Advances in Therapy最新文献

{"title":"Single-Tablet Combination Therapy of Macitentan/Tadalafil for Patients with Pulmonary Arterial Hypertension: Qualitative Interview Study of the A DUE Phase 3 Trial","authors":"Fenling Fan,&nbsp;Stacy Davis,&nbsp;Claire Burbridge,&nbsp;Kelly Chin,&nbsp;Michael Friberg,&nbsp;Ekkehard Grünig,&nbsp;Melanie Hughes,&nbsp;Pavel Jansa,&nbsp;Jörg Linder,&nbsp;Jennifer Rafalski,&nbsp;Alvaro Agustin Rodriguez,&nbsp;Jason A. Randall","doi":"10.1007/s12325-025-03159-x","DOIUrl":"10.1007/s12325-025-03159-x","url":null,"abstract":"<div><h3>Introduction</h3><p>This study explored patient and clinician perspectives on a new fixed-dose combination of macitentan and tadalafil (M/T FDC) in a once-daily single tablet for treatment of pulmonary arterial hypertension (PAH).</p><h3>Methods</h3><p>Qualitative semi-structured interviews were conducted during the open-label period of the global, phase 3 A DUE clinical trial that evaluated M/T FDC. A subset of enrolled patients (<i>N</i> = 26) and site investigators (<i>N</i> = 18 clinicians) were interviewed. Patients received four tablets during double-blind treatment and could be in one of three arms (macitentan + placebo; tadalafil + placebo; M/T FDC + placebo) followed by M/T FDC (one tablet) during the open-label period. Patients and clinicians were asked to share their experience of pre-trial PAH medication, double-blind treatment, and open-label M/T FDC. Thematic analysis was conducted on blinded data.</p><h3>Results</h3><p>Patients preferred the M/T FDC tablet (open-label) over the four tablets during double-blind treatment. Patients were satisfied with M/T FDC, highlighting its positive impact on their psychological well-being, through reducing stress associated with managing multiple pills. All patients indicated that having a single, once-a-day pill for PAH was more convenient and associated with greater treatment adherence. Clinicians highlighted that their patients have a high daily pill burden for PAH and other comorbidities, and prefer treatments with an oral mode of administration that reduce the number of daily pills required. Clinicians felt that M/T FDC would be well received in clinical practice and potentially assist in implementing guideline-recommended combination treatment of PAH.</p><h3>Conclusions</h3><p>In this qualitative analysis, all 26 patients and 18 clinicians provided positive feedback on M/T FDC treatment, which was consistent across countries. Reducing the number of pills needed to treat PAH, through use of single-tablet M/T FDC, is highly valued by patients and endorsed by clinicians, who both felt the single-tablet combination therapy could have a positive effect on patients’ well-being and increase treatment adherence.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2298 - 2313"},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03159-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-Line Tislelizumab Plus Chemotherapy for Esophageal Squamous Cell Carcinoma with Programmed Death-Ligand 1 Expression ≥ 1%: A Retrospective Analysis of RATIONALE-306","authors":"Jianming Xu,&nbsp;Ken Kato,&nbsp;Richard Hubner,&nbsp;Sook Ryun Park,&nbsp;Takashi Kojima,&nbsp;Ryu Ishihara,&nbsp;Lucjan Wyrwicz,&nbsp;Eric Van Cutsem,&nbsp;Paula Jimenez-Fonseca,&nbsp;Hongqian Wu,&nbsp;Lei Wang,&nbsp;Sebastian Yan,&nbsp;Jingwen Shi,&nbsp;Alysha Kadva,&nbsp;Harry H. Yoon","doi":"10.1007/s12325-025-03115-9","DOIUrl":"10.1007/s12325-025-03115-9","url":null,"abstract":"<div><h3>Introduction</h3><p>The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against the use of programmed cell death protein-1 inhibitors for first-line treatment of advanced or metastatic unresectable esophageal squamous cell carcinoma (ESCC) with a programmed death-ligand 1 (PD-L1) expression Tumor Area Positivity (TAP) score &lt; 1% or combined positive score &lt; 1 due to an unfavorable benefit–risk profile observed across the phase 3 CheckMate 648, KEYNOTE-590, and RATIONALE-306 trials. Therefore, we conducted a retrospective analysis of RATIONALE-306 to evaluate the efficacy and safety of tislelizumab plus investigator-chosen chemotherapy (ICC) versus placebo plus ICC in patients with advanced or metastatic unresectable ESCC and a PD-L1 TAP score ≥ 1%.