Cts-Clinical and Translational Science最新文献

{"title":"Evaluation of drug–drug interactions of a novel potent FLT3 inhibitor SKLB1028 in healthy subjects","authors":"Jingcheng Chen,&nbsp;Jingxuan Wu,&nbsp;Nini Guo,&nbsp;Yuqin Song,&nbsp;Lijun Li,&nbsp;Bingyan Wang,&nbsp;Jiangshuo Li,&nbsp;Mengyu Hou,&nbsp;Hang Yin,&nbsp;Meijuan Zhang,&nbsp;Yanhong Kong,&nbsp;Xiaofang Wu,&nbsp;Ran Li,&nbsp;Le Wu,&nbsp;Qiannan Gao,&nbsp;Ruihua Dong","doi":"10.1111/cts.70063","DOIUrl":"10.1111/cts.70063","url":null,"abstract":"<p>SKLB1028 is a novel multi-target protein kinase inhibitor under investigation for the treatment of FLT3-ITD mutated acute myeloid leukemia. Based on the preclinical characterization of SKLB1028 metabolism, three drug–drug interaction clinical studies were performed to investigate the effects of itraconazole, rifampin (CYP3A4 inhibitor and inducer, respectively), and gemfibrozil (CYP2C8 inhibitor) on the metabolism of SKLB1028. Fourteen healthy Chinese male subjects were enrolled in each study. In Study 1, subjects were administered a single dose of SKLB1028 (100 mg on days 1 and 11) and multiple doses of itraconazole (200 mg twice daily on day 8 and 200 mg once daily from days 9 to 18). Itraconazole was given with a loading dose on Day 8 and the total administration of itraconazole was 11 days. In Study 2, subjects were administered a single dose of SKLB1028 (100 mg on days 1 and 12) and multiple doses of gemfibrozil (600 mg twice daily from days 8 to 19). In Study 3, subjects were administered a single dose of SKLB1028 (150 mg on days 1 and 15) and multiple doses of rifampin (600 mg once daily from day 8 to 22). Itraconazole increased the AUC and <i>C</i>_max of SKLB1028 by approximately 28% and 41%, respectively. Compared to the single drug, co-administration with gemfibrozil increased the AUC of SKLB1028 by ~26% and the <i>C</i>_max by ~21%. Co-administration with rifampin reduced the AUC of SKLB1028 by ~30%, while the <i>C</i>_max did not change significantly. All treatments were well tolerated in all three studies.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631034","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":"Concentration-QTcF analysis of quizartinib in patients with newly diagnosed FLT3-internal-tandem-duplication-positive acute myeloid leukemia","authors":"Pavan Vaddady,&nbsp;Giovanni Smania,&nbsp;Shintaro Nakayama,&nbsp;Hiroyuki Inoue,&nbsp;Abhinav Kurumaddali,&nbsp;Malaz Abutarif,&nbsp;Ming Zheng","doi":"10.1111/cts.70065","DOIUrl":"10.1111/cts.70065","url":null,"abstract":"<p>Quizartinib prolongs QT interval through inhibition of the slow delayed rectifier potassium current (I_Ks). We used non-linear mixed-effects modeling to explore the relationship between quizartinib and its pharmacologically active metabolite AC886 and the Fridericia-corrected QT interval (QTcF) in newly diagnosed acute myeloid leukemia (AML) patients. We evaluated linear and non-linear drug effect models, using triplicate QTcF measurements with available time-matched pharmacokinetic samples from the Phase 3 QuANTUM-First trial. The effect of intrinsic and extrinsic factors on model parameters was tested using stepwise covariate model building. Simulations were conducted to predict the change from baseline in QTcF (ΔQTcF) at the maximum concentration at steady-state (<i>C</i>_max,ss) for quizartinib maintenance daily doses of 30 and 60 mg. The concentration-QTcF (C-QTcF) relationship was best described by a sigmoidal maximum effect model. After accounting for the effect of quizartinib, including AC886 concentrations did not further explain changes in QTcF. Circadian variations in QTcF were described using an empirical change from baseline based on clock times. Age and hypokalaemia were identified as statistically significant covariates on baseline QTcF; no covariates were found to impact the C-QTcF relationship. The median model-predicted ΔQTcF at <i>C</i>_max,ss was 18.4 ms (90% confidence interval (CI): 16.3–20.5) at 30 mg and 24.1 ms (90% CI: 21.4–26.6) at 60 mg. In conclusion, in newly diagnosed AML patients, ΔQTcF increased non-linearly with increasing quizartinib concentrations. The predicted ΔQTcF increase at <i>C</i>_max,ss supports the proposed dose adaptation based on observed QTcF and the dose reduction in case of strong cytochrome P450 3A (CYP3A) inhibitors coadministration.