourth-generation drugs was statistically significant (P = .0011). Of fourth-generation fluoroquinolone infections, 0.015% (1/6651) and 0.1% (6/5915) were associated with gatifloxacin and moxifloxacin, respectively. The difference between drugs was statistically significant (P = .040). CONCLUSIONS: The differences in the pharmacokinetic and pharmacodynamic properties of quinolone antibiotics may affect the endophthalmitis incidence after cataract surgery. The significant difference in endophthalmitis rates between gatifloxacin and moxifloxacin requires further study.

Utilization characteristics of topical cycolsporine and punctal plugs in a managed care database.

A retrospective administrative claims analysis of treatment options for dry eye disease (DED) evaluated treatment patterns and utilization characteristics of patients receiving cyclosporine, punctal plugs, or a combination of cyclosporine and punctal plugs, and examined differences in health plan costs with the 2 treatments. A total of 23,821 commercial health plan enrollees that initiated treatment with cyclosporine or punctal plugs between January 1, 2004, and December 31, 2005, were reviewed. There were 9065 subjects in the cyclosporine group, with a mean of 3.93 (median of 3) prescription fills reported in the 365-day follow-up period per subject. The mean health plan cost per patient was $336 (median $228), with total health plan costs of $3.05 million. In the punctal plugs cohort of 8758 subjects, there was a mean of 2.85 punctal plugs procedures per patient in the follow-up period. Total health plan costs for punctal plugs procedures were $3.28 million (mean cost per patient $375). During the follow-up period, 21.1% of punctal plugs patients subsequently received cyclosporine, whereas only 11.4% of topical cyclosporine patients subsequently received punctal plugs. Our results suggest that use of topical cyclosporine before punctal plugs insertion may be of benefit to patients with DED and could result in a savings in overall treatment costs.

Topical ophthalmic fourth-generation fluoroquinolones: Appropriate use and cost considerations.

PURPOSE: The utilization and refill rates of topical ophthalmic fourth-generation fluoroquinolones among physicians, as well as the associated costs, were studied. METHODS: A large data set of retrospective pharmacy prescription claims was obtained from multiple plans, including commercial managed care organizations, Medicaid, and Medicare. The data included the number and cost of all new and refill prescriptions for six months for gatifloxacin 0.3% and moxifloxacin 0.5% by physician specialty. New prescription and refill data were also analyzed from a state Medicaid plan to determine if similar trends existed. RESULTS: Primary care physicians wrote approximately 7,000 (7.7%) gatifloxacin and 84,000 (92.3%) moxifloxacin prescriptions, with pediatricians accounting for 4,000 (5.1%) gatifloxacin and 75,000 (94.9%) moxifloxacin prescriptions. Eye care physicians accounted for a similar amount of prescriptions for each antibiotic during the same period. The total cost of prescriptions for all primary care practitioners was approximately $170,000 for gatifloxacin and $2.5 million for moxifloxacin; prescriptions written by pediatricians accounted for $110,000 for gatifloxacin and $2.2 million for moxifloxacin. CONCLUSION: Prescription drug claims from payers using pharmacy benefit management companies during a six-month period indicated that the numbers of prescriptions written for gatifloxacin and moxifloxacin were similar among eye care physicians, but primary care physicians wrote a greater number of prescriptions for moxifloxacin. Analysis of claims to a Medicaid database revealed an increase in the prescriptions written by primary care physicians for moxifloxacin after its addition to the drug formulary.

Measurement of persistence and adherence to regimens of IOP-lowering glaucoma medications using pharmacy claims data.

PURPOSE: Determine persistence and adherence of glaucoma patients to therapeutic regimens of prostaglandin/prostamide-class IOP-lowering medications. DESIGN: Retrospective, population-based study. METHODS: Glaucoma patients in the IMS Health LifeLink database with a pharmacy claim for latanoprost (n = 1567), travoprost (n = 381), or bimatoprost (n = 476) between September, 2001 and March, 2002 who had no claims for IOP-lowering medication in the previous 180 days, and who were persistent during the first 90 days of therapy. Values reported in the quantity dispensed and days supply fields of the database were used in an algorithm that corrected anomalous data and adjusted days supply to calculate the main outcome measures, persistence, and adherence to therapy. RESULTS: The percentage of patients persistent for the 12-month observation period was 69.4% (1087/1567) for those prescribed latanoprost, 70.6% (269/381) for those prescribed travoprost, and 68.1% (324/467) for those prescribed bimatoprost. Mean adherence for patients prescribed latanoprost was 75.4% of the year, for those prescribed travoprost, 77.1% of the year, and for those prescribed bimatoprost, 78.2% of the year. The mean number of days adherent for bimatoprost-treated patients (291.2 days) was significantly greater than for latanoprost-treated patients (281.0 days), and not remarkably different from travoprost-treated patients (287.0 days). CONCLUSIONS: Overall, patients in this study who were taking IOP-lowering prostaglandin/prostamide medications had a mean adherence rate of 76% on average, suggesting that opportunities remain for improvement of adherence to therapeutic regimens for glaucoma treatment with prostamides and prostaglandins.

