Clinical Pharmacology And Therapeutics[JOURNAL]
Sun
200 papers
Carbon Footprint of Antibody-Based Drugs and Biologics Using Hybrid Life Cycle Assessment.
Taillemite S, Fenelon M, Scherlinger M … +1 more , Piffoux M
Clin Pharmacol Ther · 2026 Jul · PMID 42092334 · Full text
Biological engineering has emerged since the 1980s as one of the most efficient technologies to develop new medicines. The monoclonal antibody platform is the most widely used, representing about 15-20% of drug sales. On...
Biological engineering has emerged since the 1980s as one of the most efficient technologies to develop new medicines. The monoclonal antibody platform is the most widely used, representing about 15-20% of drug sales. Only scarce and partial monoclonal antibody life cycle assessments (LCAs) are reported. We estimate the cradle-to-pharmacy gate carbon footprint of monoclonal antibodies from the pharmacopeia on the market (n = 103) using the full life cycle inventory of the medicines, encompassing antibody production, packaging production, transport, medicine manufacturing, and associated corporate emissions using a hybrid LCA/environmentally extended input-output model. Monoclonal antibody-based drugs have an important carbon footprint with a mean of 169.7 kgCOe/vial or prefilled syringe (95% CI 10.1-621.1) and 371.4 kgCOe/month (95% CI 23.1-1,479.5) vs. 14.1 kgCOe/month (95% CI 0.33-36.2) for an oral treatment. A large fraction of emissions is emerging from corporate emissions. The 95% CI surrounding these estimations is about ±35%. Among subparts, antibody production emissions largely vary from 7.1 to 20,206 kgCOe/g of antibody (mean 472 kgCOe/g, 95% CI 8.2-2,529), depending on the production scale. As an illustration, the carbon footprint of second-line treatment options in rheumatoid arthritis ranges from 286 to 2,047 kgCOe/year. In cancer immunotherapy, alternative weight-adjusted dosing strategies lead to a 10-20% mitigation in greenhouse gas emissions, while "low-dose" strategies may mitigate emissions by 2- to 10-fold. Antibody-based drugs have a significant carbon footprint, although highly variable. This database allows for a better understanding of the carbon footprint associated with these drugs, in order to better eco-design care pathways.
Dulaglutide-associated body odor with dechallenge and rechallenge in a patient with type 2 diabetes.
Marusic S, Staresinic M, Cigrovski Berkovic M
Int J Clin Pharmacol Ther · 2026 May · PMID 42087771 · Publisher ↗
OBJECTIVE: Although uncommon, medications may induce unpleasant body odor, potentially leading to psychosocial distress and reduced treatment adherence. To date, unpleasant body odor has not been recognized as an adverse...
OBJECTIVE: Although uncommon, medications may induce unpleasant body odor, potentially leading to psychosocial distress and reduced treatment adherence. To date, unpleasant body odor has not been recognized as an adverse effect of dulaglutide. We report a novel case of dulaglutide-associated body odor, confirmed by dechallenge and rechallenge. CASE REPORT: A 57-year-old man with a 6-year history of type 2 diabetes mellitus and hypertension was initiated on dulaglutide due to inadequate glycemic control and obesity. Two weeks after treatment initiation, an unpleasant body odor was noted by family members and colleagues. No changes in diet, hygiene practices, or concomitant medications were reported. Dermatological examination and extensive laboratory evaluation excluded infectious, metabolic, and endocrine causes. The odor resolved ~ 10 days after discontinuation of dulaglutide. Upon rechallenge, the odor recurred, confirming a causal relationship. Dulaglutide was permanently discontinued, and treatment was switched to semaglutide, after which the body odor did not recur and glycemic control improved. According to the Naranjo Adverse Drug Reaction Probability Scale, the association was classified as probable. CONCLUSION: This case highlights a rare and previously unreported adverse effect of dulaglutide. Although not medically serious, drug-induced body odor may substantially impair quality of life and treatment adherence.
Pharmocracy via MCC to de-prescribing: The attempted ascent and descent of Everest.
