Fixed Combination Therapy Research Articles

Halobetasol 0.01%/tazarotene 0.045% lotion in the treatment of moderate-to-severe plaque psoriasis: Maintenance of therapeutic effect after cessation of therapy

Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Topical corticosteroids (TCS) are the mainstay of treatment. Long-term safety remains a concern, limiting use, and posttreatment flare is common. Tazarotene has also been shown to be effective in psoriasis, with efficacy maintained several weeks posttreatment. Fixed combination therapy with TCS and tazarotene may improve psoriasis signs and minimize posttreatment flare or rebound.To investigate the maintenance of effect posttreatment with a once-daily application of halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in comparison with its active ingredients and vehicle in patients with moderate-to-severe plaque psoriasis.Multicenter, randomized, double-blind, vehicle-controlled Phase 2 study in moderate or severe psoriasis (N=212). Patients randomized (2:2:2:1 ratio) to receive HP/TAZ, individual active ingredients, or vehicle, once-daily for 8 weeks with a 4-week posttreatment follow-up. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score, and 'clear' or 'almost clear'), and impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion.At the end of the 4-week posttreatment period, 38.2% of patients who had been treated with HP/TAZ were treatment successes; compared with 21.0%, 12.8% and 6.9% of patients who had been treated with HP (P=0.042), TAZ (P=0.004), or vehicle (P=0.002). HP/TAZ lotion was also superior in maintaining reductions in psoriasis signs of erythema, plaque elevation, and scaling at the target lesion. At the end of the 4-week posttreatment period, 49.1%, 54.5%, and 54.5% of patients, respectively, were treatment successes: compared with 38.7% (P=0.26), 48.4% (P=0.51), and 48.4% (P=0.51) of patients who had been treated with HP; 29.8% (P=0.049), 31.9% (P=0.022), and 23.4% (P=0.001) who had been treated with TAZ; and 13.8% (P=0.002), 20.7% (P=0.003), and 20.7% (P=0.003) who had been treated with vehicle. Side effects were minimal and tended to resolve during the posttreatment period.In conclusion, HP 0.01%/TAZ 0.045% lotion provides synergistic efficacy following 8 weeks' therapy that is sustained after a 4-week posttreatment period. J Drugs Dermatol. 2018;17(7):723-726.

The efficiency of monotherapy of patients with primary open-angle glaucoma with Bimatoprost 0.03 % (Bimoptic)

Purpose: to evaluate the hypotensive effect and adverse reactions occurrence in patients with primary open angle glaucoma (POAG) who received Bimatoprost (Bimoptic Rompharm) monotherapy.Materials and methods. 46 patients (75 eyes) with stage I–III POAG were prescribed bimatoprost therapy. Of these, 16 patients (20 eyes) had newly diagnosed glaucoma, 15 patients (27 eyes) previously received treatment with prostaglandin analogs (APG — Latanoprost), and 15 patients (28 eyes) previously received treatment with a fixed combination (FC) composed of timolol B-blocker and brinzolamide carbonic anhydrase inhibitor. The reason for transferring the patient from therapy with APG and FC to monotherapy with Bimatoprost was insufficient hypotensive effect of APG/FC therapy, and the presence of dry eye syndrome of varying severity in most patients. The results were evaluated after 1, 4 and 12 weeks of Bimatoprost therapy. Results. A hypotensive effect of monotherapy with Bimatoprost was confirmed in patients with newly diagnosed POAG. An additional hypotensive effect was revealed when patients with POAG were transferred from APG and FC therapy to monotherapy with Bimatoprost. Adverse reactions: mild and moderate hyperaemia, periorbital manifestations such as skin pigmentation, deepening of upper eyelid folds, narrowing of the palpebral fissure (ptosis) were noted, respectively, in 8, 6.7, 1.3, 2.7, 2.7 % of cases respectively, but did not require a discontinuation of the therapy in any patient. Eyelash growth was noted by 3 patients (4 %). This effect was not considered to be a side effect, since none of the patients bothered. In 47 % of patients who had previously received APG and FC therapy and had dry eye syndrome of varying severity, objective and subjective positive changes relating to dry eye syndrome was noted. A positive dynamic of morphometric parameters of the optic nerve and cells of the retinal ganglion complex was revealed in patients of all groups of study.Conclusion. Monotherapy with Bimatoprost can be recommended as therapy of choice for patients with newly diagnosed glaucoma, and those previously receiving antihypertensive therapy with PGAs or fixed combinations (-blocker + carbonic anhydrase inhibitor) including those having dry eye syndrome of varying severity.

