Pub Date : 2024-01-01Epub Date: 2023-12-02DOI: 10.1007/s40261-023-01327-x
Satomi Sakurai, Kazuhiro Matsui, Mamoru Narukawa
Background and objective: Ethnic and racial differences are key factors affecting the results of clinical studies. However, the influence of these factors on the efficacy and safety of medicinal products remains unclear. Race-dependent nature is considered to be one of the factors causing differences in clinical findings, and we investigated its influence on the safety evaluation of drugs.
Methods: We searched PubMed and a Japan drug approval list to find relevant studies, and extracted phase I studies conducted with Japanese and non-Japanese participants using the same protocol and at the same study site. Pooled estimates of odds ratios (ORs) for the incidence of major adverse events in Japanese and non-Japanese participants were calculated, using a DerSimonian-Laird method with a random-effects model.
Results: Odds ratios for some adverse events in the active drug arm were significantly lower in Japanese participants: headaches [OR 0.65 (95% confidence interval [CI] 0.52-0.82), p = 0.0003], neurological disorders NEC [OR 0.70 (95% CI 0.53-0.93), p = 0.0135] in a High-Level Group Term, nervous system disorders [OR 0.64 (95% CI 0.49-0.82), p = 0.0004], infections and infestations [OR 0.71 (95% CI 0.53-0.95), p = 0.0202], and musculoskeletal and connective tissue disorders [OR 0.66 (95% CI 0.48-0.91, p = 0.0107] in the System Organ Class.
Conclusions: Our research suggested that racial factors such as race-dependent nature influence a drug safety assessment. With knowledge of these differences, it is expected that Japan will actively conduct multi-regional clinical trials, in which more diverse populations are included.
背景与目的:民族和种族差异是影响临床研究结果的关键因素。然而，这些因素对药品疗效和安全性的影响尚不清楚。种族依赖性被认为是导致临床结果差异的因素之一，我们研究了种族依赖性对药物安全性评价的影响。方法:我们检索PubMed和一份日本药物批准清单以查找相关研究，并提取在同一研究地点、使用相同方案的日本和非日本参与者进行的I期研究。使用随机效应模型的dersimonan - laird方法，计算了日本和非日本参与者主要不良事件发生率的比值比(ORs)。结果:在日本参与者中，活性药物组中一些不良事件的优势比显著降低:高级组术语中的头痛[OR 0.65(95%可信区间[CI] 0.52-0.82)， p = 0.0003]、神经系统疾病NEC [OR 0.70 (95% CI 0.53-0.93)， p = 0.0135]、神经系统疾病[OR 0.64 (95% CI 0.49-0.82)， p = 0.0004]、感染和感染[OR 0.71 (95% CI 0.53-0.95)， p = 0.0202]、肌肉骨骼和结缔组织疾病[OR 0.66 (95% CI 0.48-0.91, p = 0.0107]。结论:本研究提示种族依赖性等种族因素影响药物安全性评价。了解了这些差异，预计日本将积极开展多区域临床试验，纳入更多不同人群。
{"title":"Comparison of the Incidence of Adverse Events Between Japanese and Non-Japanese Healthy Subjects in Phase I Studies: A Systematic Review and Meta-Analysis.","authors":"Satomi Sakurai, Kazuhiro Matsui, Mamoru Narukawa","doi":"10.1007/s40261-023-01327-x","DOIUrl":"10.1007/s40261-023-01327-x","url":null,"abstract":"<p><strong>Background and objective: </strong>Ethnic and racial differences are key factors affecting the results of clinical studies. However, the influence of these factors on the efficacy and safety of medicinal products remains unclear. Race-dependent nature is considered to be one of the factors causing differences in clinical findings, and we investigated its influence on the safety evaluation of drugs.</p><p><strong>Methods: </strong>We searched PubMed and a Japan drug approval list to find relevant studies, and extracted phase I studies conducted with Japanese and non-Japanese participants using the same protocol and at the same study site. Pooled estimates of odds ratios (ORs) for the incidence of major adverse events in Japanese and non-Japanese participants were calculated, using a DerSimonian-Laird method with a random-effects model.</p><p><strong>Results: </strong>Odds ratios for some adverse events in the active drug arm were significantly lower in Japanese participants: headaches [OR 0.65 (95% confidence interval [CI] 0.52-0.82), p = 0.0003], neurological disorders NEC [OR 0.70 (95% CI 0.53-0.93), p = 0.0135] in a High-Level Group Term, nervous system disorders [OR 0.64 (95% CI 0.49-0.82), p = 0.0004], infections and infestations [OR 0.71 (95% CI 0.53-0.95), p = 0.0202], and musculoskeletal and connective tissue disorders [OR 0.66 (95% CI 0.48-0.91, p = 0.0107] in the System Organ Class.</p><p><strong>Conclusions: </strong>Our research suggested that racial factors such as race-dependent nature influence a drug safety assessment. With knowledge of these differences, it is expected that Japan will actively conduct multi-regional clinical trials, in which more diverse populations are included.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"11-19"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138470037","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}
Pub Date : 2024-01-01Epub Date: 2023-12-19DOI: 10.1007/s40261-023-01335-x
Egídio Freitas, Maria João Paiva Lopes, Maria João Cruz, Diogo Sousa, Ana Clara Valente, Bruno Duarte, Laetitia Teixeira, Gilberto Rosas, Mónica Caetano, Alberto Mota, Paulo Filipe, Tiago Torres
{"title":"Real-World Effectiveness and Safety of Baricitinib in Patients with Atopic Dermatitis.","authors":"Egídio Freitas, Maria João Paiva Lopes, Maria João Cruz, Diogo Sousa, Ana Clara Valente, Bruno Duarte, Laetitia Teixeira, Gilberto Rosas, Mónica Caetano, Alberto Mota, Paulo Filipe, Tiago Torres","doi":"10.1007/s40261-023-01335-x","DOIUrl":"10.1007/s40261-023-01335-x","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"87-90"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138800796","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}
Pub Date : 2024-01-01Epub Date: 2023-11-28DOI: 10.1007/s40261-023-01322-2
Mona Darwish, Rene Nunez, James M Youakim, Philmore Robertson