Woodcock-Kloberdanz BG
Int J Clin Pharmacol Ther · 2026 Jun · PMID 42087770 · Publisher ↗
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Gastrointestinal symptoms in Parkinson's disease treated in a controlled trial using traditional Chinese medicine (Jia-Wei-Ji-Chuan-Jian decoction) with network pharmacology analysis of active agents and mechanism of action.
Loong SK, Wu F, Liu Y … +5 more , Voratunyakit N, Wei S, Li W, Li R, Pan W
Int J Clin Pharmacol Ther · 2026 Jul · PMID 42084228 · Publisher ↗
BACKGROUND: Gastrointestinal symptoms in Parkinson's disease (PD), in particular chronic constipation, are common and are treated in China using the traditional Chinese medicine (Jia-Wei-Ji-Chuan-Jian decoction) (JWJCJ))...
BACKGROUND: Gastrointestinal symptoms in Parkinson's disease (PD), in particular chronic constipation, are common and are treated in China using the traditional Chinese medicine (Jia-Wei-Ji-Chuan-Jian decoction) (JWJCJ)). However, information on therapeutic targets and the underlying mechanism is limited. MATERIALS AND METHODS: A total of 72 PD patients with constipation attending Departments of Neurology in Shanghai, China (Shanghai Pudong New Area Gongli Hospital and Shuguang Hospital Affiliated to Shanghai University) were recruited into the study and allocated to a Treatment group (n = 36) and a Control group (n = 36). Patients in the Control group received a combination treatment comprising anti-Parkinson agents (Western drug regimen) with the addition of a traditional Chinese patent medicine (Huang-Xing Run-Chang Tablets*) over a period of 5 weeks, whereas patients in the Treatment group received the same anti-PD Western drug regimen together with the JWJCJ decoction, also for a period of 5 weeks. An evaluation using clinical efficacy scores was carried out together with network pharmacology analysis. Identified drug targets for JWJCJ using the traditional Chinese medicine Swiss Target Prediction database (TCMSP) and disease targets for chronic constipation in PD were obtained from Genecards and the OMIM database. Therapeutic targets for JWJCJ in the treatment of chronic constipation were identified by intersecting drug targets and disease targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were carried out using the DAVID database and visualized using Cytoscape 3.9.1 software. RESULTS: CSS efficacy scores in the Treatment group were higher than that in the Control group (88.57 vs. 52.94%, p < 0.001). No significant differences were seen prior to treatment in the CSS, PDQ-39 and MDS-UPDRS scores and the corresponding total scores for the two groups. After treatment, CSS values for patients in the Treatment group were higher than values before treatment (p < 0.01). Network pharmacology analysis identified 172 active components, 9,542 drug targets, and 421 intersecting target genes for JWJCJ. PPI analysis identified 10 main and possibly key targets for JWJCJ in the treatment of chronic constipation. KEGG analysis identified 198 signaling pathways, where pathways in cancer, specific cancer pathways such as prostate cancer and non-small cell lung cancer, lipid and atherosclerosis, hepatitis B, and the AGE-RAGE signaling pathway in diabetic complications were among the pathways most significantly enriched. These findings are evidence that the active ingredients in JWJCJ in the treatment of chronic constipation in PD mainly target TP53, SRC, AKT1, PIK3R1, and PIK3CA. CONCLUSION: The efficacy of JWJCJ in treating chronic constipation in PD involves the targets SRC, PIK3R1, JUN, TP53, STAT3, PIK3CA, EGFR, ESR1, MAPK1, and AKT1 domains. These findings provide theoretical basis for the clinical application of JWJCJ decoction in the treatment of chronic constipation in PD.
A Framework for Assessing the Viability of External Control for a Single-Arm Trial.
Kiri VA
Clin Pharmacol Ther · 2026 Jul · PMID 42084196 · Publisher ↗
A single-arm trial with an external control arm (ECA) is one in which the patients in the control group do not participate in the trial. The number of approved ECA trials is on the increase, due largely to their practica...