FIXED COMBINATIONS IN THE TREATMENT OF GLAUCOMA

Glaucoma is a slowly progressive neuropathy with changes in the optic nerve, the retinal neurofibrillar layer, and the field of vision.The aim of the paper is to present the significance of detecting elevated intra ocular pressure in early glaucoma detection.Glaucoma is one of the leading causes of blindness in the world. According to the latest WHO estimates, as a challenge to global level resolution - carcinomas are in the first place, cardiovascular diseases in second, and blindness in third place. The glaucoma accounts for about 9-12% of all blind people in the world, that is, this disease is diagnosed in about 2.5 million people each year. WHO predicts that the percentage will increase to 30% by 2020.The definition of the 2014 European Glaucoma Association (EEC 2014) reads: "Glaucoma is a chronic progressive optic neuropathy with characteristic morphological changes on the optic nerve disc and the retinal neurofibrillar layer as well as the progressive death of ganglia cells with visual field loss in the absence other eye diseases and congenital anomalies. " Hence, in addition to the standard methods available to us, such as measuring the height of the intraocular pressure (IOP), gonioscopy, eyelid examination, as well as determining and monitoring visual acuity, the necessity of the standard computerized perimetry and optic coherent tomography of back eye segment.Timely diagnosis of glaucoma is the only mechanism to combat this disease. The new methods offer a variety of new possibilities for investigating the earliest changes in the optic nerve disc and the retinal neurofibrillar layer. Their use should be combined with the classic glaucoma testing methods, such as standard computerized perimeter. But the basis is the early detection of an increased IOP by means of mass measurements with screening programs in risky or general groups. According to modern ophthalmic protocols, all patients with an increased IOP must be computed perimetrically once a year. In patients with significant changes in the field of vision, more often, for six months, the findings of the visible fields are compared. The new methods provide a quick, precise and timely diagnosis of this severe disease, which, if not detected, leads to safe blindness in time. Early combination therapy may be appropriate in patients with advanced glaucoma, patients with a high progression rate in patients with high IOP and / or severe visual field impairment, as well as in younger patients. Fixed combination therapy should be considered when patients fail to achieve their individualized IOP targets with monotherapy when 2 special applications of drops are preferred.

Fixed combination of amlodipine/indapamide-retard in the treatment of uncontrolled hypertension in subjects over 55 years old

Objective . To evaluate the antihypertensive efficacy and safety of a fixed combination of amlodipine/indapamideretard in patients with uncomplicated uncontrolled arterial hypertension (HTN) in the older age group. Design and methods . We included 40 patients (average age — 62 years, men — 20 %, mean HTN duration — 9 years) with uncomplicated uncontrolled HTN in an open, single-center study. Fixed-combination therapy with amlodipine/indapamide-retard (5/1,5 mg) once a day for 4 weeks were prescribed. After 4 weeks, in patients who did not reach the target blood pressure (BP), the dose increased from 5/1,5 to 10/1,5 mg. The follow-up period was 12 weeks. Results . The initial systolic BP (SBP) was 165 [148; 171] mm Hg, diastolic BP (DBP) — 96 [80; 102] mm Hg. After a 12-week therapy with a fixed combination of amlodipine/indapamide-retard, SBP decreased by 31 mm Hg, DBP — by 17 mm Hg. Target clinical BP (< 140/90 mm Hg in patients without diabetes mellitus (DM), < 140/85 mm Hg in patients with diabetes mellitus) was achieved in 93 % patients. Central SBP measured by applanation tonometry decreased by 16 mm Hg, DBP — 10 mmHg, pulse pressure — 6 mmHg. Prior to treatment, the median of carotid-femoral pulse wave velocity (cfPWV) was 11,1 [7,8; 14,5] m/sec. After 12 weeks there was a decrease in cfPWV to 8,9 [6,7; 12,6] m/sec (p < 0,05 in comparison with the baseline). Conclusions . Fixed combination of amlodipine/thiazide-like diuretic in patients with uncomplicated uncontrolled 1–2 degree HTN has a high antihypertensive efficacy, allowing achievement of target BP in 93 % patients after 12-week therapy, with a satisfactory safety profile and metabolic neutrality. We showed the ability of a combination of amlodipine/indapamide-retard to reduce central SBP, pulse pressure in the aorta, and cfPWV.

Changes in adherence and associated factors among patients on newly introduced prostaglandin analog and timolol fixed-combination therapy.

