Clinical Drug Investigation最新文献

Background and objective: The introduction of immune checkpoint inhibitors (ICIs) in oncology presents a critical healthcare policy challenge for resource allocation due to their substantial financial burden. This study assessed the reporting quality of health economic evaluation (HEE) studies of ICIs.

Methods: This study conducted a systematic literature search of four databases (PubMed, EMBASE, Cochrane CENTRAL, and the International HTA Database) for studies published between January 1, 2014 and December 31, 2022. All ICIs approved up to December 31, 2022, in the USA, EU, China, and Japan were included. Reporting quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards published in 2013 (CHEERS 2013), which is the most widely recognised and implemented reporting guideline for HEE studies. Subgroup analyses were also performed based on the risk of sponsorship bias or citation of CHEERS 2013.

Results: A total of 5368 records were identified, 252 of which were included after full-text review. The study design, setting, and ICIs most frequently observed were cost-effectiveness and cost-utility analyses (63.5%), the USA (46.0%), and pembrolizumab (38.1%), respectively. Of the 24 items of CHEERS 2013, fully reported items were limited, particularly in the Methods section. Setting and location were not reported in 94.4% of the records. Subgroup analyses also revealed insufficient reporting of items in the Methods section, particularly "Setting and location".

Conclusion: Health economic evaluation studies on ICIs between 2014 and 2022 had limited reporting across the 24 items of CHEERS 2013, regardless of sponsorship bias risk or citations. The items on setting and location in the Methods section were particularly underreported, emphasising the need for transparent reporting in HEE studies of ICIs.

Background: Natural biomedicines (NBMs) are frequently used to manage immune-mediated and inflammatory dermatologic diseases (IMIDDs). This systematic review evaluates the efficacy, safety, and clinical relevance of NBMs in IMIDDs, providing an evidence-based analysis to guide dermatologic practice.

Methods: Following PRISMA guidelines, a systematic search was conducted in PubMed, Embase, Medline, and Google Scholar for randomized controlled trials (RCTs) investigating NBMs in IMIDDs from 1990 to 2023. Studies were included if they met predefined eligibility criteria: RCT design, relevant IMIDD condition, NBM intervention, and quantitative outcome measures. Risk of bias was assessed using the Jadad scale. Results were synthesized qualitatively due to heterogeneity in study designs and outcome measures.

Results: Of 1364 records screened, 95 RCTs were included, encompassing 5265 participants across 23 countries. Indigo naturalis, fish oil (⍵-3), and aloe vera demonstrated the most consistent efficacy in managing psoriasis, systemic lupus erythematosus (SLE), atopic dermatitis (AD), and lichen planus (LP). Indigo naturalis significantly improved erythema, scaling, and PASI scores in psoriasis patients. Fish oil showed benefits in SLE disease activity indices and AD severity, while aloe vera demonstrated improvements in SCORAD and LP severity criteria. Most NBMs exhibited favorable safety profiles, although adverse event reporting was inconsistent.

Discussion: While these findings highlight the potential of NBMs in dermatologic care, methodological limitations, including small sample sizes, heterogeneity in study designs, and lack of direct comparisons to conventional therapies, limit definitive conclusions. Additionally, not all natural agents can be easily searched and captured in systematic reviews, which may have restricted the scope of included NBMs. Future research should emphasize high-quality RCTs, standardized outcome measures, and comparative studies against conventional treatments.

Trial registration: The review protocol is registered with Open Science Framework (OSF) ( https://doi.org/10.17605/OSF.IO/UH9XJ ).

Introduction: Penpulimab is a PD-1 monoclonal antibody recommended for treating squamous non-small cell lung cancer (sqNSCLC) in combination with paclitaxel and carboplatin. This study aimed to assess the cost-effectiveness of penpulimab combined with paclitaxel and carboplatin against paclitaxel plus carboplatin as first-line treatment for locally advanced or metastatic sqNSCLC in China.

Methods: A three-state partitioned survival model was constructed using the efficacy outcomes obtained by digitizing the AK105-302 trial and was extrapolated to the lifetime horizon. Data on direct medical costs and utilities was gathered from the literature and commercial databases from the perspective of the Chinese healthcare system. Outcomes included quality-adjusted life years (QALYs), life years (LYs), and the incremental cost-effectiveness ratio (ICER). Sensitivity analysis and scenario analysis were performed to test the model robustness.

Results: The incremental efficacy of penpulimab plus paclitaxel and carboplatin was 0.821 QALYs and 1.176 LYs with an incremental cost of $20,335 compared with paclitaxel plus carboplatin combination therapy. The ICER was $24,778 per QALY, falling below the threshold of three times the per capita gross domestic product of China, a commonly applied benchmark. The results of the one-way sensitivity analysis demonstrated that the ICER values were primarily influenced by the utility of progression-free state and cost of penpulimab. Probabilistic sensitivity analysis showed that penpulimab plus paclitaxel and carboplatin was cost-effective for 98.3% of the cases. Scenario analysis yielded results similar to those of the base-case analysis.

