Advances in Therapy Journal Impact Factor & Information

Publisher: Springer Verlag

Journal description

Advances in Therapy is an international peer reviewed journal dedicated to the rapid publication of studies in clinical medicine, including research on existing drugs and drugs in development across a range of therapeutic areas. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research papers, drug reviews, case reports and other contributions to drug therapy, diagnosis, instrtumentation and related fields.

Current impact factor: 2.44

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 2.438
2012 Impact Factor 2.125
2011 Impact Factor 2.105
2010 Impact Factor 1.668
2009 Impact Factor 0.936
2008 Impact Factor 0.973
2007 Impact Factor 0.719
2006 Impact Factor 0.712
2005 Impact Factor 0.667
2004 Impact Factor 0.829
2003 Impact Factor 1.047
2002 Impact Factor 0.828
2001 Impact Factor 0.468
2000 Impact Factor 0.896
1999 Impact Factor 0.403
1998 Impact Factor 0.385
1997 Impact Factor 0.408
1996 Impact Factor 0.301
1995 Impact Factor 0.169
1994 Impact Factor 0.324
1993 Impact Factor 0.115

Impact factor over time

Impact factor
Year

Additional details

5-year impact 1.71
Cited half-life 4.40
Immediacy index 0.37
Eigenfactor 0.00
Article influence 0.45
Website Advances in Therapy website
ISSN 1865-8652
OCLC 220889595
Material type Series, Periodical
Document type Journal / Magazine / Newspaper

Publisher details

Springer Verlag

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Author's pre-print on pre-print servers such as arXiv.org
    • Author's post-print on author's personal website immediately
    • Author's post-print on any open access repository after 12 months after publication
    • Publisher's version/PDF cannot be used
    • Published source must be acknowledged
    • Must link to publisher version
    • Set phrase to accompany link to published version (see policy)
    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The once-daily long-acting muscarinic antagonist (LAMA) tiotropium and once-daily long-acting β2-agonist (LABA) olodaterol have been studied as a once-daily fixed-dose combination (FDC) in patients with chronic obstructive pulmonary disease (COPD). Two large, 52-week, double-blind, parallel-group studies in patients with moderate-very severe COPD demonstrated that tiotropium + olodaterol significantly improved lung function and symptoms versus the monocomponents. This post hoc analysis determined effects on lung function by prior LAMA or LABA maintenance treatment and initial disease severity. 5162 patients were randomized and treated with olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, tiotropium + olodaterol 2.5/5 µg, or tiotropium + olodaterol 5/5 µg (all once daily via Respimat(®) inhaler). Primary efficacy (lung-function) end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) and trough FEV1 responses (i.e., change from baseline). Pooled data are presented for the following subgroups: prior maintenance treatment with LAMA or LABA, Global initiative for chronic Obstructive Lung Disease (GOLD) 2 (predicted FEV1 50% to <80%) and 3 (30% to <50%)/4 (<30%), sex, age, and prior use of inhaled corticosteroids. Tiotropium + olodaterol FDC improved lung function over the monocomponents in patients with GOLD 2 and 3-4 disease, irrespective of prior LAMA or LABA maintenance therapy; most comparisons between FDCs and their respective monocomponents were statistically significant (P < 0.05). FEV1 AUC0-3 and trough FEV1 responses for the individual treatments were generally greater in patients with less severe COPD at baseline. Tiotropium + olodaterol 5/5 µg significantly improved FEV1 AUC0-3 and trough FEV1 in all GOLD severity groups compared to olodaterol 5 µg and tiotropium 5 µg alone, irrespective of whether patients had received prior LAMA or LABA maintenance treatment. Improvements from baseline in lung function were generally greater in patients with less severe disease. Boehringer Ingelheim. ClinicalTrials.gov numbers, NCT01431274 and NCT01431287.
