Efficacy,tolerability and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% in a broad patient population: multicenter,open-label observational study*

ABSTRACT

Objective: To evaluate intraocular pressure (IOP)-lowering efficacy, tolerability, and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% (Ganfort^?) among German patients.

Methods: Multicenter, observational, open-label study of patients with primary open angle glaucoma or ocular hypertension (n?=?606). As determined by participating physicians, patients had insufficient IOP control and required a medication change. They were switched to once-daily fixed-combination bimatoprost/timolol with no wash-out period. IOP was recorded at treated baseline, 4–6 weeks and 12 weeks after switching. Tolerability was measured using a 4-step scale (excellent, good, moderate, poor) and all adverse events were recorded.

Results: A total of 405 patients switched from monotherapy, 97 switched from other fixed combinations, and 104 switched from non-fixed combinations. Among all patients, 32.5% had used prostaglandin analog (PGA) monotherapy, 8.7% had been using a fixed combination that included a PGA, and 6.9% had been using an adjunctive combination of a PGA and a β-blocker. Mean treated baseline IOP (±SD) for all patients was 20.7?±?3.5?mmHg. Overall, changing medication to fixed-combination bimatoprost/timolol lowered IOP to 16.6?±?2.7?mmHg (p?<?0.001 vs. baseline) after 4–6 weeks and to 16.1?±?2.6?mmHg (p?<?0.001) after 12 weeks; reductions of 19.8% and 22.2%, respectively. Combined bimatoprost/timolol provided an additional IOP reduction versus baseline in most subgroups based on prior treatment. At week 12, patients who had previously used a β-blocker achieved an additional 25.8% decrease from baseline and IOP was reduced by 22.6% in former PGA monotherapy patients. At week 12, 84.6% of all eyes reached a target pressure less than or equal to 18?mmHg. Tolerability of bimatoprost/timolol was rated excellent or good by the physicians for 98.7% of patients and by 96.7% of the patients themselves. Few adverse events occurred during the treatment period.

Conclusions: Although this study was limited by its observational design, our results show that the fixed combination of bimatoprost 0.03%/timolol 0.5% was effective, well tolerated, and safe in a broad patient population.     

A systematic review to assess adherence and persistence with statins

Objective: To identify and assess studies published over a 10 year period up to February 2016 which measure adherence or persistence with statins, to summarize their methods, strengths and weaknesses and to summarize evidence linking statin adherence/persistence with risk of cardiovascular events.

Methods: Electronic databases and abstracts from four major cardiovascular disease conferences were searched from January 2005 to February 2016. The study selection process was performed by two reviewers working independently. Studies were included if they reported data regarding patient adherence or persistence with statins in adults with primary hypercholesterolemia, using any type of study design or length of follow-up. One reviewer extracted the study data and assessed study quality, which was checked by a second reviewer independently. Given the heterogeneity between the included studies a narrative critique and summary is presented.

Results: We report on 84 real world studies which aimed to assess adherence or persistence with statins. The majority of studies concluded that good adherence/persistence was associated with reduction in cardiovascular events and mortality. In two studies high intensity statin regimens were associated with poorer patient adherence when compared to low intensity statins. Adherence and persistence with statin therapy also has an impact on hospitalization costs and other cardiovascular disease (CVD) related costs.

Conclusions: Adherence and persistence are associated with a reduction in CVD events and mortality. There was limited evidence to suggest that high intensity statin regimens are associated with poorer treatment adherence when compared to lower intensity regimens. Hence, more robust studies are required to establish this association. As recommended by the 2013 ACC/AHA, 2016 ESC and several other clinical guidelines, clinicians and pharmacy managers should regularly monitor statin therapy adherence.     