<p><strong>Background and objective: </strong>Trofinetide is the first drug to be approved for the treatment of Rett syndrome, a neurodevelopmental disorder. The purpose of the study is to fully characterize the metabolic and excretion profiles of trofinetide in humans.</p><p><strong>Methods: </strong>This Phase 1, open-label, single-dose trial conducted in healthy male adults was designed to characterize the pharmacokinetics of trofinetide (absorption, metabolism, and excretion), mass balance of [<sup>14</sup>C]-trofinetide, and safety profile of trofinetide following administration of an oral 12-g dose administered as a mixture of trofinetide and [<sup>14</sup>C]-trofinetide. Blood, urine, and fecal samples were collected at prespecified timepoints. The pharmacokinetics of trofinetide were assessed in blood and urine samples using high-performance liquid chromatography (HPLC) with tandem mass spectrometric detection. Bioanalysis of radioactivity was conducted in blood, plasma, urine, and fecal samples using liquid scintillation counting. Metabolite profiling was conducted in blood, plasma, urine, and fecal samples using HPLC with liquid scintillation counting of chromatographic fractions. Safety and tolerability, including treatment-emergent adverse events (TEAEs), were assessed.</p><p><strong>Results: </strong>Blood concentration-time profiles of trofinetide and total radioactivity were almost superimposable up to ~12 h after dosing. Urine concentration-time profiles of trofinetide and total radioactivity were similar. Trofinetide was rapidly absorbed into the circulation with an initial rapid decline (half-life [t<sub>½</sub>] <sub>alpha</sub> ~2.6 h), followed by a relatively slow terminal elimination phase (t<sub>½ beta</sub> ~20 h). The blood-to-plasma total radioactivity ratios were 0.529-0.592, indicating a lack of affinity for the cellular portion of blood. Renal excretion accounted for 83.8% of the administered radiochemical dose; 15.1% was recovered in feces. Urine and fecal recovery of radioactivity accounted for 99% of the administered dose at 168 h after dosing. Parent [<sup>14</sup>C]-trofinetide was the major radiolabeled entity in blood and plasma (88.4% and 93.1% in area under the concentration-time curves from 0 to 12 h [AUC<sub>0-12</sub>] in pooled blood and plasma samples, respectively) and the major entity excreted in urine (91.5% in 0-48-h pooled urine samples) and in feces (52.7% in 0-192-h pooled fecal samples). Only small levels of metabolites were present. In blood and plasma, only two minor metabolites were identified (each metabolite ≤ 2.24% of the AUC<sub>0-12</sub> pool). These two metabolites were also observed in urine and fecal samples (≤ 2.41% of dose). In feces, one additional metabolite (0.84% of dose) was identified. Two mild TEAEs were reported in two participants and were not considered related to trofinetide. There were no clinically meaningful changes in individual laboratory parameters, vital signs, ph
{"title":"Characterization of the Pharmacokinetics and Mass Balance of a Single Oral Dose of Trofinetide in Healthy Male Subjects.","authors":"Mona Darwish, Rene Nunez, James M Youakim, Philmore Robertson","doi":"10.1007/s40261-023-01322-2","DOIUrl":"10.1007/s40261-023-01322-2","url":null,"abstract":"<p><strong>Background and objective: </strong>Trofinetide is the first drug to be approved for the treatment of Rett syndrome, a neurodevelopmental disorder. The purpose of the study is to fully characterize the metabolic and excretion profiles of trofinetide in humans.</p><p><strong>Methods: </strong>This Phase 1, open-label, single-dose trial conducted in healthy male adults was designed to characterize the pharmacokinetics of trofinetide (absorption, metabolism, and excretion), mass balance of [<sup>14</sup>C]-trofinetide, and safety profile of trofinetide following administration of an oral 12-g dose administered as a mixture of trofinetide and [<sup>14</sup>C]-trofinetide. Blood, urine, and fecal samples were collected at prespecified timepoints. The pharmacokinetics of trofinetide were assessed in blood and urine samples using high-performance liquid chromatography (HPLC) with tandem mass spectrometric detection. Bioanalysis of radioactivity was conducted in blood, plasma, urine, and fecal samples using liquid scintillation counting. Metabolite profiling was conducted in blood, plasma, urine, and fecal samples using HPLC with liquid scintillation counting of chromatographic fractions. Safety and tolerability, including treatment-emergent adverse events (TEAEs), were assessed.</p><p><strong>Results: </strong>Blood concentration-time profiles of trofinetide and total radioactivity were almost superimposable up to ~12 h after dosing. Urine concentration-time profiles of trofinetide and total radioactivity were similar. Trofinetide was rapidly absorbed into the circulation with an initial rapid decline (half-life [t<sub>½</sub>] <sub>alpha</sub> ~2.6 h), followed by a relatively slow terminal elimination phase (t<sub>½ beta</sub> ~20 h). The blood-to-plasma total radioactivity ratios were 0.529-0.592, indicating a lack of affinity for the cellular portion of blood. Renal excretion accounted for 83.8% of the administered radiochemical dose; 15.1% was recovered in feces. Urine and fecal recovery of radioactivity accounted for 99% of the administered dose at 168 h after dosing. Parent [<sup>14</sup>C]-trofinetide was the major radiolabeled entity in blood and plasma (88.4% and 93.1% in area under the concentration-time curves from 0 to 12 h [AUC<sub>0-12</sub>] in pooled blood and plasma samples, respectively) and the major entity excreted in urine (91.5% in 0-48-h pooled urine samples) and in feces (52.7% in 0-192-h pooled fecal samples). Only small levels of metabolites were present. In blood and plasma, only two minor metabolites were identified (each metabolite ≤ 2.24% of the AUC<sub>0-12</sub> pool). These two metabolites were also observed in urine and fecal samples (≤ 2.41% of dose). In feces, one additional metabolite (0.84% of dose) was identified. Two mild TEAEs were reported in two participants and were not considered related to trofinetide. There were no clinically meaningful changes in individual laboratory parameters, vital signs, ph","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"21-33"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10769996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451024","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}
Pub Date : 2024-01-01Epub Date: 2023-11-30DOI: 10.1007/s40261-023-01323-1
Valérie Horvais, Philippe Beurrier, Vincent Cussac, Brigitte Pan-Petesch, Solène Schirr-Bonnans, Johann Rose, Sophie Bayart, Catherine Ternisien, Marc Fouassier, Marianne Sigaud, Antoine Babuty, Nicolas Drillaud, Benoît Guillet, Marc Trossaërt
Background: Von Willebrand disease (VWD) is the most common inherited bleeding disorder. However, studies of hospitalisation patterns with replacement treatment are scarce.
