Initial Monotherapy Research Articles

Trends in antihypertensive drug utilization in British Columbia, 2004-2019: a descriptive study.

Clinical guidelines for hypertension were updated with lower blood pressure targets following new studies in 2015; the real-world impact of these changes on antihypertensive drug use is unknown. We aimed to describe trends in antihypertensive drug utilization from 2004 to 2019 in British Columbia. We conducted a longitudinal study to describe the annual prevalence and incidence rate of use of 5 antihypertensive drug classes (thiazides, angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor blockers [ARBs], calcium channel blockers and β-blockers) among BC residents aged 30-75 years. We also conducted a cohort study to compare the risk of discontinuation and switch or add-on therapy between incident users of the above drug classes. We used linkable administrative health databases from BC. We performed a Fine-Gray competing risk analysis to estimate subhazard ratios. Among BC residents aged 30-75 years (population: 2 376 282 [2004] to 3 014 273 [2019]), the incidence rate of antihypertensive drug use decreased from 23.7 per 1000 person-years in 2004 to 18.3 per 1000 person-years in 2014, and subsequently increased to 22.6 per 1000 person-years in 2019. The incidence rate of thiazide use decreased from 8.9 per 1000 person-years in 2004 to 3.2 per 1000 person-years in 2019, and incidence rates for the other drug classes increased. Incident users receiving thiazide monotherapy had an increased risk of discontinuing any antihypertensive treatment compared with ACE inhibitor monotherapy (subhazard ratio 0.96, 95% confidence interval [CI] 0.95-0.97), ARB monotherapy (subhazard ratio 0.84, 95% CI 0.81-0.87) and thiazide combination with ACE inhibitor or ARB (subhazard ratio 0.86, 95% CI 0.84-0.88), and had the highest risk of switching or adding on. First-line use of thiazides continued to decrease despite a marked increase in incident antihypertensive therapy following updated guidelines; incident users receiving ARB monotherapy were least likely to discontinue, and incident users receiving thiazide monotherapy were more likely to switch or add on than users of other initial monotherapy or combination. Further research is needed on the factors influencing treatment decisions to understand the differences in trends and patterns of antihypertensive drug use.

Real-world clinical practice of pulmonary arterial hypertension in Japan: Insights from a large administrative database.

Pulmonary arterial hypertension (PAH) is a fatal disease that often occurs at an early age. In recent years, aggressive treatment with multiple drugs from the early-stage diagnosis is expected to improve the prognosis. Indeed, a high rate of initial combination therapy and excellent treatment outcomes have been reported from specialized centers for PAH in Japan. However, information on PAH epidemiology, including non-PAH specialized centers in Japan, is unclear. To address the above, we conducted a retrospective observational cohort study from April 2008 to September 2020 using real-world evidence from a large-scale administrative database (Medical Data Vision) to examine baseline characteristics, comorbidities, and treatment profiles of Japanese patients with PAH. Five hundred and eighteen patients with PAH (treatment-naive PAH, age 67.2 ± 15.9) were identified through our comprehensive approach which combined PAH disease codes, medications, and diagnostic procedures. Moreover, we showed that a larger proportion of patients received monotherapy in their initial treatment (66%) compared to those receiving combination therapy (34%). During the 1-year follow-up after PAH diagnosis, 13% of patients increased their PAH medications while other patients either decreased their PAH medications (6%) or discontinued PAH treatment (27%). The 3- and 5-year event-free survival rates of all-cause death were 72% and 64%, respectively. This is the first large-scale administrative database study that provides insights into real-world PAH management in Japan. This study highlighted a different PAH clinical landscape which included a larger portion of the elderly population, higher initial monotherapy treatment, and lower survival rates than previous studies.

Model-Informed Precision Dosing Guidance of Ethosuximide Developed from a Randomized Controlled Clinical Trial of Childhood Absence Epilepsy.