Conclusions: Our analysis suggests that penpulimab plus paclitaxel and carboplatin combination therapy is cost-effective for patients with locally advanced or metastatic sqNSCLC in China.

Background: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, such as fremanezumab, are effective for migraine prevention. However, their effectiveness in treating migraine complicated by medication overuse, remains underexplored.

Objective: This systematic review aims to evaluate the effectiveness of fremanezumab in adults with migraine complicated by medication overuse.

Methods: We systematically searched PubMed and Embase (Ovid) databases for studies on fremanezumab, selecting primary studies that included adults with migraine complicated by medication overuse and reported at least one efficacy outcome. The search was performed in January 2024 and then updated in June 2024. Risk of bias for randomized controlled trials was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, while real-world studies were evaluated using both the ROBINS-I and ROB-ME tools. Data extraction and analysis followed established guidelines.

Results: Our search identified 176 records, of which 2 clinical trials and 7 real-world studies were included. Included studies recruited a total of 1422 adults with migraine complicated by medication overuse. In post hoc analyses from clinical trials, fremanezumab significantly reduced monthly migraine days, days with acute headache medication use, and Headache Impact Test (HIT-6) scores compared to placebo during a 12-week period. The real-world studies reported a reduction in monthly headache days at 6 months, and a high reversion rate from medication overuse headache (MOH) after one year of treatment.

Conclusion: Both post hoc analyses from clinical trials and real-world studies support fremanezumab benefits in reducing migraine frequency, medication use, and headache-related disability in adults with migraine complicated by medication overuse. Given the limited quality of data, further real-world research with standardized reporting criteria is needed to substantiate long-term benefits and establish optimal treatment protocols.

BACKGROUND AND OBJECTIVE: This meta-analysis aims to evaluate ligelizumab's efficacy and safety for chronic spontaneous urticaria (CSU) treatment by analyzing recent clinical trials and comparing it with placebo and omalizumab.

Methods: PubMed, Embase, and Cochrane were searched up to October 2024. Eligible studies were randomized controlled trials (RCTs) comparing ligelizumab with placebo or omalizumab, reporting relevant outcomes. Nonrandomized studies, or those without control groups, were excluded. Risk of bias was assessed using the Cochrane RoB-2 tool, and the Grading of Recommendation, Assessment, Development, and Evaluations approach rated evidence certainty. Statistical analysis used R software (v.4.4.2), assessing heterogeneity by Cochran Q and I² statistics.

Results: Four RCTs with 2488 patients were included. Ligelizumab (< 72 mg) significantly improved itch severity score over 7 days (ISS7) [risk ratio (RR) 5.07; 95% confidence interval (CI) 3.12-8.24; prediction interval (PI) 2.31-11.15; P < 0.01; I² = 0%], urticaria activity score over 7 days (UAS7) (RR 4.61; 95% CI 1.84-11.59; PI 0.34-62.49; P < 0.01; I² = 55%), and overall urticaria activity (RR 4.26; 95% CI 2.63-6.92; PI 0.18-98.29; P < 0.01; I² = 0%) versus placebo. The > 72 mg dose showed greater improvements in ISS7 (RR 5.12; 95% CI 2.72-9.64; PI 1.14-22.96; P < 0.01; I² = 45%), UAS7 (RR 5.35; 95% CI 3.04-9.40; PI 1.78-16.08; P < 0.01; I² = 31%), and overall activity (RR 4.34; 95% CI 2.67-7.04; PI 0.19-99.80; P < 0.01; I² = 0%). Compared with ligelizumab (> 72 mg), omalizumab had fewer injection site reactions (RR 3.04; 95% CI 1.95-4.73; PI 0.17-53.81; P < 0.01; I² = 0%) and erythema (RR 5.05; 95% CI 1.33-19.13; PI 0.08-312.57; P = 0.02; I² = 17%). Moderate certainty evidence indicated that ≤ 72 mg probably improved ISS7, overall urticaria activity, and UAS7. For > 72 mg, improvements in overall urticaria activity were seen, but ISS7 and UAS7 were classified as low quality of evidence.

Discussion: Ligelizumab significantly improves CSU symptoms compared with placebo, reducing disease severity, itching, and hives, with similar safety to omalizumab. Ligelizumab's higher affinity for immunoglobulin E (IgE) may provide better symptom control. Limitations include a small number of studies, short follow-up periods, and patient variability.

Protocol registration: International Prospective Register of Systematic Reviews (PROSPERO), CRD42024593072.

Background: Isavuconazole is a recent broad-spectrum triazole indicated for the treatment of invasive aspergillosis and mucormycosis when amphotericin B is inappropriate. However, limited information exists on its clinical use.

