Clinical Drug Investigation最新文献

{"title":"Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial","authors":"Yujing Du, Lixiu Yu, Bin Deng, Qinying Li, Junrui Hu, Linjie Li, Yusen Xu, Liangwei Song, Fang Xie, Yinghui Wang, Yuhao Chen, Chengxin Liu, Xuejia Zhai, Yongning Lu","doi":"10.1007/s40261-024-01359-x","DOIUrl":"https://doi.org/10.1007/s40261-024-01359-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating <i>Helicobacter pylori</i>. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14–20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21–27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (<i>C</i>_max,ss) and area under the plasma concentration–time curve over the dosing interval (AUC_τ) at steady state were 195.93% (175.52–218.71%) and 287.54% (263.28–314.04%) for tegoprazan and 423.23% (382.57–468.22%) and 385.61% (354.62–419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of <i>C</i>_max,ss and AUC_τ were 83.69% (77.44–90.45%) and 110.30% (102.74–118.41%) for clarithromycin, 126.25% (114.73–138.93%) and 146.94% (135.33–159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73–82.60%) and 94.34% (87.94–101.20%) for amoxicillin, and 158.43% (125.43–200.11%) and 183.63% (156.42–215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability.</p><h3 data-test=\"abstract-sub-heading\">Clinical Trials Registration</h3><p>CTR20230643.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":"93 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581427","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":"Impact of Viloxazine Extended-Release Capsules (Qelbree®) on Select Cytochrome P450 Enzyme Activity and Evaluation of CYP2D6 Genetic Polymorphisms on Viloxazine Pharmacokinetics","authors":"Zhao Wang, Tesfaye Liranso, Zulane Maldonado-Cruz, Alisa R. Kosheleff, Azmi Nasser","doi":"10.1007/s40261-024-01356-0","DOIUrl":"https://doi.org/10.1007/s40261-024-01356-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background and Objective</h3><p>Viloxazine extended-release (ER) [Qelbree^®] is a nonstimulant attention-deficit/hyperactivity disorder (ADHD) treatment. In vitro studies suggested potential for viloxazine to inhibit cytochrome 450 (CYP) enzymes 1A2, 2B6, 2D6 and 3A4. This clinical study therefore evaluated viloxazine ER effects on index substrates for CYP1A2, 2D6, and 3A4, and secondarily evaluated the impact of CYP2D6 polymorphisms on viloxazine pharmacokinetics.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Thirty-seven healthy subjects received a modified Cooperstown cocktail (MCC; caffeine 200 mg, dextromethorphan 30 mg, midazolam 0.025 mg/kg) on Day 1, viloxazine ER 900 mg/day on Days 3–5, and a combination of viloxazine ER 900 mg and MCC on Day 6. Viloxazine ER effects on MCC substrates were evaluated using analysis of variance. The impact of CYP2D6 genetic polymorphisms on steady-state viloxazine plasma concentrations was evaluated using Student’s <i>t</i> test assessing pharmacokinetic parameter differences between poor versus extensive metabolizers.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The least squares geometric mean ratio [GMR%] (90% CI) of MCC substrate + viloxazine ER/MCC substrate alone for caffeine maximum concentration (<i>C</i>_max), area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC_<i>t</i>), and area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC_∞) was 99.11 (95.84–102.49), 436.15 (398.87–476.92), and 583.35 (262.41–1296.80), respectively; 150.76 (126.03–180.35), 185.76 (155.01–222.61), and 189.71 (160.37–224.42) for dextromethorphan <i>C</i>_max, AUC_t, and AUC_∞, respectively; and 112.81 (104.71–121.54), 167.56 (153.05–183.45), and 168.91 (154.38–184.80) for midazolam <i>C</i>_max, AUC_<i>t</i>, and AUC_∞, respectively. At steady state, viloxazine least squares GMR (90% CI) for poor/extensive CYP2D6 metabolizers were <i>C</i>_max 120.70 (102.33–142.37) and area under the plasme concentration-time curve from time 0 to 24 hours (AUC_0–24 125.66 (105.36–149.87)).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Viloxazine ER is a strong CYP1A2 inhibitor and a weak CYP2D6 and CYP3A4 inhibitor. CYP2D6 polymorphisms did not meaningfully alter the viloxazine ER pharmacokinetic profile.