    Advances in Therapy 06/2015; DOI:10.1007/s12325-015-0218-0
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    ABSTRACT: New inhalers propelled by hydrofluoroalkanes (HFAs) have improved plume characteristics: higher fine particle fraction, and warmer plumes with reduced force and velocity. Together, this may avoid reflex interruption of inhalation and improve lung deposition of the inhaled drugs. However, even with HFA-propelled pressurized metered-dose inhalers (pMDIs), there are notable differences in device properties. Here we compared the duration, velocity, force, and temperature of two inhaled corticosteroid/long-acting β2-agonist combination therapies, administered via HFA pMDIs: fluticasone propionate/formoterol 125/5 µg (FP/FORM; flutiform(®)) and fluticasone propionate/salmeterol 125/25 µg (FP/SAL; Seretide(®) Evohaler(®)). Inhalers were fired into ambient air. Plume duration and velocity were recorded with a high-speed camera and a pulsed laser light source. A copper disc attached to a sensitive load cell measured the plume force at various distances from the device. A thermal imaging video camera recorded impaction temperature in line with the device. The average plume duration for FP/FORM was longer than that of FP/SAL: 168.3 vs. 114.0 ms, respectively. The mean maximum plume velocities observed at 95 mm (the approximate distance between mouthpiece and throat) was consistently slower for FP/FORM (10.08 m/s) compared to FP/SAL (15.55 m/s). FP/FORM had a slower velocity at the outset, remaining relatively constant before declining steadily over the plume duration. The force of the FP/SAL plume was greater than that of FP/FORM at all distances: maximum force for FP/FORM was 138.2 vs. 278.9 mN for FP/SAL. The minimum impaction temperature was +5.9 °C for FP/FORM and -37.8 °C for FP/SAL; this difference became less pronounced over distance. There were substantial differences between the plumes of the two pMDIs. FP/FORM was warmer, less forceful, had a longer plume duration and slower maximal velocity. These plume characteristics of FP/FORM may lead to improved lung deposition. Mundipharma Research Limited, Cambridge, UK.
    Advances in Therapy 06/2015; DOI:10.1007/s12325-015-0219-z
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    ABSTRACT: Among patients with chronic obstructive pulmonary disease (COPD), the frequency and severity of past exacerbations potentiates future events. The impact of current therapies on exacerbation frequency and severity in patients with different exacerbation risks is not well known. A post hoc analysis of patients at low (≤1 exacerbation [oral steroids/antibiotics requirement] and no COPD-related hospitalization in the year preceding trial entry) or high (≥2 exacerbations [oral steroids/antibiotics requirement] or ≥1 COPD-related hospitalization[s] in the year preceding trial entry) exacerbation risk, from the Prevention of Exacerbations with Tiotropium in Chronic Obstructive Pulmonary Disease (POET-COPD(®)) database. Compared with salmeterol, tiotropium significantly increased time to first COPD exacerbation (hazard ratio 0.84; 95% confidence interval [CI] 0.76-0.92; p = 0.0002) and reduced the number of COPD exacerbations (rate ratio 0.90; 95% CI 0.81-0.99; p = 0.0383) in patients at high exacerbation risk. With treatment, the risk of remaining in the high-risk exacerbator subgroup was statistically lower with tiotropium versus salmeterol (risk ratio [RR] 0.89; 95% CI 0.80-1.00; p = 0.0478). For low-risk patients, time to first COPD exacerbation and number of COPD exacerbations were numerically lower with tiotropium versus salmeterol. With treatment, the risk of transitioning from a low to a high exacerbation risk was lower with tiotropium versus salmeterol (RR 0.87; 95% CI 0.71-1.07; p = 0.1968). This analysis confirms the higher efficacy of tiotropium versus salmeterol in prolonging time to first COPD exacerbation and reducing number of exacerbations in patients both at low and high exacerbation risk. Boehringer Ingelheim and Pfizer. ClinicalTrials.gov NCT00563381.
    Advances in Therapy 06/2015; DOI:10.1007/s12325-015-0216-2
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    ABSTRACT: A combination of magnetic resonance imaging (MRI) with real-time high-resolution ultrasound (US) known as fusion imaging may improve visualization of musculoskeletal (MSK) sports medicine injuries. The aim of this study was to evaluate the applicability of MRI-US fusion technology in MSK sports medicine. This study was conducted by the medical services of the FC Barcelona. The participants included volunteers and referred athletes with symptomatic and asymptomatic MSK injuries. All cases underwent MRI which was loaded into the US system for manual registration on the live US image and fusion imaging examination. After every test, an evaluation form was completed in terms of advantages, disadvantages, and anatomic fusion landmarks. From November 2014 to March 2015, we evaluated 20 subjects who underwent fusion imaging, 5 non-injured volunteers and 15 injured athletes, 11 symptomatic and 4 asymptomatic, age range 16-50 years, mean 22. We describe some of the anatomic landmarks used to guide fusion in different regions. This technology allowed us to examine muscle and tendon injuries simultaneously in US and MRI, and the correlation of both techniques, especially low-grade muscular injuries. This has also helped compensate for the limited field of view with US. It improves spatial orientation of cartilage, labrum and meniscal injuries. However, a high-quality MRI image is essential in achieving an adequate fusion image, and 3D sequences need to be added in MRI protocols to improve navigation. The combination of real-time MRI and US image fusion and navigation is relatively easy to perform and is helping to improve understanding of MSK injuries. However, it requires specific skills in MSK imaging and still needs further research in sports-related injuries. Toshiba Medical Systems Corporation.