</p><h3>Methods</h3><p>Adult patients with advanced or metastatic unresectable ESCC enrolled in the global, randomized, phase 3 RATIONALE-306 trial randomly received tislelizumab 200 mg every 3 weeks plus ICC or matched placebo plus ICC. Efficacy and safety outcomes were evaluated among patients who were retrospectively assessed for PD-L1 expression defined by a TAP score ≥ 1%.</p><h3>Results</h3><p>At primary analysis data cutoff (February 28, 2022), a clinically meaningful improvement in median overall survival was observed among 230 patients in the tislelizumab plus ICC arm {16.8 [95% confidence interval (CI) 15.3–20.8] months} versus 248 patients in the placebo plus ICC arm [9.6 (95% CI 8.9–11.8) months] [stratified hazard ratio 0.64 (95% CI 0.51–0.80)]; this was maintained at a 3-year follow-up data cutoff (November 24, 2023). Similar findings at primary analysis were observed for progression-free survival, objective response rate, disease control rate, and duration of response. Tislelizumab plus ICC was tolerable and no new safety signals were observed.</p><h3>Conclusions</h3><p>Tislelizumab plus ICC is an effective and well tolerated first-line treatment option for patients with advanced or metastatic unresectable ESCC and a tumor PD-L1 TAP score ≥ 1%.</p><h3>Trial Registration Number</h3><p>ClinicalTrials.gov NCT03783442.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2269 - 2284"},"PeriodicalIF":3.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03115-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Oxidative Stress and Inflammation in Patients with Symptomatic Dry Eye Disease Treated with a Preservative-Free Ophthalmic Emulsion Combining Alpha-Lipoic Acid and High Molecular Weight Sodium Hyaluronate","authors":"Laure Chauchat,&nbsp;Camille Guerin,&nbsp;Marwan Sahyoun,&nbsp;Michel Guillon,&nbsp;Margarita Calonge","doi":"10.1007/s12325-025-03139-1","DOIUrl":"10.1007/s12325-025-03139-1","url":null,"abstract":"<div><h3>Introduction</h3><p>This study aimed to explore the beneficial effect of a preservative-free (PF) emulsion eyedrop combining high molecular weight sodium hyaluronate (HMW-HA) and alpha-lipoic acid on oxidative stress and ocular surface inflammation in patients with dry eye disease (DED).</p><h3>Methods</h3><p>In this prospective exploratory study, patients with moderate to severe DED symptoms were treated with the study eyedrop, 4–6 times/day for 1 month. Two visits were scheduled: baseline (D0) and after 35 days (D35). The following parameters were assessed: quality of life (OSDI score); superoxide dismutase (SODase) concentration in tears; goblet cell (GC) density (impression cytology); conjunctival hyperemia (Efron scale); corneal, conjunctival, and eyelid staining (Oxford scale); and meibomian gland (MG) blockage. Data were compared between D0 and D35 in subgroups of patients with a significant abnormality of the study outcome at baseline.</p><h3>Results</h3><p>Forty patients were involved, with a highly significant improvement of OSDI score at D35. The mean concentration of SODase significantly increased by 3.2 and 2.4 times for SODase1 and SODase2 respectively, in patients with deficient SODase at baseline. In patients with abnormal GC density at baseline, GC count increased by five times at D35. Conjunctival hyperemia and corneal staining scores significantly improved in the subpopulation of patients with a baseline grade ≥ 2. Eyelid margin staining was significantly reduced at D35 in patients with significant abnormalities at baseline. A significant reduction of MG obstruction was shown in the lower eyelid in patients with significant blockage at baseline.