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":"38 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581489","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":"An Open-Label Study to Assess Monthly Risperidone Injections (180 mg) Following Switch from Daily Oral Risperidone (6 mg) in Stable Schizophrenic Patients.","authors":"David P Walling, Sunita N Shinde, Janice M Pogoda, Jahnavi Kharidia, Celine M Laffont","doi":"10.1007/s40261-024-01347-1","DOIUrl":"10.1007/s40261-024-01347-1","url":null,"abstract":"<p><strong>Background and objective: </strong>Long-acting injectable antipsychotics have shown benefits over oral medications with reduced hospitalization rates and improved health-related quality of life. RBP-7000 (PERSERIS^®) is a monthly risperidone formulation (90 or 120 mg) for the treatment of schizophrenia administered by subcutaneous abdominal injection. The objective of this study was to assess a higher dose of 180 mg RBP-7000 and an alternate injection site.</p><p><strong>Methods: </strong>Following stabilization on 6 mg/day (3 mg twice daily) oral risperidone, clinically stable schizophrenic participants received 3 monthly doses of 180 mg RBP-7000 in the abdomen followed by a fourth monthly dose of 180 mg RBP-7000 in the upper arm (each dose administered as two 90-mg injections). The primary endpoint was the steady-state average plasma concentration (C_avg(ss)) of risperidone and total active moiety after oral and RBP-7000 administration. Secondary endpoints included measures of clinical efficacy (Positive and Negative Syndrome Scale, Clinical Global Impression Scale for Severity of Illness), safety, and local injection-site tolerability to assess the switch from oral risperidone and compare injection sites.</p><p><strong>Results: </strong>In all, 23 participants received at least one dose of RBP-7000, 16 received all four doses, and 15 completed the study. Monthly doses of 180 mg RBP-7000 provided similar C_avg(ss) of total active moiety compared with 6 mg/day oral risperidone. The pharmacokinetics of RBP-7000 were similar after injection in the abdomen versus upper arm. Clinical efficacy measures remained stable throughout the study. All RBP-7000 injections were well tolerated with no unexpected safety findings.</p><p><strong>Conclusions: </strong>The results support the use of 180 mg RBP-7000 in schizophrenic patients stable on 6 mg/day oral risperidone and a second injection site in the upper arm.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03978832.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"251-260"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139930364","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":"Experience of Tofacitinib Use in Pregnancy in Patients with Ulcerative Colitis.","authors":"María Chaparro, Daniel Ceballos, Raquel Vicente, Javier P Gisbert","doi":"10.1007/s40261-024-01353-3","DOIUrl":"10.1007/s40261-024-01353-3","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"285-288"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157731","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":"Effectiveness of Dose Increase in Upadacitinib from 15 mg to 30 mg for Patients with Moderate-to-Severe Atopic Dermatitis: A Real-World Clinical Practice in Japan.","authors":"Teppei Hagino, Risa Hamada, Mai Yoshida, Hidehisa Saeki, Eita Fujimoto, Naoko Kanda","doi":"10.1007/s40261-024-01352-4","DOIUrl":"10.1007/s40261-024-01352-4","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis is characterized by persistent eczema and pruritus. Janus kinase inhibitors, including upadacitinib, are effective treatments for moderate-to-severe atopic dermatitis. If patients do not respond well to a certain dose of a Janus kinase inhibitor, increasing the dose may improve their treatment responsiveness.</p><p><strong>Objectives: </strong>We assessed the outcomes of a dose increase in upadacitinib from 15 mg to 30 mg for Japanese patients with moderate-to-severe atopic dermatitis.</p><p><strong>Methods: </strong>In 23 patients who showed insufficient responses to upadacitinib 15-mg treatment, the dose of upadacitinib was increased to 30 mg. We evaluated total Eczema Area and Severity Index (EASI), EASI on the head and neck, trunk, upper, or lower limbs, EASI of erythema, edema/papulation, excoriation, or lichenification, and Peak Pruritus Numerical-Rating Scale at baseline (onset of upadactinib 15 mg), week 0 (time of increase), and weeks 4 and 12 after the increase.