A single-arm trial with an external control arm (ECA) is one in which the patients in the control group do not participate in the trial. The number of approved ECA trials is on the increase, due largely to their practical advantages. To assist this process, we have developed an ECA Viability Checklist as a framework for making initial assessments of the viability of the ECA in meeting regulatory requirements. Its purpose is to inform exploratory discussions with regulatory agencies, who would expect study sponsors to establish the appropriateness of the proposed design, including data sources and statistical analyses. The Checklist is based on the guidance documents by the United States Food and Drug Administration (FDA), European Medicines Agency (EMA), and the UK Medicines & Healthcare products Regulatory Agency (MHRA), using data from 40 FDA-approved ECA trials across different therapeutic areas. It is structured on the critical aspects of design and analytical considerations on the use of real-world data and past trials, presented as 10 thematic questions with recommendations on possible solutions to issues arising from each theme. We evaluated the Checklist against 4 FDA-approved ECA trials. Ideally, all responses should be affirmative to be most confident of regulatory acceptance of the proposed ECA; non-affirmative responses would require an adequate rationale, guided by the associated recommendations for progression. The Checklist will enable decision-makers to conduct an initial viability assessment of the proposed ECA and make an informed decision on the required next steps to help ensure acceptance of the design.
Reply to "A Comment about AI Methods that May Help Advance Pharmacovigilance".
Khouri C, Hlavaty A, Fusaroli M … +5 more , Joshi N, Salvo F, Bate A, Pariente A, Raschi E
Clin Pharmacol Ther · 2026 Jul · PMID 42084188 · Publisher ↗
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Comparative Analysis of Additional Risk Minimization Measures in the Risk Management Plan in the European Union and Japan.
Honda T, Narukawa M
Clin Pharmacol Ther · 2026 Jul · PMID 42084175 · Publisher ↗
In this study, we aimed to characterize differences in additional risk minimization measures within the risk management plan for medicinal products approved in both the European Union and Japan. We examined the proportio...
In this study, we aimed to characterize differences in additional risk minimization measures within the risk management plan for medicinal products approved in both the European Union and Japan. We examined the proportion requiring additional risk minimization measures, types implemented, and content of the related educational materials. Products approved in both regions as of December 2023 were identified. Safety concerns, additional risk minimization measures, and educational materials for healthcare professionals and patients were retrieved and analyzed for each product. We compared the number and proportion of safety concerns covered by additional risk minimization measures, as well as the volume of educational materials, between the two regions. Among 259 products, additional risk minimization measures were present in 33.2% of European Union products and 73.0% of Japanese products. Direct healthcare professional communications were observed only in the European Union, whereas early post-marketing phase vigilance was characteristic of Japan. Controlled access programs were similarly implemented but rarely overlapped. Japanese educational materials covered a greater number of safety concerns and were generally more extensive, whereas European Union materials tended to be more targeted and concise. Japan applies additional risk minimization measures more broadly and gathers information into one material, whereas the European Union emphasizes selective, purpose-specific risk minimization. These differences reflect the distinct regulatory frameworks and healthcare environments. Optimizing additional risk-minimization strategies in Japan may enhance risk mitigation and resource efficiency.
Methotrexate-Induced Nephrotoxicity and Exposure Thresholds in Primary Central Nervous System Lymphoma: A Population PKPD Model.
Wu R, Sun H, Li Y … +7 more , Zhu B, Huo J, Zhang D, Sun X, Zhao Z, Fu L, Mei S
Clin Pharmacol Ther · 2026 Jul · PMID 42083006 · Publisher ↗
High-dose methotrexate (HD-MTX)-induced nephrotoxicity remains a critical clinical challenge in primary central nervous system lymphoma (PCNSL) treatment, yet quantitative tools for individualized risk prediction are cur...