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630923","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":"The needs and gaps in pharmacogenomics knowledge and education among healthcare professionals in Malaysia: A multisite Delphi study","authors":"Safa Omran,&nbsp;Siew Lian Leong,&nbsp;Ali Blebil,&nbsp;Devi Mohan,&nbsp;Wei Chern Ang,&nbsp;Siew Li Teoh","doi":"10.1111/cts.70057","DOIUrl":"10.1111/cts.70057","url":null,"abstract":"<p>Lack of pharmacogenomics knowledge among healthcare professionals is the most significant cited barrier to implementing pharmacogenomics in clinical settings. Despite the growth in research initiatives and awareness of pharmacogenomics, healthcare professionals continue to report a lack of knowledge and confidence in practicing pharmacogenomics. This study aims to assess the current pharmacogenomics knowledge gaps and learning needs of healthcare professionals in Malaysia. A modified Delphi with a multidisciplinary expert panel was conducted, and a purposive sampling method was used with predefined selection criteria. Fourteen study sites in Malaysia were included. The cut-off value to approach consensus was predefined as a threshold of 60% or higher, and a quantitative descriptive statistical analysis was performed. The study demonstrated that all experts rated the suggested educational content components as essential/important to be included in the educational intervention. Additionally, experts highlighted the significant barriers and gaps to adopting and practicing pharmacogenomics. To conclude, this multisite Delphi study enabled the development of a tailored, effective, evidence-based, competency-based educational intervention in pharmacogenomics for healthcare professionals in Malaysia. To keep up with the rapid evolution of the pharmacogenomics field, healthcare professionals should be equipped with the necessary competencies required to practice pharmacogenomics for better health outcomes. Future research is needed to determine the feasibility of the proposed educational intervention.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631007","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":"Safety, pharmacokinetics, and pharmacodynamics of sofnobrutinib, a novel non-covalent BTK inhibitor, in healthy subjects: First-in-human phase I study","authors":"Kyoko Miyamoto,&nbsp;Robert M. Miller,&nbsp;Christine Voors-Pette,&nbsp;Jart A. F. Oosterhaven,&nbsp;Marieke van den Dobbelsteen,&nbsp;Katsuhiro Mihara,&nbsp;Marian Geldof,&nbsp;Yuji Sato,&nbsp;Naomi Matsuda,&nbsp;Shirou Kirita,&nbsp;Masaaki Sawa,&nbsp;Akinori Arimura","doi":"10.1111/cts.70060","DOIUrl":"10.1111/cts.70060","url":null,"abstract":"<p>Bruton's tyrosine kinase (BTK) is a potential therapeutic target for allergic and autoimmune diseases. This first-in-human phase I study evaluated safety, pharmacokinetic, and pharmacodynamic profiles of sofnobrutinib (formerly AS-0871), a highly selective, orally available, non-covalent BTK inhibitor, in healthy adult subjects. Single ascending doses (SAD; 5–900 mg) and multiple ascending doses (MAD; 50–300 mg twice daily [b.i.d.] for 14 days [morning dose only on Day 14]) of sofnobrutinib were tested. In the entire study, all adverse events (AEs) were mild or moderate, and no apparent dose-proportional trend in severity or frequency was observed. No serious treatment-emergent AEs, cardiac arrythmias, or bleeding-related AEs were reported. In the SAD part, sofnobrutinib exhibited approximately dose-dependent systemic exposures up to 900 mg with rapid absorption (median time to maximum concentration of 2.50–4.00 h) and gradual decline (mean half-lives of 3.7–9.0 h). In the MAD part, sofnobrutinib showed low accumulation after multiple dosing (mean accumulation ratios of ≤1.54) and reached a steady state on ≤Day 7. Single dosing of sofnobrutinib rapidly and dose-dependently suppressed basophil and B-cell activations in ex vivo whole blood assays. Multiple dosing of sofnobrutinib achieved 50.8%–79.4%, 67.6%–93.6%, and 90.1%–98.0% inhibition of basophil activation during the dosing interval of 50, 150, and 300 mg b.i.d., respectively. Based on pharmacokinetic-pharmacodynamic analysis, half-maximal inhibitory concentration (IC₅₀) of sofnobrutinib for basophil activation was 54.06 and 57.01 ng/mL in the SAD and MAD parts, respectively. Similarly, IC₅₀ for B-cell activation was 187.21 ng/mL. These data support further investigation of sofnobrutinib in allergic and autoimmune diseases.