Annals of Pharmacotherapy最新文献

Background: Numerous studies have investigated the feasibility of home administration of bortezomib by nurses for the management of multiple myeloma. However, the impact of patient self-administration remains largely unexplored.

Objective: The objective of this study was to evaluate the impact and feasibility of patient self-administration of subcutaneous bortezomib.

Methods: This prospective feasibility study aimed to assess the efficacy and safety of this intervention as well as quantify the impact on patients and their caregivers. Patient and caregiver satisfaction were assessed using validated questionnaires at monthly intervals. An analysis of both direct system and indirect patient costs was also conducted.

Results: Thirty-four patients received 1194 doses of bortezomib for self-administration over the study period. Patient self-administration was determined to have minimal impact of treatment efficacy, and with only 8 grade 3 higher adverse events occurring, there was no effect on safety since none were due to patient self-administration. Patient satisfaction with the intervention was highly rated with 99% of responses indicating that the patient would choose this clinic again. Caregiver quality of life remained stable for the duration of the intervention. Institutional cost savings totaled an estimated $CAD 1 800 000 over the trial period, while patients collectively saved an estimated $CAD 23 000.

Conclusion and relevance: Patient self-administration of bortezomib is efficacious, safe, cost effective, and was well received by both patients and caregivers.

Background: Neuromuscular blocking agents (NMBAs) are suggested as an option in moderate to severe acute respiratory distress syndrome (ARDS) to improve ventilator synchrony (VS) and overall oxygenation. However, NMBA titration strategies have not been adequately compared.

Objective: The purpose of this study was to compare the oxygenation change in ARDS patients that received continuous NMBAs titrated to nonprotocolized VS versus train of four (TOF).

Methods: This multicenter, propensity matched, retrospective cohort study assessed patients with ARDS on an NMBA infusion for 24 hours. The primary endpoint was the percent change in PaO₂:FiO₂ at 24 hours.

Results: A total of 191 patients were included in this propensity score matched analysis (VS = 72; TOF = 119). The study cohort was mostly composed of severe ARDS (VS = 63.9%; TOF = 58.0%) and managed on cisatracurium (VS = 100.0%; TOF = 87.4%). Ventilator synchrony titration patients implemented more prone positioning (VS = 65.3%; TOF = 41.2%; P = 0.002) but had fewer plateau pressures maintained at < 30 cm H₂O (VS = 50.0%; TOF = 73.1%; P = 0.002). The percentage change in PaO₂:FiO₂ at 24 hours was +23.5% in the VS group and +23.2% in the TOF group (P = 0.459). There were no significant differences found in the percentage change in PaO₂:FiO₂ at 12 hours or 48 hours, cumulative cisatracurium dose, duration of mechanical ventilation, or hospital or intensive care unit length of stay. 28-day mortality occurred in 61.1% of the VS group and 43.7% of the TOF group (P = 0.029).

Conclusion and relevance: In ARDS patients on continuous NMBAs, TOF titration had similar improvement in PaO₂:FiO₂ ratio at 24 hours and was associated with reduced 28-day mortality, as compared with nonprotocolized VS titration. Prospective studies are warranted to validate and further investigate optimal NMBA titration strategies.

Objective: To describe the properties of a newly approved intranasal powder formulation of dihydroergotamine (DHE) for the acute treatment of migraine headaches.

Data sources: A literature search of MEDLINE was performed without date range exclusions using the search terms dihydroergotamine [title] and intranasal powder. Additional articles were identified from review of clinical trial bibliographies and product monographs.

Study selection and data abstraction: Four English-language articles were identified for analysis of this product, with no date exclusion criteria.

Data synthesis: Two phase 1 studies compared DHE intranasal powder with DHE nasal spray or intramuscular injection. At the approved dose, the authors found the intranasal powder to have a C_max of 1870 to 2230 pg/mL, a T_max of roughly 0.5 hours, and a t_1/2 of 12.0 hours. The phase 3 study was open-label and assessed safety across 12 months of use. It yielded expected adverse events, mostly mild to moderate in intensity. In an exploratory efficacy assessment, pain freedom was noted in 12.7%, 36.6%, and 67.1% at 1, 2, and 4 hours post-DHE intranasal powder dose.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:The intranasal powder has no trials to date comparing tolerability or efficacy against other abortive migraine agents. Thus, other drug classes, such as triptans with or without analgesics, remain preferred.

Conclusions: The design and pharmacokinetic properties of DHE intranasal powder appear to offer advantages over other DHE dosage forms, but current data do not support its use as a first-line agent for the treatment of migraine headaches.

Background: Dapsone is an alternative prophylactic agent for opportunistic infection in kidney transplant recipients (KTRs) with sufficient glucose-6-phosphate dehydrogenase levels. Potential disadvantages include increased risk for anemia and urinary tract infection (UTI) with dapsone.