High-dose methotrexate (HD-MTX)-induced nephrotoxicity remains a critical clinical challenge in primary central nervous system lymphoma (PCNSL) treatment, yet quantitative tools for individualized risk prediction are currently lacking. Here, a population pharmacokinetic/pharmacodynamic analysis was performed using 5,918 plasma concentration samples from 743 Chinese adult patients. Nonlinear mixed-effects modeling was employed to establish toxicodynamic structural models driven by MTX alone, 7-Hydroxy-MTX alone, or their combination. Although all models exhibited comparable predictive performance, the MTX linear model was selected as it offered the optimal balance between predictive performance and clinical feasibility. Covariate analysis identified hemoglobin as the most significant predictor, with higher levels correlating with reduced susceptibility to renal injury. To facilitate clinical translation, exposure-toxicity probability curves were constructed, enabling clinicians to identify dynamic concentration thresholds tailored to specific toxicity grades (Grade 1 vs. ≥2 nephrotoxicity) and individualized risk tolerance. Using a 10% risk probability for Grade ≥2 nephrotoxicity as the safety monitoring threshold, the corresponding MTX concentration thresholds at 24, 48, and 72 h were 9.71, 0.81, and 0.26 μmol/L, respectively. This quantitative framework serves as an exploratory tool to complement therapeutic drug monitoring, assisting in the early identification of MTX-induced renal injury among PCNSL patients with normal to mildly impaired renal function.
Repurposing Drugs for Malaria through a Human Dose Prediction: A Case Study with Berzosertib.
Redhi D, Mulubwa M, Mmonwa MM … +3 more , Njoroge M, Krugmann L, Chibale K
Clin Pharmacol Ther · 2026 May · PMID 42080628 · Publisher ↗
Repurposing drugs whose clinical safety has been established offers a valuable approach to reduce the cost and time associated with the development of new drugs for malaria. Here, we investigate the potential to repurpos...
Repurposing drugs whose clinical safety has been established offers a valuable approach to reduce the cost and time associated with the development of new drugs for malaria. Here, we investigate the potential to repurpose the anticancer kinase inhibitor berzosertib for the treatment of malaria, by assessing whether a predicted efficacious human dose for malaria is within the clinically established safety and tolerability profile. First, an oral dose fractionation study was performed in a Plasmodium falciparum-infected humanized mouse model to evaluate the antimalarial pharmacokinetic-pharmacodynamic properties of berzosertib. The activity of berzosertib was shown to be strongly dependent on the time in which the concentrations remain above the minimum parasiticidal concentration (MPC). A human physiologically based pharmacokinetic model was then developed and used to simulate the exposure-response relationships and determine the effective human dose which fulfilled the target pharmacokinetic profile of sustained concentrations above the MPC. Our prediction indicates that six daily intravenous doses of 75 mg of berzosertib will be required for the treatment of an uncomplicated blood stage malaria infection, which is comparatively lower than the clinical maximum tolerated dose for cancer therapy, which was identified as 440 mg administered intravenously twice weekly over a 21-day cycle for up to 18 weeks. Despite berzosertib's potential for repurposing, further preclinical development is necessary to ensure it meets the standard of current and emerging antimalarials.
Reply to "Reframing the 'Rescue Window': From Physiological Upper Bounds to Actionable Thresholds".
Thrasher B, Li Z
Clin Pharmacol Ther · 2026 Jul · PMID 42080215 · Publisher ↗
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The Visual Predictive Check and Real-World Data.
Hughes JH, Bergstrand M, Keizer RJ
Clin Pharmacol Ther · 2026 May · PMID 42067900 · Publisher ↗
The visual predictive check (VPC) is a standard tool for assessing pharmacometric model suitability, producing visualizations that compare observed data with simulated data such that both model structure and model variab...
The visual predictive check (VPC) is a standard tool for assessing pharmacometric model suitability, producing visualizations that compare observed data with simulated data such that both model structure and model variability terms can be assessed. However, real-world data commonly reflect clinical decision-making that adapts therapy in response to patient data. As a result, VPCs constructed from such data may display apparent model misspecification, even when models are well-specified. To illustrate possible confounders, four common real-world therapy adaptation scenarios were simulated: (1) varying dose amount with constant interval, (2) varying dosing interval with constant dose amount, (3) patient dropout after identification of a suitable maintenance dose, and (4) variability in sample timing based on individual pharmacokinetic parameter estimates. For all scenarios, simulated observations were generated using the same model used to produce the VPC simulations, ensuring that the model was unbiased. When only the dose amount varied, the prediction-corrected VPC (pcVPC) appropriately indicated a well-specified model. In all other cases, both VPC and pcVPC erroneously suggested a misspecified model. These simulated results, together with our broader experience with complex real-world data, demonstrate that VPCs can be misleading when applied to real-world data if dosing interval, sample timing, or sample frequency varies in response to measured drug concentrations. We propose these four scenarios as benchmarks for evaluating the robustness of current and future model diagnostics to real-world data characteristics.