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631036","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":"Comparing machine learning and deep learning models to predict cognition progression in Parkinson's disease","authors":"Edgar A. Bernal,&nbsp;Shu Yang,&nbsp;Konnor Herbst,&nbsp;Charles S. Venuto","doi":"10.1111/cts.70066","DOIUrl":"10.1111/cts.70066","url":null,"abstract":"<p>Cognitive decline in Parkinson's disease (PD) varies widely. While models to predict cognitive progression exist, comparing traditional probabilistic models to deep learning methods remains understudied. This study compares sequential modeling techniques to identify cognitive progression in individuals with and without PD. Using data from the Parkinson's Progression Marker Initiative, shallow Markov, deep recurrent (long short-term memory [LSTM]), and nonrecurrent (temporal fusion transformer [TFT]) models were compared to predict cognitive status over time. Cognitive status was categorized into normal cognition (NC), mild cognitive impairment (MCI), and dementia. Predictions were made annually for up to 3 years using clinical data, including demographics, cognitive assessments, PD severity, and medical history. Each approach was evaluated using inverse probability weighted (IPW-) F1 scores. An ensemble method combined outputs from the Markov, LSTM, and TFT models. The dataset included 917 individuals (53% PD; 30% at risk for PD; 17% Healthy Controls). The TFT model outperformed others across all annual periods (IPW-F1 = 0.468) compared to the Markov (IPW-F1 = 0.349) and LSTM (IPW-F1 = 0.414) models, with improved performance using an ensemble approach (IPW-F1 = 0.502). For MCI and dementia predictions, which were rarer occurrences compared to NC status (ratios: 50:8:1), the TFT model consistently outperformed competing models, achieving IPW-F1 scores of 0.496 and 0.533 for MCI and dementia, respectively. In conclusion, sequential deep learning models like TFT, which mitigate long-term memory loss and can interpret complex, high-dimensional data, perform best overall in predicting clinically important cognitive transitions. These methods should be further explored for predicting degenerative conditions.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607465","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":"Clinical pharmacokinetics and pharmacodynamics of ongericimab: A potential long-acting PCSK9 monoclonal antibody in healthy subjects and patients with hypercholesterolemia: Randomized, double-blind, placebo-controlled phase Ia and Ib/II studies","authors":"Juanjuan Jiang,&nbsp;Li Xu,&nbsp;Lin Chai,&nbsp;Xiaoyuan Guan,&nbsp;Li Zhang,&nbsp;Hong Liu,&nbsp;Yan Yan,&nbsp;Lili Li,&nbsp;Yi Zhao,&nbsp;Xuelian Bai,&nbsp;Lei Tian,&nbsp;Youhong Jia","doi":"10.1111/cts.70061","DOIUrl":"https://doi.org/10.1111/cts.70061","url":null,"abstract":"<p>Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low-density lipoprotein-cholesterol (LDL-C) by decreasing the expression of the LDL-receptor on hepatic cells. Ongericimab (JS002) is a novel PCSK9 monoclonal antibody that exhibits a long-acting LDL-C lowering effect by exclusively inhibiting PCSK9 in pre-clinical studies. Two randomized, double-blind, placebo-controlled trials were conducted to evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetic, and pharmacodynamic profiles of ongericimab in healthy subjects and patients with hypercholesterolemia. Eighty-four healthy subjects in the phase Ia study received a single dose of placebo or ongericimab (15–450 mg). Ninety patients with hypercholesterolemia in the phase Ib/II study received placebo or ongericimab 150 mg Q2W, 300 mg Q4W, or 450 mg Q4W for 12 weeks. Ongericimab exhibited non-linear kinetics. The apparent clearance decreased as the dosage increased, with terminal elimination half-life (t_1/2) values of 4.5–6.5 days. Overall, ongericimab was well tolerated in both studies. A single dose of ongericimab reduced LDL-C levels by 30%–73% in healthy subjects, and repeated doses of ongericimab reduced LDL-C levels by 67%–80% in patients with hypercholesterolemia. At the end of the dosing interval in the phase Ib/II study, over 70% of patients' LDL-C levels decreased by more than 50% from baseline. The results showed that ongericimab had a significant long-acting LDL-C lowering effect with good safety and potential for clinical application.