Objectives: The aim of this study was to investigate the current therapeutic management of VWD and determine the key drivers of coagulation factor uses in patients during hospitalisation.
Methods: Hopscotch-WILL was a multi-centric retrospective study conducted over a 48-month period in any patients with VWD. The data were collected from the BERHLINGO Research Database and the French Hospital database.
Results: A total of 988 patients were included; 153 patients (15%) were hospitalised during 293 stays requiring treatment with von Willebrand factor (VWF) concentrates-pure or in association with Factor VIII (FVIII). Their median basal concentrations of VWF and FVIII were significantly lower than in untreated patients: VWF antigen < 30 IU/dL, VWF activity < 20 IU/dL and FVIII:C < 40 IU/dL. The median (interquartile range) concentrate consumption was similar between highly purified VWF or VWF combined with FVIII (72 [110] vs 57 [89] IU/kg/stay, p = 0.154). The use of VWF was highly heterogeneous by VWD type; type 3 had a particularly high impact on VWF consumption in non-surgical situations. The main admissions were for ear/nose/throat, hepato-gastroenterology, and trauma/orthopaedic conditions, besides gynaecological-obstetric causes in women.
Conclusions: The use of VWF concentrates is mostly influenced by low basal levels of VWF and FVIII, but also by VWD type or the cause for hospitalisation. These results could inform future studies of newly released recombinant VWF.
{"title":"Key Drivers of Coagulation Factor Use in Von Willebrand Disease During Hospitalization: An Overview of the French BERHLINGO Cohort.","authors":"Valérie Horvais, Philippe Beurrier, Vincent Cussac, Brigitte Pan-Petesch, Solène Schirr-Bonnans, Johann Rose, Sophie Bayart, Catherine Ternisien, Marc Fouassier, Marianne Sigaud, Antoine Babuty, Nicolas Drillaud, Benoît Guillet, Marc Trossaërt","doi":"10.1007/s40261-023-01323-1","DOIUrl":"10.1007/s40261-023-01323-1","url":null,"abstract":"<p><strong>Background: </strong>Von Willebrand disease (VWD) is the most common inherited bleeding disorder. However, studies of hospitalisation patterns with replacement treatment are scarce.</p><p><strong>Objectives: </strong>The aim of this study was to investigate the current therapeutic management of VWD and determine the key drivers of coagulation factor uses in patients during hospitalisation.</p><p><strong>Methods: </strong>Hopscotch-WILL was a multi-centric retrospective study conducted over a 48-month period in any patients with VWD. The data were collected from the BERHLINGO Research Database and the French Hospital database.</p><p><strong>Results: </strong>A total of 988 patients were included; 153 patients (15%) were hospitalised during 293 stays requiring treatment with von Willebrand factor (VWF) concentrates-pure or in association with Factor VIII (FVIII). Their median basal concentrations of VWF and FVIII were significantly lower than in untreated patients: VWF antigen < 30 IU/dL, VWF activity < 20 IU/dL and FVIII:C < 40 IU/dL. The median (interquartile range) concentrate consumption was similar between highly purified VWF or VWF combined with FVIII (72 [110] vs 57 [89] IU/kg/stay, p = 0.154). The use of VWF was highly heterogeneous by VWD type; type 3 had a particularly high impact on VWF consumption in non-surgical situations. The main admissions were for ear/nose/throat, hepato-gastroenterology, and trauma/orthopaedic conditions, besides gynaecological-obstetric causes in women.</p><p><strong>Conclusions: </strong>The use of VWF concentrates is mostly influenced by low basal levels of VWF and FVIII, but also by VWD type or the cause for hospitalisation. These results could inform future studies of newly released recombinant VWF.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"35-49"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458317","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}
Pub Date : 2023-12-19DOI: 10.1007/s40261-023-01334-y
Linlin Hu, Qiuyue Sun, Lu Tang, Mingmin Cai, Wei Qian, Ting Dou, Huiping Wang, Yong Wu, Yongqiang Liu
Background and Objective
VC004 is a novel next-generation tropomyosin receptor kinase (TRK) inhibitor that is approved for the treatment of advanced or metastatic NTRK fusion-positive solid tumors and abrogated the drug resistance of the first-generation TRK inhibitors. The objective of the present study was to evaluate the effect of food on the pharmacokinetics and safety of VC004.
