Annals of Pharmacotherapy最新文献

Objective: To determine the efficacy and safety of mifepristone and misoprostol together (intervention) compared to misoprostol alone (comparator) for the resolution of miscarriage and intrauterine fetal death.

Data sources: A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology through July 2024 that evaluated the efficacy and safety of mifepristone and misoprostol together compared to misoprostol alone for the resolution of miscarriage and intrauterine fetal death through July 2024.

Study selection and data extraction: Primary endpoints were overall delivery success, 24-hour delivery success, and incidence of safety outcomes. A P-value of <0.05 was considered statistically significant, and heterogeneity was reported as the I² value.

Data synthesis: Twelve randomized controlled trials (RCTs) were included. Overall delivery success was higher in the intervention group (0.73 [CI 0.64-0.82], P < 0.01). Twenty-four-hour delivery rate was higher (1.54 [CI 1.32-1.77], P = 0.06), and a shorter time to delivery interval (9.22-18.78 vs 15.47-37.1 hours) was observed in the intervention group. Gastrointestinal adverse effects were more frequent in the intervention group (0.04 [CI -0.03 to 0.12], P < 0.01).

Relevance to patient care and clinical practice: Mifepristone and misoprostol together demonstrated higher delivery success rates and comparable safety outcomes to misoprostol alone, demonstrating the potential of improving patient care and positively impacting the time to successful delivery for patients at the bedside.

Conclusions: The use of mifepristone and misoprostol together for the resolution of miscarriage and intrauterine fetal death is warranted over the use of misoprostol alone.

Background: Bimekizumab is a biologic targeting interleukin (IL)-17A/17F, approved by the Food and Drug Administration (FDA) for moderate-to-severe plaque psoriasis in 2023.

Data sources: A PubMed search was performed using the keywords "bimekizumab," "plaque psoriasis," and "bimekizumab clinical trials," from origin to August 1, 2024. We included phase I to III trials of bimekizumab for plaque psoriasis, studies published post-FDA approval, and information from the package insert.

Study selection, data extraction: We summarized 1 phase I, 4 phase II, and 4 phase III trials, and 3 real-world studies published post-FDA approval.

Data synthesis: Bimekizumab was effective; >85% and 70% of patients achieved PASI90 and PASI100, respectively, in phase III trials. Head-to-head, 85% of bimekizumab patients achieved PASI90 versus 50% of ustekinumab patients. The most frequent adverse event was oral candidiasis (4%-10%); serious adverse events were rare (<1%). Long-term studies confirmed sustained efficacy and consistent safety profile.

Relevance to patient care and clinical practice in comparison to existing drugs: Bimekizumab was more efficacious than other IL-17 inhibitors, ustekinumab, and adalimumab. Real-world data corroborate bimekizumab's efficacy. Bimekizumab had a safety profile like other IL-17 inhibitors, with higher rates of mucocutaneous candidiasis.

Conclusion: Many patients who failed other IL-17 inhibitors and switched to bimekizumab experienced clearance. The efficacy of bimekizumab in patients who failed other IL-17 blockers may be attributable to bimekizumab's ability to block multiple IL-17 isoforms. Bimekizumab also outperformed tumor necrosis factor (TNF)-alpha inhibitors. There may be patients who fail previously available drugs, for reasons including nonadherence, antidrug antibodies, or adverse effects; bimekizumab, which targets additional cytokines, may bridge that gap.

Objective: To evaluate the efficacy, safety, and clinical implications of insulin icodec, a novel once-weekly basal insulin for the treatment of type 1 diabetes (T1D) and type 2 diabetes (T2D), with an emphasis on its advantages and challenges in comparison with existing daily basal insulins.

Data sources: A literature search was performed using PubMed, Google Scholar, Embase, and ClinicalTrials.gov up to August 26, 2024, using the search terms icodec and ONWARDS trial. Studies involving patients living with T1D or T2D on once-weekly insulin icodec compared with once-daily insulins glargine U100, glargine U300, and degludec were considered for this review.