Correction to "Real-World Outcomes of Pembrolizumab Monotherapy in Metastatic Non-Small Cell Lung Cancer by Age and Sex: A National Population-Based Study in Australia".
Clin Pharmacol Ther · 2026 Jun · PMID 42062778 · Publisher ↗
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Drug Critical Limits for Urgent Physician Notification.
Kuang E, Ibrahim Y, Cheng K … +1 more , Kost GJ
Clin Pharmacol Ther · 2026 Jul · PMID 42062777 · Full text
Critical limits represent quantitative decision thresholds for drugs that require immediate clinician notification and potential life-saving intervention. United States hospitals lack a national standard for drug critica...
Critical limits represent quantitative decision thresholds for drugs that require immediate clinician notification and potential life-saving intervention. United States hospitals lack a national standard for drug critical limits. We collected critical limits from 417 US hospitals across all 50 states and Washington, D.C.; of these, 411 maintained drug critical limit lists. We classified hospitals by US Census division and network-affiliated vs. independent status. We applied non-parametric statistical analyses, examined critical limits for 111 drugs, and observed significant inter-institutional variability. Listing frequencies were highest for digoxin 99.8% (410/411), theophylline 72.3% (297/411), lithium 94.9% (390/411), and acetaminophen 86.9% (357/411). Non-therapeutic measurands also appeared, led by ethanol 47.2% (194/411). Kruskal-Wallis analysis revealed highly significant differences (P < 0.01) across census divisions. Mann-Whitney U analysis comparing network vs. independent hospitals yielded significant differences (P < 0.05) in 16 analytes. Qualitative critical values were listed for volatile alcohols and methotrexate. All digoxin critical limits exceeded levels associated with increased hazard ratios. Only 33.9% of hospitals aligned with consensus guidelines for acetaminophen poisoning. Vancomycin and aminoglycoside critical limits showed wide ranges, overlapping peaks and troughs, and random values inconsistently aligned with peak and troughs. Immunosuppressant critical limits often exceeded thresholds associated with toxicity. Psychotropic drugs, including antiepileptics, tricyclic antidepressants, and lithium, demonstrated variability and misalignment relative to consensus guidelines. Drugs of abuse did not appear in critical notification lists. Results provide hospitals with references that will enhance hospital notification practices and patient safety. We encourage sharing of critical notification lists to foster future research efforts and enhance standards of care.
Polypharmacy and hyperpolypharmacy in elderly (≥ 65 years) pacemaker recipients: Prevalence and association with frailty, physical activity, adherence, and healthcare utilization in a prospective single-center study.
Costa M, António N, Félix C … +6 more , Jordão I, Paiva P, Guimarães J, Fernandes D, Gonçalves L, Parente F
Int J Clin Pharmacol Ther · 2026 Jul · PMID 42057633 · Publisher ↗
OBJECTIVES: To quantify polypharmacy (≥ 5 drugs) and hyperpolypharmacy (≥ 10 drugs) in pacemaker recipients aged ≥ 65 years and to assess associations with frailty (FRAIL), physical activity (IPAQ), medication adherence...