Factors associated with medication adherence and persistence of treatment for hypertension in a Medicaid population

BackgroundNon-adherence with antihypertensive therapy is a significant problem. Prior research has generally focused upon one drug or one drug class. Current information across multiple antihypertensive drug classes is limited.ObjectivesTo describe the initial treatment of recipients of Louisiana Medicaid with newly-diagnosed hypertension; evaluate differences in adherence and persistence rates among multiple antihypertensive drug classes; and test the association of drug classes, race, gender, age and comorbidity with adherence and persistence to drug therapy.MethodsIn a retrospective analysis of administrative claims data, initial therapy was described by type and drug class for 4544 Medicaid recipients with newly-diagnosed hypertension. Recipients were placed into cohorts based upon drug classes (diuretics, beta-blockers, angiotensin-II receptor blockers, angiotensin converting enzyme inhibitors, and calcium channel blockers). Persistence with drug therapy and Medication Possession Ratios (MPR) were calculated for 6-month and 12-month periods following diagnosis. Drug class and demographic variables were used as predictor variables in logistic regression analyses of persistence and MPR.ResultsRecipients in the study group were primarily female (66%) and Black (65%). Recipients initially were treated with monotherapy (33%), multiple drugs (11%), fixed combinations (8%) or no drugs (48%). After one year, 62% of recipients were not receiving drug therapy. Persistence rates by cohort ranged from 26% to 42% at 6-months following diagnosis, and 14%–28% at 12-months. The proportion of recipients by cohort with MPRs of 0.8 or above ranged from 43% to 60% at 6-months and 25%–42% at 12-months. Race, comorbidities, and initial drug therapy were significant predictors of both persistence and MPR.ConclusionsWithin this study group, adherence and persistence to medication therapy were less than optimal. Future efforts to improve compliance with medication therapy could be focused upon specific groups having poor adherence and/or persistence within the drug class cohorts analyzed in this study.     

A 6 month,prospective, observational study of PDE5 inhibitor treatment persistence and adherence in Latin American men with erectile dysfunction

Abstract

Objectives:

To assess persistence/adherence rates of phosphodiesterase type-5 inhibitor (PDE5I) on-demand dosing in Latin American men with erectile dysfunction (ED), and explore patient characteristics and treatment factors that may be predictive for PDE5I persistence and adherence.     

Comparison of persistence and adherence between fixed-dose combinations and two-pill combinations in Japanese patients with type 2 diabetes

Objective: To compare treatment patterns, persistence and adherence between fixed-dose combinations (FDCs) and two-pill combinations (TPCs) of oral antidiabetic drug (OAD) classes in Japanese patients with type 2 diabetes mellitus (T2DM) using administrative claims databases (Japan Medical Data Center [JMDC] and Medical Data Vision [MDV]).

Methods: This was a retrospective, longitudinal cohort analysis conducted between 2011 and 2015, in patients with T2DM receiving OADs as FDC or TPC. Outcomes included prescribing patterns, treatment persistence and adherence.

Results: Data from 3474 and 3066 patients receiving FDCs, and 4325 and 5192 patients receiving TPCs from the JMDC and MDV databases, respectively, was extracted. The most common OAD combination received by over half of all patients was dipeptidyl peptidase-4 inhibitor (DPP-4i) + thiazolidinediones (TZDs) (64.1% [JMDC] and 70.5% [MDV]). Overall, 12-month persistence rates were higher in patients receiving FDCs compared with TPCs (70.4 vs. 66.2% [JMDC], 75.6 vs. 55.7% [MDV]). In the JMDC population receiving FDCs or TPCs, persistence rates were highest with DPP-4i schedules (67.5–83.5%). Median time to discontinuation was significantly longer with biguanide?+?TZD, and DPP-4i?+?TZD FDC schedules (p < .05) than TPC; adherence rates were ≥80% across all antidiabetic drug classes in both database populations.

Conclusions: Persistence with and adherence to OADs in Japanese patients with T2DM were greater with FDCs than with TPCs, which may suggest increased patient satisfaction due to reduced treatment burden. Further studies are warranted to investigate the impact of adherence and persistence of FDCs of OADs on glycemic control.     