    Advances in Therapy 06/2015; DOI:10.1007/s12325-015-0217-1
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    ABSTRACT: The oral, potent poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, is well tolerated at doses of ≤400 mg twice daily (BID) (administered as capsules), and has shown efficacy in patients with advanced BRCA-mutated ovarian and breast cancer. This Phase I, open-label, randomized trial investigates the effect of food on the pharmacokinetics of olaparib in patients with refractory/resistant advanced solid tumors. In Part A, a three-period crossover study, patients received a single oral dose of olaparib 400 mg (8 × 50 mg capsules) in three prandial states: fasted, a high-fat meal or a standard meal (with a 5-14 day washout). Blood samples for pharmacokinetic (PK) assessments were taken pre-dose and up to 72 h post-dose. After completing Part A, patients could enter Part B, where they would receive olaparib 400 mg BID. 32 patients were randomized; 31 contributed to the PK statistical analysis and entered Part B. The presence of food slowed the rate of absorption (time to maximal plasma concentration [t max] was delayed by ~2 h). Maximum plasma concentration (C max) was increased by 10% following a standard meal and was unchanged with a high-fat meal (ratio of geometric means [90% confidence interval (CI)]: 1.10 [1.02-1.20] for standard and 1.00 [0.92-1.09] for high-fat meal). The extent of olaparib absorption (AUC) was increased by ~20% in the fed state (ratio of geometric means: 1.21 [1.10-1.33] for standard and 1.19 [1.08-1.31] for high-fat meal). The presence of food decreased the rate and increased the extent of absorption of olaparib following oral dosing of the capsule formulation. However, the effects of food on olaparib PK were not deemed clinically important, according to predefined criteria. Safety data were consistent with the known safety profile of olaparib. AstraZeneca.
    Advances in Therapy 06/2015; DOI:10.1007/s12325-015-0214-4
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    ABSTRACT: The aim of this study was to establish the feasibility of using computed tomography (CT) in a multicenter setting to assess structural airway changes. This was a 12-week, randomized, double-blind, placebo-controlled, Phase IIb trial using CT to investigate the effect of a novel, oral, reversible neutrophil elastase inhibitor, AZD9668 60 mg twice daily (BID), on structural airway changes in patients aged 50-80 years with chronic obstructive pulmonary disease (COPD) (ex-smokers). Primary outcome variable: airway wall thickness at an extrapolated interior perimeter of 10 mm (AWT-Pi10). Secondary outcome variables: fifth-generation wall area %; air trapping index; pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1); morning and evening peak expiratory flow and FEV1; body plethysmography; EXAcerbations of Chronic pulmonary disease Tool (EXACT); Breathlessness, Cough, and Sputum Scale (BCSS); St George's Respiratory Questionnaire for COPD; and proportion of reliever-medication-free trial days. Safety variables were also assessed. There was no difference between placebo (n = 19) and AZD9668 (n = 17) for AWT-Pi10 at treatment end. This was consistent with results for most secondary variables. However, patients randomized to AZD9668 experienced an improvement versus placebo for morning and evening FEV1, and EXACT and BCSS cough and sputum scores. AZD9668 60 mg BID was well tolerated and no new safety concerns were identified. This study confirmed the feasibility of using CT to assess structural airway changes in COPD. However, there was no evidence of improvements in CT structural measures following 12 weeks' treatment with AZD9668 60 mg BID. AstraZeneca.