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142579591","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 first-in-human, randomized study of the safety, pharmacokinetics and pharmacodynamics of povetacicept, an enhanced dual BAFF/APRIL antagonist, in healthy adults","authors":"Rupert Davies,&nbsp;Stanford L. Peng,&nbsp;Jason Lickliter,&nbsp;Kristi McLendon,&nbsp;Amanda Enstrom,&nbsp;Allison G. Chunyk,&nbsp;Lori Blanchfield,&nbsp;NingXin Wang,&nbsp;Tiffany Blair,&nbsp;Heather M. Thomas,&nbsp;Alina Smith,&nbsp;Stacey R. Dillon","doi":"10.1111/cts.70055","DOIUrl":"10.1111/cts.70055","url":null,"abstract":"<p>Therapeutic agents targeting the tumor necrosis factor (TNF) superfamily cytokines B-cell activating factor (BAFF, BLyS) and/or A PRoliferation Inducing Ligand (APRIL) have demonstrated clinical effectiveness in multiple autoimmune diseases, such as systemic lupus erythematosus, lupus nephritis, and immunoglobulin A nephropathy (IgAN). However, their clinical utility can often be limited by incomplete and/or prolonged times to clinical response and inconvenient dosing regimens, which may be improved by more potent dual inhibition of both cytokines. Povetacicept (ALPN-303; TACI vTD-Fc) is a crystallizable fragment (Fc) fusion protein of an engineered transmembrane activator and CAML interactor (TACI) domain which mediates more potent inhibitory activity than wild-type TACI-Fc or BAFF- or APRIL-specific antibodies and demonstrates superior pharmacokinetic and pharmacodynamic activity in multiple preclinical disease models. In this first-in-human study in healthy adults, povetacicept was well-tolerated as single ascending doses of up to 960 mg administered intravenously or subcutaneously. Dose-dependent pharmacokinetics were observed. Coverage of BAFF and APRIL was observed for 2–3 weeks and ≥4 weeks after doses of 80 mg and ≥240 mg, respectively. Maximal pharmacodynamic effects were observed at dose levels ≥80 mg for a single dose, associated with on-target reductions in antibody-secreting cells as well as in all circulating immunoglobulin isotypes, including the IgAN disease-related biomarker galactose-deficient-immunoglobulin A1 (Gd-IgA1), and were superior to results reported for wild-type TACI-Fc. These data strongly support further development of povetacicept for the treatment of B-cell-mediated automimmune diseases.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570287","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":"Correction to “implementing pain, agitation, delirium, and sleep deprivation protocol in critically ill patients: A pilot study on pharmacological interventions”","authors":"","doi":"10.1111/cts.70068","DOIUrl":"10.1111/cts.70068","url":null,"abstract":"<p>Luetrakool P, Taesotikul S, Susantitapong K, Suthisisang C, Morakul S, Sutherasan Y, Tangsujaritvijit V, Dilokpattanamongkol P. Implementing pain, agitation, delirium, and sleep deprivation protocol in critically ill patients: A pilot study on pharmacological interventions. <i>Clin Transl Sci</i>. 2024 Mar;17(3):e13739. doi: 10.1111/cts.13739. PMID: 38421247; PMCID: PMC10903435.</p><p>On page 8, under the section titled “FUNDING INFORMATION”, the sentence “The authors confirm that this research received no external funding. The study was conducted without financial support, and the authors have no financial interests or affiliations that could be perceived as a conflict of interest in connection with this work.” were incorrect. This should have read: “This research project is supported by Mahidol University. The authors have no financial interests or affiliations that could be perceived as a conflict of interest in connection with this work.”</p><p>We apologize for this error.