Ethosuximide was identified as the optimal option for new-onset childhood absence epilepsy (CAE) in a randomized, two-phase dose escalation comparative effectiveness trial of ethosuximide, lamotrigine, and valproic acid. However, 47% of ethosuximide initial monotherapy participants experienced short-term treatment failure. This study aimed to characterize the initial monotherapy ethosuximide exposure-response relationship and to propose model-informed precision dosing guidance. Dose titration occurred over a 16-20-week period until patients experienced seizure freedom or intolerable side effects. Subjects with initial monotherapy failure were randomized to one of the other two medications and dose escalation was repeated. A population pharmacokinetic model was created using plasma concentration data (n = 1,320), collected at 4-week intervals from 211 unique participants during both the initial and second monotherapy phases. A logistic regression analysis was performed on the initial monotherapy cohort (n = 103) with complete exposure-response data. Eighty-four participants achieved seizure freedom with a wide range of ethosuximide area under the curves (AUC) ranging from 420 to 2,420 μg·h/mL. AUC exposure estimates for achieving a 50% and 75% probability of seizure freedom were 1,027 and 1,489 μg·h/mL, respectively, whereas the corresponding cumulative frequency of intolerable adverse events was 11% and 16%. Monte Carlo Simulation indicated a daily dose of 40 and 55 mg/kg to achieve 50% and 75% probability of seizure freedom in the overall population, respectively. We identified the need for adjusted mg/kg dosing in different body weight cohorts. This ethosuximide proposed model-informed precision dosing guidance to achieve seizure freedom carries promise to optimize initial monotherapy success for patients with CAE.

P11 Evaluation of in vitro activity of double β-lactam ‘therapy’ in Escherichia coli: what is the association between ‘synergy’ and in vitro susceptibility?

Abstract Background Emerging antimicrobial resistance is a leading cause of patient morbidity/mortality worldwide. A potential strategy in the treatment of resistant infections is the use of combination antibiotics, with the hope of achieving greater in vitro activity, including synergy. It is currently assumed that combinations generating the greatest synergistic effect in vitro will be associated with the greatest improvement in in vitro susceptibility (as defined by EUCAST—see Methods). The aim of this study was to determine if this was indeed the case. Methods We systematically determined the relationship between double β-lactam therapy against 7 Escherichia coli strains of variable resistance in vitro (4 clinical/3 purchased). This included fully susceptible and low-level resistance isolates (N = 4), extended-spectrum β-lactamase producers (ESBLs) (N = 2) and carbapenemase producers (CPEs) (N = 1). For each of 10 β-lactam antibiotics, the MIC was determined individually, and subsequently in combination, using the MTS™ ‘cross’ synergy method (Liofilchem, 2012). The fractional inhibitory concentration (FIC) was calculated by dividing the MIC of each drug in combination by the MIC of each drug alone and adding the results. See Figure 1. Results were analysed according to EUCAST clinical breakpoints to determine if synergistic combinations correlated with a potentially improved in vitro susceptibility phenotype. A susceptibility phenotype improvement was defined: R/R or R/I or I/I monotherapy, improving to R/S, I/S or S/S combination therapy (where S = susceptible, I = intermediate and R = resistant). Results Overall, 86/630 (13.7%) combinations showed synergy; 408/630 (64.7%) = additive; 136/630 (21.6%) = indifferent. No antagonism was identified. Synergy was most detected in ESBL producers (32% of combinations; Figure 2) and less frequently in CPEs (2% combinations) and fully susceptible isolates (4% combinations). 31/630 (5%) combinations showed improvement in EUCAST susceptibility between mono/combination therapy (according to our definitions). Of these 31 combinations, 8 (26%) were synergistic, 15 (48%) additive and 8 (26%) indifferent (by FIC index). Of 599/630 combinations that showed no improvement in susceptibility, 78 (13%) = synergistic, 393 (65.6%) = additive and 128 (21.4%) = indifferent. It is however important to note that in 284/630 (45%), initial monotherapy susceptibility was S/S (i.e. further improvement not possible). Synergy was more common in combinations that improved EUCAST susceptibility versus those that did not; χ2, P = 0.04). Ceftazidime/avibactam + amoxicillin was the combination most commonly associated with synergy (12/86 synergistic combinations). Conclusions In the β-lactam combinations tested, synergy or additive effects were common (78.4%), similar to our previous work with Fosfomycin/β-Lactam combinations (89%), but higher than fosfomycin/non-β-lactam combinations (28%). Synergy was most detected in ESBL producers with most synergistic combinations containing one/two β-lactamase inhibitors. Overall, however, this rarely leads to an improvement in in vitro susceptibility by EUCAST criteria and is highly bug–drug–drug combination dependent. Further work using alternative validating methodology and in more isolates is required.

EE222 Healthcare Costs Associated with Initial Combination Therapy Versus Monotherapy for Patients with Hypertension

Initiation of antihypertensive medication with combination therapy requires less treatment modifications which may result in lower healthcare costs compared with initiation of antihypertensive monotherapy. We compared direct medical costs for patients with hypertension who initiated antihypertensive medication with combination therapy versus monotherapy in a US integrated healthcare system.