A 6-month,prospective, observational study of PDE5 inhibitor treatment persistence and adherence in Middle Eastern and North African men with erectile dysfunction

Abstract

Background:

Erectile dysfunction (ED) negatively impacts quality of life. Phosphodiesterase type 5 inhibitors (PDE5Is) are effective in treating ED; however, rates of discontinuation remain high.     

A comparative study on the efficacy, safety, and cost-effectiveness of bimatoprost/timolol and dorzolamide/timolol combinations in glaucoma patients

Aim:

This study was designed to compare the bimatoprost/timolol combination and dorzolamide/timolol combination in glaucoma for efficacy, safety, and cost-effectiveness in a local population of Trichy in the state of Tamilnadu.

Materials and Methods:

Eight-week, randomized, parallel group, open-label study was conducted on 48 patients of open angle glaucoma or ocular hypertension. After initial clinical assessment and baseline investigations, bimatoprost/timolol combination (Group A) was prescribed to 22 patients (2 patients lost after initial assessment) and dorzolamide/timolol combination (Group B) to 24 patients. The patients were reviewed after second and eighth weeks for cure rate and adverse drug reaction monitoring.

Results:

At the end of 8 weeks, the mean reduction in intraocular pressure from baseline was 13.04 mmHg (95% confidence interval (CI): 10.67–14.70) with bimatoprost/timolol combination once daily (P < 0.01) and 9.46 mmHg (95% CI: 7.47–10.5) with dorzolamide/timolol combination twice daily. Both the treatments were safe. Cost-effective range of bimatoprost/timolol combination was lower than that of dorzolamide/timolol combination.

Conclusion:

The fixed combination of bimatoprost/timolol was slightly more effective than that of dorzolamide/timolol combination in reducing IOP, and both treatments were generally well tolerated. Bimatoprost/timolol combination was more cost-effective (cost-effective analysis) than dorzolamide/timolol combination.     

Oral anticoagulant adherence and switching in patients with atrial fibrillation: A prospective observational study

BackgroundAdherence to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) is important in preventing stroke. The dominance of retrospective studies using administrative data has led to a lack of data on psychosocial determinants of adherence and prevented comparison of adherence between OAC drug classes. OAC switching is another aspect of adherence that is unexplored.MethodsA prospective design was utilized to measure AF patients’ self-reported adherence and OAC switching, and to identify their clinical, demographic, and psychosocial determinants. Participants were recruited from specialized AF clinics in Canada and followed for up to 2 years. Data were collected via telephone every 3–4 months using a structured survey. Adherence was measured using the Morisky Medication Adherence scale (©MMAS-8).ResultsThe included participants (N = 306) were followed for a median follow up time of 14.1 months and had an average of 3.2(SD 1.4) study visits. The mean self-reported adherence on the ©MMAS-8 was 7.28(SD 0.71) for patients receiving care at specialized AF clinics. Older age, experiencing a bleed, and higher satisfaction with the burden of medications were significantly associated with higher adherence. Drug class did not have any significant impact on adherence. 7.8% of the cohort experienced a switch with most of them being from warfarin to DOAC. Taking warfarin as the index medication, experiencing a bleed and older age were significantly associated with higher odds of switching.ConclusionPatients with AF reported high adherence to their OAC therapy however being on DOAC may not translate to better adherence compared to VKA. Improving satisfaction with the burden of therapy is important in improving adherence.     

Preparation of topical bimatoprost with enhanced skin infiltration and in vivo hair regrowth efficacy in androgenic alopecia