PurposeWe investigated patient adherence and factors related to a newly introduced prostaglandin analog and timolol fixed-combination eye drops (PGTFC).Patients and methodsThe Glaucoma Research on Adherence to fixed-Combination Eye drops in Japan (GRACE) study group performed a nationwide prospective questionnaire survey. Participants in this study were patients with glaucoma who were scheduled to receive any type of PGTFC for the first time. The participants answered a questionnaire on the day of PGTFC introduction and again at a return visit 4–6 weeks after PGTFC introduction. The physicians in charge were asked to complete a separate questionnaire on the day of PGTFC introduction. One of two leaflets was randomly delivered to each participant before the description of the PGTFC. One leaflet explained how to correctly instill the eye drops, and the other explained the clinical meaning of intraocular pressure reduction in addition to explaining how to correctly instill the eye drops. Nonadherence was defined as forgetting to instill the eye drops one or more times during the week before the return visit.ResultsIn total, 3,597 patients (age, 68.4±12.2 years) met the study protocol requirements. PGTFC introduction significantly reduced the number of antiglaucoma eye drops from 1.93±0.78 to 1.34±0.54 (P<0.0001) and significantly improved adherence (P<0.00001). Factors significantly associated with nonadherence at the return visit included a history of nonadherence as reported by either the patient or their physician before introduction, acceptable instillation times as reported by the patient, and burdensome eye drop instillation as reported by the patient. No significant difference was observed between the two leaflets in terms of their effects on adherence.ConclusionPGTFC significantly improved adherence and some of the factors that were significantly associated with adherence.Registration numberUMIN000013696

The Effect of Exforge-HCT on Blood Pressure Control in Omani Hypertensive Patients Attending Sultan Qaboos University Hospital

Background: Hypertension is worldwide health burden. The major concern about hypertension is that it is usually asymptomatic until it causes end organ damages. The management of hypertension usually starts with monotherapy which fails in achieving targeted BP control in many patients. Therefore, they are switched to combination therapy. Fixed combination therapy is proven to be more effective in controlling hypertension than free combination therapy. Exforge-HCT is a fixed combination drug consisting of Amlodipine, Valsartan and Hydrochlorothiazide. Its effectiveness is not known in Omani hypertensive patients. Aim: To evaluate the role of exforge-HCT in control of blood pressure in Omani hypertensive patients attending SQUH and its effectiveness based on gender. Method: This is a retrospective study. Data was gathered using HIS from January 2013 to June 2016. Patients taking Exforge-HCT were screened for eligibility for the study. Blood pressure measurements before and after using Exforge-HCT were recorded. Patients were grouped according to gender, number of co-morbidities and number of medications used before EXFORGE-HCT into two groups; group one: those who were on triple free drug combination therapy and group two: those who were on dual free drugs. P value of less than 0.05 was considered significant. Results: Total number of patients was 115 with female being 57% and male being 42%. The Level of control of hypertension increased from 22% to 33%. Over all Significant reduction in blood pressure was observed, but there was no gender difference in response to Exforge-HCT. There was significant difference in the response to Exforge-HCT between the medication groups but the response according to gender in each group remains the same. Response to Exforge-HCT was the same regardless the number of co-morbidities in both gender. Conclusion: Exforge-HCT showed significant reduction in BP but no gender difference in response. There was significant difference in the response between the two medication groups. However, the response between genders remains the same in each co-morbidity and medication group. Further prospective study is needed to confirm these findings.

Proper oral health can protect from developing gingival hyperplasia induced by calcium channel blockers

Cardiovascular diseases including hypertension affect 40% of the adult population in Hungary. Calcium channel blockers are frequently prescribed for the treatment of hypertension either in monotherapy or in fixed-combination therapy. Their main effect is vasodilatation with gingival hyperplasia as a side effect. Our aim is to draw our colleagues' attention to the practical importance of the fact that calcium channel blocker-induced gingival hyperplasia correlates closely with the dental status and the quantity of plaque on the surface of teeth and dental implants. Once established, gingival hyperplasia makes it more difficult for the patient to maintain individual tooth cleaning and increases plaque formation. Thus proliferation of Gram-negative bacteria is enabled in the plaque which promotes gingival overgrowth and can pose a risk factor for further cardiovascular diseases. If proper individual oral hygiene and professional interventions are carried out, healthy and hyperplasia-free gingival state can be sustained in the long term in most cases, even with calcium channel blocker therapy. In order to protect patients' oral health, a closer cooperation of internists and dentists would be desirable. Orv Hetil. 2018; 159(29): 1183-1187.