</p><p><strong>Results: </strong>Total EASI, EASI on each anatomical site, EASI of each clinical sign, and Peak Pruritus Numerical-Rating Scale were markedly reduced at weeks 4 or 12 compared with week 0. After the dose increase, the achievement rates of EASI 75 and EASI 90 significantly improved; EASI 75 4.3%, 68.2%, and 66.7%; EASI 90 0%, 18.2%, and 38.1% at weeks 0, 4, and 12, respectively.</p><p><strong>Conclusions: </strong>These results suggest that upadacitinib 30 mg can ameliorate rash and pruritus insufficiently improved by upadacitinib 15 mg, and that the dose increase to 30 mg may be considered as a treatment option for patients with atopic dermatitis with a limited response to upadacitinib 15 mg.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"261-269"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038885","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":"Real-World Effectiveness of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists (OW GLP-1RAs) in Comparison with Dipeptidyl Peptidase-4 Inhibitors (DPP-4is) for Glycemic Control and Weight Outcomes in Type 2 Diabetes Mellitus (RELATE).","authors":"Xi Tan, Victoria Divino, James Amamoo, Lin Xie, Katharine B Coyle, Cory L Gamble, Mico Guevarra, Yurek Paprocki, Aaron A King","doi":"10.1007/s40261-024-01354-2","DOIUrl":"10.1007/s40261-024-01354-2","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1RAs) has been established in several trials in people with type 2 diabetes mellitus (T2DM); however, real-world evidence on their effectiveness is limited. This study evaluated the effectiveness of OW GLP-1RA regarding glycemic and weight outcomes, and relative to DPP-4i in a comparator analysis.</p><p><strong>Methods: </strong>This observational cohort study evaluated glycated hemoglobin (HbA_1c) and weight outcomes in people with T2DM with two or more prescription claims for the same OW GLP-1RA using a pre-post study design (including for a semaglutide OW T2DM subgroup, hereafter referred to as semaglutide). Comparator analysis for the same outcome was performed for OW GLP-1RAs versus DPP-4i and semaglutide subgroup versus DPP-4i. A linked patient population from the IQVIA PharMetrics^® Plus database and the Ambulatory Electronic Medical Records (AEMR) database was analyzed using data from January 2017 to April 2022. HbA_1c and weight were assessed at baseline and at the end of the 12-month post-index period. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline patient characteristics in the comparator analysis.</p><p><strong>Results: </strong>In the pre-post analysis, a greater numerical reduction in HbA_1c and weight was observed for the semaglutide subgroup (N = 354) relative to the OW GLP-1RA cohort (N = 921). In the semaglutide subgroup, 52.5% and 34.2% of patients achieved HbA_1c of < 7.0% and ≥ 5% weight loss, respectively. For the comparator analysis, the OW GLP-1RAs (N = 651) were significantly more effective (p < 0.001) in reducing HbA_1c (- 1.5% vs. -  1.0%) and weight (- 3.2 kg vs. -  1.0 kg) than the DPP-4is (N = 431). Similarly, the semaglutide cohort (N = 251) also displayed more effectiveness (p < 0.001) in reducing HbA_1c (- 1.7% vs. -  0.9%) and weight (- 4.1 kg vs. -  1.3 kg) than the respective DPP-4i cohort (N = 417). Patients initiating OW GLP-1RAs, including the semaglutide cohort, were at least twice as likely to achieve HbA_1c and weight outcomes as well as composite outcomes compared with those initiating DPP-4is.</p><p><strong>Conclusion: </strong>The study reinforces that OW GLP-1RAs are more effective in glycemic control and weight reduction compared with DPP-4is in people with T2DM in the real-world setting. These findings align with the recommendation in the current guidelines for utilizing glucose-lowering treatment regimens that support weight-management goals in people with T2DM.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"271-284"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174015","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":"Should Glucokinase be Given a Chance in Diabetes Therapeutics? A Clinical-Pharmacological Review of Dorzagliatin and Lessons Learned So Far.","authors":"Upinder Kaur, Bhairav Kumar Pathak, Tharik Jalal Meerashahib, Dondapati Venkata Vamshi Krishna, Sankha Shubhra Chakrabarti","doi":"10.1007/s40261-024-01351-5","DOIUrl":"10.1007/s40261-024-01351-5","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Despite advances in the management of type 2 diabetes mellitus (T2DM), one-third of patients with diabetes do not achieve the desired glycemic goal. Considering this inadequacy, many agents