To prepare a topical formulation of bimatoprost (BIM) with high skin permeability, we designed a solvent mixture system composed of ethanol, diethylene glycol monoethyl ether, cyclomethicone, and butylated hydroxyanisole, serving as a volatile solvent, nonvolatile co-solvent, spreading agent, and antioxidant, respectively. The ideal topical BIM formulation (BIM–TF#5) exhibited 4.60-fold higher human skin flux and a 529% increase in dermal drug deposition compared to BIM in ethanol. In addition, compared to the other formulations, BIM–TF#5 maximally activated human dermal papilla cell proliferation at a concentration of 5 μM BIM, equivalent to 10 μM minoxidil. Moreover, BIM–TF#5 (0.3% [w/w] BIM) significantly promoted hair regrowth in the androgenic alopecia mouse model and increased the area covered by hair at 10 days by 585% compared to the vehicle-treated mice, indicating that entire telogen area transitioned into the anagen phase. Furthermore, at day 14, the hair weight of mice treated with BIM–TF#5 (5% [w/w] BIM) was 8.45- and 1.30-fold greater than in the 5% (w/w) BIM in ethanol and 5% (w/v) minoxidil treated groups, respectively. In the histological examination, the number and diameter of hair follicles in the deep subcutis were significantly increased in the BIM–TF#5 (0.3 or 5% [w/w] BIM)-treated mice compared to the mice treated with vehicle or 5% (w/w) BIM in ethanol. Thus, our findings suggest that BIM–TF#5 is an effective formulation to treat scalp alopecia, as part of a novel therapeutic approach involving direct prostamide F2α receptor-mediated stimulation of dermal papilla cells within hair follicles.     

Methods for evaluation of medication adherence and persistence using automated databases

PURPOSE: Our aim was to perform a systematic review of the methods currently being used to assess adherence and persistence in pharmacoepidemiological and pharmacoeconomic studies using automated databases. METHODS: A MEDLINE search of English language literature was performed to identify studies published between January 1, 1980 and March 31, 2004 that evaluated adherence, compliance, persistence, switching, or discontinuations of medications using automated dispensing data (pharmacy records). Two study investigators independently reviewed the abstracts and articles to determine relevant studies according to specified criteria. RESULTS: A total of 136 articles met the criteria for evaluation. The types of measures of adherence and persistence commonly reported include the medication possession ratio and related measures of medication availability (77 studies), discontinuation/continuation (58 studies), switching (34 studies), medication gaps (13 studies), refill compliance (7 studies), and retentiveness/turbulence (4 studies). Specific issues considered include the assessment of exposed time to drug therapy and specification of the follow-up period. CONCLUSIONS: The terminology, definitions, and methods to determine adherence and persistence differ greatly in the published literature. The appropriateness and choice of the specific measure employed should be determined by the overall goals of the study, as well as the relative advantages and limitations of the measures.     

A comparison of the safety and intraocular pressure lowering of bimatoprost/timolol fixed combination versus latanoprost/timolol fixed combination in patients with open-angle glaucoma*

ABSTRACT

Purpose: To compare the efficacy and tolerability of a once daily evening dose of the latanoprost/timolol fixed combination (LTFC) with that of a once-daily evening dose of the bimatoprost/timolol fixed combination (BTFC) in patients with open-angle glaucoma with elevated intrao­cular pressure (IOP) insufficiently responsive to mono­therapy with prostaglandin analogues/prostamides.

Design: Prospective, randomized, evaluator masked, single-center study.

Participants: 36 patients with a diagnosis of open-angle glaucoma, with or without pseudoexfoliation, and inadequate control of IOP, insufficiently responsive to monotherapy with prostaglandin analogues/prostamides.

Main outcome measure: The primary end-points were the change in IOP at 9:00?am from baseline to week 4, and the difference between treatment groups in the mean diurnal IOP reduction from baseline to week 4.

Results: BTFC provided significantly greater mean diurnal IOP reduction [mean (standard deviation)] 2.8 (0.9)?mmHg, compared with LTFC 2.1 (0.6)?mmHg, p = 0.0214. Both treatments significantly reduced the IOP from baseline at each IOP time-point measured, p < 0.0001, and for the mean diurnal IOP; p = 0.0049 for the LTFC, and p < 0.0001 for the BTFC. There were no significant differences in average hyperemia scores among groups, 1.25 (0.5) vs. 1.62 (0.69), p = 0.3835, for the LTFC and the BTFC, respectively.

Conclusions: The results of this study showed a significantly higher IOP-lowering effect of a once-daily evening dose of the BTFC compared to that of a once-daily evening administration of the LTFC.