OBJECTIVES: To quantify polypharmacy (≥ 5 drugs) and hyperpolypharmacy (≥ 10 drugs) in pacemaker recipients aged ≥ 65 years and to assess associations with frailty (FRAIL), physical activity (IPAQ), medication adherence (MAT), and healthcare utilization over 6 months. BACKGROUND: Polypharmacy is common in elderly patients with cardiac devices, but prospective data from European pacemaker clinics on frailty, physical activity, adherence, and prescribing quality are limited. MATERIALS AND METHODS: Prospective, single-center observational study in a Portuguese tertiary pacemaker outpatient clinic (n = 104). Participants (≥ 65 years) were assessed at enrolment and at 3 and 6 months. FRAIL, IPAQ, and MAT were recorded at each timepoint. Healthcare utilization was defined as emergency department visits and/or hospital admissions. STOPP/START v3 was applied descriptively at 6 months. RESULTS: Mean age was 79.1 ± 7.5 years; 69.2% were men. Polypharmacy and hyperpolypharmacy were present in 49.0% and 38.5% at enrolment and 47.5% and 43.4% at 6 months. A higher number of chronic medications was associated with higher FRAIL scores, lower IPAQ scores and more frequent healthcare utilization, whereas MAT scores remained uniformly high. Cardiovascular drugs, diuretics, and proton-pump inhibitors (PPIs) were the most frequently used classes. STOPP/START identified potentially inappropriate medications (notably PPIs and benzodiazepines) and prescribing omissions according to START (notably cardiovascular therapies). CONCLUSION: Polypharmacy and hyperpolypharmacy are frequent and persistent in elderly pacemaker recipients and are associated with frailty, lower physical activity and higher healthcare utilization. Structured medication review during routine follow-up may help identify PIMs and PPOs and optimize pharmacotherapy.
Frequency of Key Pharmacogenes CYP2C9, CYP2C19, CYP2D6, and SLCO1B1 in the Yogyakarta Population: Implications for Precision Prescribing in Indonesia.
Nugrahaningsih DAA, Chintyasari S, Wijayaningsih RA … +3 more , Mustofa, Pratiwi WR, Mayasari DS
Clin Pharmacol Ther · 2026 Apr · PMID 42050991 · Publisher ↗
Genetic variations in CYP2C9, CYP2C19, CYP2D6, and SLCO1B1 significantly influence drug metabolism and transport, impacting therapeutic response and adverse event risk. While pharmacogenomic guidelines advocate for genot...
Genetic variations in CYP2C9, CYP2C19, CYP2D6, and SLCO1B1 significantly influence drug metabolism and transport, impacting therapeutic response and adverse event risk. While pharmacogenomic guidelines advocate for genotype-guided therapy, no population-specific frequency data exist for these pharmacogenes in Yogyakarta, Indonesia-a region where medication use and polypharmacy are common. This study aims to determine the allele and genotype frequencies of CYP2C9, CYP2C19, CYP2D6, and SLCO1B1 in the Yogyakarta, Indonesia population to inform regionally appropriate prescribing practices. Genotyping was performed using probe-specific real-time PCR (RT-PCR) platforms. The panel targeted clinically relevant variants across CYP2C9, CYP2C19, CYP2D6, and SLCO1B1, integrating SNP and copy number variant analysis where applicable. High frequencies of CYP2C19 *2/*3 and CYP2D6*10 alleles were observed, consistent with Southeast Asian profiles. SLCO1B1 reduced-function variants were prevalent, suggesting elevated risk for statin-induced myopathy. CYP2C9*3 allele was also detected, warranting caution in warfarin and NSAID prescribing. The observed genotype distributions highlight the need for region-specific pharmacogenomic strategies in Indonesia. This foundational dataset supports the development of precision prescribing protocols and reinforces the importance of integrating genotyping into clinical practice to improve therapeutic safety and effectiveness.
Correction to "Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2025 Update".
Clin Pharmacol Ther · 2026 Jun · PMID 42050374 · Publisher ↗
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Cardiorenal Outcomes of Dapagliflozin vs. Empagliflozin in Advanced Chronic Kidney Disease and Diabetes.
Lin SH, Chen JJ, Hsiao CC … +4 more , Fang YW, Chen MT, Tsai MH, Yang HY
Clin Pharmacol Ther · 2026 Jul · PMID 42045736 · Full text
Although sodium-glucose co-transporter-2 (SGLT2) inhibitors provide cardiorenal benefits, direct comparisons between dapagliflozin and empagliflozin-the two most commonly used and studied agents in this class-remain limi...