    Advances in Therapy 06/2015; DOI:10.1007/s12325-015-0215-3
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    ABSTRACT: Acute pain, prevalent as part of postoperative and traumatic pain, is often sub-optimally or inadequately treated. Fixed-dose combination analgesic products that combine a reduced amount of opioid with a nonopioid analgesic such as acetaminophen (paracetamol) in a single tablet offer potential pharmacodynamic and/or pharmacokinetic benefits, and may also result in an opioid-sparing effect. A new analgesic product (XARTEMIS™ XR, Mallinckrodt Brand Pharmaceuticals, Dublin, Ireland) combines oxycodone (7.5 mg) with acetaminophen (325 mg) in an immediate-release/extended-release (ER) formulation that is indicated for the treatment of acute pain. The ER formulation of this product provides stable serum drug concentrations that in this case lasts 12 h. Oxycodone/acetaminophen is a drug combination that offers safe and effective pain relief in a variety of acute pain syndromes such as postoperative pain. The combination formulation allows a smaller amount of oxycodone per tablet and the biphasic-layered matrix of the pill for ER may present obstacles to potential abusers. No opioid is totally abuse resistant, but the lower opioid content and tamper-resistant formulation of this product might discourage abuse. Clinicians must still be mindful of the acetaminophen part of this product in the patient's overall daily intake (in light of acetaminophen hepatotoxicity). The new product appears to provide an important new choice in the armamentarium against acute pain.
    Advances in Therapy 05/2015; DOI:10.1007/s12325-015-0213-5
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    ABSTRACT: Cost-utility assessment of first-line actinic keratosis (AK) treatments for max 25 cm(2) AK field. A probabilistic, 2-year decision tree model was used to assess costs, quality-adjusted life-years (QALY), incremental cost-effectiveness ratio (ICER), cost-effectiveness efficiency frontier, cost-effectiveness acceptability frontier (CEAF), and expected value of perfect information (EVPI) of AK treatments from the Finnish health care payer perspective with 3% discounting per annum. In the model, the first-line AK treatment resulted in complete clearance (CC) or non-CC with or without local skin responses (LSR), or AK recurrence. Non-CC AK was treated with methyl aminolevulinate + photodynamic therapy (MAL + PDT), and AK recurrence was retreated with the previous effective treatment. Costs included primary and secondary health care, outpatient drugs, and LSR management. QALYs were assessed with the EuroQol (EQ-5D-3L). Result robustness was assessed with sensitivity analyses. The mean simulated per patient QALYs (costs) were 1.526 ( 982) for MAL + PDT, 1.524 ( 794) for ingenol mebutate gel (IngMeb) 0.015% (3 days), 1.522 ( 869) for IngMeb 0.05% (2 days), 1.520 ( 1062) for diclofenac 3% (12 weeks), 1.518 ( 885) for imiquimod 3.75% (6 weeks), 1.517 ( 781) for imiquimod 5% (4/8 weeks), and 1.514 ( 1114) for cryosurgery when treating AK affecting any body part. IngMeb 0.015% was less costly and more effective (dominating) than other AK treatments indicated for face and scalp area with the exception of imiquimod 5% for which the ICER was estimated at 1933/QALY gained and MAL + PDT, which had an ICER of 82,607/QALY gained against IngMeb 0.015%. With willingness-to-pay 2526-18,809/QALY gained, IngMeb 0.015% had >50% probability for cost-effectiveness on the CEAF. IngMeb 0.05% dominated AK treatments indicated for trunk and extremities. EVPIs for face and scalp (trunk and extremities) analyses were 26 ( 0), 86 ( 58), and 250 ( 169) per patient with the willingness-to-pay of 0, 15,000, and 30,000 per QALY gained, respectively. IngMebs were cost-effective AK treatments in Finland. LEO Pharma.