that activate glucokinase have been investigated over the last two decades but were withdrawn before submission for marketing permission. Dorzagliatin is the first glucokinase activator that has been granted approval for T2DM, only in China. As overstimulation of glucokinase is linked with pathophysiological disturbances such as fatty liver and cardiovascular issues and a loss of therapeutic efficacy with time. This review aims to highlight the benefits of glucokinase activators vis-à-vis the risks associated with chronic enzymatic activation. We discuss the multisystem disturbances expected with chronic activation of the enzyme, the lessons learned with glucokinase activators of the past, the major efficacy and safety findings with dorzagliatin and its pharmacological properties, and the status of other glucokinase activators in the pipeline. The approval of dorzagliatin in China was based on the SEED and the DAWN trials, the major pivotal phase III trials that enrolled patients with T2DM with a mean glycosylated hemoglobin of 8.3-8.4%, and a mean age of 53-54.5 years from multiple sites in China. Patients with uncontrolled diabetes, cardiac diseases, organ dysfunction, and a history of severe hypoglycemia were excluded. Both trials had a randomized double-blind placebo-controlled phase of 24 weeks followed by an open-label phase of 28 weeks with dorzagliatin. Drug-naïve patients with T2DM with a disease duration of 11.7 months were enrolled in the SEED trial while the DAWN trial involved patients with T2DM with a mean duration of 71.5 months and receiving background metformin therapy. Compared with placebo, the decline in glycosylated hemoglobin at 24 weeks was more with dorzagliatin with an estimated treatment difference of - 0.57% in the SEED trial and - 0.66% in the DAWN trial. The desired glycosylated hemoglobin (&lt; 7%) was also attained at more than two times higher rates with dorzagliatin. The glycemic improvement was sustained in the SEED trial but decreased over 52 weeks in the DAWN trial. Hyperlipidemia was observed in 12-14% of patients taking dorzagliatin versus 9-11% of patients receiving a placebo. Additional adverse effects noticed over 52 weeks with dorzagliatin included an elevation in liver enzymes, hyperuricemia, hyperlacticacidemia, renal dysfunction, and cardiovascular disturbances. Considering the statistically significant improvement in glycosylated hemoglobin with dorzagliatin in patients with T2DM, the drug may be given a chance in treatment-naïve patients with a shorter disease history. However, with the waning therapeutic efficacy witnessed in patients with long-standing diabetes, which was also one of the potential concerns with previously tested molecules, extended studies involving patients with chronic and uncontrolled diab","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"223-250"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068208","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":"Tolvaptan Treatment and Long-Term Impact on Quality of Life in Autosomal Dominant Polycystic Kidney Disease Patients: A Pilot Study.","authors":"Gianni Carraro, Valentina Di Vico, Loris Martinetti, Elisabetta Bettin, Martina Cacciapuoti, Lucia Federica Stefanelli, Laura Gobbi, Federico Nalesso, Francesca Katiana Martino, Lorenzo A Calò","doi":"10.1007/s40261-024-01350-6","DOIUrl":"10.1007/s40261-024-01350-6","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"289-291"},"PeriodicalIF":3.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012347","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":"Cost-Effectiveness Analysis of Camrelizumab Plus Rivoceranib Versus Sorafenib as a First-Line Therapy for Unresectable Hepatocellular Carcinoma in the Chinese Health Care System.","authors":"Wenwang Lang, Lian Deng, Bei Huang, Dongmei Zhong, Gaofeng Zhang, Meijun Lu, Ming Ouyang","doi":"10.1007/s40261-024-01343-5","DOIUrl":"10.1007/s40261-024-01343-5","url":null,"abstract":"<p><strong>Background and objectives: </strong>Camrelizumab plus rivoceranib showed significant clinical benefits in progression-free survival and overall survival compared to sorafenib in patients with unresectable hepatocellular carcinoma (HCC). This study aimed to assess its cost effectiveness from the perspective of Chinese health care system.