Methods
The study was a randomized, open-label, two-period crossover, single-dose, phase I clinical trial. A total of 16 healthy subjects participated the trial. Subjects fasted for 10 h before drug administration in both fasting and fed states. Subjects received VC004 50 mg orally in the fasting state and after a high caloric food in the fed state. Blood samples at the designated time points were collected to determine the plasma concentration of VC004. Safety evaluation in both the fasted and fed periods were assessed via vital sign monitoring and clinical laboratory tests.
Results
The maximum plasma concentration (Cmax) of VC004 in fed group decreased by 32.8%, corresponding with the slower absorption rate (time to Cmax (Tmax) delayed by almost 3 h) compared with the fasting group. Ratios of geometric means (GMRs) and 90% confidence intervals (90% CIs) of Cmax, the area under the curve of plasma concentration-time from zero to the last measurable concentration (AUC0–t), and AUC from zero to infinity (AUC0–∞) for VC004 between the two states were 67.18 (58.16–77.60), 103.59 (95.04–112.92) and 103.55 (95.63–112.11), respectively. No serious adverse events (AEs) occurred; only three grade 1 or grade 2 adverse events occurred in the fasted group, who recovered by the end of the study.
Conclusions
The intake of high calorie food decreased the absorption rate and increased the Tmax of VC004, while the AUC values were similar in both groups. No serious adverse event was reported. In conclusion, food does not alter the pharmacokinetics and safety profile of VC004 in a clinically meaningful manner.
{"title":"Food Effect on the Pharmacokinetics of VC004, a Tropomyosin Receptor Kinase Inhibitor: A Randomized Crossover Trial in Healthy Chinese Subjects","authors":"Linlin Hu, Qiuyue Sun, Lu Tang, Mingmin Cai, Wei Qian, Ting Dou, Huiping Wang, Yong Wu, Yongqiang Liu","doi":"10.1007/s40261-023-01334-y","DOIUrl":"https://doi.org/10.1007/s40261-023-01334-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background and Objective</h3><p>VC004 is a novel next-generation tropomyosin receptor kinase (TRK) inhibitor that is approved for the treatment of advanced or metastatic NTRK fusion-positive solid tumors and abrogated the drug resistance of the first-generation TRK inhibitors. The objective of the present study was to evaluate the effect of food on the pharmacokinetics and safety of VC004.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The study was a randomized, open-label, two-period crossover, single-dose, phase I clinical trial. A total of 16 healthy subjects participated the trial. Subjects fasted for 10 h before drug administration in both fasting and fed states. Subjects received VC004 50 mg orally in the fasting state and after a high caloric food in the fed state. Blood samples at the designated time points were collected to determine the plasma concentration of VC004. Safety evaluation in both the fasted and fed periods were assessed via vital sign monitoring and clinical laboratory tests.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The maximum plasma concentration (<i>C</i><sub>max</sub>) of VC004 in fed group decreased by 32.8%, corresponding with the slower absorption rate (time to <i>C</i><sub>max</sub> (<i>T</i><sub>max</sub>) delayed by almost 3 h) compared with the fasting group. Ratios of geometric means (GMRs) and 90% confidence intervals (90% CIs) of <i>C</i><sub>max</sub>, the area under the curve of plasma concentration-time from zero to the last measurable concentration (<i>AUC</i><sub>0–<i>t</i></sub>), and <i>AUC</i> from zero to infinity (<i>AUC</i><sub>0–<i>∞</i></sub>) for VC004 between the two states were 67.18 (58.16–77.60), 103.59 (95.04–112.92) and 103.55 (95.63–112.11), respectively. No serious adverse events (AEs) occurred; only three grade 1 or grade 2 adverse events occurred in the fasted group, who recovered by the end of the study.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The intake of high calorie food decreased the absorption rate and increased the<i> T</i><sub>max</sub> of VC004, while the AUC values were similar in both groups. No serious adverse event was reported. In conclusion, food does not alter the pharmacokinetics and safety profile of VC004 in a clinically meaningful manner.</p><h3 data-test=\"abstract-sub-heading\">Trial Registration</h3><p>ClinicalTrials.gov ID: NCT055528120.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":"234 2 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138743171","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}
Pub Date : 2023-12-17DOI: 10.1007/s40261-023-01336-w
Abstract
Background and Objectives
Upadacitinib is an oral selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients (ge) 12 years of age. In real life, upadacitinib currently represents a valid therapeutic option for patients failing available systemic therapies, in particular patients who discontinued dupilumab because of lack of efficacy or occurrence of adverse events. The objectives of the present study were to compare the effectiveness and safety of upadacitinib in patients affected by AD who had previously failed dupilumab therapy versus biologic naïve patients.
Methods
A retrospective, multi-centre, observational, real-life study was conducted in four Italian dermatological referral centres (Milan, Perugia, Naples and Vicenza). Baseline characteristics included age, sex, AD history and severity, prior treatments, comorbidities and concomitant therapies. AD severity was assessed at baseline and at week 4 (W4), W16, W24 and W52, using Eczema Area Severity Index (EASI), Dermatology Life Quality Index (DLQI) and Pruritus Numerical Rating Scale (P-NRS) scores. Full blood count, hepatic and renal function, lipid panel, and muscle enzymes [lactate dehydrogenase (LDH) and creatine phosphokinase (CPK)] were assessed at baseline and at each follow-up visit.