Effectiveness and tolerability of perampanel monotherapy in children with newly diagnosed focal epilepsy.

To examine the clinical effectiveness and tolerability of perampanel (PER) as initial monotherapy in pediatric patients with newly diagnosed focal epilepsy. A retrospective analysis was conducted on 62 children with newly diagnosed focal epilepsy who were treated with PER at the Epilepsy Center of Jinan Children's Hospital from July 2021 to July 2022. The treatment status, prognosis, and adverse reactions were followed up for a minimum of 6 months after the initiation of PER monotherapy. The effectiveness of the patients was estimated by the PER effective rate at 3-, 6-, and 12-month follow-up evaluations and adverse reactions were also recorded. The effective rates of PER in different etiologies and epilepsy syndromes were also statistically analyzed. The effective rates of PER treatment at the different time points of evaluation were 88.7% (3 months), 79.1% (6 months), and 80.4% (12 months). With PER treatment, seizure freedom varied over time, with 61.3%, 71.0%, and 71.7% of patients at the 3-, 6-, and 12-month follow-ups, respectively. Among the etiologies of epilepsy, the effective rates of genetic etiology, structural etiology, and unknown etiology were generally above 50% at the 3-, 6-, and 12-month follow-ups. Among the epilepsy syndromes, the categories with higher treatment efficacy were self-limiting epilepsy with centrotemporal spikes (SeLECTs), self-limited epilepsy with autonomic seizures (SeLEAS), and childhood occipital visual epilepsy (COVE), with an effective rate of above 80%. Adverse events were documented in 22 patients (35.5%), but they were mild and tolerable. The most common adverse events comprised irritability, drowsiness, dizziness, and increased appetite. PER has favorable effectiveness and tolerability as initial monotherapy for children with newly diagnosed focal epilepsy, which could be a potential option for long-term medication in the treatment of focal epilepsy in children. The current study provided potential evidence for PER as initial monotherapy in children with focal epilepsy in clinical practice.

Survival time and prognostic factors in canine leishmaniosis in a non-endemic country treated with a two-phase protocol including initial allopurinol monotherapy

BackgroundLeishmania infantum is an intracellular protozoan parasite which is endemic in countries of the Mediterranean Basin. Leishmaniosis is increasingly diagnosed in non-endemic areas due to the relocation of dogs from endemic areas and the travel of dogs to and from these areas. The prognosis of leishmaniosis in these dogs may differ from that of those in endemic areas. The aims of this study were (1) to determine the Kaplan–Meier estimated survival time for dogs with leishmaniosis in the Netherlands (a non-endemic country), (2) to determine if clinicopathological variables at the time of diagnosis predicted the survival of these dogs, and (3) to evaluate the effect of a two-phase therapy protocol of allopurinol monotherapy followed by meglumine antimoniate and/or miltefosine in the case of incomplete remission or relapse.MethodsThe database of the Department of Clinical Sciences of Companion Animals of the Faculty of Veterinary Medicine, Utrecht University was investigated for leishmaniosis patients. Patient records were reviewed for signalment and clinicopathological data at the time of diagnosis. Only treatment-naive patients were included. Follow-up was performed during the study by phone contact and included treatment received and date and cause of death. Univariate analysis was performed using the Cox proportional hazards regression model.ResultsThe estimated median Kaplan–Meier survival time was 6.4 years. In the univariate analysis, increases in monocyte, plasma urea and creatinine concentrations, and urine protein to creatinine ratio were all significantly associated with decreased survival time. The majority of patients only received allopurinol monotherapy.ConclusionsCanine leishmaniosis patients in our study population in the Netherlands, which is non-endemic for the disease, had an estimated Kaplan–Meier median survival time of 6.4 years, which is comparable to the outcome of other reported therapy protocols. Increased plasma urea and creatinine concentrations and monocyte concentration were statistically associated with an increased risk of death. We conclude that initial allopurinol monotherapy for 3 months should be effective in more than half of canine leishmaniosis cases, provided there is adequate follow-up, and that meglumine antimoniate or miltefosine therapy should be started as the second phase of the protocol in cases where remission is incomplete or there is a relapse.Graphical

Persistence with first-line antihypertensive therapy in Germany: A retrospective cohort study with 2,801,469 patients.