THE EFFICACY OF FIXED TRIPLE COMBINATION THERAPY IN ROUTINE CLINICAL PRACTICE

Objective: Treatment of arterial hypertension reduces cardiovascular mortality and morbidity. Currently, the majority of patients during the treatment does not reach the target blood pressure (BP). One common cause of reaching the target pressure is poor adherence to treatment, which can improve the use of fixed combination therapy. The aim of our work is to analyze the effect on office blood pressure and influence of the number of antihypertensive medications deployment of fixed triple combination therapy (perindopril/indapamide/amlodipine) Design and method: We enrolled 194 patients (122 men, average age 63.9 years). All patients underwent a clinical examination and office blood pressure measurements. It was subsequently modified antihypertensive therapy according to current guidelines ESH/ESC using a fixed combination of perindopril/indapamide/amlodipine. The effect of changes in therapy was evaluate the next clinical control, with an average interval of 15 weeks. Results: Mean baseline office BP values were 168.9 ± 22.1/87.9 ± 12.6 mmHg. Patients received treatment prior to the change was averaged 3.9 ± 1.4 antihypertensive drugs, which represented 3.3 ± 2.0 daily tablet antihypertensive drugs. After adjusting treatment insignificantly increased the number of daily used antihypertensive agent by 0.2 ± 1.0 (p = 0.099) and significantly reduced the number of antihypertensive tablets per day 1.2 ± 1.4 (p < 0.001). Systolic blood pressure after changing average decreased by 23.6 ± 3.7 mmHg (p < 0.001) and diastolic blood pressure by 9.7 ± 2.3 mmHg (p < 0.001). The average office blood pressure achieved after treatment therapies were 132.7/83.0 mmHg. Conclusions: The use of fixed triple combination therapy of arterial hypertension significantly reduced systolic and diastolic office blood pressure. At the same time there is a significant decrease in the number of antihypertensive tablets per day, which probably contributes to better adherence to treatment.

Effectiveness and safety of switching from prostaglandin analog monotherapy to prostaglandin/timolol fixed combination therapy or adding ripasudil.

To compare the effectiveness and safety of either switching from topical prostaglandin (PG) analog monotherapy to topical PG/timolol fixed combination therapy or adding topical ripasudil therapy. An open-label, prospective, randomized, parallel group, comparative study METHODS: Fifty-one patients (51 eyes) with primary open-angle glaucoma who experienced insufficient intraocular pressure (IOP) control while taking a PG analog were enrolled. The participants were divided into the following treatment groups: PG/timolol fixed combination (switched group) or ripasudil therapy addition (added group). Blood pressure, IOP, and pulse rate were measured at baseline and after 1 and 3 months of study treatment. Adverse reactions and decreased effectiveness were examined. The mean IOP after 3 months of therapy was 14.3 ± 2.2 mmHg in the switched group and 14.7 ± 3.0 mmHg in the added group, both of which were significantly lower than those at baseline (switched, 16.3 ± 3.0 mmHg; added, 16.6 ± 2.8 mmHg; both P < .001). At 3 months, the IOP was reduced by 2.0 ± 1.7 mmHg (11.7 ± 9.6%) in the switched group and by 1.8 ± 2.1 mmHg (10.7 ± 12.5%) in the added group. In the added group, the diastolic blood pressure after 1 month of therapy was significantly lower than that at baseline (P < .05). In the switched group, 10 (40.0%) and 2 (8.0%) participants experienced adverse reactions at 1 and 3 months, respectively. In the added group, 6 (23.1%) and 4 (15.4%) participants experienced adverse reactions at 1 and 3 months, respectively. Treatment was discontinued in 4 participants (16.0%) in the switched group and in 1 participant (3.8%) in the added group. Treatment changes involving either switching from a PG analog to PG/timolol fixed combination eye drops or adding ripasudil to PG analog therapy were equally safe and effective in reducing IOP.

Comparison of Adherence to Glimepiride/Metformin Sustained Release Once-daily Versus Glimepiride/Metformin Immediate Release BID Fixed-combination Therapy Using the Medication Event Monitoring System in Patients With Type 2 Diabetes

PurposeThe purpose of this study was to compare the adherence of the glimepiride/metformin sustained release (GM-SR) once-daily fixed-dose combination and glimepiride/metformin immediate release (GM-IR) BID fixed-dose combination in type 2 diabetes therapies. MethodsAn open-label, randomized, multicenter, parallel-group study was conducted at 11 hospitals in the Republic of Korea. A total of 168 patients with type 2 diabetes treated with >4 mg of glimepiride and 1000 mg of metformin by using free or fixed-dose combination therapy for at least 2 weeks were enrolled. Patients were randomized to receive GM-SR 4/1000 mg once-daily or GM-IR 2/500 mg BID for 24 weeks. Adherence was compared by using the Medication Event Monitoring System (MEMS). FindingsA significant difference in adherence was observed between the 2 groups. Overall adherence, defined by the number of container openings divided by the number of prescribed doses, was 91.7% in the GM-SR group and 88.6% in the GM-IR group (P < 0.001). The percentage of treatment days with the correct number of doses taken was 85.3% in the GM-SR group and 75.1% in the GM-IR group (P < 0.001). The percentage of missed doses was 11.7% in the GM-SR group and 15.3% in the GM-IR group (P < 0.001). The percentage of doses taken in the correct time window and therapeutic coverage were higher in the GM-SR group (P < 0.001). There was no significant difference in glycosylated hemoglobin changes or number of adverse events between the 2 groups. A total of 168 patients randomized to receive GM-SR once daily (86 patients) or GM-IR twice daily (82 patients). Mean Age were 57.8 ± 9.6 years old. Male : female ratio was 47.6 : 52.4 %. Body mass index were 66.3 ± 12.0 kg/m2, Diabetes duration were 10.5 ± 6.6 years. ImplicationsThis study showed that patient adherence with GM-SR once daily was significantly better than with GM-IR BID. ClinicalTrials.gov identifier: NCT01620489.