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570300","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":"Implementing sensor-based digital health technologies in clinical trials: Key considerations from the eCOA Consortium","authors":"Elena S. Izmailova,&nbsp;Danielle Middleton,&nbsp;Reem Yunis,&nbsp;Julia Lakeland,&nbsp;Kristen Sowalsky,&nbsp;Julia Kling,&nbsp;Alison Ritchie,&nbsp;Christine C. Guo,&nbsp;Bill Byrom,&nbsp;Scottie Kern","doi":"10.1111/cts.70054","DOIUrl":"10.1111/cts.70054","url":null,"abstract":"<p>The increased use of sensor-based digital health technologies (DHTs) in clinical trials brought to light concerns about implementation practices that might introduce burden on trial participants, resulting in suboptimal compliance and become an additional complicating factor in clinical trial conduct. These concerns may contribute to the lower-than-anticipated uptake of DHT deployment and data use for regulatory decision-making, despite well-articulated benefits. The Electronic Clinical Outcome Assessment (eCOA) Consortium gathered collective experience on deploying sensor-based DHTs and supplemented this with relevant literature focusing on mechanisms that may enhance participant compliance. The process for DHT implementation starts with identifying a clinical concept of interest followed by a digital measure selection, defining active or passive data capture and their sources, the number of sensors with respective body location, plus the duration and frequency of use in the context of perceived participant burden. Roundtable discussions among patient groups, physicians, and technology providers prior to protocol development can be very impactful for optimizing trial design. While diversity and inclusion are essential for any clinical trial, patient populations should be considered carefully in the context of trial-specific aims, requirements, and anticipated patient burden. Minimizing site burden includes assessment of training, research engagement, and logistical burden which needs to be triaged differently for early and late-stage clinical trials. Additional considerations include sharing trial results with study participants and leveraging publicly available data for compliance modeling. To the best of our knowledge, this report provides holistic considerations for sensor-based DHT implementation that may optimize participant compliance.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570301","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":"Efficacy and safety of tofacitinib in rheumatoid arthritis: Nine years of real-world data.","authors":"Ali Ekin, Salim Misirci, Selin İldemir, Belkıs Nihan Coskun, Burcu Yagiz, Ediz Dalkilic, Yavuz Pehlivan","doi":"10.1111/cts.70084","DOIUrl":"10.1111/cts.70084","url":null,"abstract":"<p><p>Tofacitinib is a targeted JAK inhibitor used to treat rheumatoid arthritis. Despite some recent safety concerns, it is considered effective and safe with appropriate patient selection. Between May 2015 and May 2024, data were retrospectively analyzed from 112 patients with a diagnosis of RA in a tertiary care hospital who had received tofacitinib for at least 1 month, with or without prior biologic DMARDs. The mean disease duration was 12 years, and the median duration of tofacitinib use was 32.5 months. The p-value for all disease activity parameters evaluated for effectiveness between the 1st- and 3rd-month visits was <0.001, except CRP (p = 0.097). Adverse events occurred in 15 (13.4%) patients, with an incidence rate of 4.54 per 100 patient-years. Observed were one myocardial infarction (0.3/100 patient-years), two pulmonary embolisms (0.6/100 patient-years), three herpes zoster (HZ) (0.9/100 patient-years), and one basal cell carcinoma (BCC) (0.3/100 patient-years). Median drug-free survival was 68 (95% CI: 54.8-81.2) months. The drug was discontinued in 28 (25%) patients due to ineffectiveness and in 13 (11.6%) due to side effects. A significant difference in drug survival rates was observed between patients who had not previously used bDMARDs and those who had received at least one bDMARD before tofacitinib (p < 0.001). Drug survival was 46.35 months in the prior bDMARD group and 71.09 months in the bDMARD-naive group. This study found significant reductions in disease activity indices at 3 and 6 months after starting tofacitinib, with sustained effectiveness. Although adverse event rates were somewhat higher than reported in the literature, tofacitinib can be used effectively and safely in appropriate patient populations for RA treatment.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 11","pages":"e70084"},"PeriodicalIF":3.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649555","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}