The goal of this retrospective cohort study was to investigate 3-year persistence with antihypertensive drug therapy and the association between antihypertensive drug classes and therapy discontinuation risk in Germany. The present retrospective cohort study was based on the IQVIA longitudinal prescription database (LRx) and included adult outpatients (≥18 years) with an initial prescription of antihypertensive monotherapy alone including diuretics (DIU), β-blockers (BB), calcium channel blockers (CCB), ACE inhibitors (ACEi), and angiotensin II receptor blockers (ARB) in Germany between January 2017 and December 2019 (index date). A Cox proportional hazards regression model was also used to assess the relationship between antihypertensive drug classes and non-persistence adjusted for age and sex. This study included 2,801,469 patients. Patients on ARB monotherapy exhibited the highest persistence within 1 year (39.4%) and 3 years (21.7%) after the index date. Patients on DIU monotherapy showed the lowest persistence (16.5% after 1 year, 6.2% 3 years after the index date). In the overall population, initial monotherapy with DIU (HR: 1.48) was positively associated with monotherapy discontinuation, whereas ARB monotherapy was (HR=0.74) negatively associated with monotherapy discontinuation compared to BB. However, in the age group >80, there was a slight negative association between DIU intake and monotherapy discontinuation (HR=0.91). This large cohort study reveals significant differences in 3-year persistence with antihypertensives, which were strongest for ARB and weakest for DIU. However, the differences also depended on age, with much better DIU persistence in the elderly.

Monotherapy with oxcarbazepine and controlled-release carbamazepine in newly diagnosed adult focal epilepsy (open comparative study)

Introduction. Oxcarbazepine is the first-line therapy for newly diagnosed focal epilepsy in children, but data on its use in adult patients in the Russian population are limited.Aim. Improvement of the efficacy of initial therapy with oxcarbazepine and controlled-release carbamazepine for newly diagnosed focal epilepsy in adults.Patients and methods. The study included 74 adult patients, 39 of them were included in the oxcarbazepine group and 35 in the controlledrelease carbamazepine group. During the 6-month follow-up period, patients completed 5 visits, during which adverse events and effectiveness were assessed, as well as video-EEG monitoring with an assessment of the epileptiform activity index. Results. The proportion of patients with a reduction in seizure frequency of more than 50 % was comparable in both groups, constituting 82.4 % (n = 28) and 85.2 % (n = 23) in the oxcarbazepine and carbamazepine group, respectively. Adverse events developed in 20 % (n = 7) of patients taking carbamazepine, and in the oxcarbazepine group in 12.8 % (n = 5) of patients. The 6-month initial monotherapy retention rate was higher in oxcarbazepine group (71.8 %) compared to carbamazepine group (65.7 %). In both groups, a 2.0–3.5-fold decrease in the average and total epileptiform activity index and epileptiform activity index during sleep was registered.Conclusions. The obtained results indicate similar effectiveness of oxcarbazepine and controlled-release carbamazepine in the treatment of newly diagnosed focal epilepsy in adults and better tolerability of oxcarbazepine in terms of both adverse events rate and lower frequency of drug discontinuation due to adverse events. A decrease in the epileptiform activity index by 2.0–3.5 times is evidence of possible use of the epileptiform activity index as an objective marker of the disease dynamics

Should substitution monotherapy or combination therapy be used after failure of the first antiseizure medication? Observations from a 30-year cohort study.

To assess the temporal trends in the use of second antiseizure (ASM) regimens and compare the efficacy of substitution monotherapy and combination therapy after failure of initial monotherapy in people with epilepsy. This was a longitudinal observational cohort study conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland. We included patients who were newly treated for epilepsy with ASMs between July 1982, and October 2012. All patients were followed up for a minimum of 2 years. Seizure freedom was defined as no seizure for at least 1 year on unchanged medication at the last follow up. During the study period, 498 patients were treated with a second ASM regimen after failure of the initial ASM monotherapy, of whom 346 (69%) were prescribed combination therapy and 152 (31%) were given substitution monotherapy. The proportion of patients receiving second regimen as combination therapy increased during the study period from 46% in first epoch (1985 to 1994) to 78% in the last (2005 to 2015) (RR=1.66, 95% CI: 1.17-2.36, corrected-p=0.010). Overall, 21% (104/498) of the patients achieved seizure freedom on the second ASM regimen, which was less than half of the seizure-free rate on the initial ASM monotherapy (45%, p<0.001). Patients who received substitution monotherapy had similar seizure-free rate compared with those who received combination therapy (RR=1.17, 95% CI: 0.81-1.69, p=0.41). Individual ASMs used, either alone or in combination, had similar efficacy. However, the subgroup analysis was limited by small sample sizes. The choice of second regimen used based on clinical judgement was not associated with treatment outcome in patients whose initial monotherapy failed due to poor seizure control. Alternative approaches such as machine learning should be explored to aid individualized selection of the second ASM regimen.