    Advances in Therapy 05/2015; 32(5). DOI:10.1007/s12325-015-0211-7
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    ABSTRACT: Rare cases of thrombotic microangiopathy (TMA), manifested as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS), have been reported with interferon β products. We performed a cumulative review of TMA cases recorded in a Global Safety Database for patients with multiple sclerosis who received subcutaneous interferon β-1a treatment. Search criteria were: all reported cases, serious and non-serious, from all sources (including non-health care professionals and clinical trial reports), regardless of event ranking and causality assessment by reporter or company. Data lock was May 3, 2014, with additional analysis of cases reported between August 1, 2014-November 30, 2014. Ninety-one patient cases (76.9% female) with 105 events were retrieved. Time to onset varied from 2 months to 14 years, and in 31.9% of patients the event occurred within 2 years of treatment initiation. Seven patients had a fatal outcome (five were secondary to other causes and two reported insufficient information). Forty-four patients recovered, 32 patients had not recovered at the time of the report, and in eight cases outcome was either not reported or unknown. Treatment was discontinued in 84.6% (77/91) of patients. In 67% (61/91) of patients, the reporter suspected a causal association between treatment and TMA/TTP-HUS. Risk factors and/or confounding factors were present in 45.1% (41/91) of patients. Early prodromal syndrome or specific patterns were not detected, although 54.9% (50/91) of cases contained insufficient information. Overall reporting rate of TMA/TTP-HUS was estimated as 7.2 per 100,000 patient-years. Reporting rates for human serum album (HSA)-containing and HSA-free formulations were 5.72 and 7.68 per 100,000 patient-years, respectively. No new signal relating specifically to increased frequency of TMA/TTP-HUS with HSA-free subcutaneous interferon β-1a was detected and no additional risk mitigation measures are required regarding the different formulations. The benefit-risk balance of subcutaneous interferon β-1a remains positive, and routine pharmacovigilance monitoring is appropriate. Ares Trading SA, Aubonne, Switzerland, a subsidiary of Merck Serono SA.
    Advances in Therapy 05/2015; 32(5). DOI:10.1007/s12325-015-0212-6
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    ABSTRACT: Prior to registration, no clinical trial evaluating safety and tolerability of Zolafren(®) (Adamed Sp. z o.o., Czosnów, Poland), a generic olanzapine formulation, had been performed. Therefore, the aim of this post-authorization safety study (PASS) was to evaluate the safety and tolerability of Zolafren in patients with bipolar disorder (BD). Adverse events (AEs) associated with the use of Zolafren were recorded in a PASS, in an open-label, non-randomized, multicenter observational study involving 20,698 outpatients with BD. Zolafren was used in both monotherapy (82.8%) and polytherapy (17.2%) at a mean dose of 12.1 ± 4.2 mg. The most commonly used formulation was coated tablets (70.9%). Orally dissolving tablets (19.7%) and hard capsules (9.4%) were less commonly used. During a period of 171 ± 47 days of exposure to Zolafren, 5883 AEs were reported in 2138 patients (10.3% of the study population). None of the reported AEs were severe. Zolafren-associated AEs were the reason for discontinuation in 43 patients and the reason for dose reduction in a further 762 patients. The most common AE was weight gain (by 1.6 ± 3.3 kg) which was considered unrelated to the dose of Zolafren. During follow-up, the percentage of patients with very good tolerance with Zolafren increased from 44.4% to 59.8%. The percentage of patients who had confidence in Zolafren also increased. The results of this PASS support the safety of Zolafren use and indicate a high tolerance in patients treated for BD. Adamed Sp. z o.o., Czosnów, Poland.
    Advances in Therapy 05/2015; 32(5). DOI:10.1007/s12325-015-0210-8
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    ABSTRACT: We investigated the possibilities of drug-drug interactions between luseogliflozin, a sodium-glucose co-transporter-2 inhibitor, and oral antidiabetic drugs (OADs) in healthy Japanese males. We conducted six independent studies to investigate potential drug-drug interactions between 5 mg luseogliflozin and the following OADs usually used in Japan: 1 mg glimepiride, 250 mg metformin, 30 mg pioglitazone, 50 mg sitagliptin, 50 mg miglitol, or 0.6 mg voglibose (0.2 mg before each meal). Twelve subjects were enrolled in each study. The glimepiride, metformin, sitagliptin, and miglitol studies were randomized, open-label, single-dose, three-way crossover studies. The pioglitazone and voglibose studies were open-label studies, where a single dose of luseogliflozin was added to multiple doses of pioglitazone or voglibose. The endpoints were the area under the curve from 0 to 24 h (AUC0-24h) or to infinity (AUCinf) and the maximum concentration (C max) of each drug administered alone or in combination. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) for C max of luseogliflozin in the pioglitazone and miglitol studies were beyond the reference range for bioequivalence (0.80-1.25) (miglitol: 0.851 [0.761, 0.952]; pioglitazone: 1.16 [1.04, 1.30]). However, the 90% CIs for AUC0-24h were within the reference range. The 90% CIs of the GMRs for C max and AUC0-24h of pioglitazone were beyond the reference range (C max 0.884 [0.746, 1.05]; AUC0-24h 0.896 [0.774, 1.04]), but the 90% CIs for the active metabolites of pioglitazone were within the reference range. For the other combinations tested, the 90% CIs and GMRs for luseogliflozin and the individual OADs were within the reference range. No clinically meaningful interactions were observed between luseogliflozin and six commonly used OADs in Japan, although there were some changes in the pharmacokinetics of pioglitazone co-administered with luseogliflozin and for luseogliflozin co-administered with miglitol or pioglitazone. Taisho Pharmaceutical Co., Ltd.
