Annals of Pharmacotherapy最新文献

Objective: Aztreonam-avibactam (ATM-AVI) is used for difficult-to-treat gram-negative infections. The objective of this review is to analyze the pharmacology, safety, and clinical application of ATM-AVI.

Data sources: PubMed, Embase, and ClinicalTrials.gov were searched using the terms aztreonam avibactam, PF-06947387, Emblaveo, and ATM-AVI.

Study selection and data extraction: Articles written in English and published from January 1, 1985, to June 10, 2025, that related to pharmacology, safety, clinical trials, and clinical application of ATM-AVI were reviewed.

Data synthesis: The ATM-AVI has shown similar efficacy to comparator antibiotics in complicated intra-abdominal infection (cIAI) and hospital/ventilator-acquired pneumonia (HAP/VAP). The REVISIT trial showed cIAI clinical cure rates of 76.4% and 74% for the ATM-AVI and meropenem groups, respectively (treatment difference 2.4% [95% confidence interval, CI = -7.4 to 13.0]). For HAP/VAP, clinical cure rates were 45.9% and 41.7% for the ATM-AVI and meropenem groups, respectively (treatment difference 4.3% [95% CI = -15.1 to 23.1]). The ATM-AVI was generally well tolerated, with hepatic adverse effects being the most commonly reported.Relevance to patient care and clinical practice comparison to existing drugs:The ATM-AVI has demonstrated clinical efficacy for the treatment of cIAI. However, its role needs to be further studied for other infections such as HAP/VAP, urinary tract, and other serious infections. Pharmacoeconomic analysis may be needed to assess the cost-benefit impact in the United States.

Conclusion: The ATM-AVI may be an alternative option for the treatment of cIAI and other complicated gram-negative infections. Further studies are needed to delineate the role of ATM-AVI in clinical practice.

Background: Voriconazole is widely used for patients with fungal infections, but the correlations between the unbound concentration (C_free) of voriconazole in plasma and clinical outcomes remains unclear.

Objective: The aim of this study was to analyze the correlation between C_free and clinical outcomes.

Methods: A retrospective analysis was conducted at the Second Hospital of Hebei Medical University from February 2021 to March 2024 (Shijiazhuang, China). Patients who received voriconazole with at least one measured concentration in our center were enrolled. Based on determined the C_free of voriconazole, factors that might affect C_free were analyzed in conjunction with patient characteristics, and the correlations between voriconazole C_free and the clinical efficacy as well as AEs in patients were investigated.

Results: A total of 60 blood samples were collected from 56 patients. Voriconazole C_free was positive correlation with creatinine, while negative correlation with creatinine clearance. The C_free of patients in the clinical effective group was significantly higher than that in the clinical ineffective group, and the C_free of patients in the group with AEs was significantly higher than that in the group without AEs (P = 0.006, 0.025). Voriconazole C_free (odds ratio [OR] = 2.617, 95% confidence interval [CI]:1.142-6.000, P = 0.023) and albumin level (OR = 1.085, 95% CI: 1.000-1.177, P = 0.050) were independent influencing factors of clinical efficacy, the receiver operating characteristic (ROC) cut off for C_free and efficacy was 0.8 μg·mL^-1. Voriconazole C_free (OR = 1.979, 95% CI: 1.008-3.888, P = 0.048) was an independent risk factor for AEs, the ROC cut off for C_free and AEs was 1.2 μg·mL^-1.

Conclusions and relevance: Voriconazole C_free was positively correlated with clinical efficacy and the incidence of AEs in patients.

Celiac disease can significantly impair levothyroxine absorption, complicating hypothyroidism management despite appropriate dosing. While a gluten-free diet often improves absorption, some patients continue to require high doses. Switching to liquid or softgel formulations can enhance levothyroxine bioavailability and symptom control. Optimizing therapy requires individualized approaches, including dietary intervention, formulation changes, and close monitoring, to achieve and maintain a euthyroid state. Relevant studies were reviewed and incorporated into this commentary to support evidence-based recommendations and highlight clinical considerations.

Background: Poor colon preparation may negatively affect colonoscopy accuracy, result in cancelation, or need for repeat procedure. The glucagon-like peptide-1 receptor agonist (GLP-1RA) class of medications delay gastric emptying, although the clinical impact of this on the quality of colon preparation is not known.

Methods: This was a retrospective matched cohort study in a multi-center, outpatient setting. Colonoscopy reports for patients prescribed GLP-1RA at the time of procedure were compared to a cohort matched for diabetes and cirrhosis who were not prescribed GLP-1RA at the time of procedure. The primary endpoint was a composite of indicators for inadequate bowel preparation.