Study selection and data extraction: Relevant English-language studies and those conducted in humans were considered.

Data synthesis: Insulin icodec offers reduced dosing frequency and potentially superior glycemic management with a safety profile comparable to existing basal insulins.

Relevance to patient care and clinical practice: Insulin icodec once-weekly dosing could significantly improve convenience and efficacy over daily basal insulins, representing a significant innovation in insulin therapy.

Conclusions: Insulin icodec emerges as a promising option for diabetes management, potentially improving treatment adherence and quality of life.

Background: Olanzapine and quetiapine are frequently administered atypical antipsychotic medications and their effects on the corrected QT (QTc) in the critically ill population remain understudied.

Objective: The objective of this study was to compare the impact of olanzapine and quetiapine on QTc changes in critically ill patients.

Methods: This was a single-center, retrospective analysis. Adult patients admitted to the intensive care unit (ICU) from January 2023 through July 2023 were included if they received ≥2 doses of either olanzapine or quetiapine within a 48-hour period and had one QTc evaluated within 48 hours of antipsychotic initiation. The major endpoint was a composite of the incidence of QTc prolongation (defined as QTc > 500 ms or QTc > 60 ms above baseline) following antipsychotic initiation. Univariable and multivariable analyses were performed to identify risk factors for QTc prolongation.

Results: There was no statistical difference in the major composite endpoint between patients in the olanzapine and quetiapine groups (8/83 [9.6%] vs 19/129 [14.7%]; P = .28). The incidence of QTc > 500 ms (7/244 [2.9%] vs 20/427 [4.7%]; P = .25) and change from baseline >60 ms (5/244 [2.0%] vs 17/427 [4.0%]; P = .26) were not statistically different between the olanzapine and quetiapine groups, respectively. There were no occurrences of Torsades de Pointes or extrapyramidal symptoms in either group.

Conclusion and relevance: The results of this study suggest olanzapine and quetiapine may have similar impact on QTc prolongation in critically ill patients. These findings could contribute to safer prescribing practices in the ICU.

Background: Sympathomimetic vasopressors may be administered through a peripheral catheter, but there are limited data available on the safety of peripheral use.

Objective: The purpose of this study was to analyze the safety of peripherally infused sympathomimetic vasopressors.

Methods: A multicenter, retrospective observational study was conducted to evaluate patients who received peripheral vasopressors. The study's primary outcome was to assess the incidence of extravasation during the administration of peripheral vasopressors. Secondary outcomes include avoidance of central venous catheter (CVC) placement and institution protocol deviations.

Results: There were 198 patients included in the study, of which 142 patients received norepinephrine, 48 patients received phenylephrine, and 8 patients received epinephrine peripherally. Extravasation events occurred in 11 (5.6%) patients. Seven patients required a pharmacologic antidote and 10 patients required a warm compress. No significant differences were seen in characteristics of patients who extravasated compared with those who did not. Protocol deviations identified during the study included 24 (12.1%) patients receiving doses above the protocol maximum, 19 (9.6%) with a body mass index above the protocol maximum, and 45 (22.7%) patients receiving peripheral vasopressor over 24 hours. The majority of patients were able to avoid CVC placement (59.1%).

Conclusion and relevance: Peripherally infused sympathomimetic vasopressors are safe to administer up to 24 hours with a low incidence of extravasation events while avoiding CVC placement in the majority of patients.

Objective: To review the therapeutic profile of elranatamab, a novel bispecific T-cell-redirecting therapy, in treating relapsed or refractory (R/R) multiple myeloma (MM).

Data sources: A PubMed search was conducted for English-language articles published from January 2000 through June 2024, using the search terms: PF-06863135, elranatamab, Elrexfio, and "Multiple Myeloma." Additional data were obtained from ClinicalTrials.gov and other pertinent publications and meeting abstracts.