    Advances in Therapy 05/2015; 32(5). DOI:10.1007/s12325-015-0209-1
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    ABSTRACT: Patients with major depressive disorder (MDD) often fail to respond to first-line antidepressant treatments (ADTs); subsequent strategies include dosage increase, switch to a different ADT, or addition of another ADT or other drug. The objective of this prospective, case review study was to identify factors that influence the decision to prescribe adjunctive antipsychotics for patients with MDD and inadequate response to ADT. Psychiatrists or primary care physicians (n = 411) based in the USA and Europe each completed an online survey for ten consecutive adults with MDD and inadequate response to ADTs, and for whom a treatment change was considered. A t test was used to compare survey responses between groups of patients. The survey was completed for 4018 patients; an adjunctive antipsychotic was considered for 961/4018 patients (23.9%) and actually prescribed for 514/4018 (12.8%). Compared with patients not considered for an adjunctive antipsychotic, those who were considered for this treatment had more previous major depressive episodes (MDEs), longer duration of the current MDE, more severe illness both at ADT initiation and current consultation, and more treatment changes. Patients who were prescribed adjunctive antipsychotics had at baseline more functional impairment and absences from work than those considered for but not prescribed this treatment. Key symptoms that prompted physicians to consider antipsychotics were psychotic symptoms, psychomotor agitation, hostility, irritability, impulsivity, and anger bursts. Anxious mood and irritability were mentioned significantly more often by physicians who actually prescribed adjunctive antipsychotics. Obstacles to prescribing included a tendency to wait to see if symptoms improved and concern over side effects. This real-world study suggested that the decision to prescribe an adjunctive antipsychotic for patients with MDD and inadequate response to ADT is influenced by a broad spectrum of factors, predominantly related to severity of illness, functional impairment, and symptom profile. Otsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, USA) and H. Lundbeck A/S (Valby, Denmark).
    Advances in Therapy 05/2015; 32(5). DOI:10.1007/s12325-015-0207-3
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    ABSTRACT: Due to the progressive nature of type 2 diabetes (T2D), the majority of patients require increasing levels of therapy to achieve and maintain good glycemic control. At present, once patients become uncontrolled on oral antidiabetic therapies, the two primary treatment options are glucagon-like peptide-1 receptor agonists (GLP-1RAs) or basal insulin, although earlier use of GLP-1RAs has also been advocated. While both of these drug classes have proven efficacy in treating T2D, there can be limitations to their use in some patients, and resistance to further treatment intensification among both patients and physicians. More recently, treatment incorporating both a GLP-1RA and a basal insulin has been used successfully in the clinic and the first such combination product, IDegLira (insulin degludec + liraglutide), has recently been approved for use in Europe. IDegLira combines insulin degludec and the GLP-1RA liraglutide in a single injection. In both insulin-naïve and basal insulin-treated individuals with T2D, IDegLira has demonstrated greater reductions in glycated hemoglobin (HbA1c) than either of the individual components, with a low rate of hypoglycemia and weight loss. IDegLira may provide a new option for patients requiring treatment intensification but for whom increased weight or a higher risk of hypoglycemia are barriers. This article discusses the rationale behind combining these two drug classes and reviews the available clinical evidence for the efficacy and safety of IDegLira.