ANTIHYPERTENSIVE EFFICACY OF CHRONOPHARMACOTHERAPEUTICAL APPROACH TO ARTERIAL HYPERTENSION IN POST TRANSIENT ISCHEMIC ATTACK PATIENTS

Aim. To assess antihypertensive efficacy of various 24-hour regimens of antihypertensive drugs prescription and the influence on 24-hour profile of blood pressure (BP) and aortic pressure, in systemic hypertension patients post transient ischemic attack. Material and methods. Totally, 174 patients were included, with grade 1-2 hypertension and previous non-effective treatment; who during the previous 4 weeks had transient ischemic attack. All patients were randomized to 3 groups according to the treatment variant: group 1 (n=59) — valsartan 160 mg and thiazide-like diuretic in the morning, group 2 (n=58) — thiazide-like diuretic in the morning and valsartan 160 mg at bedtime, group 3 (n=57) — thiazide-like diuretic in the morning and valsartan 80 mg b.i.d. (morning and bedtime). At baseline and in 12 months of therapy all patients underwent BP monitoring (ABPM) with assessment of mean 24 hour, daytime, nocturnal systolic BP (SBP) and diastolic BP (DBP), mean pulse pressure, time index of hypertension, SBP and DBP variability at daytime and at night, prominence and velocity of morning SBP and DBP raise, heart rate, central aortic pressure (CAP): SBP and DBP in aorta, variability of SBP and DBP in aorta, pulse BP in aorta, augmentation index in aorta, pulse pressure amplification, ejection period duration, efficacy index of subendocardial blood flow. Valsacor (KRKA, Slovenia) was included in the study as valsartan. Results. In 12 weeks of fixed combination therapy, the target levels of BP were registered: in group 1 — 43 patients (72,9%), group 2 — 48 (82,7%), group 3 — 55 (96,4%). Reached target BP was more common in b.i.d. intake of valsartan (group 3) comparing to group 1 (p=0,001) and group 2 (p=0,03). Statistically significant positive shifts of ABPM and CAP values were registered in all three regimens. However, in group 2 there was significantly more prominent decrease of the main parameters of ABPM and CAP, than in group 1. Valsartan two times daily (group 3) led to more prominent (p<0,05) improvement of ABPM and CAP value comparing to any variant of its once per day usage (group 1 and 2). In 12 months of treatment, there was a significant (p<0,05) increase in all groups of patients with normalized 24 hour BP profile (“dipper”): in group 1 — 28 (65%), group 2 — 37 (77%), group 3 — 48 (87%). Normalized 24 hour BP trend was registered more commonly in the group 3 patients comparing to those of groups 1 and 2. The differences in the number of “dipper” patients were significant between groups 3 and 1 (p=0,01). Conclusion. The study showed that b.i.d. or bedtime valsartan intake in combination with diuretic leads to more prominent improvement of the main ABPM and CAP parametes in comparison with the drug intake in the morning, in patients with transient ischemic attack. Two times daily intake of valsartan leads significantly (p<0,05) to normalization of 24 hour BP profile in most patients (87%) and more prominent improvement of the main ABPM, CAP values comparing to once per day morning or evening intake of the drug.

Efficacy and Safety of Switching Prostaglandin Analog Monotherapy to Tafluprost/Timolol Fixed-Combination Therapy.

Purpose To assess the efficacy and safety of switching from prostaglandin analog (PGA) monotherapy to tafluprost/timolol fixed-combination (Taf/Tim) therapy. Subjects and Methods Patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had received PGA monotherapy for at least 3 months were enrolled. Patients were examined at 1, 2, and 3 months after changing therapies. Subsequently, the patients were returned to PGA monotherapy. The examined parameters included intraocular pressure (IOP) and adverse events. A questionnaire survey was conducted after the switch to Taf/Tim therapy. Results Forty patients with a mean age of 66.5 ± 10.3 years were enrolled; 39 of these patients completed the study protocol. Switching to Taf/Tim significantly reduced the IOP from 18.2 ± 2.6 mmHg at baseline to 14.8 ± 2.5 mmHg at 1 month, 15.2 ± 2.8 mmHg at 2 months, and 14.9 ± 2.5 mmHg at 3 months (P < 0.001). Switching back to the original PGA monotherapy returned the IOP values to baseline levels. Taf/Tim reduced the pulse rate insignificantly. No significant differences were observed in blood pressure, conjunctival hyperemia, or corneal adverse events. A questionnaire showed that the introduction of Taf/Tim did not significantly influence symptoms. Conclusions Compared with PGA monotherapy, Taf/Tim fixed-combination therapy significantly reduced IOP without severe adverse events.

Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial

Benralizumab is a humanised, anti-interleukin 5 receptor α monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma. The objective of this trial was to assess the safety and efficacy of benralizumab for patients with mild to moderate, persistent asthma. In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients aged 18-75 years, weighing at least 40 kg, and with a postbronchodilator reversibility in forced expiratory volume in 1 s (FEV1) of at least 12% at screening, from 52 clinical research centres in six countries. Patients must have been receiving either low- to medium-dosage inhaled corticosteroids (ICS) or low-dosage ICS plus long-acting β2 agonist fixed-combination therapy at screening, had a morning prebronchodilator FEV1 of more than 50% to 90% predicted at screening, and had one or more of the following symptoms within the 7 days before randomisation: a daytime or night-time asthma symptom score of at least 1 for at least 2 days, rescue short-acting β2 agonist use for at least 2 days, or night-time awakenings due to asthma for at least one night. We converted patients' ICS treatments to 180 μg or 200 μg budesonide dry powder inhaler twice daily for the entire duration of the study using the approved dosages in the patients' respective countries and randomly allocated them (1:1; stratified by blood eosinophil count [<300 cells per μL vs ≥300 cells per μL] and region [USA vs the rest of the world]) with an interactive web-based voice response system to receive subcutaneous placebo or benralizumab 30 mg injections every 4 weeks for 12 weeks. All patients and investigators involved in patient treatment or clinical assessment and those assessing outcomes were masked to treatment allocation. The primary endpoint was change from baseline prebronchodilator FEV1 at week 12. Efficacy analyses used an intention to treat approach. This trial is registered with ClinicalTrials.gov, number NCT02322775. Between Feb 2, 2015, and April 24, 2015, we enrolled 351 patients, with 211 (60%) randomly assigned (105 [50%] to placebo and 106 [50%] to benralizumab). Benralizumab resulted in an 80 mL (95% CI 0-150; p=0·04) greater improvement (least-squares mean difference) in prebronchodilator FEV1 after 12 weeks than did placebo (placebo group: 2246 mL [SD 768] at baseline vs 2261 mL [796] at week 12, change from baseline of 0 mL; benralizumab group: 2248 mL [606] vs 2310 mL [670], 70 mL). 44 (42%) patients in the benralizumab group had adverse events compared with 49 (47%) in the placebo group. The most common adverse events for both groups were nasopharyngitis (eight [8%] patients in each group) and upper respiratory tract infections (five [5%] patients in each group). Serious adverse events occurred in two (2%) patients each in the benralizumab (pancytopenia and a suicide attempt, both considered unrelated to treatment) and placebo (cervix carcinoma and colon adenoma) groups. This study suggests that active and modifiable disease processes might be ongoing in patients with mild to moderate, persistent asthma receiving ICS. Although the lung function improvement observed does not warrant use of benralizumab in this population because it did not reach the minimum clinically important difference of 10%, further studies to assess this finding should be considered. AstraZeneca.

Additive effects and safety of fixed combination therapy with 1% brinzolamide and 0.5% timolol versus 1% dorzolamide and 0.5% timolol in prostaglandin-treated glaucoma patients.

PurposeTo compare the additive effects and safety of 1% brinzolamide/0.5% timolol fixed combination (BTFC) versus the low‐dose regimen of 1% dorzolamide/0.5% timolol fixed combination (DTFC) in patients with open‐angle glaucoma and ocular hypertension (OAG/OH) following treatment with prostaglandin analogues (PGAs).MethodsA prospective, randomized, double‐masked, multicentre, parallel‐group and active‐controlled study included 201 Japanese OAG/OH patients who had been treated with PGA. Efficacy was assessed as the change in intra‐ocular pressure (IOP) from baseline after weeks 4 and 8. Safety was assessed with adverse event rates, ocular discomfort score, blur scale, blood pressure and heart rates, best‐corrected visual acuity (BCVA) and slit lamp examinations.ResultsIntra‐ocular pressure (IOP) change from baseline at 9 AM/11 AM pooled over the 8 weeks was −3.3/−3.3 mmHg in the BTFC group and −2.9/−3.4 mmHg in the DTFC group, demonstrating non‐inferiority of BTFC to DTFC. Ocular irritation was frequently seen in DTFC group. Although blurred vision was frequently seen in BTFC group, it was transient and blurring became the equivalent 3 min after instillation between two groups. No noteworthy issue was observed in other safety outcome.ConclusionNon‐inferiority of BTFC to DTFC in IOP reduction was demonstrated after adding onto PGA therapy in Japanese OAG/OH patients. Although the score of blurred vision was transiently higher in BTFC than DTFC, treatment difference decreased and disappeared with time. Thus, BTFC can be considered as a safe and effective agent for glaucoma treatment.