Cost-effectiveness evaluation based on two models of first-line atezolizumab monotherapy and chemotherapy for advanced non-small cell lung cancer with high-PDL1 expression.

Atezolizumab may provide clinical benefits to patients with advanced non-small cell lung cancer (NSCLC). However, the price of atezolizumab is relatively high, and its economic outcomes have remained unclear. In this study, we used two models to examine the cost-effectiveness of initial atezolizumab monotherapy versus chemotherapy for patients with PD-L1 high-expressing EGFR and ALK wild-type advanced NSCLC in the context of the Chinese healthcare system. Partitioned Survival model and Markov model were performed to evaluate the cost-effectiveness of first-line single-agent atezolizumab versus platinum-based chemotherapy for patients with advanced NSCLC with PD-L1 high-expressing EGFR and ALK wild-type disease. Clinical outcomes and safety information were obtained from the most recent data from the IMpower110 trial, while cost and utility values were obtained from Chinese hospitals and relevant literature. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed to explore model uncertainty. Scenario analyses were also conducted for the Patient Assistance Program (PAP) and various provinces in China. In the Partitioned Survival model, the total cost of atezolizumab was $145,038, providing 2.92 LYs and 2.39 QALYs, while the total cost of chemotherapy was $69,803, providing 2.12 LYs and 1.65 QALYs. The ICER for atezolizumab versus chemotherapy was $102,424.83/QALY; in the Markov model, the ICER was $104,806.71/QALY. Atezolizumab was not cost-effective at the WTP threshold of three times China's per capita gross domestic product (GDP). Sensitivity analysis showed that the cost of atezolizumab, the utility of PFS, and the discount rate had a significant impact on ICER; PAP significantly reduced ICER, but atezolizumab was still not cost-effective in China. First-line monotherapy with atezolizumab for patients with PD-L1 high-expressing EGFR and ALK wild-type advanced NSCLC was estimated to be less cost-effective than chemotherapy in terms of the Chinese healthcare system; offering PAP increased the likelihood that atezolizumab would be cost-effective. In some areas of China with higher levels of economic development, atezolizumab was likely to be cost-effective. To improve the cost-effectiveness of atezolizumab, drug prices would need to be reduced.

Efficacy, safety, and molecular response predictors of oral ixazomib and short-course rituximab in untreated iNHL.

Patients with indolent B-cell non-Hodgkin lymphoma (iNHL) generally require treatment but experience normal survival, emphasizing the need for simpler, safer therapies. Proteasome inhibitors target aberrant signaling pathways within iNHL and have manageable toxicities. We evaluated the oral proteasome inhibitor ixazomib as initial monotherapy, and combined with rituximab, for first-line treatment of iNHL. Treatment-naïve patients with iNHL needing therapy received oral ixazomib 4 mg weekly until progressive disease or unacceptable adverse events. A 4-week course of rituximab was added during month 7. The primary end point was overall response rate (ORR) during the ixazomib monotherapy window. Correlations included gene expression profiling and response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Thirty-three patients with follicular lymphoma (FL) (n= 20), marginal zone lymphoma (n= 7), and other iNHL were treated with a median follow-up of 30.3 months. During the 6-month ixazomib window, the ORR was 24%, including 35% in FL. The best ORR over the entire study period was 52% overall and 65% in FL; complete response was achieved in 33% and 45%, respectively. The median duration of response was 25.8 months (range, 0-49.7), and the 24-month progression-free and overall survival rates were 51% (95% confidence interval [CI], 32-67) and 91% (95% CI, 74-97), respectively. Ixazomib was well tolerated. Baseline downregulation of proteasome genes, PSMB9 (P= .03) and PSMB8 (P= .007), were associated with response. All evaluated patients generated anti-S antibodies to SARS-CoV-2 vaccination, with a median of 254.9 binding arbitrary unit per mL. Ixazomib demonstrated efficacy alone and with short-course rituximab in untreated iNHL while exhibiting favorable toxicity, convenience, and retention of the B-cell immune response. This trial is registered at www.clinicaltrials.gov as NCT02339922.

