Drugs in Research & Development最新文献

{"title":"Safety and Effectiveness of Rasburicase in the Control of Hyperuricemia in Pediatric Patients with Non-Hodgkin's Lymphoma and Acute Leukemia: An Open-Label, Single-Arm, Multi-center, Interventional Study.","authors":"Tianyou Wang,&nbsp;Xiaofan Zhu,&nbsp;Yumei Chen,&nbsp;Shuhong Shen,&nbsp;Yongmin Tang,&nbsp;Jingying Zhang,&nbsp;Yingyi He,&nbsp;Hui Zhang,&nbsp;Ju Gao,&nbsp;Jianpei Fang,&nbsp;Rong Liu,&nbsp;Xiaoyan Wu,&nbsp;Jinchuan Sun,&nbsp;Minlu Zhang","doi":"10.1007/s40268-023-00420-y","DOIUrl":"https://doi.org/10.1007/s40268-023-00420-y","url":null,"abstract":"<p><strong>Introduction: </strong>Despite rasburicase's proven efficiency in Caucasians, Japanese, and Koreans, studies evaluating the safety and effectiveness of rasburicase in Chinese pediatric patients with non-Hodgkin's lymphoma (NHL) and acute leukemia (AL) in particular are lacking.</p><p><strong>Objective: </strong>The aim was to evaluate the safety and effectiveness of rasburicase in Chinese pediatric patients with NHL and AL.</p><p><strong>Methods: </strong>In this phase IV, open-label, non-randomized, single-arm, multi-center, interventional study (NCT04349306), children newly diagnosed with NHL or AL who received 0.20 mg/kg/day of rasburicase were included. The primary objective was to assess the safety of rasburicase by the incidence of adverse events (AEs). The secondary objective was to determine the effectiveness of rasburicase in the control of hyperuricemia.</p><p><strong>Results: </strong>Out of 50 patients, 25 reported a total of 76 treatment-emergent adverse events (TEAEs), including eight TEAEs of grade ≥ 3 in 12 patients. A drug-related serious AE was reported in one patient, and there was no incidence of death. The response rate in the intent-to-treat population was 100.0% (95% confidence interval 82.4-100.0) in patients (n = 19) with baseline uric acid level of > 8.0 mg/dL. Similarly, the response rate was 86.2% (n = 25) among 29 patients (60.4%) with baseline uric acid levels of ≤ 8.0 mg/dL. The maximum mean percentage decrease of plasma uric acid level in the overall patients was 96.9%.</p><p><strong>Conclusion: </strong>Rasburicase was well tolerated and effective in controlling hyperuricemia in Chinese pediatric patients with NHL and AL.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 2","pages":"129-140"},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/f2/40268_2023_Article_420.PMC10293550.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10224901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estetrol: From Preclinical to Clinical Pharmacology and Advances in the Understanding of the Molecular Mechanism of Action.","authors":"Céline Gérard,&nbsp;Jean-Michel Foidart","doi":"10.1007/s40268-023-00419-5","DOIUrl":"https://doi.org/10.1007/s40268-023-00419-5","url":null,"abstract":"<p><p>Estetrol (E4) is the most recently described natural estrogen. It is produced by the human fetal liver during pregnancy and its physiological function remains unclear. E4 is the estrogenic component of a recently approved combined oral contraceptive. It is also in development for use as menopausal hormone therapy. In the context of these developments, the pharmacological activity of E4, alone or in combination with a progestin, has been extensively characterized in preclinical models as well as in clinical studies in women of reproductive age and postmenopausal women. Despite the clinical benefits, the use of oral estrogens for contraception or menopause is also associated with unwanted effects, such as an increased risk of breast cancer and thromboembolic events, due to their impact on non-target tissues. Preclinical and clinical data for E4 point to a tissue-specific activity and a more selective pharmacological profile compared with other estrogens, including a low impact on the liver and hemostasis balance. This review summarizes the characterization of the pharmacological properties of E4 as well as recent advances made in the understanding of the molecular mechanisms of action driving its activity. How the unique mode of action and the different metabolism of E4 might support its favorable benefit-risk ratio is also discussed.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 2","pages":"77-92"},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/55/40268_2023_Article_419.PMC10293541.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Baricitinib in Patients with Refractory Adult-Onset Still's Disease.","authors":"Ziyi Sun,&nbsp;Rongqi Li,&nbsp;Yingai Wang,&nbsp;Feng Han,&nbsp;Wei Wei,&nbsp;Xin Li","doi":"10.1007/s40268-023-00417-7","DOIUrl":"https://doi.org/10.1007/s40268-023-00417-7","url":null,"abstract":"<p><strong>Background and objective: </strong>Adult-onset Still's disease (AOSD) is an idiopathic systemic inflammatory disease of unknown aetiology. Some patients exhibit resistance to conventional treatment during long-term therapy. Janus kinase inhibitors (JAKinibs) may contribute to the improvement in AOSD symptoms via the JAK-signal transducer and activator of transcription (STAT) pathway. We aimed to explore the efficacy and safety of baricitinib in patients with refractory AOSD.