Changes in Glaucoma Medication during the Past Eight Years and Future Directions in Japan Based on an Insurance Medical Claim Database.

Purpose To investigate changes in the status of glaucoma care between 2006 and 2013 and to predict future directions of glaucoma care in Japan. Subjects and Methods Japanese subjects registered in the largest national insurance claim database in Japan from 2006 to 2013 were analyzed. Estimations of the number of glaucoma patients during the past eight years and of the number of future patients were calculated. Changes in prescription trends among the same patients in the three-year period after initiating antiglaucoma medication were also investigated. Results There was a total of 3,016,000 subjects in the database. The proportion of glaucoma patients increased consistently from 2.5% in 2006 to 4.5% in 2013. This trend was predicted to continue until 2025, followed by a constant decrease with age. The most frequently prescribed antiglaucoma medications were prostaglandin analogues (PGs); however, in recent years, fixed combination therapy has emerged as a major treatment. Among 2856 newly diagnosed glaucoma patients; 94.7% of the patients initially received a single medication, but 25% of the patients received additional medications within 3 years. Conclusions The prevalence of glaucoma patients has significantly increased during the past eight years. The number of antiglaucoma medications continuously increased during the treatment period.

Achievements and Limits of Current Medical Therapy of Glaucoma.

Prescribing medical therapy for the treatment of glaucoma can be a complex process since many parameters should be taken into consideration regarding its achievements and limits. Today, a variety of options, including multiple drug classes and multiple agents within classes, are available to the clinician, but caution should be given to their side effects and contraindications. Glaucoma patients with preexisting ocular surface disease should be treated with caution, and preferably with preservative-free formulations, as there is an increased risk for symptom deterioration. The development and use of fixed-combination therapies has reduced the preservative-related side effects that threaten patient adherence and has minimized the washout effect of multiple instillations. Adherence to medical treatment is not only crucial to its efficacy but also to its cost-effectiveness. Further factors to consider are that there are patients who are nonresponders to treatment, and also that the target intraocular pressure (IOP) cannot be reached in all patients, regardless of the response to treatment. The progression of damage can occur even under maximum medical treatment or maximally tolerated medical treatment, and regardless of whether low IOP levels are reached. Furthermore, there is some conflict between medical treatment and quality of life due to long-term everyday use and to side effects of treatment. New molecules and new delivery systems are being investigated to open new horizons in glaucoma management. Although the general rule is to initiate glaucoma management with medical treatment, the limits of medical therapy should be considered to identify those patients in need of surgical management.

PCV38 - Budget Impact Analysis of Cosyrel for The Treatment of Hypertension in Italy

The objective of the study was to perform a Budget Impact Analysis (BIA) assessing the introduction of Cosyrel for the treatment of hypertension into the Italian market. Cosyrel is a single pill combination of a beta-blocker (bisoprolol fumarate) and an angiotensin-converting enzyme inhibitor (perindopril arginine) indicated as substitution therapy for the treatment of hypertension and/or stable coronary artery and/or stable chronic heart failure with reduced systolic left ventricular function in adult patients adequately controlled with bisoprolol and perindopril. BIA compared two different scenarios: Scenario 1 without a dual fixed combination therapy vs. Scenario 2 with the introduction of Cosyrel. Population data were obtained from IMS database. The time horizon was 3 years from the introduction of Cosyrel. Total number of patients was the same for the two scenarios, as the model allows only the switch of patients from monotherapy (bisoprolol) or dual combination (perindopril+bisoprolol) to Cosyrel. The perspective of the Italian National Healthcare Service was considered. The study showed that the introduction of Cosyrel leads to a reduction in the quantity of packages (13.369.949, 11.175.633 and 8.213.623 in Scenario 1 and 11.815.421, 8.615.834 and 5.604.864 in Scenario 2, respectively in year 1, 2 and 3). At a cost of 6,27 €/month, the introduction of Cosyrel generates savings for the Italian NHS of 512.994, 844.733 and 860.890 € respectively in year 1, 2 and 3 over a total expenditure of 43.238.583, 36.689.857 and 27.064.154 € related to year 1, 2 and 3 in the first scenario. The present study indicates that the introduction of Cosyrel generates savings for the Italian NHS, also improving the adherence to the therapy, thanks to the reduction in the number of pills taken by patients. Better adherence is also linked to a reduction in the number of hospitalizations and related costs.