TRELAGLIPTIN'S REAL WORLD EFFICACY AMONG TYPE 2 DIABETES PATIENTS IN CAMBODIA (TRELA -REAL STUDY)

Background: Trelagliptin is the rst once-weekly oral therapy for type 2 diabetes in Cambodia. The afrmation of its efcacy and safety in Cambodian Type 2 Diabetes patients is to be established for extending the clinical benet of this unique oral anti-diabetic agent in this population Objective: To conrm the effect of Trelagliptin (TRELA), a selective once weekly dipeptidyl peptidase-4 (DPP-4) inhibitor, on glycemic control in the management of Type 2 Diabetes Mellitus (T2DM) in real-world practice settings in Cambodia Methods: An open-label, multicentric prospective, observational single-arm study was conducted across Phnom Penh and three other provinces in Cambodia which will include Siem Reap, Kampong Cham, and Battambang in outpatient settings. One hundred and fty patients with Type 2 Diabetes were enrolled after seeking informed consent. Trelagliptin 100 mg one tablet per week was administered to patients with type 2 diabetes who showed poor glycemic control (HbA1c ≥6.5% ) on diet/exercise therapy alone or diet/exercise therapy plus other oral antidiabetic agents or insulin. The study primary endpoint(s) included changes in glycated hemoglobin (HbA1c) from baseline at the end of three months, and at the end of six months of the study. The secondary endpoints included patient satisfaction and investigator assessment at the end of treatment (6 months) to once weekly treatment to Trelagliptin. Result: Treatment with Trelagliptin 100 mg/week led to a mean change in HbA1c 0.86% (from 8.76 ± 2.02 to 7.9 ± 1.60, p &lt; 0.05, CI 95) at the end of 3 months. At the end of 6 months, the mean change in HbA1c was 1.26% (from 8.76 ± 2.02 to 7.5 ± 1.34), p&lt;0.05, CI 95) (p-value signicant) Patient satisfaction and preference with once-weekly trelagliptin treatment was reported in 97.04 % (n=131) patients. As per the investigator's assessment, 77.04 % (n=104) of the patients reported a “good” response to Trelagliptin treatment at the end of the study over a period of 6 months. In 14.07 % (n=19) patients investigators reported that “excellent” response was achieved. Whereas 5.19% (n=7) and 3.7% (n=5) patients reported average and poor responses, respectively. Trelagliptin treatment once a week was demonstrated to be clinically efcacious as monotherapy and in combination with other anti-hyperglycemic agents. Trelagliptin treatment was found to be efcacious in treatment naïve and treatment-experienced patients. The clinical benets of Trelagliptin were consistent across age groups, body mass index (BMIs), and associated co-morbidities like hypertension. Trelagliptin was well tolerated and was safely used in addition to Metformin, Sulfonylureas, Thiazolidinediones, SGLT2-inhibitors &amp; Insulin treatment. The glucose-lowering effect of Trelagliptin was comparable to other DPP4 inhibitors (gliptins), and other classes of oral anti-diabetic medications with the additional advantage of once-a-week dosing treatment regime. Conclusion: Treatment with once-a-week trelagliptin as initial monotherapy and in combination therapy with other anti-hyperglycemic agents for glucose control in Type 2 Diabetes was efcacious and well-tolerated. Trelagliptin 100 mg once a week treatment achieved treatment satisfaction in most patients and reported “good” investigator response in majority of type 2 diabetes patients. Trelagliptin 100 mg once-a-week treatment is a useful consideration in the management of type 2 diabetes patients

Cost-effectiveness analysis of initial treatment with single-pill combination antihypertensive medications.

Hypertension guidelines recommend initiating treatment with single pill combination (SPC) antihypertensive medications, but SPCs are used by only one-third of treated hypertensive US adults. This analysis estimated the cost-effectiveness of initial treatment with SPC dual antihypertensive medications compared with usual care monotherapy in hypertensive US adults.The validated BP Control Model-Cardiovascular Disease (CVD) Policy Model simulated initial SPC dual therapy (two half-standard doses in a single pill) compared with initial usual care monotherapy (half-standard dose when baseline systolic BP < 20 mmHg above goal and one standard dose when ≥20 mmHg above goal). Secondary analyses examined equivalent dose monotherapy (one standard dose) and equivalent dose dual therapy as separate pills (two half-standard doses). The primary outcomes were direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) over 10 years from a US healthcare sector perspective.At 10 years, initial dual drug SPC was projected to yield 0.028 (95%UI 0.008 to 0.051) more QALYs at no greater cost ($73, 95%UI -$1 983 to $1 629) than usual care monotherapy. In secondary analysis, SPC dual therapy was cost-effective vs. equivalent dose monotherapy (ICER $8 000/QALY gained) and equivalent dose dual therapy as separate pills (ICER $57 000/QALY gained). At average drug prices, initiating antihypertensive treatment with SPC dual therapy is more effective at no greater cost than usual care initial monotherapy and has the potential to improve BP control rates and reduce the burden of CVD in the US.