Objective: The objective of this study was to compare the risks of anemia and UTI in KTRs who received prophylaxis for opportunistic infection after renal transplant with dapsone versus sulfamethoxazole-trimethoprim (SMX-TMP).

Methods: This single-center, retrospective, cohort review was conducted at a large academic health system. Adult patients who received SMX-TMP or dapsone prophylaxis after renal transplant were included. The primary outcome was risk of acute anemia within 90 days of transplant. Secondary outcomes included the risk of UTI post-transplant. Log-rank test was used for time-to-event analysis for the primary outcome.

Results: A total of 153 patients were included in the analysis. Patients were more likely to experience acute anemia while on dapsone compared with SMX-TMP (hazard ratio = 2.13, 95% confidence interval = 1.04-4.38, P = 0.04). No differences were observed in the rates of blood transfusion (14.5% vs 18.4%, P = 0.52) or use of erythropoiesis-stimulating agents (40.2% vs 48.7%, P = 0.331) between SMX-TMP and dapsone groups, respectively. The prevalence of UTI was comparable between groups (23.4% vs 23.7%, P > 0.999).

Conclusion and relevance: The risk of anemia was twofold higher in KTRs who received dapsone compared with SMX-TMP but did not appear to affect the rates of erythropoiesis-stimulating agent use or blood transfusion. There was no difference in the risk of UTI. These findings may inform agent selection and monitoring of prophylaxis for opportunistic infection in KTRs.

Background: Dalbavancin's pharmacokinetic parameters suggest obesity may affect serum and tissue concentrations, but currently there is no outcome data in the obese population with invasive infections.

Objective: The purpose of this study is to determine whether body mass index (BMI) correlates with dalbavancin 90-day treatment failure (TF) in patients with invasive infections.

Methods: A multicenter, retrospective observational study analyzed adult patients who received one or more dose of dalbavancin 1500 mg for an invasive infection at 2 community teaching hospitals. Patients admitted ≥3 times within 90 days or received ≥28 days of intravenous antibiotics prior to the initiation of dalbavancin were excluded. The primary outcome was TF at 90 days defined as the need for additional antibiotics or surgery, intolerance, readmission, death, or lost to follow-up. Logistic regression models tested the relationship between BMI and TF. A secondary analysis removed patients lost to follow-up. A conditional probability plot was generated to display the relationship of BMI and TF.

Results: Of 197 patients, 159 met inclusion criteria. Demographics included 64.8% males (n = 103), median age 46 years (34.5-60), and 48.4% (N = 77) persons who inject drugs. Bone/joint accounted for 50% (N = 80) of infections, with Staphylococcus aureus commonly isolated (N = 108, 67.9%). Sixty-eight patients experienced TF. The median BMI in the TF versus cure group was 26.0 kg/m² (21.0-30.3) and 26.0 kg/m² (23.0-30.5), P = 0.56. Significant predictors in the model included hospital site (OR = 0.28, 95% CI: 0.08-0.95) and methicillin-resistant S. aureus (OR = 3.01, 95% CI: 1.43-6.34). BMI was not a predictor of TF in the primary (OR = 1.00, 95% CI: 0.96-1.05) or secondary analysis (OR = 1.02, 95% CI: 0.97-1.07). The conditional probability plot found no relationship between BMI and TF in BMI <50 kg/m².

Conclusion and relevance: This observational study did not show an association between BMI and TF in patients treated with dalbavancin with invasive gram-positive infections.

Objective: To review the pharmacology, efficacy, and safety profile of crinecerfont as adjunctive therapy in treating classic congenital adrenal hyperplasia (CAH).

Data sources: A literature search was conducted in PubMed from January 2008 to August 2025. The relevant manuscripts, abstracts, and clinical trials (ClinivalTrials.gov) were reviewed. The keywords used were crinecerfont, CYP21A2, androstenedione, 17 hydroxyprogesterone, glucocorticoids, CAH, and clinical trials.

Data extraction: All crinecerfont-related publications, abstracts, packet inserts, and clinical trials were reviewed.

Data synthesis: Crinecerfont is a specific CRF1R antagonist used as adjunctive therapy to treat classic CAH. Crinecerfont led to over a 50% reduction in adrenocorticotropic hormone (ACTH) and 17OHP levels in both adult and pediatric participants during phase II trials. Testosterone levels decreased by 32% to 74% in adults and 61% to 76% in pediatric participants. In phase III trials, Crinecerfont reduced glucocorticoid doses by 27.3% in adults and 18% in pediatric participants (both P < 0.001). In general, crinecerfont is well tolerated with adverse effects that are mild to moderate.Relevance to patient care and clinical practice in comparison to existing drugs:Crinecerfont is an orphan drug used as adjunctive therapy for patients with classic CAH. It can effectively decrease supraphysiological levels of glucocorticoids and control androstenedione levels, thereby reducing complications related to supraphysiological glucocorticoids in classic CAH.