A retrospective study of endophtalmitis rates comparing quinolone antibiotics.

PURPOSE: To compare endophthalmitis rates between topical quinolone antibiotics over a four-year period in a university setting. DESIGN: Retrospective, cross-sectional (prevalence) study. STUDY POPULATION: Nine thousand seventy-nine patients who underwent a phacoemulsification procedure at a University Eye Center. INTERVENTIONS: The following interventions were conducted: use of a nosocomial infectious reporting database retrospective analysis of prospectively collected data to establish endophthalmitis rates; prevalence analysis of postoperative quinolone antibiotics; analysis of endophthalmitis rate vs postoperative quinolone prescribed. MAIN OUTCOME MEASURES: Occurrence of endophthalmitis after cataract surgery. RESULTS: During a four-year period involving 9079 phacoemulsification procedures, 26 cases of bacterial postoperative endophthalmitis were reported (rate = 0.286%). Eight of the 26 cases were considered complicated; 18 cases were uncomplicated. Among cases performed during this period, postoperative prescription volumes for ciprofloxacin (Ciloxan, Alcon Laboratories, Inc., Fortworth, Texas) and ofloxacin (Ocuflox, Allergan, Inc., Irvine, California) antibiotic drops were nearly identical, with 4538 patients receiving ciprofloxacin (49.98%) and 4541 patients receiving ofloxacin (50.02%). There were 22 endophthalmitis patients (85%) who had used topical ciprofloxacin and 4 patients (15%) who had used topical ofloxacin postoperatively. The difference in infectious rates between antibiotics was highly significant (P < .00026). For uncomplicated cases, 14 patients received ciprofloxacin and 4 patients received ofloxacin. This difference was also significant (P < .015). CONCLUSIONS: Differences in pharmacokinetic and pharmacodynamic properties exist among quinolone antibiotics, which may affect endophthalmitis incidence following cataract surgery.

Safety of verteporfin for treatment of subfoveal choroidal neovascular membranes associated with age-related macular degeneration.

Photodynamic therapy (PDT) is a novel treatment entity that exploits the photophysical properties of various photosensitive chemical entities which, upon light activation, results in targeted photooxidation and subsequent tissue destruction. The antiangiogenic properties of PDT have been adapted for treatment of subfoveal choroidal neovascular membranes due to disease states such as age-related macular degeneration (AMD). Historically, PDT has been limited by a lack of suitable photosensitive dyes. However, agents such as verteporfin, a second-generation benzoporphyrin derivative, appear to be free from the extensive phototoxicity that limited the success of previous agents. Verteporfin has a high affinity for choroidal neovascular membranes, typically found with exudative AMD, and upon photoactivation results in targeted microvascular damage and thrombus formation with resultant vessel occlusion. Scrutiny of diagnostic indicators for verteporfin administration, including critical angiographic evaluation of lesion size and visual acuity, is essential to treatment success. Large lesions with relatively good visual acuity (20/50 or better) may be at particular risk for marked vision loss following verteporfin administration. Lesion composition also appears to influence visual outcome with verteporfin use. The safety of verteporfin is directly dependent upon the appropriate integration of dosage, infusion and light activation required for a suitable pharmacotherapeutic outcome. When used appropriately, and with adequate patient education regarding photosensitivity, the risk-benefit of verteporfin for the medical treatment of neovascular AMD is favourable.

Aqueous and vitreous penetration of linezolid (Zyvox) after oral administration.