Although sodium-glucose co-transporter-2 (SGLT2) inhibitors provide cardiorenal benefits, direct comparisons between dapagliflozin and empagliflozin-the two most commonly used and studied agents in this class-remain limited, particularly in patients with advanced chronic kidney disease (CKD). In the current study, we aimed to compare the cardiorenal effectiveness and safety of dapagliflozin versus empagliflozin in adults with type 2 diabetes (T2D) and stage 3B-5 CKD. We used the TriNetX network and identified adults with T2D and stage 3B-5 CKD newly initiating dapagliflozin or empagliflozin. Following a target trial emulation framework, we applied 1:1 propensity score matching and Cox proportional hazards models to estimate hazard ratios (HRs) for major adverse kidney events (MAKE), major adverse cardiovascular events (MACE), all-cause mortality, and adverse events. After matching, 4,361 participants were included per group. The mean age was 67.6-67.9 years and men comprised 45.3-45.9% with a median follow-up duration of 780-790 days. Dapagliflozin users showed comparable HRs for MAKE (1.04; 95% CI: 0.94-1.16), MACE (1.02; 95% CI: 0.95-1.09), all-cause mortality (0.86; 95% CI: 0.74-1.00), and adverse events (1.03; 95% CI: 0.92-1.14). However, the risk of end-stage kidney disease (ESKD) was higher with dapagliflozin (1.28; 95% CI: 1.11-1.48). We concluded that in adults with T2D and advanced CKD, dapagliflozin and empagliflozin demonstrated comparable cardiorenal effectiveness and safety. Dapagliflozin was associated with a modestly higher ESKD risk, but this finding warrants cautious interpretation and further study given the observational design and potential residual confounding.
Inflammatory cytokines, autoantibodies and salivary gland function in Sjögren's syndrome: Effects of T. wilfordii as Hook F medical wine and Tripterygium glycosides tablets.
Yu X, Chu P, Yu C … +1 more , Zhao L
Int J Clin Pharmacol Ther · 2026 Apr · PMID 42021716 · Publisher ↗
OBJECTIVE: This study was conceived to compare the clinical efficacy of Tripterygium wilfordii Hook F (TWHF) medical wine and Tripterygium glycoside tablets (TGTs) in patients with primary Sjögren's syndrome (pSS), mainl...
OBJECTIVE: This study was conceived to compare the clinical efficacy of Tripterygium wilfordii Hook F (TWHF) medical wine and Tripterygium glycoside tablets (TGTs) in patients with primary Sjögren's syndrome (pSS), mainly focusing on inflammatory markers, autoantibody profiles, and salivary gland function. MATERIALS AND METHODS: In this prospective, randomized controlled trial, 90 pSS patients were enrolled and randomly assigned into a TWHF medical wine group (Observation) or TGTs group (Control), receiving either TWHF medical wine (8 mL, twice daily) or TGTs (10 mg, 3 times daily) for 12 weeks. Primary outcomes included unstimulated whole saliva (UWS) flow rate, EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), and positivity rates of anti-SSA/SSB antibodies. Secondary outcomes included subjective symptom scores (EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI)), serum IgG levels, and safety profiles. RESULTS: Baseline characteristics were comparable between the two groups. After 12 weeks, the Observation group showed significantly greater improvements in UWS and ESSDAI scores. The positive rates of anti-SSA and anti-SSB had decreased in both groups, with a more pronounced decline observed in the observation group, though between-group differences were not statistically significant. ESSPRI scores and IgG levels were significantly reduced in both groups, with more pronounced changes in the Observation group. No severe adverse events occurred, and both treatments were well tolerated with comparable safety profiles. CONCLUSION: TWHF medical wine is more effective than TGTs in improving salivary gland function, systemic disease activity, and immunological profiles in pSS patients, with comparable safety. These results suggest that TWHF medical wine is a suitable alternative treatment for primary Sjögren's syndrome.
Epidemiological Characteristics, Target Distribution, and Clinical Value of Targeted Anticancer Drugs Approved in China: A Cross-Sectional Study.