</p><h3>Conclusion</h3><p>The use of a PF ophthalmic emulsion combining alpha-lipoic acid and HMW-HA shows a beneficial effect on the ocular surface through the improved quality of life score. Noteworthy, patients presenting high oxidative and inflammatory conditions experienced significant improvement in oxidative stress and inflammation markers; this synergic effect is likely due to the well-known properties of alpha-lipoic acid and HMW-HA, enhancing DED management.</p><h3>Trial Registration</h3><p>ISRCTN.com identifier, 17861788.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2219 - 2233"},"PeriodicalIF":3.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Falls and Fractures in Patients with Geographic Atrophy: A US Claims Data Analysis","authors":"Allen Hu,&nbsp;Rachel E. Teneralli,&nbsp;Rachelle Rodriguez,&nbsp;Alyshah Abdul Sultan,&nbsp;Colleen Garey,&nbsp;Jessica Ackert,&nbsp;Rose Ong","doi":"10.1007/s12325-025-03134-6","DOIUrl":"10.1007/s12325-025-03134-6","url":null,"abstract":"<div><h3>Introduction</h3><p>The increased risk of falls in elderly people represents a substantial public health burden that may be compounded by impaired visual acuity. The present study aimed to assess the independent risk of incident falls and fractures in patients with geographic atrophy (GA).</p><h3>Methods</h3><p>This retrospective, noninterventional, cohort study analyzed three US claims datasets (Optum’s de-identified Clinformatics^® Data Mart Database [Clinformatics^®], Merative™ MarketScan^® Commercial and Medicare Databases [MarketScan], and IQVIA US PharMetrics^® [PharMetrics]). Patients were defined as having at least one International Classification of Diseases, Tenth Revision code (H35.31x3, H35.31x4) for GA. A propensity score-matched control cohort, matched on age, sex, index year, and disease history, was also included. Relative risks (RRs) for incident falls, fractures, and health care resource utilization (HCRU) were calculated between GA and control cohorts.</p><h3>Results</h3><p>The Clinformatics^®, MarketScan, and PharMetrics datasets included 44,591, 9470, and 27,428 patients with GA, respectively. Across the three databases, mean (SD) age ranged from 75.9 (8.3) to 80.5 (7.2) years, and 61% to 64% were female. The largest subgroup was patients with bilateral GA without subfoveal involvement (35–37%), followed by unilateral GA without subfoveal involvement (23–24%). Risks of falls (RR 1.16–1.36) and fractures (RR 1.17–1.29) in the 4 years following the index date were higher in patients with GA compared with controls. Patients with bilateral GA and subfoveal involvement had the most pronounced increase in risk of falls (RR 1.42–1.49) and fractures (RR 1.33–1.45). Compared to controls, patients with GA also had an increased risk for hospitalization (RR 1.18–1.27), emergency department visits (RR 1.18–1.21), nursing home or assisted living admissions (RR 1.06–1.28), and outpatient visits (RR 1.05–1.08).</p><h3>Conclusion</h3><p>GA represents an independent risk factor for falls, fractures, and higher HCRU. These data reveal the substantial public health burden of GA associated with the management of falls and fractures.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2234 - 2247"},"PeriodicalIF":3.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03134-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-Line Tislelizumab Plus Chemotherapy for Advanced Gastric Cancer with Programmed Death-Ligand 1 Expression ≥ 1%: A Retrospective Analysis of RATIONALE-305","authors":"Markus Moehler,&nbsp;Do-Youn Oh,&nbsp;Ken Kato,&nbsp;Tobias Arkenau,&nbsp;Josep Tabernero,&nbsp;Keun-Wook Lee,&nbsp;Sun Young Rha,&nbsp;Hidekazu Hirano,&nbsp;David Spigel,&nbsp;Kensei Yamaguchi,&nbsp;Lucjan Wyrwicz,&nbsp;Umut Disel,&nbsp;Roberto A. Pazo-Cid,&nbsp;Lorenzo Fornaro,&nbsp;Yaling Xu,&nbsp;Tao Sheng,&nbsp;Silu Yang,&nbsp;Alysha Kadva,&nbsp;Marcia Cruz-Correa,&nbsp;Rui-Hua Xu","doi":"10.1007/s12325-025-03133-7","DOIUrl":"10.1007/s12325-025-03133-7","url":null,"abstract":"<div><h3>Introduction</h3><p>Tislelizumab plus investigator-chosen chemotherapy (ICC) demonstrated a statistically significant improvement in overall survival (OS) versus placebo plus ICC in RATIONALE-305 in patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) in the intent-to-treat population and in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 5%. The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against first-line treatment with programmed cell death protein-1 inhibitors in this setting in patients with a PD-L1 combined positive score &lt; 1 or TAP score &lt; 1%, due to an unfavorable benefit–risk profile. Thus, we retrospectively analyzed data from RATIONALE-305 in patients with a PD-L1 TAP score ≥ 1%.