Results
A total of 113 patients (72 males, 63.7%; mean age: 37.22 ± 16.8 years) were included in the analysis, all patients were in treatment and underwent follow-up period until W16, whilst 91 (80.5%) and 75 (66.4%) patients were in treatment and in follow-up period until W24 and W52, respectively.
Mean EASI score significantly changed from 24.30 ± 10.27 to 1.28 ± 4.34, 0.74 ± 2.31 and 0.25 ± 1.34 at W16, W24 and W52, respectively (p < 0.0001). Specifically, at W16 the percentage of patients achieving EASI-75, EASI-90 and EASI-100 was 85.21, 76.35 and 66.11%, respectively. At W24, EASI-75, EASI-90 and EASI-100 were reached by 88.54, 85.42, and 78.37% of patients, respectively. Finally, 90.1% of patients achieved EASI-75, 88.3% achieved EASI-90 and 83.0% achieved EASI-100 at W52.
Conclusions
This study confirmed the clinical effectiveness of upadacitinib treatment in adult patients in a real-world setting with moderate-to-severe AD who had discontinued dupilumab due to poor effectiveness or adverse events and who were biologic naïve; therefore, previous treatments do not seem to affect the response to upadacitinib treatment.
{"title":"Comparison of Long-Term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis Between Dupilumab-Exposed and Dupilumab-Naïve Patients","authors":"","doi":"10.1007/s40261-023-01336-w","DOIUrl":"https://doi.org/10.1007/s40261-023-01336-w","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Background and Objectives</h3> <p>Upadacitinib is an oral selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients <span> <span>(ge)</span> </span> 12 years of age. In real life, upadacitinib currently represents a valid therapeutic option for patients failing available systemic therapies, in particular patients who discontinued dupilumab because of lack of efficacy or occurrence of adverse events. The objectives of the present study were to compare the effectiveness and safety of upadacitinib in patients affected by AD who had previously failed dupilumab therapy versus biologic naïve patients.</p> </span> <span> <h3>Methods</h3> <p>A retrospective, multi-centre, observational, real-life study was conducted in four Italian dermatological referral centres (Milan, Perugia, Naples and Vicenza). Baseline characteristics included age, sex, AD history and severity, prior treatments, comorbidities and concomitant therapies. AD severity was assessed at baseline and at week 4 (W4), W16, W24 and W52, using Eczema Area Severity Index (EASI), Dermatology Life Quality Index (DLQI) and Pruritus Numerical Rating Scale (P-NRS) scores. Full blood count, hepatic and renal function, lipid panel, and muscle enzymes [lactate dehydrogenase (LDH) and creatine phosphokinase (CPK)] were assessed at baseline and at each follow-up visit.</p> </span> <span> <h3>Results</h3> <p>A total of 113 patients (72 males, 63.7%; mean age: 37.22 ± 16.8 years) were included in the analysis, all patients were in treatment and underwent follow-up period until W16, whilst 91 (80.5%) and 75 (66.4%) patients were in treatment and in follow-up period until W24 and W52, respectively.</p> <p>Mean EASI score significantly changed from 24.30 ± 10.27 to 1.28 ± 4.34, 0.74 ± 2.31 and 0.25 ± 1.34 at W16, W24 and W52, respectively (<em>p</em> < 0.0001). Specifically, at W16 the percentage of patients achieving EASI-75, EASI-90 and EASI-100 was 85.21, 76.35 and 66.11%, respectively. At W24, EASI-75, EASI-90 and EASI-100 were reached by 88.54, 85.42, and 78.37% of patients, respectively. Finally, 90.1% of patients achieved EASI-75, 88.3% achieved EASI-90 and 83.0% achieved EASI-100 at W52.</p> </span> <span> <h3>Conclusions</h3> <p>This study confirmed the clinical effectiveness of upadacitinib treatment in adult patients in a real-world setting with moderate-to-severe AD who had discontinued dupilumab due to poor effectiveness or adverse events and who were biologic naïve; therefore, previous treatments do not seem to affect the response to upadacitinib treatment.</p> </span>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":"19 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138688657","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}
Pub Date : 2023-12-16DOI: 10.1007/s40261-023-01333-z
Abstract
Background and Objective
Ankylosing spondylitis is a chronic, progressive, inflammatory, multidimensional, musculoskeletal disease primarily involving the axial skeleton. In addition, ankylosing spondylitis is associated with increased morbidity and mortality, significantly affecting productivity and overall quality of life. The aim of the present study was to evaluate the cost effectiveness of tofacitinib compared to currently marketed biologic treatment in patients with active ankylosing spondylitis who have responded inadequately to conventional therapy (biologic-naïve population) or previous biologic therapy (biologic-experienced population) in Greece.
Methods
A published model comprising a decision tree and a three-state Markov model was adapted from a public payer perspective over a lifetime horizon. Adalimumab and secukinumab, having the highest market shares among biologics for the treatment of ankylosing spondylitis in Greece (standard practice), were selected as comparators in the analysis. Clinical parameters captured treatment response defined per Assessment of Spondyloarthritis International Society 20 response, short-term and long-term changes in Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index scores, long-term biologic treatment discontinuation, and adverse events. Efficacy, safety data, and utility values were elicited from the published literature. Direct costs pertaining to drug acquisition, monitoring, adverse events, and disease management costs were considered in the analysis (€2022). Model outcomes were patients’ quality-adjusted life-years, total costs, and incremental cost-effectiveness ratios. All future outcomes were discounted at 3.5% per annum. A probabilistic sensitivity analysis was conducted to account for model uncertainty.
