Drugs - Real World Outcomes最新文献

Background: Major depressive disorder (MDD) affects over 332 million people globally. Although antidepressants are effective, adverse drug reactions (ADRs) may reduce adherence and quality of life (QoL). In Nepal, where mental health and pharmacovigilance (PV) systems are developing, assessing self-reported ADRs is essential. This study evaluated the antidepressant-induced ADRs among patients visiting the psychiatry outpatients department of a tertiary care hospital in Nepal.

Methods: A 3-month, single-center, cross-sectional study was conducted at the psychiatry outpatient department of Dhulikhel Hospital, Nepal. Using purposive sampling, 204 patients diagnosed with depression and receiving antidepressant therapy were assessed through structured interviews using validated tools like the Antidepressant Side-Effect Checklist (ASEC), Naranjo ADR Probability Scale, and Schumock and Thornton Criteria.

Results: Among 204 patients, the mean number of ADRs was 7.8 ± 6.2 per patient. Most participants were middle-aged (mean 42.8±11.2 years), urban residents (61.3%), and female (53.4%). Severe depression was the most frequent diagnosis (69.6%). Escitalopram (17.6%), amitriptyline (16.2%), and mirtazapine (14.7%) were most commonly prescribed. The most frequently reported ADRs were dry mouth (65.7%), blurred vision (61.3%), weight gain (59.8%), drowsiness (54.9%), and increased appetite (53.9%). Combination antidepressants therapy (26.9%) was associated with higher odds of increased appetite (adjusted odds ratio [AOR] 2.21, p < 0.05) and weight gain (AOR 1.87, p < 0.05). Naranjo assessment (mean score 2.1 ± 1.8) indicated that most ADRs were 'possible' (33.8%), a small proportion were 'probable' (3.4%), and none met criteria for 'definite' or 'doubtful'. All ADRs were predictable Type A reactions. The ASEC-based severity assessment showed most ADRs were mild (23.6%) to moderate (26.5%) with a lower proportion being severe (15.5%); thus, no treatment adjustments were made but counselling was provided as ADRs were clinically manageable through routine monitoring and counselling.

Conclusion: Given the high frequency of predictable Type A ADRs and the increased metabolic effects observed with combination therapy, these findings emphasize the need for routine monitoring and strengthened PV practices to improve antidepressant safety in resource-limited settings like Nepal.

Background and objectives: Respiratory tract infections and skin and soft-tissue infections are some of the most common causes of outpatient visits. Upper respiratory tract infections (URTIs) are the most common type of infection globally, as well as in India. In 2019, its global incidence was 17.2 billion. Additionally, the Infectious Diseases Society of America 2012 guidelines for the management of Group A streptococcal pharyngitis strongly recommend penicillin or amoxicillin for individuals without penicillin allergy. Therefore, we conducted this study to assess the real-world safety and efficacy of a fixed-dose combination of cephalexin extended release and clavulanate potassium (cephalexin CV) in patients with URTIs and uncomplicated skin and soft-tissue infections (uSSTIs).

Methods: In this phase IV, multicentre, open-label, single-arm study, patients with URTIs and uSSTIs were prescribed cephalexin CV (375 mg + 125 mg or 750 mg + 125 mg for severe infection) orally twice daily for 10 days. Patients were assessed for adverse events (AEs), clinical success defined as a clinical cure or clinical improvement, and microbiological success defined as a microbiological outcome of documented eradication or presumed eradication at the end of the study.

Results: A total of 230 patients were enrolled, 115 patients each with URTIs and uSSTIs. Only eight AEs were reported; seven were treatment-emergent AEs. In the URTI group, 1/115 (0.9%) patients reported one treatment-emergent AE and in the uSSTI group, 6/115 (5.2%) patients reported six treatment-emergent AEs. The most commonly reported treatment-emergent AE was diarrhoea. Three events of diarrhoea were related to the treatment (one in the URTI group and two in the uSSTI group). All AEs were of mild intensity and no serious AEs were reported. All patients with URTIs and 113 (98.3%) patients with uSSTIs showed clinical success; 16 (100%) patients with URTIs and 59 (96.7%) patients with uSSTIs showed microbiological success.