Objective: The current study's objective is to analyze the effects of GLP-1RA medications on the quality of colonoscopy preparation.

Results: There were 503 patients in each cohort and baseline characteristics were similar. Use of GLP-1RA at the time of colonoscopy was associated with a greater odds of the composite outcome (125 vs 56, odds ratio [OR] = 2.6; 95% CI, 1.9-3.7). There were also increased odds for individual outcome components including proceduralist documenting inadequate, suboptimal, or poor bowel preparation, narrative comments related to inadequate bowel preparation, and recommendation for extended bowel preparation with future colonoscopy. Repeat procedure was also more common in the GLP-1RA cohort (26 vs 9, OR = 3.0; 95% CI, 1.4-6.5).

Conclusion and relevance: This study assessed the impact of the GLP-1RA class of medication on the quality of bowel preparation for lower endoscopies. Glucagon-like peptide-1 receptor agonist use increased the odds of inadequate bowel preparation and repeat procedure.

Background: Novel interventions, particularly biologic therapies, have been shown to be efficacious and safe in treating atopic dermatitis (AD) in adolescents. However, the comparative efficacy and safety of biologic interventions in adolescents with moderate-to-severe AD have not been explored.

Objective: To compare efficacy and safety measures in clinical trials of biologic interventions in adolescents aged 12 to 17 with moderate-to-severe AD.

Methods: MEDLINE, Embase, and trial registries were searched for double-blind, randomized placebo-controlled clinical trials assessing the efficacy of biologic therapies in adolescents with moderate-to-severe AD. Arm-level Bayesian network meta-analyses (NMAs) were performed and certainty of evidence was assessed through the Confidence in Network Meta-Analysis grading tool. Primary outcomes included the proportion of participants who achieved 75% improvement in Eczema Area and Severity Index score (EASI-75) and the proportion of participants who achieved 0 (clear) or 1 (almost clear) value on the Investigators' Global Assessment (IGA 0/1) at week 16.

Results: Four trials evaluating 3 drugs, dupilumab, lebrikizumab, and tralokinumab, representing 642 study participants were analyzed. Two dosing options were assessed for dupilumab and tralokinumab. Compared with placebo, the greatest effect was observed with dupilumab 200/300 mg every 2 weeks in both EASI-75 (risk ratio [RR]: 5.2; 95% credible interval [CrI]: 2.6, 12.0) and IGA 0/1 (RR: 12.0; 95% CrI: 3.3, 78.0). No differences were found between treatments. Certainty of the evidence was low.

Conclusion and relevance: Although there is some evidence that dupilumab may be more efficacious than lebrikizumab or tralokinumab, our findings suggest that there is no strong evidence of superiority of one treatment over another.

Objective: This review summarizes current evidence on the efficacy and safety of tofersen (Qalsody) in treating amyotrophic lateral sclerosis (ALS).

Data sources: PubMed, MEDLINE, Google Scholar, and ClinicalTrials.gov were searched using the keywords: Qalsody, BIIB067, antisense oligonucleotides, SOD1, and amyotrophic lateral sclerosis. Articles published from inception to November 2025 were included.

Study selection and data extraction: English-language studies assessing the pharmacokinetics, pharmacology, efficacy, and safety of tofersen were included. Prescribing information and real-world evidence were also reviewed.

Data synthesis: Tofersen is an intrathecally administered antisense oligonucleotide targeting superoxide dismutase 1 (SOD1) mRNA. Early trials demonstrate dose-dependent reductions in cerebrospinal fluid (CSF) SOD1 protein levels of -33% and slower ALS Functional Rating Scale (ALSFRS-R) decline compared to placebo (-1.19 vs -5.63 points). In Phase 3 trials, tofersen reduced CSF SOD1 by 29% and plasma neurofilament light chain (NfL) by 60%, while biomarkers increased in the placebo group. There was no significant difference in ALSFRS-R decline between tofersen and placebo (-6.98 vs -8.14; P = 0.97). Real-world data show favorable patient-related outcomes and improvement in ALSFRS-R. Adverse effects are primarily lumbar puncture related with serious neurologic events documented in 7% of tofersen recipients.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:As the first Food and Drug Administration (FDA)-approved gene-directed therapy for SOD1 ALS, tofersen directly targets the underlying genetic cause. Barriers include the need for genetic confirmation and intrathecal administration.

Conclusion: Tofersen provides a promising targeted treatment option for pathogenic SOD1 ALS. Ongoing studies will clarify its long-term clinical impact.