    Advances in Therapy 05/2015; 32(5). DOI:10.1007/s12325-015-0208-2
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    ABSTRACT: Oral formulations of 5-aminosalicylic acid (5-ASA) for treatment of ulcerative colitis have been developed to minimize absorption prior to the drug reaching the colon. In this study, we investigate the release of 5-ASA from available oral mesalamine formulations in physiologically relevant pH conditions. Release of 5-ASA from 6 mesalamine formulations (APRISO(®), Salix Pharmaceuticals, Inc., USA; ASACOL(®) MR, Procter & Gamble Pharmaceuticals UK Ltd.; ASACOL(®) HD, Procter & Gamble Pharmaceuticals, USA; MEZAVANT XL(®), Shire US Inc.; PENTASA(®), Ferring Pharmaceuticals, Ltd., UK; SALOFALK(®), Dr. Falk Pharma UK Ltd.) was evaluated using United States Pharmacopeia apparatus I and II at pH values of 1.0 (2 h), 6.0 (1 h), and 6.8 (8 h). Dissolution profiles were determined for each formulation, respectively. Of the tested formulations, only the PENTASA formulation demonstrated release of 5-ASA at pH 1.0 (48%), with 56% cumulative release after exposure to pH 6.0 and 92% 5-ASA release after 6-8 h at pH 6.8. No other mesalamine formulation showed >1% drug release at pH 1.0. The APRISO formulation revealed 36% 5-ASA release at pH 6.0, with 100% release after 3 h at pH 6.8. The SALOFALK formulation revealed 11% 5-ASA release at pH 6.0, with 100% release after 1 h at pH 6.8. No 5-ASA was released by the ASACOL MR, ASACOL HD, and MEZAVANT XL formulations at pH 6.0. At pH 6.8, the ASACOL MR and ASACOL HD formulations exhibited complete release of 5-ASA after 4 and 2 h, respectively, and the MEZAVANT XL formulation demonstrated complete 5-ASA release over 6-7 h. 5-Aminosalicylic acid release profiles were variable among various commercially available formulations. Shire Development LLC.
    Advances in Therapy 05/2015; 32(5). DOI:10.1007/s12325-015-0206-4
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    ABSTRACT: The aim of the present study was to compare the confocal and clinical features of newly diagnosed glaucoma patients receiving unpreserved prostaglandins (tafluprost) versus preserved prostaglandins (latanoprost). 40 patients were randomized to tafluprost 0.0015% (20 patients; 32 eyes) or latanoprost 0.005% + benzalkonium chloride 0.02% (20 patients; 35 eyes) once daily for 1 year. Inclusion criteria were new glaucoma diagnosis, and no ocular treatments for 6 months before the study. Patients were evaluated at baseline and every 3 months with a complete ophthalmologic evaluation, Schirmer's test, break-up time test, confocal microscopy of the central cornea, and measurement of intraocular pressure (IOP). Investigators were masked to treatment. Both eyes were analyzed if they fulfilled inclusion criteria. Treatments and changes between follow-up and baseline were compared by analysis of variance (ANOVA), t test and Chi-square test. At baseline, the two groups had similar age, ocular surface and confocal findings; keratocyte activation was present in 40%, branching pattern in 85%, and beading in 75%, with no inter-group differences. At follow-up, no significant clinical changes were detected, apart from a drop of IOP by 3.6-4.2 mmHg in the two groups (p < 0.001, with no difference between treatments). Despite inter-treatment ANOVA for confocal microscopy being negative, subtle changes were present. During follow-up, all eyes without nerve branching pattern at baseline progressively developed it when treated with latanoprost, whereas no change occurred using tafluprost treatment (p = 0.05). None of the eyes without beading at baseline developed it at the end of the study in the tafluprost group, whereas beading did occur in 75% of patients treated with latanoprost (p = 0.05). Both treatments were associated with increased keratocyte activation at follow-up; the change from baseline was statistically significant after month 3 with latanoprost (p = 0.02) and after month 6 with tafluprost (p = 0.04). The two study treatments had similar clinical effects, but tafluprost had a more favorable profile for some confocal parameters of the cornea. Merck Sharp & Dohme International.
    Advances in Therapy 04/2015; 32(4). DOI:10.1007/s12325-015-0205-5
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    ABSTRACT: In recent years, defibrotide (DFT) has emerged as a promising therapy for veno-occlusive disease (VOD). The aim of this study was to investigate whether DFT prophylaxis affects neutrophil engraftment in patients undergoing hematopoietic stem cell transplantation (HSCT). A cohort of 44 consecutive pediatric patients who underwent HSCT was retrospectively analyzed to see the role of DFT on engraftment. Patients were assigned into two groups based on the use or non-use of prophylaxis with DFT. The mean time to engraftment was statistically different between the two groups for both polymorphonuclear neutrophils (PMN) and white blood cells. Our study supports the hypothesis that prophylaxis with DFT for VOD leads to a delay to the engraftment of PMN in pediatric patients that underwent HSCT.