</p><p><strong>Methods: </strong>Patients were enrolled if they fulfilled the Yamaguchi AOSD classification criteria in China between 2020 and 2022. All patients were recognized as having refractory AOSD and were treated with oral baricitinib at a dosage of 4 mg once daily. A systemic score and prednisone dosage were used to evaluate the efficacy of baricitinib at months 1, 3, and 6 and at the last follow-up visit. The safety profiles were recorded and analysed at every assessment.</p><p><strong>Results: </strong>Seven female patients with refractory AOSD received baricitinib. The median age was 31 (IQR 10) years. Treatment was terminated in one patient due to progressive macrophage activation syndrome (MAS). Others continued baricitinib treatment until the last assessment. The systemic score decreased significantly at 3 months (p = 0.0216), 6 months (p = 0.0007), and the last follow-up visit (p = 0.0007) compared with baseline. One month after the initiation of baricitinib, the rates of improvement in fever, rash, sore throat, and myalgia symptoms were 71.4% (5/7), 40% (2/5), 80% (4/5), and 66.7% (2/3), respectively. Five patients remained symptom-free at the last follow-up visit. In most patients, their laboratory values had returned to normal by the last follow-up visit. A significant reduction in the levels of C-reactive protein (CRP) (p = 0.0165) and ferritin (p = 0.0047) was observed at the last visit compared with baseline. The daily prednisolone dosage significantly decreased from 35.7 ± 15.1 mg/day at baseline to 8.8 ± 4.4 mg/day by month 6 (p = 0.0256), and it was 5.8 ± 4.7 mg/day at the last assessment (p = 0.0030). Leukopenia due to MAS was noted in one patient. Except for mild abnormalities in lipid parameters, no other severe adverse events occurred during follow-up.</p><p><strong>Conclusions: </strong>Our findings suggest that baricitinib therapy could provide rapid and durable clinical and laboratory improvement in patients with refractory AOSD. Treatment seemed to be well tolerated by these patients. The long-term efficacy and safety of baricitinib therapy for AOSD should be assessed further in prospective controlled clinical trials in the future.</p><p><strong>Trial registration: </strong>Trial registration number (TRN): ChiCTR2200061599. Date of registration: 29 June 2022 (retrospectively registered).</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 2","pages":"109-120"},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/44/8b/40268_2023_Article_417.PMC10293510.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9705900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Randomized, Double-Blind, Parallel-Controlled Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of SCT510 to Bevacizumab (Avastin^®) in Healthy Chinese Males.","authors":"Jing Wu,&nbsp;Guolan Wu,&nbsp;Liangzhi Xie,&nbsp;Duo Lv,&nbsp;Chang Xu,&nbsp;Huili Zhou,&nbsp;Lihua Wu,&nbsp;Jingjing Zhang,&nbsp;Jianzhong Shentu","doi":"10.1007/s40268-023-00424-8","DOIUrl":"https://doi.org/10.1007/s40268-023-00424-8","url":null,"abstract":"<p><strong>Background: </strong>SCT510 is a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), which is intended as a candidate biosimilar of bevacizumab that is approved for various metastatic cancers.Please confirm change in wording to match definition for VEGF belowYes.</p><p><strong>Objective: </strong>This study aimed to compare the pharmacokinetics profiles, safety, and immunogenicity of SCT510 to bevacizumab (Avastin^®) in healthy Chinese males.</p><p><strong>Methods: </strong>This was a single-center, double-blind, parallel-group phase I study. A total of 84 participants were randomly assigned (1:1) to receive a single 3 mg/kg infusion of either SCT510 or bevacizumab and followed up for 99 days. Primary endpoints were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC_0-∞), area under the serum concentration-time curve from time 0 to last quantifiable concentration (AUC_0-t), and the maximum observed concentration (C_max). Secondary endpoints included safety and immunogenicity.Kindly check and confirm the edit made in the article title.Yes.</p><p><strong>Results: </strong>A total of 82 subjects completed the study. Geometric means ratios (GMR) for AUC_0-∞, AUC_0-t, and C_max were 0.88, 0.89, and 0.97, respectively, for SCT510 versus bevacizumab (USA). The 90% confidence intervals for GMRs of AUC_0-∞, AUC_0-t, and C_max were all within the prespecified criteria (80-125%). No adverse events (AEs) led to study termination, and no serious adverse events (SAEs) were reported. None of the anti-drug antibodies (ADAs) identified were found to be neutralizing antibodies (NAbs), and only one subject from the SCT510 group tested positive for the ADA at the day 99 visit.