Conclusion: Crinecerfont is the first approved adjunctive therapy for classic CAH that effectively decreases supraphysiological glucocorticoids levels and associated symptoms.

Objective: To review the pharmacology, efficacy, and safety of revumenib (Revuforj) for relapsed or refractory (r/r) acute leukemia with a lysine methyltransferase 2A (KMT2A) gene rearrangement or translocation (KMT2Ar).

Data sources: A literature search was conducted using PubMed/MEDLINE, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and April 23, 2025. Keywords included Revuforj, revumenib, SNDX-5613, KMT2A, MLL1, and menin.

Study selection and data extraction: All English-language studies involving revumenib for r/r acute leukemia with a KMT2Ar were included.

Data synthesis: Revumenib, a protein-protein inhibitor that interrupts the interaction between the KMT2A protein and the scaffold protein menin, was granted approval by the Food and Drug Administration (FDA) for r/r acute leukemia with KMT2Ar based on a phase 2 clinical trial in adult and pediatric patients (n = 57), which reported a complete remission or complete remission with partial hematologic recovery of 22.8%. Common grade 3/4 adverse reactions reported for revumenib include infectious (febrile neutropenia 33%; infection 29%; bacterial infection 20%) and hematologic events (differentiation syndrome 13%; hemorrhage 9%; thrombosis 5%). Grade 3/4 QT prolongation, the primary dose-limiting adverse effect, was present in 12% of patients. Differentiation syndrome, related to revumenib's antileukemic effect, was observed in 29% of patients (grade 3/4: 13%; grade 5: <1%). We also include long-term follow-up for a total of 104 and 135 patients for efficacy and safety results, respectively.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:In the high-risk disease of r/r acute leukemia with KMT2Ar, given limited treatment options, revumenib appears to be a viable, novel treatment option demonstrating clinical efficacy and a manageable adverse effect profile that can be utilized as a bridge to stem cell transplant. Existing therapy options in this setting may include additional traditional chemotherapy, chimeric antigen receptor T-cell therapy (CAR-T), antibody-drug conjugates (eg, gemtuzumab, inotuzumab), bispecific T-cell engager (BiTE) therapies (eg, blinatumomab), DNA methyltransferase inhibitors (eg, azacitidine, decitabine), histone deacetylase inhibitors (eg, vorinostat, panobinostat), and BCL-2 inhibitors (venetoclax).

Conclusions: Revumenib is an innovative targeted treatment with promising activity in r/r acute leukemia with KMT2Ar.

Background: Therapeutic intensity unfractionated heparin (UFH) infusions require titration to target a therapeutic activated partial thromboplastin time (aPTT) or UFH anti-Xa. At The Johns Hopkins Hospital (JHH) and Johns Hopkins Bayview Medical Center (JHBMC), a computerized nurse-managed UFH calculator was built into the electronic health record (EHR) to improve adherence to institutional nomograms.

Objective: This study evaluated the impact of implementation of an EHR-embedded UFH calculator on nurse-managed UFH nomogram adherence.

Methods: A retrospective, observational cohort study was conducted at 2 institutions within one health system. Patients admitted to adult services who received nurse-managed UFH for at least 4 consecutive hours were included. Patients admitted between March 2019 and March 2021 constituted the pre-implementation cohort and patients admitted August 2021 through August 2023 were included in the post-implementation cohort. The primary outcomes were nurse-managed UFH nomogram adherence, management of critical aPTT results, and therapeutic aPTT achievement.

Results: A total of 2128 patients were included in the pre-implementation cohort and 2517 in the post-implementation cohort. The mean age was 61 for both the pre- and post-implementation cohorts. The post-implementation cohort experienced an increase in adherence to initial bolus dose recommendations when compared with the pre-implementation cohort (85.9% vs 92%, P < 0.001) as well as increased adherence to correct initial infusion doses (80.8% vs 95.9%, P < 0.001). Infusion dose adjustment error rates were reduced in the post-implementation cohort (4.9% vs 1.5%, P < 0.001). Fewer patients experienced nomogram nonadherence errors in the post-implementation cohort (20.2% vs 5.3%, P < 0.001). Critical aPTT nomogram adherence improved after calculator implementation for resumption at the recommended dose (72.4% vs 94.0%, P < 0.001). However, the time to therapeutic aPTT achievement was similar between pre-implementation and post-implementation cohorts.

Conclusion and relevance: A stewardship initiative to implement an EHR-embedded nurse-managed UFH calculator significantly increased adherence to nomogram-recommended initial doses and dose adjustments.