Study selection and data extraction: Clinical trials, guidelines, and prescribing information pertaining to elranatamab were included.

Data synthesis: The phase II MagentisMM-3 trial demonstrated an overall response rate of 61.0% (95% confidence interval, 51.8-69.6) in patients naïve to B-cell maturation antigen targeting therapy (cohort A, n = 123), establishing elranatamab monotherapy as a viable treatment option for patients with R/R MM who have received at least 4 prior lines of therapy. The duration of response and progression-free survival at 12 months were 75.3% and 56.6%, respectively.

Relevance to patient care and clinical practice in comparison with existing drugs: Despite the promising activity of elranatamab in R/R MM, the significant treatment-related adverse effects (AEs) associated with this therapy necessitate careful monitoring and expert management. Common AEs include cytokine release syndrome, neurotoxicity, hematologic toxicity, and infectious complications. The cost-effectiveness of elranatamab has yet to be evaluated.

Conclusions: Elranatamab is approved by the Food and Drug Administration as a treatment option for patients with heavily pretreated R/R MM. Further studies are warranted to identify the optimal treatment strategy for elranatamab and other bispecific antibodies in the management of R/R MM.

Objective: To review the pharmacology, efficacy, safety, dosing and administration, and relevance to patient care and clinical practice of B-cell maturation antigen (BCMA) directed immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAb), for the management of relapsed/refractory multiple myeloma (RRMM).

Data sources: A literature review of PubMed (1966 to July 2024) was conducted using the keywords idecabtagene vicleucel, ciltacabtagene autoleucel, teclistamab, elranatamab, and multiple myeloma. Data was also obtained from unpublished meeting abstracts and prescribing information.

Study selection and data extraction: All relevant published articles, unpublished abstracts, and prescribing information on anti-BCMA immunotherapies for the treatment of RRMM were reviewed.

Data synthesis: Idecabtagene vicleucel and ciltacabtagene autoleucel are BCMA-directed CAR-T cell therapies that have been compared to standard of care (SOC) regimens for MM in early relapse in the phase III trials KarMMa-3 and CARTITUDE-4, respectively. Both studies demonstrated a significantly improved in response rates, depth of response, and progression-free survival compared to SOC. BsAbs teclistamab and elranatamab have been evaluated in the phase II trials MajesTEC-1 and MagnetisMM-3, respectively. Overall response rates of 63 and 61% were observed with teclistamab and elranatamab, respectively, in a population of patients with heavily pretreated RRMM.

Relevance to patient care and clinical practice in comparison with existing drugs: BCMA-directed immunotherapies have demonstrated efficacy in the treatment of RRMM. Safety issues with BCMA-directed immunotherapies include cytokine release syndrome, neurotoxicity, infections, and cytopenias. Operational challenges and issues with access to care exist with these therapies as they may be limited to institutions with the infrastructure to safely administer and monitor patients for toxicities.

Conclusion: BCMA-directed immunotherapies represent an important advancement in the management of RRMM and have significantly added to the available treatment options for this disease.

Background: Hypoalbuminemia is common in patients with advanced solid tumor malignancies. However, despite the increased use of highly protein-bound tyrosine kinase inhibitors (TKIs) in cancer treatments, the tolerability of these agents in patients with hypoalbuminemia is not fully known.

Objective: Our aim is to assess whether patients on oral TKIs with hypoalbuminemia are at higher risk for experiencing medication-related adverse events, therefore requiring careful considerations.

Methods: This is a single-center, retrospective study including patients ≥18 years of age with a solid tumor malignancy who had taken at least one dose of oral TKIs with a protein binding of ≥90% between June 1, 2016, and June 1, 2021. The primary outcome was to compare time to TKI discontinuation due to adverse events between patients with and without hypoalbuminemia. Key secondary outcomes include TKI discontinuation and dose reduction rates, time to TKI dose reduction, and severity of adverse events.