</p><p><strong>Conclusion: </strong>This study demonstrated that the pharmacokinetics, safety, and immunogenicity of SCT510 were equivalent to bevacizumab (Avastin^®). As a proposed biosimilar drug to bevacizumab, SCT510 was well tolerated in healthy Chinese males.</p><p><strong>Clinical trials registration: </strong>NCT05113511.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 2","pages":"175-183"},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/17/40268_2023_Article_424.PMC10293153.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9706556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Biosimilar of Agalsidase Beta for the Treatment of Fabry Disease: Preclinical Evaluation.","authors":"André B P van Kuilenburg,&nbsp;Carla E M Hollak,&nbsp;Ana Travella,&nbsp;Melisa Jacobs,&nbsp;Lucas D Gentilini,&nbsp;René Leen,&nbsp;Karen M M Ghauharali-van der Vlugt,&nbsp;Femke S Beers Stet,&nbsp;Susan M I Goorden,&nbsp;Sanne van der Veen,&nbsp;Marcelo Criscuolo,&nbsp;Mariana Papouchado","doi":"10.1007/s40268-023-00421-x","DOIUrl":"https://doi.org/10.1007/s40268-023-00421-x","url":null,"abstract":"<p><strong>Background and objective: </strong>Fabry disease (FD) is a rare lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A (aGal A). Since 2001, two different enzyme replacement therapies have been authorized, with agalsidase beta being used in most parts of the Western world. Currently, biosimilars of several expensive enzyme therapies are under development to improve their accessibility for patients. We present the preclinical results of the development of a biosimilar to agalsidase beta.</p><p><strong>Methods: </strong>Produced in a Chinese hamster ovary (CHO)-cell system, the biosimilar aGal A Biosidus (AGABIO), was compared with agalsidase beta with respect to amino acid sequence, glycosylation, specific α-galactosidase activity, stability in plasma, and effects on cultured human Fabry fibroblasts and Fabry mice.</p><p><strong>Results: </strong>AGABIO had the same amino acid composition and similar glycosylation, enzymatic activity, and stability as compared with agalsidase beta. After uptake in fibroblasts, α-galactosidase A activity increased in a dose-dependent manner, with maximum uptake observed after 24 h, which remained stable until at least 48 h. Both enzymes were localized to lysosomes. Reduction of accumulated globotriaosylceramide (Gb3) and lysoGb3 in cultured Fabry fibroblasts by AGABIO and agalsidase beta showed comparable dose-response curves. In Fabry knockout mice, after a single injection, both enzymes were rapidly cleared from the plasma and showed equal reductions in tissue and plasma sphingolipids. Repeated dose studies in rats did not raise any safety concerns. Anti-drug antibodies from patients with FD treated with agalsidase beta showed equal neutralization activity toward AGABIO.</p><p><strong>Conclusion: </strong>These findings support the biosimilarity of AGABIO in comparison with agalsidase beta. The clinical study phase is currently under development.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 2","pages":"141-153"},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/bf/40268_2023_Article_421.PMC10293523.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9709367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioavailability of Cariban^® Capsules: A Modified-Release Fixed-Dose Combination of Doxylamine and Pyridoxine to Relieve Nausea and Vomiting During Pregnancy.","authors":"Paula Saz-Leal, Laura Zamorano-Domínguez, Jesús Frías, Pedro Guerra, Marc Saura-Valls, Ramón Roca-Juanes, Joaquín Nebot-Troyano, Eva García-Aguilar, Tatiana Vilchez, Katia Urso","doi":"10.1007/s40268-023-00425-7","DOIUrl":"10.1007/s40268-023-00425-7","url":null,"abstract":"<p><strong>Background: </strong>Nausea and vomiting is a very prevalent condition during pregnancy. Combination of doxylamine and pyridoxine is placed as first-line pharmacological option for its treatment in most clinical guidelines. Among different release forms available, Cariban^® is a fixed-dose combination of doxylamine/pyridoxine 10/10 mg, formulated as modified-release capsules.</p><p><strong>Objectives: </strong>In the present study, we aimed to characterize the bioavailability performance of Cariban^® in vitro and in vivo.</p><p><strong>Methods: </strong>An in vitro dissolution test was performed to evaluate the release profile of Cariban^®, together with immediate- and delayed-release formulations available on the market. A single-center, single-dose, open-label bioavailability study following Cariban^® administration in 12 healthy adult female patients was carried out to explore the drug behavior in vivo (protocol NBR-002-13; EUDRA-CT 2013-005422-35). These data were additionally used to perform a computational pharmacokinetic simulation of the posology approved for this drug.