Conclusions: In this real-world study, the fixed-dose combination of cephalexin CV was safe, well tolerated and efficacious in terms of clinical and microbiological success for the treatment of URTIs and uSSTIs. In the current era of antimicrobial resistance, the fixed-dose combination of cephalexin CV can be an alternative therapeutic option.

Clinical trial registration: This study was prospectively registered on Clinical Trials Registry, India [CTRI/2022/07/044190] on 20 July, 2022; URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NzA4MTA=&Enc=&userName= .

Background: Treatment strategies for pulmonary arterial hypertension (PAH) depend on patients' 1-year mortality risk; however, real-world practices and outcomes remain inadequately described.

Objective: We aimed to investigate real-world experience with selexipag, an oral selective prostacyclin I2 receptor agonist used to treat PAH.

Methods: This analysis of two large, prospective, observational studies: SPHERE (NCT03278002; USA; completed) and EXPOSURE (EUPAS19085; Europe and Canada; ongoing, data cutoff November 2021) included adults newly initiating selexipag with follow-up available.

Results: Of 1366 selexipag users, 894 met eligibility criteria. At selexipag initiation, the median (Q1-Q3) age was 61 (48-70) years and the time since diagnosis was 2.7 (0.8-7.4) years. Most patients initiated selexipag within triple oral combination therapy (67%) with WHO-FC III symptoms (61%). During a median 10.8 (Q1-Q3: 3.3-18.6) months of selexipag exposure, 388 (43%) patients discontinued selexipag, mostly as a result of tolerability (n = 173, 19%) and death (n = 69, 8%). The median individualised dose was 800 μg twice-daily (n = 742). One-year mortality risk at selexipag initiation (assessable for 591 patients using a four-strata method): 22% were low-risk, 40% intermediate-low, 29% intermediate-high, and 9% high-risk. From low to high risk: 86%, 73%, 57% and 45% were free from all-cause hospitalisation at 1 year, and 1-year survival was 100%, 96%, 91%, and 59%, respectively.

Conclusions: Despite current guidelines, over half of patients started selexipag almost 3 years after diagnosis, and 38% were already intermediate-high or high risk of 1-year mortality. Lower hospitalisation rates and better survival were observed for selexipag-treated patients in the low and intermediate-low risk groups versus higher risk groups.

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as a first-line therapy for type 2 diabetes in Japan. Precautions of the package inserts for ethical drugs containing DPP-4 inhibitors were revised for pemphigoid between 2016 and 2018.

Study design and methods: This is a retrospective study that investigated the number of DPP-4 inhibitor-associated pemphigoid events using the Japanese Adverse Drug Event Report and its estimated annual incidence rate using a nationwide claims database to assess the trend in reported DPP-4 inhibitor-associated pemphigoid events after the release of the revised precautions in Japan.

Results: We identified 2175 DPP-4 inhibitor-associated pemphigoid events in 2069 case reports. The most common suspected DPP-4 inhibitor was vildagliptin (45.3%), followed by teneligliptin (17.5%), sitagliptin (16.0%), and linagliptin (11.0%). The number of DPP-4 inhibitor-associated pemphigoid events increased from 30 in 2015 to 373 in 2016, reaching a peak of 412 in 2018. Although the estimated annual incidence rate did not exceed 50 per 1,000,000 patients mostly, it exceeded 100 per 1,000,000 for vildagliptin in 2016 and 2018.

Conclusions: The number of reported DPP-4 inhibitor-associated pemphigoid events increased after the revised precautions of package inserts for DPP-4 inhibitors were released.

Background: Pediatric-inspired regimens (PIR) yield excellent outcomes for acute lymphoblastic leukemia (ALL). Despite national guidelines recommending PIR for adolescents and young adults (AYAs; aged 15-39 years), the use of guideline-concordant PIR in AYAs is inconsistent across treatment settings.

Methods: This retrospective observational study compared overall survival (OS) and stem cell transplant (SCT) use among AYAs treated with PIR versus non-PIR. Using a deidentified, geographically representative USA health claims database, we analyzed a cohort of AYAs with newly diagnosed ALL between 1 July 2007 and 30 September 2020.