Results: Out of 282 included patients, 134 (48%) patients had hypoalbuminemia and 148 (52%) had normal albumin levels. Compared with patients without hypoalbuminemia, patients with hypoalbuminemia had shorter median time on treatment at 2.8 months (95% CI = 2.3-4.5 months) versus 4.3 months (95% CI = 2.8-6.4 months; P = 0.003). In patients who had TKI discontinuation, dose reduction was associated with longer time on treatment in patients in the normal albumin group compared with patients in the hypoalbuminemia group or patients without dose reduction (P < 0.0001). Patients in the hypoalbuminemia group experienced significantly more grade 3/4 adverse events compared with those in the normal albumin group (73% vs 27%, P < 0.0001).

Conclusion and relevance: Hypoalbuminemia is a risk factor for both shorter time on treatment and more severe adverse events in patients with solid tumor malignancies taking highly protein-bound oral TKIs. This study highlights the need for closer monitoring of this patient population by health care providers.

Objective: To review the pharmacologic and clinical profile of etrasimod in the treatment of ulcerative colitis (UC).

Data sources: A PubMed search was conducted from inception to November 2023 using the keywords etrasimod, ulcerative colitis, and sphingosine-1-phosphate receptor modulator. Information was also obtained from published abstracts and package insert.

Study selection and data extraction: Phase 2 and 3 studies plus relevant literature on etrasimod pharmacologic and clinical profile were reviewed.

Data synthesis: Per ELEVATE, 2 phase 3 studies, a higher proportion of patients with moderately to severely active UC achieved clinical remission in the induction and maintenance phase with etrasimod compared with placebo. In addition, a higher proportion of patients achieved secondary endpoints of clinical response, endoscopic improvement-histologic remission, corticosteroid-free remission, and endoscopic improvement with etrasimod vs placebo. Common adverse events include anemia and headache.

Relevance to patient care and clinical practice in comparison with existing drugs: Etrasimod is now the second orally administered sphingosine-1-phosphate modulator approved for UC, providing patients with additional treatment options. Efficacy rates of this treatment are in line with other UC medication options. Similar to other sphingosine-1-phosphate receptor modulators, various assessments are required at baseline and during treatment to ensure safe and appropriate use.

Conclusion: Etrasimod is another possibility in the armamentarium of UC treatment, providing patients with more oral medication options. Prior to treatment initiation, several assessments relating to safety, drug interactions, and pharmacogenomics factors are advised.

Background: Patients with type 2 diabetes (T2D) are at an increased risk of genital urinary (GU) infections, with the risk increasing with higher A1Cs. Given the broad adoption of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in patients with T2D, both providers and patients need to be aware of common adverse effects associated with these medications, specifically GU infections. However trials involving SGLT2is looked at patients with an average A1C of less than 9%, and thus, the incidence of GU infections may not truly reflect the general diabetic population.

Objective: The purpose of this study is to assess the association between GU infections in patients started on SGLT2is and A1C levels.

Methods: A retrospective study was conducted on patients seen in an adult, primary care clinic, at New York City Health and Hospitals, South Brooklyn Health. Men and nonpregnant, nonlactating women >18 years old with a diagnosis of T2D who were initiated on an SGLT2i between January 2018 and January 2023 were included in the analysis. The primary endpoint is to compare the risk of GU infections in patients with T2D who were started on SGLT2is, regardless of dose, with hemoglobin A1C of >9% to those with hemoglobin A1C <9% at baseline.

Results: Three hundred and twenty-eight patients were eligible based on specified inclusion and exclusion criteria. Overall, there was a statistically significant difference in the number of GU infections that occurred in patients with a baseline A1C >9% compared with those with an A1C <9% (95% confidence interval [CI] = 1.05-2.88; P = 0.041).

Conclusions and relevance: Type 2 diabetes patients initiated on SGLT2is may experience an increased risk of GU infection, especially in those patients with an A1C of 9% or greater. Further research is necessary to validate and expand upon these findings.