    Advances in Therapy 04/2015; 32(4). DOI:10.1007/s12325-015-0203-7
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    ABSTRACT: Luseogliflozin, a potent, selective sodium glucose cotransporter 2 inhibitor, promotes urinary glucose excretion (UGE) and reduces plasma glucose concentrations. Luseogliflozin was approved for use in Japan after favorable pharmacokinetic, pharmacodynamic, and safety profiles were reported in healthy Japanese subjects and patients with type 2 diabetes mellitus (T2DM) in clinical development studies. We aimed to investigate the pharmacokinetics, pharmacodynamics, and safety of multiple doses of luseogliflozin administered once daily for 7 days in Japanese patients with T2DM. We conducted a randomized, placebo-controlled, single-blind, parallel-group, clinical pharmacology study at the P-One Clinic, Keikokai Medical Corporation (Tokyo, Japan) between August 2009 and November 2009. Forty Japanese patients with T2DM were randomly assigned to receive once-daily 0.5, 1, 2.5 or 5 mg luseogliflozin or placebo for 7 days. We assessed the pharmacokinetics, pharmacodynamics (including changes in UGE and plasma glucose concentrations), and safety of luseogliflozin. The plasma concentrations of luseogliflozin and its active metabolite, M2, were dose proportional, without accumulation. 24-h UGE was greater in all luseogliflozin groups versus placebo. Least-squares mean differences in 24-h UGE on Day 7 increased dose dependently in the luseogliflozin groups, with values of 49.2, 66.5, 89.4, and 101 g/day at 0.5, 1, 2.5, and 5 mg, respectively. On Day 7, the areas under the concentration-time curves for post-meal plasma glucose and the mean plasma glucose for 0-16 h were significantly lower in all luseogliflozin groups versus placebo. Seven patients had mild adverse events (AEs); all were resolved. No AEs led to study discontinuation. Once-daily administration of luseogliflozin for 7 days increased 24-h UGE in a dose-dependent manner, reduced plasma glucose concentrations, and was well tolerated in Japanese patients with T2DM. The pharmacokinetic and pharmacodynamic profile of luseogliflozin observed in this study supports its once-daily dosing regimen. Taisho Pharmaceutical Co., Ltd.
    Advances in Therapy 04/2015; 32(4). DOI:10.1007/s12325-015-0200-x
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    ABSTRACT: The aim of this randomized, double-blind, parallel-group study was to investigate the safety and efficacy of empagliflozin monotherapy for 52 weeks in Japanese patients with type 2 diabetes (T2DM). In a 12-week dose-finding period, patients [N = 547; mean baseline glycosylated hemoglobin (HbA1c) 7.92-8.02%] received empagliflozin (5, 10, 25, or 50 mg) or placebo. In a 40-week extension period, patients on empagliflozin 10 or 25 mg continued the same treatment and patients on other doses were reallocated to empagliflozin 10 or 25 mg. Outcomes at week 52 included changes from baseline in HbA1c, fasting plasma glucose (FPG), weight and blood pressure (BP) in patients who received empagliflozin 10 or 25 mg in both the initial 12 weeks and the extension and safety in patients treated with ≥1 dose of empagliflozin 10 or 25 mg. Adjusted mean ± SE changes in HbA1c from baseline at week 52 were -0.67 ± 0.09% and -0.86 ± 0.09%, in FPG were -24.7 ± 3.2 mg/dL and -31.3 ± 3.4 mg/dL, and in body weight were -3.1 ± 0.4 kg and -3.1 ± 0.4 kg, with empagliflozin 10 and 25 mg, respectively. Both doses reduced systolic and diastolic BP. Adverse events were reported in 70.8% and 66.8% of patients on empagliflozin 10 and 25 mg, respectively. Confirmed hypoglycemic adverse events (plasma glucose ≤70 mg/dL and/or requiring assistance) were reported in one patient per group. Empagliflozin monotherapy for 52 weeks led to sustained reductions in HbA1c, FPG, weight and BP and was well tolerated in Japanese patients with T2DM. Boehringer Ingelheim and Eli Lilly and Company.
    Advances in Therapy 04/2015; 32(4). DOI:10.1007/s12325-015-0198-0