OBJECTIVE: To investigate the penetration of linezolid, a synthetic oxazolidinone antibiotic, into the aqueous and vitreous humor after oral administration. DESIGN: Noncomparative interventional, prospective case series study, randomized into group 1 (dose, one 600-mg tablet) or group 2 (2 doses of 600 mg given 12 hours apart). PARTICIPANTS: Patients undergoing pars plana vitrectomy between March 2001 and August 2002 at the University of Illinois at Chicago Eye Center who had not had prior vitrectomy surgery. METHODS: Aqueous, vitreous, and plasma samples were obtained and analyzed from 29 patients after oral administration of 1 dose (group 1A, 13 patients [13 eyes] sampled less than 2 hours after administration; group 1B, 9 patients [9 eyes] sampled more than 2 hours after administration) or 2 doses 12 hours apart (group 2, 7 patients [7 eyes]) before surgery. MAIN OUTCOME MEASURES: Aqueous, vitreous, and plasma concentrations of linezolid (micrograms per milliliter). RESULTS: Group 1A achieved mean aqueous, vitreous, and plasma levels of 0.77+/-0.6 microg/mL, 0.3+/-0.3 microg/mL, and 5.0+/-3.3 microg/mL, respectively. Group 1B achieved mean aqueous, vitreous, and plasma levels of 3.8+/-1.2 microg/mL, 2.3+/-1.4 microg/mL, and 7.6+/-2.7 microg/mL, respectively. Group 2 achieved mean aqueous, vitreous, and plasma levels of 6.6+/-2.7 microg/mL, 5.7+/-2.7 microg/mL, and 10.3+/-4.1 microg/mL, respectively. CONCLUSIONS: Mean inhibitory aqueous and vitreous minimum inhibitory concentrations for 90% of isolates (MIC(90)) were achieved against all gram-positive bacteria, including vancomycin-resistant enterococcus, methicillin-resistant Staphylococcus aureus, and streptococcal species after 2 doses given 12 hours apart. Mean MIC(90) were achieved for many gram-positive pathogens after only one dose in many patients after approximately 4 hours.

Medical therapy cost considerations for glaucoma.

PURPOSE: To determine the calculated daily patient cost (cost minimization) of medical glaucoma therapy and review cost trends. DESIGN: Experimental, controlled, prospective study. METHODS: The actual volume of various glaucoma medications or glaucoma medications with redesigned bottles was determined for most commercially available sizes of the tested products. The drops per milliliter based on the actual volume and the daily costs of the dosage schedules recommended by the manufacturers were compared. The cost of each bottle of medication was determined from the average wholesale price (AWP) in the United States. A comparison to 1999 prices where applicable will be analyzed to review costing trends. RESULTS: The generic timolol products (range, US dollars 0.38-US dollars 0.46 per day) were similar on a cost per day basis vs Betimol (Santen, Napa Valley, California, USA), Optipranolol (Bausch and Lomb Pharmaceuticals, Tampa, Florida, USA) and Timoptic (Merck, West Point, Pennsylvania, USA). Their percentage cost increase ranged from 5% to 22% since 1999, except for generic timolol XE gel-forming solution (48%). Betagan (Allergan, Irvine, California, USA), Betoptic S (Alcon Laboratories, Fort Worth, Texas, USA), and Ocupress (Novartis, Duluth, Georgia, USA) ranged from US dollars 0.88 to US dollars 1.11 per day, and their percentage cost increase ranged from 33% to 53%. Some brand-only products have raised their AWPs a greater percentage, including Betoptic S (37%), Iopidine (Alcon, Fort Worth, Texas, USA) (50%), Ocupress (Novartis Ophthalmics, Duluth, Georgia, USA) (53%), and Pilopine gel (Alcon, Fort Worth, Texas, USA) (32%). The mean cost per day for the topical carbonic anhydrase inhibitors Azopt (Alcon Laboratories; US dollars 1.33 per day) and Trusopt (Merck; US dollars 1.05 per day) differed from 1999 when prices were almost identical. Cosopt (Merck; timolol 0.5% plus dorzolamide 2%, US dollars 1.04 per day) was less than the cost of separate bottles of a topical carbonic anhydrase inhibitor and a beta-blocker. The selective alpha-2 agonist brimonidine 0.15% with Purite (Alphagan-P, Allergan, 5 ml) twice daily was US dollars 1.29 per day. The prostaglandin analogs were comparably priced with Lumigan (Allergan) US dollars 0.95 per day, Xalatan (Pharmacia and Upjohn, Kalamazoo, Michigan, USA) US dollars 1.25 per day, Travatan (Alcon Laboratories) US dollars 1.01 per day, and Rescula (Novartis) US dollars 0.90 per day. CONCLUSIONS: All generic timolol, Betimol, Optipranolol, Timoptic, and Timoptic XE (Merck) ranged from US dollars 0.38 to US dollars 0.50 per day. Other beta-blocker products were about twice as costly, ranging from US dollars 0.88 to US dollars 1.11 per day. Cosopt (US dollars 1.05 per day) was less costly than separate bottles of a topical beta-blocker and a topical carbonic anhydrase inhibitor dosed three times daily or twice daily. The prostaglandin analogs ranged from US dollars 0.90 per day (Rescula) to US dollars 1.25 per day (Xalatan). Newer glaucoma medications exhibit similar costs per day in many cases, compared with more traditional medications, especially with greater price increases in older brand-only products.