</p><h3>Methods</h3><p>Adult patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC were randomized to tislelizumab 200 mg or placebo with ICC every 3 weeks. Efficacy and safety outcomes of tislelizumab plus ICC versus placebo plus ICC were retrospectively assessed in those with a PD-L1 TAP score ≥ 1%.</p><h3>Results</h3><p>At the final analysis cutoff (February 28, 2023), 432 patients received tislelizumab plus ICC and 453 received placebo plus ICC, and had a PD-L1 TAP score ≥ 1%. Clinically meaningful improvements to OS were observed with tislelizumab plus ICC compared with placebo plus ICC [15.0 months (95% confidence interval [CI] 13.3–16.7) vs. 12.8 months (95% CI 12.1–14.1), respectively; stratified hazard ratio 0.77 (95% CI 0.67–0.90)]. Progression-free survival, overall response rate, duration of response, and disease control rate, were also improved. OS improvements were maintained at a 3-year data cutoff (February 28, 2024). Tislelizumab plus ICC had an acceptable safety profile with no new safety signals.</p><h3>Conclusions</h3><p>Tislelizumab plus ICC is an effective and tolerable first-line treatment for patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC with a PD-L1 TAP score ≥ 1%.</p><h3>Trial registration number</h3><p>NCT03777657.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2248 - 2268"},"PeriodicalIF":3.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03133-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden of Comorbidities and Concomitant Medications and Their Associated Costs in Patients with Gastroenteropancreatic or Lung Neuroendocrine Tumors: Analysis of US Administrative Data","authors":"Jennifer A. Chan,&nbsp;Antonio Ribeiro-Oliveira Jr.,&nbsp;Aude Houchard,&nbsp;Syvart Dennen,&nbsp;Yutong Liu,&nbsp;Sai Sriteja Boppudi Naga,&nbsp;Yajin Zhao,&nbsp;Christelle Pommie,&nbsp;Timon Vandamme,&nbsp;Jason Starr","doi":"10.1007/s12325-025-03126-6","DOIUrl":"10.1007/s12325-025-03126-6","url":null,"abstract":"<div><h3>Introduction</h3><p>This study investigated the burden of comorbidities and concomitant non-cancer medications and their cost in patients with neuroendocrine tumors (NETs).</p><h3>Methods</h3><p>Adults with gastroenteropancreatic (GEP)-NETs and lung-NETs, with or without carcinoid syndrome (CS), who initiated first-line NET treatment (index date) with a somatostatin analog or telotristat and had ≥ 1 inpatient or ≥ 2 distinct outpatient claims (study period January 1, 2016–December 31, 2022) were identified from the US MarketScan database and matched (age, sex, insurance type) with up to four adults without cancer (reference group). At 0–90 and 91–180 days post-index, medication counts (generalized linear model, GLM), medication frequency distributions (chi-squared test), and medication costs in USD (two-part model: logit model and GLM for the first and second parts, respectively) were assessed. Frequencies of comorbidities of interest (≥ 1 diagnosis claim) in the 6 months post-index were calculated.</p><h3>Results</h3><p>A total of 662 patients with GEP-NETs (279 with CS) and 84 with lung-NETs (30 with CS) were included. Irrespective of CS status, mean medication counts in the 0–90 and 91–180 days post-index was 1.5–1.8 times higher for GEP-NETs (<i>p</i> &lt; 0.001) and 1.6–1.9 times higher for lung-NETs (<i>p</i> &lt; 0.005) than reference groups. Medications most frequently prescribed for both NET groups were oral cardiovascular, central nervous system, and gastrointestinal agents. The most common comorbidities of interest in patients with NETs (vs reference groups) were hypertension (GEP-NETs: 68.7% vs 55.0%; lung-NETs: 73.8% vs 58.3%) and type 2 diabetes (GEP-NETs: 35.5% vs 24.1%; lung-NETs: 50.0% vs 28.3%). Excluding anticancer medications, mean per-patient-per-month medication costs (vs reference groups) were $276–811 (vs $176–349) and $390–647 (vs $210–$302) for 0–90 days and 91–180 days post-index, respectively.