Objective: We set up a retrospective multicentre study to describe the clinical practice of isavuconazole including indications, exposure, and hepatic safety.

Methods: From January 2021 to June 2023, all patients who received isavuconazole and had at least one therapeutic drug monitoring (TDM) measurement, were included. To identify independent predictors of isavuconazole trough concentrations (C_min), linear regression analyses were performed. Causal relationship between the occurrence of liver injury and isavuconazole was also analysed.

Results: Most of the included patients (n = 102) were admitted into haematology units (41.1% [n = 42]) or intensive care units (ICU) (30.4% [n = 31]). Aspergillosis (47.0% [n = 48]), mucormycosis (25.6% [n = 26]), and off-label empirical treatments (18.6% [n = 19]), were the three most common indications. About half of the patients (46.1% [n = 47]) had an optimal exposure, while 42.2% (n = 43) were underexposed, and 11.7% (n = 12) were overexposed. Albumin level on the day of TDM was a significant factor associated with an increase in isavuconazole C_min (p = 0.010). Among the 11 patients who had liver test abnormalities, isavuconazole was discontinued in six (n = 6) patients and liver injury was attributable to isavuconazole in two (n = 2) patients.

Conclusions: This multicentre analysis highlighted the common use of isavuconazole as an off-label indication, as well as the frequent underexposure of patients to isavuconazole. Albumin on the day of TDM appeared to be an important factor driving isavuconazole exposure, especially in ICU patients.

Obesity is associated with increased psoriasis severity and reduced effectiveness of psoriasis treatments. This is a summary of a research article that reports a study evaluating the efficacy and safety of brodalumab (a subcutaneous injectable therapy) in participants with and without obesity who have moderate-to-severe psoriasis. Data were analyzed from two large, phase 3 clinical trials (AMAGINE-2 and AMAGINE-3) of participants with psoriasis who were treated with brodalumab or another subcutaneous injectable therapy, ustekinumab. After brodalumab treatment for 52 weeks, participants with obesity experienced similar rates of skin clearance to those without obesity (90% improvement: 88% versus 85%; 100% improvement: 65% versus 73%, respectively). Brodalumab safety profiles were generally similar between participants with and without obesity. This study demonstrated that brodalumab is effective and safe for treating moderate-to-severe psoriasis, regardless of obesity status.

Background and objective: D-1553 (garsorasib) is a novel and selective oral KRAS^G12C inhibitor. This study aims to evaluate the effect of food on the single-dose pharmacokinetics (PK) of D-1553 tablet in healthy Chinese subjects. Also the safety and tolerability of single-dose D-1553 in subjects are also evaluated.

Methods: A randomized, open-label, single-dose, two-intervention (fed vs fasting), two-period, two-sequence crossover study was performed on 14 healthy Chinese subjects. Plasma concentrations of D-1553 were determined by the liquid chromatography-tandem mass spectrometry method. Safety evaluations were carried out during the study period. The main PK parameters of the two formulations of D-1553 were calculated by non-compartmental analysis using Phoenix WinNonlin (Version 8.3) software.

Results: The geometric mean ratios (90% confidence interval [CI]) of AUC_0-t and AUC_0-∞ in the high-fat meal condition versus the fasting condition were 86.19% (78.30%, 94.87%) and 83.30% (75.77%, 91.58%), respectively. The geometric mean ratio (90% CI) of C_max values in high-fat meal condition to that observed in fasting condition were 109.74% (100.22%,120.15%). The p value of T_max was 0.1484 (fed vs fasting). Two subjects (14.3%) reported 4 treatment-emergent adverse events (TEAEs) in the fasting condition, and no subjects reported TEAEs in the fed condition. All adverse reactions were mild and had recovered by the end of the study.

Conclusion: The study indicated that a high-calorie and high-fat meal has no clinically relevant impact on the PK and bioavailability of D-1553 in healthy Chinese subjects. D-1553 was generally safe and well-tolerated under both fasting and fed conditions. The findings suggest that D-1553 could be administered orally with or without food.

Clinical trials: ClinicalTrials.gov Identifer CTR20212761; registered on 4 Nov 2021.

Recent evidence highlights the increasing utilization of guanfacine in the intensive care unit. While dexmedetomidine is a widely used sedative and anti-anxiety agent in the intensive care unit, prolonged use can lead to withdrawal effects when attempting to reduce the dosage. This has generated interest in using guanfacine to manage agitation in patients being weaned off dexmedetomidine. Clonidine has been used for dexmedetomidine weaning, but its use has been associated with adverse cardiovascular events. Some observational studies and case reports have explored the use of guanfacine and have shown its benefits and tolerability for patients taking dexmedetomidine experiencing adverse effects. Guanfacine is increasingly being used in the intensive care unit instead of clonidine and is commonly prescribed for the management of withdrawal effects. While there are limited data from observational studies, it holds promise for future clinical research and broader adoption of guanfacine in the intensive care unit.