</p><p><strong>Methods: </strong>A Markov state-transition model was developed based on the Phase 3 randomized CARES-310 clinical trial data. Health state utility values were obtained from the CARES-310 clinical trial, and direct medical costs were derived from the relevant literature and local charges. The measured outcomes included quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER). Probabilistic and one-way sensitivity analyses were performed to assess the uncertainty of the model.</p><p><strong>Results: </strong>In the base-case analysis, the incremental effectiveness and cost of camrelizumab plus rivoceranib versus sorafenib were 0.41 QALYs and $13,684.84, respectively, resulting in an ICER of $33,619.98/QALY, lower than the willingness-to-pay threshold of China ($35,864.61/QALY). Subgroup analyses revealed that the ICERs of camrelizumab plus rivoceranib versus sorafenib were $35,920.01 and $29,717.98 in patients with ALBI grade 1 and grade 2, respectively. One-way sensitivity analyses indicated that the cost of camrelizumab, the proportion of patients receiving subsequent treatment in the camrelizumab plus rivoceranib group, and the cost of rivoceranib were the most significant factors in the base-case analysis. Probabilistic sensitivity analysis suggested that the probabilities of cost effectiveness of camrelizumab plus rivoceranib were 61.27%, 51.46%, and 82.78% for any grade, and ALBI grade 1 and grade 2, respectively.</p><p><strong>Conclusions: </strong>Camrelizumab plus rivoceranib was more cost effective than sorafenib as first-line therapy for unresectable HCC in the Chinese setting.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"149-162"},"PeriodicalIF":3.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650377","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":"Cost-Effectiveness Evaluation of Oral CGRP Antagonists, Atogepant and Rimegepant, for the Preventative Treatment of Episodic Migraine: Results from a US Societal Perspective Model.","authors":"Ryan Thaliffdeen, Anthony Yu, Karen Rascati","doi":"10.1007/s40261-024-01345-3","DOIUrl":"10.1007/s40261-024-01345-3","url":null,"abstract":"<p><strong>Background and objectives: </strong>Two oral calcitonin gene-related peptide (CGRP) antagonists, atogepant and rimegepant, were approved in 2021 for the preventive treatment of episodic migraine (EM), yet no formal cost-effectiveness analysis has been published. The objective of this study was to evaluate the cost-effectiveness of atogepant 60 mg and rimegepant 75 mg compared with placebo.</p><p><strong>Methods: </strong>A decision tree model was constructed over a 1-year time horizon from a US societal perspective. Patient cohorts were simulated using baseline and change from baseline monthly migraine days (MMDs) reported in the trials to incorporate responder rates and within patient response into the model. Due to heterogeneity between the trial populations, each medication was compared with its respective trial's placebo group. Direct healthcare resource costs, productivity costs, acute medication costs, and quality-of-life values were obtained from the literature.</p><p><strong>Results: </strong>The atogepant cohort experienced an incremental increase in healthcare plus productivity costs of $11,978 when compared with placebo, with a gain of 0.026 quality-adjusted life-years (QALYs). This yielded an incremental cost-effectiveness ratio (ICER) of more than $450,000/QALY. The rimegepant cohort experienced an incremental increase of $21,692 when compared with placebo, with a gain of 0.024 QALYs. This yields an ICER of more than $890,000/QALY when comparing rimegepant with placebo. Cost savings between atogepant and atogepant placebo were greatest with respect to acute medication costs at $735 of savings over 1 year, followed by savings of $135 for healthcare resource utilization and $34 for productivity costs. A similar relationship was seen between rimegepant and rimegepant placebo. One-way deterministic sensitivity analysis found that monthly acquisition costs of atogepant and rimegepant had the largest impact on the ICER, respectively.</p><p><strong>Conclusions: </strong>Atogepant and rimegepant were both unable to meet generally accepted cost-effectiveness thresholds < 150,0000/QALY. Additional studies are needed to better guide decision making regarding oral CGRPs' place in therapy.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"209-217"},"PeriodicalIF":3.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912189","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}