Results
In a biologic-naïve population, compared with adalimumab, tofacitinib produced an estimated 0.06 additional quality-adjusted life-years [QALYs] (10.67 vs 10.73), at additional costs of €2403 (€147,096 vs €149,500) resulting in an incremental cost-effectiveness ratio of €41,378 per QALY gained. In a biologic-experienced population, the total cost per patient for tofacitinib and secukinumab was estimated to be €151,371 and €145,757, respectively. In terms of health outcomes, tofacitinib was associated with a 0.13 increment in QALYs compared with secukinumab resulting in an incremental cost-effectiveness ratio of €42,784 per QALY gained. The probabilistic sensitivity analysis confirmed the deterministic results for both populations.
Conclusions
Tofacitinib was estimated to be a cost-effective option for the treatment of active ankylosing spondylitis in Greece for both biologic-naive and biologic-experienced patients.
摘要 背景和目的 强直性脊柱炎是一种慢性、进行性、炎症性、多发性肌肉骨骼疾病，主要累及轴向骨骼。此外，强直性脊柱炎还与发病率和死亡率的增加有关，严重影响工作效率和整体生活质量。本研究的目的是评估托法替尼与目前市场上销售的生物制剂治疗相比，在希腊对常规治疗（生物制剂无效人群）或既往生物制剂治疗（有生物制剂治疗经验人群）反应不佳的活动性强直性脊柱炎患者中的成本效益。 方法 从公共支付者的角度出发，对已发表的包含决策树和三态马尔可夫模型的终身范围模型进行了调整。在希腊治疗强直性脊柱炎的生物制剂中，阿达木单抗和secukinumab的市场份额最高（标准疗法），因此被选为分析中的比较药。临床参数包括按脊柱关节炎国际协会 20 项反应评估定义的治疗反应、巴斯强直性脊柱炎疾病活动指数和巴斯强直性脊柱炎功能指数评分的短期和长期变化、长期生物制剂治疗停药情况以及不良事件。疗效、安全性数据和效用值均来自已发表的文献。分析中考虑了与药物购买、监测、不良事件和疾病管理成本相关的直接成本（2022 欧元）。模型结果为患者的质量调整生命年、总成本和增量成本效益比。所有未来结果的贴现率为每年 3.5%。为考虑模型的不确定性，进行了概率敏感性分析。 结果 在生物制剂无效人群中，与阿达木单抗相比，托法替尼估计可增加0.06个质量调整生命年（10.67 vs 10.73），额外成本为2403欧元（147096欧元 vs 149500欧元），因此每获得一个质量调整生命年的增量成本效益比为41378欧元。在有生物治疗经验的人群中，托法替尼和赛库单抗的每位患者总成本估计分别为151,371欧元和145,757欧元。在健康结果方面，与secukinumab相比，托法替尼的QALYs增加了0.13，因此每QALY获得的增量成本效益比为42,784欧元。概率敏感性分析证实了两种人群的确定性结果。 结论 据估计，在希腊，对于无生物制剂治疗经验和有生物制剂治疗经验的患者而言，托法替尼是治疗活动性强直性脊柱炎的一种具有成本效益的选择。
{"title":"Cost Effectiveness of Tofacitinib for the Treatment of Active Ankylosing Spondylitis in Greece","authors":"","doi":"10.1007/s40261-023-01333-z","DOIUrl":"https://doi.org/10.1007/s40261-023-01333-z","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Background and Objective</h3> <p>Ankylosing spondylitis is a chronic, progressive, inflammatory, multidimensional, musculoskeletal disease primarily involving the axial skeleton. In addition, ankylosing spondylitis is associated with increased morbidity and mortality, significantly affecting productivity and overall quality of life. The aim of the present study was to evaluate the cost effectiveness of tofacitinib compared to currently marketed biologic treatment in patients with active ankylosing spondylitis who have responded inadequately to conventional therapy (biologic-naïve population) or previous biologic therapy (biologic-experienced population) in Greece.</p> </span> <span> <h3>Methods</h3> <p>A published model comprising a decision tree and a three-state Markov model was adapted from a public payer perspective over a lifetime horizon. Adalimumab and secukinumab, having the highest market shares among biologics for the treatment of ankylosing spondylitis in Greece (standard practice), were selected as comparators in the analysis. Clinical parameters captured treatment response defined per Assessment of Spondyloarthritis International Society 20 response, short-term and long-term changes in Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index scores, long-term biologic treatment discontinuation, and adverse events. Efficacy, safety data, and utility values were elicited from the published literature. Direct costs pertaining to drug acquisition, monitoring, adverse events, and disease management costs were considered in the analysis (€2022). Model outcomes were patients’ quality-adjusted life-years, total costs, and incremental cost-effectiveness ratios. All future outcomes were discounted at 3.5% per annum. A probabilistic sensitivity analysis was conducted to account for model uncertainty.</p> </span> <span> <h3>Results</h3> <p>In a biologic-naïve population, compared with adalimumab, tofacitinib produced an estimated 0.06 additional quality-adjusted life-years [QALYs] (10.67 vs 10.73), at additional costs of €2403 (€147,096 vs €149,500) resulting in an incremental cost-effectiveness ratio of €41,378 per QALY gained. In a biologic-experienced population, the total cost per patient for tofacitinib and secukinumab was estimated to be €151,371 and €145,757, respectively. In terms of health outcomes, tofacitinib was associated with a 0.13 increment in QALYs compared with secukinumab resulting in an incremental cost-effectiveness ratio of €42,784 per QALY gained. The probabilistic sensitivity analysis confirmed the deterministic results for both populations.</p> </span> <span> <h3>Conclusions</h3> <p>Tofacitinib was estimated to be a cost-effective option for the treatment of active ankylosing spondylitis in Greece for both biologic-naive and biologic-experienced patients.</p> </span>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":"24 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138688648","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}
The approval of lecanemab by the US Food and Drug Administration has been touted as a defining moment in the treatment of Alzheimer’s disease. Lecanemab, an anti-amyloid beta monoclonal antibody, is the first Alzheimer’s disease drug targeting amyloid beta that has shown statistically significant cognitive benefits in phase III trials. However, there have been many questions raised over the clinical relevance of the otherwise minimal cognitive improvements. Furthermore, its rapid approval has been mired in controversy, in addition to the reports of adverse events such as amyloid-related imaging abnormalities and several deaths of participants in the lecanemab trials. Here, we analyze the evidence supporting lecanemab as an amyloid beta therapy and also discuss the concerns raised about its efficacy and safety.