PCV41 - Budget Impact Analysis of Triveram for The Treatment of Hypertension in Italy

The objective of the study was to perform a Budget Impact Analysis (BIA) assessing the introduction of Triveram for the treatment of hypertension into the Italian market. Triveram is a single pill combination of statin (atorvastatin calcium trihydrate), calcium channel blocker (amlodipine besilate) and angiotensin-converting enzyme inhibitor (perindopril arginine) indicated for the treatment of essential hypertension and/or stable coronary artery disease. BIA compared two different scenarios: Scenario 1 without the triple fixed combination therapy vs. Scenario 2 with the introduction of Triveram. Population data were obtained from Local Project Database by Cegedim. The time horizon considered was 3 years from the introduction of Triveram. Total number of patients in each of the 3 years was the same for the two Scenarios, as the model allows only the switch of patients from the dual or triple combinations to the fixed dose treatment with Triveram. The perspective of the Italian National Healthcare Service was considered. The study showed that the introduction of Triveram leads to a reduction in the quantity of pills taken by patients (247.893.255, 270.691.934 and 287.356.690 in Scenario 1 and 224.916.946, 222.121.000 and 214.892.239 in Scenario 2, respectively in year 1, 2 and 3). At a cost of 12,90 €/month, the introduction of Triveram generates savings for the Italian NHS of 10.6, 22.4 and 33.5 million € respectively in year 1, 2 and 3 over the total expenditure of 95, 114.8 and 126.1 million € related to year 1, 2 and 3 in the first scenario. The present study indicates that the introduction of Triveram generates important savings for the Italian NHS and improves the adherence to the therapy, thanks to the reduction in the number of pills taken by patients. Better adherence is also linked to a reduction in the number of hospitalizations and related costs.

PP.LB01.10] PREFERRED DRUG CLASSES TO INITIATE ANTIHYPERTENSIVE TREATMENT IN SWEDISH PRIMARY CARE

Objective: To assess which antihypertensive drug classes are the most preferred in patients newly initiated on treatment in Swedish primary care. Design and method: The Swedish Primary Care Cardiovascular Database (SPCCD) comprises almost 75000 patients attending primary care with a diagnosis of hypertension in two geographically defined rural and urban regions in Sweden. All primary care physicians and patients at the 48 primary care centres are included and data are automatically extracted, minimizing potential selection bias due to voluntary participation. The current observational cohort study included patients aged > = 30 years with previously untreated hypertension and a first prescription of an antihypertensive drug during 2006–2007. Preferred drug class was analysed according to sex, age and concurrent diseases. Results: We identified 5225 patients (mean age 61.4 years, 55% women) with first time prescribed antihypertensive treatment. Around one in ten patients had diabetes, with a lower prevalence in women than men (8.0 vs 11.1%, P < 0.01). The most preferred drug class was angiotensin converting enzyme inhibitors (36.2%), although substantially less common in women than in men (30.5 vs 43.1%; P < 0.001). However, diuretics were more common in women (32.4 vs. 19.7%; P < 0.001), while we observed no differences between women and men in the prescriptions of angiotensin receptor blockers (3.6 vs 4.3%), beta blockers (21.8 vs 19.5%), calcium channel blockers (7.0 vs 8.0%), fixed combination therapy (1.6 vs 2.2%), and those with more than one antihypertensive drug prescription (3.1 vs 3.2%). Furthermore, there were less diabetic women than men with a prescription of an angiotensin converting enzyme inhibitor (60.2 vs 73.9%, < 0.01). Conclusions: In conclusion, angiotensin converting enzyme inhibitors is the most preferred initial antihypertensive drug class in primary care, indicating a high concordance with contemporary guidelines.

The COMmon control of hypErtenSion and Therapeutic Attitudes in BelgIum and Luxemburg study (COME STAI)

Study aim The aim of this study was to assess hypertension management in general practice in Belgium and Luxembourg, shortly before the publication of the 2013 ESH/ESC Guidelines for arterial hypertension management.Methods A total of 516 general physicians evaluated 10,078 consecutive hypertensive patients. All used the same definitions to assess cardiovascular risk.Results Systolic (S) blood pressure (BP) was 139 ± 19 mmHg, diastolic (D) BP 80 ± 11 mmHg, patients were 64 ± 13 years old and their body mass index (BMI) was 28 ± 5 kg/m² (mean ± SD). Treatment remained unchanged in 71% of the patients with a SBP ≥ 140 mmHg. Those on ≥ 2 antihypertensive drugs were older, had higher BMI, slower HR, higher perceived cardiovascular risk, but lower BP (all P≤ 0.001 vs no and monotherapy groups). Patients in whom treatment was intensified were at higher cardiovascular risk, as substantiated by an increased prevalence of males, a higher BP, a faster HR and a larger BMI (all P≤ 0.0001). High cardiovascular risk patients underwent more frequent treatment simplifications with fixed-combination therapies or the addition of another antihypertensive class (all P≤ 0.0001 vs not at high cardiovascular risk). Among the 523 patients older than 80 years with SBP ≥ 140 mmHg, treatment intensification occurred in 32% when SBP ≥ 150 mmHg, and in 10% when SBP was between 140 and 149 mmHg (P ≤ 0.0001).Conclusion The COME STAI study suggests that there is still room for improvement in hypertension control in Belgium and Luxembourg.