Comparison of the efficacy and safety of Metformin versus Sitagliptin among treatment naïve patients of Type-2 Diabetes.

Objective: To compare the efficacy and safety of metformin versus Sitagliptin among treatment naïve patients of type-2 diabetes mellitus (T2DM). Study Design: Randomized Controlled Trial. Setting: Department of Medicine, Unit-III, Bahawal Victoria Hospital, Bahawalpur. Period: September 2021 to August 2022. Material &amp; Methods: During the study period, a total of 320 treatment naïve T2DM patients (160 in each group) were randomly enrolled and followed up. Baseline demographics of all patients including gender, age, BMI (kg/m2), fasting plasma glucose (FPG) and baseline HbA1c were recorded. Patients of Group-A were given oral Sitagliptin 100mg once daily whereas patient in Group-B were prescribed oral metformin as 500-2000 mg per day aiming achievement of glycemic goals. Repeat HbA1c and FPG levels were tested at the end of 12th and 24th weeks therapy among both study groups. Side effects related to studied drugs were also observed and recorded. Results: Out of a total of 320 patients, 57 patients (27 in Group-A and 30 in Group-B) lost follow up so 263 patients were included in the final analysis. Majority of the patients, 134 (51.0%) were male. Mean age, BMI and duration of diabetes among study participants were 53.07+9.62 years, 29.44+4.74 kg/m2 and 1.96+2.3 years respectively. No statistically significant difference was noted at zero, 12 or 24 weeks in between both study groups (p&gt;0.05) in terms of reduction in HbA1c or FPG levels during the study period (p&gt;0.05). Conclusion: Both metformin and Sitagliptin effectively reduce HbA1c and FPG levels among treatment naïve T2DM patients with relatively good tolerability and safety. Both study drugs can be used as initial monotherapy among T2DM patients with relatively mild-to-moderate disease.

Initial monotherapy of patients with epilepsy is the key to further therapeutic success

Initial monotherapy of patients with epilepsy is the key to further therapeutic success

1325. Macrolide versus Non-macrolide in Combination with Steroids for the Treatment of Lobar or Segmental Mycoplasma Pneumoniae Pneumonia Unresponsive to Initial Macrolide Monotherapy

Abstract Background Mycoplasma pneumoniae (MP) is one of the most common causes of bacterial pneumonia in children. In the recent decade, macrolide-resistant MP (MRMP) has been increasing in proportion, leading to children unresponsive to initial macrolide therapy. The purpose of this study was to evaluate the outcomes of children with lobar or segmental MP pneumonia unresponsive to initial macrolide therapy, who received non-macrolide (NM), macrolide plus steroids (M+S), and non-macrolide plus steroids (NM+S) according to the 2019 guideline during the 2019-2020 Mycoplasma epidemic in South Korea. Methods This was a retrospective cohort study of children below 18 years old, admitted during the 2019-2020 MP outbreak for lobar or segmental MP pneumonia. The inclusion criteria were as follows: 1) sputum or nasopharyngeal swab MP PCR positive, 2) no history of pneumonia within one month of positive MP PCR, 3) lobar or segmental pneumonia on chest x-ray, and 4) initial treatment with macrolide monotherapy. Children that were unresponsive to the initial 3-5-day macrolide monotherapy were divided into 3 groups depending on the next regimen: NM, M+S, and NM+S group. Their outcomes were assessed. Results During May 2019 to March 2020 MP epidemic, a total 190 patients that fit all of the inclusion criteria were included as study participants. Of these, 16.8% (n=32/190) were responsive to initial macrolide monotherapy and 83.2% (158/190) were unresponsive. Of the 158 patients unresponsive during the initial 5-day macrolide therapy, 8.2% (n=13) were switched to a NM, 75.9% (n=120) were added steroids (M+S), and 15.8% (25/158) were switched to a non-macrolide plus steroids (NM+S). Treatment success rates were 46%, 81%, and 100% in the NM, M+S, and NM+S groups, respectively (P=0.001). Compared to patients in the NM+S group, those in the M+S group were 8.0 (Confidence interval [CI], 1.3-61.7; P=0.046) times more likely to have prolonged fever ≥4 days after the switch in treatment regimen compared to patients with NM+S, and 10.7 (CI, 1.5-108.7; P=0.046) times more likely in the NM group. Conclusion In patients with severe mycoplasma pneumonia with failure of response to initial macrolide therapy, a non-macrolide antibiotic plus steroid combination had the highest treatment success rate and shorter duration of fever. Disclosures All Authors: No reported disclosures.