{"title":"Lecanemab: More Questions Than Answers!","authors":"Upinder Kaur, Jaideep Reddy, Ashutosh Tiwari, Sasanka Chakrabarti, Sankha Shubhra Chakrabarti","doi":"10.1007/s40261-023-01331-1","DOIUrl":"https://doi.org/10.1007/s40261-023-01331-1","url":null,"abstract":"<p>The approval of lecanemab by the US Food and Drug Administration has been touted as a defining moment in the treatment of Alzheimer’s disease. Lecanemab, an anti-amyloid beta monoclonal antibody, is the first Alzheimer’s disease drug targeting amyloid beta that has shown statistically significant cognitive benefits in phase III trials. However, there have been many questions raised over the clinical relevance of the otherwise minimal cognitive improvements. Furthermore, its rapid approval has been mired in controversy, in addition to the reports of adverse events such as amyloid-related imaging abnormalities and several deaths of participants in the lecanemab trials. Here, we analyze the evidence supporting lecanemab as an amyloid beta therapy and also discuss the concerns raised about its efficacy and safety.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":"36 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138631178","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}
Pub Date : 2023-12-13DOI: 10.1007/s40261-023-01332-0
Vazula Zulfra Bekkers, Claire Van Eijsden, Qi Yin, Albert Wolkerstorfer, Errol Prospero Prens, Martijn Bastiaan Adriaan van Doorn
Background
Keloids and hypertrophic scars can cause severe pain, pruritus, and psychological distress. Conventional intralesional corticosteroid treatment with needle injections remains challenging, especially in children with needle phobia.
Objective
We aimed to evaluate the effectiveness, tolerability, and patient satisfaction of intralesional treatment with triamcinolone acetonide using a needle-free electronic pneumatic jet injector in children with keloids and hypertrophic scars.
Methods
A retrospective study was performed in children with keloids and hypertrophic scars who received intralesional triamcinolone acetonide treatments using an electronic pneumatic jet injector. Effectiveness was evaluated using the Patient and Observer Scar Assessment Scale and Global Aesthetic Improvement Score at follow-up versus baseline. Tolerability was assessed with reported adverse effects and injection-related pain using a visual analog scale. Satisfaction questionnaires were used to evaluate treatment-related patient satisfaction.
Results
Six female patients and five male patients aged 5–17 years, with a total of >118 keloids or hypertrophic scars were included. Electronic pneumatic jet injector treatment led to a significant reduction in the total Patient and Observer Scar Assessment Scale observer and patient scores compared with baseline, with a median reduction of 28.9% and 23.8%, respectively (p = 0.005; p = 0.009). Median visual analog scale pain scores for electronic pneumatic jet injector treatment were significantly lower compared with needle injections, 3.0 versus 7.0, respectively (p = 0.027). No severe adverse effects were reported. Overall, 6 patients were ‘satisfied’ and five patients were ‘very satisfied’ with the treatment.
Conclusions
Electronic pneumatic jet injector-assisted intralesional triamcinolone acetonide is an effective and well-tolerated treatment for keloids and hypertrophic scars in children. It should be considered as an alternative non-traumatic delivery method, especially in children with needle phobia or severe pain during previous needle injections.