</p><h3>Conclusion</h3><p>Compared with people without cancer, patients with NETs had a higher prevalence of comorbidities and concomitant medication use, which was associated with a greater economic burden.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2190 - 2218"},"PeriodicalIF":3.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03126-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic, Pharmacokinetic/Pharmacodynamic, and Safety Investigations of Cefiderocol in Chinese Healthy Subjects","authors":"Chuhan Zhang,&nbsp;Shuyan Yu,&nbsp;Size Li,&nbsp;Xiaojie Wu,&nbsp;Qiong Wei,&nbsp;Jinjie He,&nbsp;Guoying Cao,&nbsp;Haijing Yang,&nbsp;Jingjing Wang,&nbsp;Kohei Fujitani,&nbsp;Takayuki Katsube,&nbsp;Jing Zhang,&nbsp;Honghong Dou","doi":"10.1007/s12325-025-03147-1","DOIUrl":"10.1007/s12325-025-03147-1","url":null,"abstract":"<div><h3>Introduction</h3><p>We aim to evaluate the safety and pharmacokinetic (PK) properties of cefiderocol in Chinese participants, following single and subsequent multiple administrations of 2 g q8h with 3-h intravenous infusion, and to predict its efficacy for the treatment of Gram-negative bacilli (GNB) infection based on PK/pharmacodynamic (PD) analysis.</p><h3>Methods</h3><p>This was an open-label, single-center, single- and multiple-dose phase I study, conducted from September 2022 to October 2022, with 12 eligible healthy Chinese adults (6 men and 6 women). The PK profiles were described by noncompartmental analysis and a two-compartment model using WinNonlin (v.8.1). Monte Carlo simulations (MCS) were performed by R (v.4.3.1) to obtain the probability of target attainment (PTA) as well as the cumulative fraction of response (CFR), based on the previously published data of susceptibility studies for cefiderocol in China.</p><h3>Results</h3><p>Both single and multiple doses of 2 g cefiderocol were well tolerated in healthy Chinese subjects, and no severe treatment-emergent adverse events occurred. The maximum plasma concentration of cefiderocol was observed approximately 3 h after administration and the half-life was about 2.6 h, with no accumulation after multiple dosing. It is worth noting that, the PK profiles, including CL, V1,<i> C</i>_max, <i>C</i>_trough, and AUC_0–τ, were consistent with those of other populations, e.g., Caucasian. PK/PD analysis and MCS suggested that standard dosage regimen of cefiderocol would achieve satisfactory PTA and CFR (exceeding 90%) for Gram-negative pathogens with MICs up to 4 μg/mL, using the proposed <i>f</i><i>T</i>_&gt;MIC target of 75.0%. Consistently, more than 90% of PTA was reached for <i>Enterobacterales</i>, <i>P. aeruginosa</i>, and <i>Acinetobacter</i> spp. with MICs up to 4 μg/mL at their respective 73.3%, 72.2%, and 88.1% <i>f</i><i>T</i>_&gt;MIC targets, with CFR exceeding 95%. Especially for <i>S. maltophilia</i>, both the PTA and CFR reached nearly 100% for those with MICs as high as 8 μg/mL.</p><h3>Conclusions</h3><p>Cefiderocol is well tolerated by Chinese healthy participants at the dosage regimen of 2 g cefiderocol q8h via 3-h infusion, which is expected to achieve satisfactory efficacy in treating GNB infections in China, although further data for model optimization might still be required. To our knowledge, this is the first study to describe the PK properties of cefiderocol in Chinese subjects, and to predict its microbiological efficacy for treating GNB infection in China.</p><h3>Trial Registration</h3><p>ChiCTR2300076607.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2285 - 2297"},"PeriodicalIF":3.