Treatment patterns and satisfaction in patients with type 2 diabetes newly initiating oral monotherapy with antidiabetic drugs in Japan: results from the prospective Real-world Observational Study on Patient Outcomes in Diabetes (RESPOND)

IntroductionTo present longitudinal data from the Real-world Observational Study on Patient Outcomes in Diabetes (RESPOND) in Japan.Research design and methodsIn this multicenter, prospective, observational cohort study, patients with type 2...

Update on the drug treatment of hypertension: perspectives in clinical pharmacology

Drug therapy to achieve the recommended target blood pressure remains the cornerstone of the management of hypertension. Today, there are strong evidences from randomized controlled trials that antihypertensive drugs are more effective than placebo at reducing cardiovascular mortality and morbidity. According to more recent guidelines, there are three main classes of drugs that have been used for initial monotherapy: inhibitors of the renin-angiotensin system, calcium channel antagonists, and diuretics. The use of beta blockers has been restricted for initial monotherapy in the absence of a specific indication associated with adverse effects on some outcomes, particularly in older patients. Many studies have demonstrated that antihypertensive agent classes can be combined effectively and nowadays, it is strongly recommended to use single-pill combinations containing two or three antihypertensive agents. Combination therapy provides greater antihypertensive potential, reduced risks for side effects, lower medical cost, increase compliance, and promotes long-term adherence, this latter being the major challenge of drug therapy for hypertension. Key words: hypertension, drug therapy.

Choice of Glucose-Lowering Drugs as Initial Monotherapy for Type 2 Diabetes Patients with Contraindications or Intolerance to Metformin: A Systematic Review and Meta-Analysis.

There are multiple glucose-lowering drugs available as alternative initial monotherapy for type 2 diabetes patients with contraindications or intolerance to metformin. However, little comparative and systematic data are available for them as initial monotherapy. This study estimated and compared the treatment effects of glucose-lowering drugs as initial monotherapy for type 2 diabetes. PubMed, Web of Science, Embase, CNKI, Chongqing VIP, and WanFang Data from 1 January 1990 until 31 December 2020 were searched for randomized controlled trials which compared a glucose-lowering drug with placebo/lifestyle-intervention for type 2 diabetes. Drug classes included metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), glinides (NIDEs), α-glucosidase inhibitors (AGIs), dipeptidyl peptidase-4 inhibitors (DPP-4is), sodium-glucose cotransporter-2 inhibitors (SGLT2is), insulins (INSs), and glucagon-like peptide-1 receptor agonists (GLP-1RAs). A total of 185 trials were included, identifying 38,376 patients from 56 countries across six continents. When choosing an initial drug monotherapy alternative to metformin, SUs were most efficacious in reducing HbA1c (-1.39%; 95% CI -1.63, -1.16) and FPG (-2.70 mmol/L; 95% CI -3.18, -2.23), but increased hypoglycemia risks (5.44; 95% CI 2.11, 14.02). GLP-1RAs were most efficacious in reducing BMI (-1.05 kg/m2; 95% CI -1.81, -0.29) and TC (-0.42 mmol/L; 95% CI -0.61, -0.22). TZDs were most efficacious in increasing HDL-C (0.12 mmol/L; 95% CI 0.07, 0.17). SGLT2is were most efficacious in lowering SBP (-4.18 mmHg; 95% CI -4.84, -3.53). While AGIs conferred higher risk of AE-induced discontinuations (2.57; 95% CI 1.64, 4.03). Overall, only GLP-1RAs showed an integrated beneficial effect on all outcomes. Our results also confirmed the intraclass differences in treatment effects across drugs. Most trials were short-term, and no significant differences in mortality, total vascular events, myocardial infarction, heart failure, stroke, or diabetic nephropathy were observed across drug classes. Our results suggest a potential treatment hierarchy for decision-makers, with GLP-1RAs being the preferred alternative therapy to metformin regarding their favorable efficacy and safety profiles.