{"title":"Needle-Free Jet Injector-Assisted Triamcinolone Treatment of Keloids and Hypertrophic Scars is Effective and Well Tolerated in Children","authors":"Vazula Zulfra Bekkers, Claire Van Eijsden, Qi Yin, Albert Wolkerstorfer, Errol Prospero Prens, Martijn Bastiaan Adriaan van Doorn","doi":"10.1007/s40261-023-01332-0","DOIUrl":"https://doi.org/10.1007/s40261-023-01332-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Keloids and hypertrophic scars can cause severe pain, pruritus, and psychological distress. Conventional intralesional corticosteroid treatment with needle injections remains challenging, especially in children with needle phobia.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>We aimed to evaluate the effectiveness, tolerability, and patient satisfaction of intralesional treatment with triamcinolone acetonide using a needle-free electronic pneumatic jet injector in children with keloids and hypertrophic scars.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A retrospective study was performed in children with keloids and hypertrophic scars who received intralesional triamcinolone acetonide treatments using an electronic pneumatic jet injector. Effectiveness was evaluated using the Patient and Observer Scar Assessment Scale and Global Aesthetic Improvement Score at follow-up versus baseline. Tolerability was assessed with reported adverse effects and injection-related pain using a visual analog scale. Satisfaction questionnaires were used to evaluate treatment-related patient satisfaction.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Six female patients and five male patients aged 5–17 years, with a total of >118 keloids or hypertrophic scars were included. Electronic pneumatic jet injector treatment led to a significant reduction in the total Patient and Observer Scar Assessment Scale observer and patient scores compared with baseline, with a median reduction of 28.9% and 23.8%, respectively (<i>p</i> = 0.005; <i>p</i> = 0.009). Median visual analog scale pain scores for electronic pneumatic jet injector treatment were significantly lower compared with needle injections, 3.0 versus 7.0, respectively (<i>p</i> = 0.027). No severe adverse effects were reported. Overall, 6 patients were ‘satisfied’ and five patients were ‘very satisfied’ with the treatment.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Electronic pneumatic jet injector-assisted intralesional triamcinolone acetonide is an effective and well-tolerated treatment for keloids and hypertrophic scars in children. It should be considered as an alternative non-traumatic delivery method, especially in children with needle phobia or severe pain during previous needle injections.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":"4 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138631179","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}
Pub Date : 2023-12-01Epub Date: 2023-11-08DOI: 10.1007/s40261-023-01319-x
Xiaojuan Jiao, Ping Peng, Qin Zhang, Yunfeng Shen
Background: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) exhibit glucose-lowering, weight-reducing, and blood pressure-lowering effects. Nevertheless, a debate exists concerning the association between GLP-1RA treatment and the risk of diabetic retinopathy (DR) in patients diagnosed with type 2 diabetes mellitus (T2DM).
Objective: To ascertain the risk of DR in patients with T2DM undergoing GLP-1RA treatment, we conducted a meta-analysis utilizing data derived from randomized placebo-controlled studies (RCTs).
Methods: A comprehensive literature search was conducted using PubMed, Cochrane Library, Web of Science, and EMBASE. We focused on RCTs involving the use of GLP-1RAs in patients with T2DM. Utilizing R software, we compared the risk of DR among T2DM patients undergoing GLP-1RA treatment. The Cochrane risk of bias method was employed to assess the research quality.
Results: The meta-analysis incorporated data from 20 RCTs, encompassing a total of 24,832 T2DM patients. Across all included trials, randomization to GLP-1 RA treatment did not demonstrate an increased risk of DR (odds ratio = 1.17; 95% CI 0.98-1.39). Furthermore, no significant heterogeneity or publication bias was detected in the analysis.
Conclusion: The results of this systematic review and meta-analysis indicate that the administration of GLP-1 RA is not associated with an increased risk of DR. PROSPERO REGISTRATION IDENTIFIER: CRD42023413199.
背景：胰高血糖素样肽1受体激动剂（GLP-1RA）具有降血糖、减肥和降压作用。然而，关于GLP-1RA治疗与2型糖尿病（T2DM）患者糖尿病视网膜病变（DR）风险之间的关系仍存在争议，我们利用随机安慰剂对照研究（RCTs）的数据进行了荟萃分析。方法：使用PubMed、Cochrane Library、Web of Science和EMBASE进行全面的文献检索。我们重点研究了在T2DM患者中使用GLP-1RA的随机对照试验。利用R软件，我们比较了接受GLP-1RA治疗的T2DM患者发生DR的风险。采用Cochrane偏倚风险法评估研究质量。结果：荟萃分析纳入了20项随机对照试验的数据，共包括24832名T2DM患者。在所有纳入的试验中，随机分组接受GLP-1 RA治疗并未显示DR风险增加（比值比=1.17；95%CI 0.98-1.39）。此外，在分析中未检测到显著的异质性或发表偏倚。结论：这项系统综述和荟萃分析的结果表明，GLP-1 RA的给药与DR风险增加无关。PROSPERO注册标识符：CRD42023413199。
{"title":"Glucagon-Like Peptide-1 Receptor Agonist and Risk of Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials.","authors":"Xiaojuan Jiao, Ping Peng, Qin Zhang, Yunfeng Shen","doi":"10.1007/s40261-023-01319-x","DOIUrl":"10.1007/s40261-023-01319-x","url":null,"abstract":"<p><strong>Background: </strong>Glucagon-like peptide 1 receptor agonists (GLP-1RAs) exhibit glucose-lowering, weight-reducing, and blood pressure-lowering effects. Nevertheless, a debate exists concerning the association between GLP-1RA treatment and the risk of diabetic retinopathy (DR) in patients diagnosed with type 2 diabetes mellitus (T2DM).</p><p><strong>Objective: </strong>To ascertain the risk of DR in patients with T2DM undergoing GLP-1RA treatment, we conducted a meta-analysis utilizing data derived from randomized placebo-controlled studies (RCTs).</p><p><strong>Methods: </strong>A comprehensive literature search was conducted using PubMed, Cochrane Library, Web of Science, and EMBASE. We focused on RCTs involving the use of GLP-1RAs in patients with T2DM. Utilizing R software, we compared the risk of DR among T2DM patients undergoing GLP-1RA treatment. The Cochrane risk of bias method was employed to assess the research quality.</p><p><strong>Results: </strong>The meta-analysis incorporated data from 20 RCTs, encompassing a total of 24,832 T2DM patients. Across all included trials, randomization to GLP-1 RA treatment did not demonstrate an increased risk of DR (odds ratio = 1.17; 95% CI 0.98-1.39). Furthermore, no significant heterogeneity or publication bias was detected in the analysis.</p><p><strong>Conclusion: </strong>The results of this systematic review and meta-analysis indicate that the administration of GLP-1 RA is not associated with an increased risk of DR. PROSPERO REGISTRATION IDENTIFIER: CRD42023413199.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"915-926"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478815","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}
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