Results: Among 599 patients who met the inclusion criteria, 187 (31%) received PIR, 303 (51%) received non-PIR, and for 109 (18%), treatment was undetermined. PIR and non-PIR groups were propensity score matched (n = 187 each). Using Kaplan-Meier methodology, OS was significantly higher for those treated with PIR versus non-PIR (log-rank P = 0.0001; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.18-0.55). For PIR and non-PIR, 1-, 3-, and 5-year survival estimates (95% CI) were 98.1% (95.3-99.3%) versus 88.3% (83.5-91.7%); 88.5% (82.6-92.5%) versus 69.1% (62.1-75.1%); and 87.3% (81.0-91.6%) versus 63.3% (55.2-70.3%). Sensitivity and subgroup analyses were consistent with primary results. By Kaplan-Meier methodology, SCT use was significantly lower among AYAs treated with PIR than non-PIR (log-rank P = 0.0004; HR, 0.46; 95% CI 0.30-0.71); use by 2 years was 16.5% (12.2-22.2%) and 33.4% (27.6-40.0%), respectively.

Conclusions: These results support the use of guideline-concordant PIR for AYA ALL.

Background: Hypertension is a major global health burden associated with significant cardiovascular morbidity and mortality. Fixed-dose combinations (FDC) may improve blood pressure (BP) control and prevent associated complications. This study aimed to evaluate the effectiveness and safety of telmisartan and amlodipine FDC in Indian patients with hypertension.

Methods: This prospective, multicenter (n = 982), observational, real-world study enrolled patients aged ≥ 18 years diagnosed with hypertension and prescribed telmisartan and amlodipine FDC. The primary outcome was the mean change in systolic blood pressure (SBP) from baseline to 8 weeks. Safety was assessed on the basis of the incidence of adverse events reported by patients or observed by clinicians.

Results: Out of 8541 individuals screened, 6232 were enrolled. A significant reduction in mean SBP was observed, decreasing from 155.12 mmHg at baseline to 135.96 mmHg at week 8 (P < 0.0001). Similarly, a reduction in mean diastolic blood pressure (DBP) was seen from 104.47 mmHg at baseline to 88.45 mmHg at week 8 (P < 0.0001). Around 70% of patients achieved the target BP (< 140/90 mmHg). Within the context of the study design, the physicians' global efficacy assessment suggested that 51.35% were extremely satisfied and 48.01% were satisfied with the treatment outcomes. Similarly, the tolerability assessment indicated that 52.95% of physicians were extremely satisfied and 45.84% were satisfied, while only a small proportion (0.54-0.64%) reported neutrality.

Conclusions: Treatment with telmisartan and amlodipine FDC demonstrated significant antihypertensive effectiveness and was well-tolerated in the real-world among Indian patients with hypertension.

Introduction: Opioid use is common in rheumatoid arthritis (RA) for pain management; however, evidence of opioid-associated adverse events is increasing. While biological (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) improve functional outcomes such as pain, little is known about their impact on opioid utilization patterns. This study investigated opioid utilization before and after b/tsDMARD initiation and assessed effect modification by sex.

Methods: Using 5% Medicare claims data from 2012 to 2020, this cohort study included older adults (≥ 65 years) with RA who initiated b/tsDMARDs (first prescription = index date), and had continuous Medicare Parts A, B, and D, but not Part C enrollment, during 12 months before and after initiation. The outcomes of interest were any opioid use and long-term opioid therapy (LTOT). McNemar's test was performed to compare outcomes before and after b/tsDMARD initiation. Sex-based differences in changes in opioid use after b/tsDMARD initiation were also evaluated.

Results: The study cohort included 3585 individuals with RA initiating b/tsDMARDs; most were female (75.87%) with a mean (SD) age of 73.15 (5.99) years. Following b/tsDMARD initiation, any opioid use decreased significantly from 2094 (58.41%) to 2017 (56.26%) (p = 0.015). However, LTOT use increased significantly from 733 (20.45%) to 900 (25.10%) (p < 0.001), following b/tsDMARD initiation. No evidence of sex differences in the association between b/tsDMARD initiation and opioid utilization was identified.

Conclusions: Initiating b/tsDMARDs was associated with a modest reduction in any opioid use. However, LTOT use in RA remained persistently high. The impact of different b/tsDMARD initiation on opioid utilization patterns needs further investigation.

