Annals of Pharmacotherapy最新文献

Objective: The purpose of this study was to determine the place in therapy of intravenous (IV) fosfomycin (Contepo) for the new Food and Drug Administration (FDA)-approved indication of complicated urinary tract infection (cUTI).

Data sources: ClinicalTrials.gov and PubMed (through 11/2025).

Study selection and data extraction: Data sources were searched and filtered to identify randomized controlled trials (RCTs) studying IV fosfomycin in cUTIs. Two primary phase III trials evaluating IV fosfomycin in cUTI were identified and analyzed. Additional ancillary studies were selected to contextualize primary studies.

Data synthesis: The ZEUS trial showed IV fosfomycin was noninferior to piperacillin-tazobactam (PIP-TAZ) in cUTI/acute pyelonephritis (AP), with similar results between cUTI, AP, and extended spectrum beta-lactamase (ESBL) subgroups. The FOREST trial showed fosfomycin did not meet noninferiority to comparators (ceftriaxone, meropenem) in multi-drug resistant (MDR) bacteremia with urinary source and had more treatment-limiting adverse effects that prevented attainment of the primary endpoint. Clinical practice guidelines were referenced to compare IV fosfomycin to existing antibiotic recommendations.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Intravenous fosfomycin is a promising carbapenem- and fluoroquinolone-sparing therapy in cUTI/AP. It is an efficacious option empirically or as a targeted therapy. The best case to support the use of IV fosfomycin may be in ESBL-producing, non-bacteremic cUTI/AP, in hemodynamically stable patients.

Conclusion: Intravenous fosfomycin is a newly approved antibiotic formulation in the United States that may have a role in preventing the emergence of drug-resistant cUTI.

The 2025 update to the community-acquired pneumonia guideline illustrates the complex balance between evidence, methodology, and clinical priorities. Discussion among key stakeholders highlights that guidelines are not merely neutral summaries of evidence, but rather structured tools that shape bedside care in numerous ways. Rigorous methodology and transparent consideration of value judgments support recommendations even when evidence is limited or conflicting. Conditional guidance reflects deliberate judgment in areas of uncertainty. Differences between societies often arise from competing priorities, such as balancing antimicrobial stewardship with the risk of undertreatment, rather than from flaws in methodology. For clinicians, understanding how and why recommendations are made is crucial for the safe and evidence-informed application of these guidelines. The 2025 CAP guideline experience offers a practical case study in navigating uncertainty, interpreting conditional guidance, and integrating structured judgment into clinical decision-making.

Background: Inflammation-driven mechanisms play a central role in adverse outcomes after non-ST-elevation myocardial infarction (NSTEMI), yet simple, widely available biomarkers for early risk stratification remain insufficiently defined. Hemogram-derived indices and iron-related inflammatory markers may provide complementary prognostic information.

Objective: To evaluate the prognostic significance of the mean platelet volume-to-monocyte ratio (MMR) and serum ferritin in predicting major adverse cardiovascular events (MACE) in patients with NSTEMI, and to assess the association of angiotensin-converting enzyme (ACE) inhibitor therapy with clinical outcomes.

Methods: This prospective cohort study included 170 consecutive NSTEMI patients admitted to the University Clinical Center Tuzla between February 2022 and January 2023. All patients received dual antiplatelet therapy and high-intensity statins. The baseline evaluation included a complete blood count, serum ferritin, and C-reactive protein. MMR was calculated as the ratio of mean platelet volume to absolute monocyte count. Patients were followed for 12 months for the occurrence of MACE, defined as cardiovascular death, non-fatal myocardial infarction, urgent revascularization, stroke, or hospitalization for heart failure.

Results: During follow-up, 103 patients (60.6%) experienced MACE. Admission MMR (18.1 ± 11.7 vs 13.2 ± 5.5; P = 0.003) and ferritin levels (284 ± 396 vs 152 ± 109 µg/L; P = 0.001) were significantly higher in patients with events. In multivariable analysis, both MMR (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02-1.11; P = 0.008) and ferritin (OR 1.28 per 100 µg/L, 95% CI 1.10-1.55; P = 0.003) independently predicted MACE, while ACE inhibitor therapy was associated with a lower risk (OR 0.24, 95% CI 0.08-0.70; P = 0.01). The combined model demonstrated good discriminative performance (AUC 0.72; 95% CI 0.64-0.80).

Conclusion and relevance: Elevated admission MMR and ferritin were independently associated with a higher 1-year risk of MACE in patients with NSTEMI. ACE inhibitor therapy was associated with improved outcomes, although causality cannot be inferred. These findings suggest that readily available inflammatory biomarkers may complement established clinical parameters for early risk stratification and support continued guideline-directed pharmacotherapy in NSTEMI.

Background: With the shortage of innovator semaglutide or tirzepatide products resolved, compounding pharmacies can only legally sell unique products. Unique products could have a different route of administration or dosing, or could include additional pharmaceutical ingredients.

Objective: To identify and characterize compounded semaglutide and tirzepatide products that differ from available FDA-approved products.

Methods: We searched compounding sites between February 3, 2025, and March 20, 2025, using key terms ["compounded semaglutide," "compounded tirzepatide," and "compounded GLP-1s"] on Google looking for products with a strength, route of administration, and/or formulation that differed from commercially available products.

Results: We identified 33 unique semaglutide and/or tirzepatide products. Two-thirds contained semaglutide, and one-third contained tirzepatide. Forty-eight percent of products contained either semaglutide or tirzepatide with some combination of cyanocobalamin, glycine, niacinamide, docusate, or ondansetron. The 17 single active ingredient products were provided in sublingual (82%) or oral disintegrating tablet (ODT) (18%) formulations. Only 18% of included compounded products reported information about beyond use date and preferred storage conditions. Twenty-eight percent reported preferred storage conditions.

Conclusion and relevance: We found little justification for adding nutrients or docusate sodium to combination subcutaneous semaglutide or tirzepatide products. There is a rationale for adding ondansetron, but evidence for subcutaneous administration is lacking. There is a rationale for fashioning sublingual or ODT formulations, but whether these formulations offer advantages over innovator oral tablets has not been determined. The popularity of these products as an alternative to FDA-approved medications is concerning, given the lack of evidence for safety and efficacy.

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.