Zhu T, Wang R, Huang Y
Clin Pharmacol Ther · 2026 Apr · PMID 42002705 · Publisher ↗
China has advanced both domestic innovation and the introduction of imported targeted anticancer drugs (TADs). However, characteristics of these TADs remain unclear. In this cross-sectional study, we identified TADs appr...
China has advanced both domestic innovation and the introduction of imported targeted anticancer drugs (TADs). However, characteristics of these TADs remain unclear. In this cross-sectional study, we identified TADs approved in China from 2017 to 2024. Trend in number, target distributions, endpoint evidence, clinical benefit (via European Society for Medical Oncology-Magnitude of Clinical Benefit Scale [ESMO-MCBS]), and the price were analyzed. Of the approved 143 TADs (315 indications), 64 (44.8%) (145 indications [46.0%]) were domestically developed and 79 (55.2%) (170 indications [54.0%]) were imported, with annual growth rates of 31.0% for domestic TADs (incidence rate ratio 1.310, 95% CI; 1.158-1.482; P < 0.001) vs. 9.8% for imported TADs (1.098, 95% CI; 0.992-1.215; P = 0.071). A total of 52 drug targets were identified (23 domestic; 47 imported). Imported TAD indications more often reported overall survival (OS) than domestic drugs (44.1% vs. 29.0%; P = 0.006), but domestic TAD indications showed better OS (hazard ratio 0.69, 95% CI 0.66-0.71 vs. 0.73, 95% CI 0.71-0.76). Domestic TAD indications were predominantly rated as having intermediate clinical benefit (57.9% vs. 35.9% for imported), while high benefit was less frequent (22.1% vs. 35.3%) and low benefit slightly less common (20.0% vs. 28.8%). Median monthly treatment prices were consistently higher for imported than domestic TADs across all drug categories. In conclusion, both domestic and imported TADs continued to increase. Domestic TAD targets were highly concentrated. Fewer than half of domestic and imported TAD indications reported OS, and less than 40% in either group achieved high-grade clinical benefit. Imported TADs had higher monthly treatment prices than domestic TADs.
Comparative Use Human Factors Study of a Manual vs. A Partially Automated Pen Injector for GLP-1 Receptor Agonist Delivery.
Natarajan K, Clerman A, Soosaar J … +12 more , Sye S, Giacomini J, Conti DS, Bhalodia A, Flint J, Chattopadhyay S, Hartka K, Lieu S, Feibus K, Kim S, Klingensmith R, Luke MC
Clin Pharmacol Ther · 2026 Jul · PMID 41997744 · Publisher ↗
Injectable glucagon-like peptide-1 receptor agonists are developed as drug-device combination products, with delivery facilitated by pen- or autoinjectors. As generic alternatives with different device designs emerge, ev...
Injectable glucagon-like peptide-1 receptor agonists are developed as drug-device combination products, with delivery facilitated by pen- or autoinjectors. As generic alternatives with different device designs emerge, evidence is needed to support therapeutic equivalence for Abbreviated New Drug Application approval. Comparative use human factors studies represent one FDA-accepted approach for this demonstration. This comparative use human factors study evaluated whether a proposed generic manual pen injector could substitute for a reference partially automated pen injector for critical task performance and dose delivery. We conducted a randomized, two-period, two-sequence crossover study evaluating use success rates in 100 adult patients experienced with partially automated pen injectors. The study population included 16 current reference device and 84 current surrogate device (similar pen injector design) users. Subjects performed critical tasks with both devices in randomized sequence across two simulated scenarios. Co-primary endpoints were use success rates for dose selection and injection in Scenarios 1 and 2, analyzed using noninferiority testing with a prespecified 10% margin. Both co-primary endpoints demonstrated noninferiority. For Scenario 1 (0.6 mg dose selection), both devices achieved 95% success rates with 0% difference (95% one-sided upper confidence limit: 5.7%, P = 0.0045). For Scenario 2 (3 mg dose selection and simulated injection), the reference device achieved 100% vs. 95% for the test device, with a 5% difference (95% one-sided upper confidence limit: 9.92%, P = 0.0475). All confidence bounds remained below the 10% noninferiority margin. This study provides evidence supporting substitutability of the proposed manual generic device for the partially automated reference device.
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