</p><p><strong>Results: </strong>Cariban^® capsules demonstrate a prolonged-release performance, with an early, gradual, and progressive release of both actives until reaching a complete dissolution after 4-5 h in solution. The pharmacokinetic features of these capsules show that doxylamine and pyridoxine metabolites are early absorbed, being all detectable in plasma within 1 h following oral administration. Computational pharmacokinetic simulation predicts that different posology provides distinct profiles of metabolites in plasma, with 1-1-2 (morning-midafternoon-night) being the one that concentrates higher plasma levels but lower dose dumping for 24 h.</p><p><strong>Conclusion: </strong>Cariban^® behaves as a prolonged-release formulation, which correlates with rapid absorption and arising of the actives in the plasma, but also long-lasting and sustained bioavailability, especially when administered following the complete posology. These results would underlie its demonstrated efficacy to relieve nausea and vomiting of pregnancy (NVP) under clinical settings.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 2","pages":"185-195"},"PeriodicalIF":2.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/42/40268_2023_Article_425.PMC10293548.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10084391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetics of Napabucasin Combined with Sorafenib in Japanese Patients with Unresectable Hepatocellular Carcinoma.","authors":"Takuji Okusaka, Manabu Morimoto, Yuichiro Eguchi, Shinichiro Nakamura, Shuichi Iino, Rie Kageyama","doi":"10.1007/s40268-023-00416-8","DOIUrl":"10.1007/s40268-023-00416-8","url":null,"abstract":"<p><strong>Background and objective: </strong>For patients with advanced hepatocellular carcinoma (HCC), the standard of care for many years has been sorafenib. Preliminary data have suggested that the combination of the NAD(P)H:quinone oxidoreductase 1 bioactivatable agent napabucasin plus sorafenib may improve clinical outcomes in patients with HCC. In this phase I, multicenter, uncontrolled, open-label study, we evaluated napabucasin (480 mg/day) plus sorafenib (800 mg/day) in Japanese patients with unresectable HCC.</p><p><strong>Methods: </strong>Adults with unresectable HCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled in a 3 + 3 trial design. The occurrence of dose-limiting toxicities was assessed through 29 days from the start of napabucasin administration. Additional endpoints included safety, pharmacokinetics, and preliminary antitumor efficacy.</p><p><strong>Results: </strong>In the six patients who initiated treatment with napabucasin, no dose-limiting toxicities occurred. The most frequently reported adverse events were diarrhea (83.3%) and palmar-plantar erythrodysesthesia syndrome (66.7%), all of which were grade 1 or 2. The pharmacokinetic results for napabucasin were consistent with prior publications. The best overall response (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) was stable disease in four patients. Using Kaplan-Meier methodology, the 6-month progression-free survival rate was 16.7% per RECIST 1.1 and 20.0% per modified RECIST for HCC. The 12-month overall survival rate was 50.0%.</p><p><strong>Conclusions: </strong>These findings confirm the viability of napabucasin plus sorafenib treatment, and there were no safety or tolerability concerns in Japanese patients with unresectable HCC.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier NCT02358395, registered on 9 February 2015.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 2","pages":"99-107"},"PeriodicalIF":2.2,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9b/41/40268_2023_Article_416.PMC10293504.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9704732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Simultaneously Induced Neutropenia and Hemolysis After a Single Metamizole Dose.","authors":"Raphael Allgaier,&nbsp;Arne Kandulski,&nbsp;Karsten Gülow,&nbsp;Lars Maier,&nbsp;Martina Müller,&nbsp;Hauke Christian Tews","doi":"10.1007/s40268-023-00415-9","DOIUrl":"https://doi.org/10.1007/s40268-023-00415-9","url":null,"abstract":"<p><strong>Background and objective: </strong>Metamizole is a non-opioid ampyrone sulfonate compound with potent analgesic, antipyretic, and spasmolytic effects. Agranulocytosis is a rare life-threatening complication of metamizole.</p><p><strong>Case: </strong>Here, we present the case of a 62-year-old patient who developed agranulocytosis as well as hemolysis after a single administration of metamizole.</p><p><strong>Conclusion: </strong>This case illustrates the inherent allergic potential of metamizole and its effects on different hematopoietic cell types.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 2","pages":"93-98"},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/47/97/40268_2023_Article_415.PMC10293139.