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03147-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Adults with Underlying Medical Conditions: Systematic Literature Review and Pairwise Meta-Analysis Using GRADE","authors":"Xuan Wang,&nbsp;Ankit Pahwa,&nbsp;Mary T. Bausch-Jurken,&nbsp;Anushri Chitkara,&nbsp;Pawana Sharma,&nbsp;Mia Malmenäs,&nbsp;Sonam Vats,&nbsp;Michael Gordon Whitfield,&nbsp;Kira Zhi Hua Lai,&nbsp;Priyadarsini Dasari,&nbsp;Ritu Gupta,&nbsp;Maria Nassim,&nbsp;Nicolas Van de Velde,&nbsp;Nathan Green,&nbsp;Ekkehard Beck","doi":"10.1007/s12325-025-03117-7","DOIUrl":"10.1007/s12325-025-03117-7","url":null,"abstract":"<div><h3>Introduction</h3><p>This systematic literature review and pairwise meta-analysis evaluated the comparative effectiveness of mRNA-1273 versus BNT162b2 in patients with at least one underlying medical condition at high risk for severe COVID-19.</p><h3>Methods</h3><p>MEDLINE, Embase, and Cochrane databases were searched for relevant articles from January 1, 2019 to February 9, 2024. Studies reporting effectiveness data from at least two doses of mRNA-1273 and BNT162b2 vaccination in adults with medical conditions at high risk of developing severe COVID-19 according to the US Centers for Disease Control and Prevention were included. Outcomes of interest were SARS-CoV-2 infection (overall, symptomatic, and severe), hospitalization due to COVID-19, and death due to COVID-19. Risk ratios (RRs) were calculated with random effects models. Subgroup analyses by specific medical conditions, number of vaccinations, age, and SARS-CoV-2 variant were conducted. Heterogeneity between studies was estimated with chi-square testing. The certainty of evidence was assessed using the Grading of Recommendations, Assessments, Development, and Evaluations framework.</p><h3>Results</h3><p>Sixty-five observational studies capturing the original/ancestral-containing primary series to Omicron-containing bivalent original-BA4-5 vaccinations were included in the meta-analysis. mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.79–0.92]; <i>I</i>² = 92.5%), symptomatic SARS-CoV-2 infection (RR, 0.75 [95% CI, 0.65–0.86]; <i>I</i>² = 62.3%), severe SARS-CoV-2 infection (RR, 0.83 [95% CI, 0.78–0.89]; <i>I</i>² = 38.0%), hospitalization due to COVID-19 (RR, 0.88 [95% CI, 0.82–0.94]; <i>I</i>² = 38.7%), and death due to COVID-19 (RR, 0.84 [95% CI, 0.76–0.93]; <i>I</i>² = 1.3%) than BNT162b2. Findings were generally consistent across subgroups. Evidence certainty was low or very low because sufficiently powered randomized controlled trials are impractical in this heterogeneous population.</p><h3>Conclusion</h3><p>Meta-analysis of 65 observational studies showed that vaccination with mRNA-1273 was associated with a significantly lower risk of SARS-CoV-2 infection and COVID-19-related hospitalization and death than BNT162b2 in patients with medical conditions at high risk of severe COVID-19.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2040 - 2077"},"PeriodicalIF":3.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03117-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Response to: Letter to the Editor Regarding “Efficacy of Cooled-Radiofrequency Ablation of the Genicular Nerve as Treatment for Chronic Knee Pain: A Retrospective Study”","authors":"Alaa Abd-Elsayed,&nbsp;Andrew Matta","doi":"10.1007/s12325-025-03111-z","DOIUrl":"10.1007/s12325-025-03111-z","url":null,"abstract":"","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2542 - 2544"},"PeriodicalIF":3.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03111-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor Regarding “Efficacy of Cooled-Radiofrequency Ablation of the Genicular Nerve as Treatment for Chronic Knee Pain: A Retrospective Study”","authors":"Xinjie Wang,&nbsp;Hui Ma","doi":"10.1007/s12325-025-03108-8","DOIUrl":"10.1007/s12325-025-03108-8","url":null,"abstract":"","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 5","pages":"2539 - 2541"},"PeriodicalIF":3.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}