Background: Vulvovaginal candidiasis (VVC) is a common gynecological complaint. Ibrexafungerp (brand name: Brexafemme®) is a new, first-in-class oral antifungal medication approved as a 1-day treatment for VVC and as a monthly treatment to reduce frequency of recurrent VVC.

Objective: This article describes characteristics of patients who received ibrexafungerp and potential ibrexafungerp-related side effects in order to help inform optimal future use of this medication.

Methods: We used a large, national commercial health insurance claims database (the Merative^TM MarketScan® Commercial/Medicare Database) to identify female patients with one or more outpatient ibrexafungerp prescription during 1 July 2021 to 31 December 2023. We examined patient demographic characteristics, medical conditions and medications, type of healthcare provider seen, diagnostic testing performed, and potential ibrexafungerp side effects.

Results: Among 1368 female patients who received ibrexafungerp, most were also prescribed fluconazole or topical antifungals (84.7%) or had one or more vaginitis/vulvitis-related healthcare visit (76.9%) in the previous year. Few patients (2.9%) experienced a potential ibrexafungerp-related side effect.

Conclusions: Our results suggest that ibrexafungerp was generally used as non-first-line treatment for VVC.

Background and objectives: Oropharyngeal dysphagia (OD), a dysfunction in swallowing food or drink, can result from various diseases and adverse drug reactions. OD is a risk factor for aspiration pneumonia (AP). However, the specific drugs causing OD and their incidence rates are not fully understood. This study aimed to identify drugs associated with OD, their incidence rates, and AP risk factors in patients taking these drugs on the basis of the information provided in package inserts.

Methods: This study identified candidate dysphagia-inducing drugs (CDIDs) from Japanese package inserts that listed OD as an adverse reaction. The age, sex, medications, and comorbidities of patients taking CDIDs were analyzed using the JammNet insurance database, purchased from JammNet Co., Ltd. (Tokyo, Japan).

Results: Overall, 54 ingredients were identified as CDIDs. Out of 24,276 patients taking CDIDs, 146 (0.6%) were diagnosed with OD and 76 (0.3%) with AP. Among those with AP, 23 patients (30%) also had OD. OD or AP occurred in patients taking 28 (52%) of the 54 target ingredients. In addition, 13 ingredients had an adverse reaction incidence of 1% or greater for either condition. The top five CDIDs with the highest incidence rates for each diagnosis were clobazam, baclofen, zonisamide, tiapride hydrochloride, and topiramate. Incidence rates of OD and AP were significantly higher with multiple CDIDs than with a single drug (p < 0.05). Logistic regression analysis showed that AP occurrence was significantly associated with males, late-stage elderly individuals, a diagnosis of OD, and constipation.

Conclusions: The results of this study suggest that careful attention should be given to the risk of AP when prescribing CDIDs, particularly for elderly male patients.

Introduction: Pulmonary arterial hypertension (PAH) is a rare, chronic and progressive disease with a significant clinical, social, and economic impact. Despite available therapies, none address the underlying cause but rather focus on symptom management.

Objectives: This study aims to estimate the economic and social burden of PAH in Italy, including direct healthcare costs, direct nonhealthcare costs, and indirect costs related to productivity loss.

Methods: A bottom-up prevalence-based cost-of-illness model was developed using epidemiological data and healthcare resource consumption from national and international literature, validated by a panel of expert clinicians with extensive experience in the management of the condition across different regions of Italy. The analysis was conducted from a societal perspective over a 1-year horizon. The economic burden included direct healthcare costs (hospitalization, pharmaceuticals, and specialist care), direct nonhealthcare costs, and indirect costs related to productivity loss.

Results: In Italy, the prevalent population of patients with PAH is estimated between 2100 and 3500 individuals, with 2-5% in functional class (FC) I, 28-31% in FC II, 53-57% in FC III, and 7-11% in FC IV. The total annual expenditure for treatment and management is estimated between 263 million and 438 million euros, with 74% attributable to direct healthcare costs, 9% to direct nonhealthcare costs, and 17% to indirect costs. The mean annual cost per patient is approximately 125,000 € and increases with disease severity, ranging from 46,303 € for FC I to 252,176 € for FC IV.

Conclusions: PAH has a substantial economic burden, increasing with disease severity. Early diagnosis and targeted interventions could improve patient outcomes, reduce complications, and optimize resource allocation for the National Health Service and society.