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10082156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Centre Real-World Study on Drug Survival and Effectiveness of Brodalumab for Treatment of Psoriasis and Psoriatic Arthritis.","authors":"Cathrine Dawn Büttner Elgaard,&nbsp;Lars Iversen,&nbsp;Kasper Fjellhaugen Hjuler","doi":"10.1007/s40268-023-00422-w","DOIUrl":"https://doi.org/10.1007/s40268-023-00422-w","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials have established the efficacy of brodalumab in treatment of psoriasis and psoriatic arthritis. Real-world evidence is needed to fully evaluate the drug.</p><p><strong>Objective: </strong>Here we investigate drug survival and clinical effectiveness of brodalumab in patients with psoriasis and psoriatic arthritis in a real-world setting.</p><p><strong>Methods: </strong>This was a retrospective single-centre study enrolling patients receiving brodalumab for psoriasis at the Department of Dermatology, Aarhus University Hospital, Denmark. The primary endpoints were drug survival, reasons for discontinuation, percentage of patients achieving a Psoriasis Area and Severity Index (PASI) ≤ 2 and clinical effectiveness against psoriatic arthritis.</p><p><strong>Results: </strong>Eighty-three patients were included (mean age 49.2 ± 17.4 years, 59.0% male, 9.6% bio-naïve, mean baseline PASI 10.9 ± 6.9). Twenty-seven patients discontinued treatment primarily due to ineffectiveness and adverse events (AEs). Kaplan-Meier-estimated 1-year drug survival was 65.7%. An absolute Psoriasis Area and Severity Index (PASI) ≤ 2 was achieved by 68.2% of patients at end of follow-up, by 70.0% at weeks 12-17 and by 76.2% after 40-60 weeks of treatment. Neither drug survival nor PASI ≤ 2 was associated with baseline PASI ≥ 10, body mass index ≥ 30, previous treatment with > 2 biologics or other IL-17 inhibitors in particular (P > 0.05). Psoriatic arthritis remission or partial remission was achieved by 10 out of 18 patients with psoriatic arthritis; treatment failure was reported in 5 patients.</p><p><strong>Conclusions: </strong>Brodalumab was effective against psoriasis and psoriatic arthritis in a real-world setting. The drug survival was lower than reported in other real-world settings.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 2","pages":"155-163"},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/ed/40268_2023_Article_422.PMC10293129.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9697898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-Acetyl-L-Cysteine Reduces Cervical Carcinogenesis by Promoting Apoptosis.","authors":"Wenping Guo,&nbsp;Wang Jing","doi":"10.1007/s40268-023-00423-9","DOIUrl":"https://doi.org/10.1007/s40268-023-00423-9","url":null,"abstract":"<p><strong>Background and objective: </strong>Cervical cancer is the fourth leading cause of cancer death in women, and is one of the most common malignant tumors of the reproductive system. However, more effective treatment for cervical cancer is needed. In this study, we aim to investigate whether N-acetyl-L-cysteine (NAC) could inhibit the proliferation of human papillomavirus (HPV)-positive cells, and reduce cervical carcinogenesis.</p><p><strong>Methods: </strong>The cervical cancer cell lines SiHa, HeLa, HPV-negative cell line C33A, and the immortalized human cervical keratinocyte cells S12 were used. The protein expression was determined using Western blot assay. mRNA expression was determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation was determined by Cell Counting Kit-8 assay. Cell apoptosis was evaluated using Annexin V-FITC apoptosis kits. The numbers of colonies were measured using colony-forming assay. Xenograft tumor necrosis and HPV16 E7 expression were determined using hematoxylin and eosin (H&E) staining and immunohistochemistry.</p><p><strong>Results: </strong>Our results showed that NAC treatment at the concentration of 1.5 mM significantly promoted cell apoptosis and reduced cell growth by inhibiting HPV16 E7 expression. NAC inhibited HPV16-oncoprotein-induced hypoxia-inducible factor (HIF)-1α protein expression and Akt activation in vitro. Additionally, NAC suppressed tumor growth, as evidenced by the smaller tumor size in the xenograft mouse model and decreased HPV16 E7 expression in tumor tissues.</p><p><strong>Conclusion: </strong>Our findings demonstrate that NAC exhibits the potential to promote HPV-positive cell apoptosis, and suppress the proliferation of HPV-positive cells by inhibiting cell inhibitor of apoptosis protein 2 and HIF-1α.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":"23 2","pages":"165-174"},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6a/7e/40268_2023_Article_423.PMC10293158.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9698917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}