AIMS:This study aims to characterize the clinical spectrum, elucidate the temporal relationship and assess the causality of checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM) in a cohort of patients receiving anti-programmed cell death-1 (PD-1)/anti-programmed death ligand-1 (PD-L1) inhibitor therapy. METHODS:Individuals who developed CIADM were identified among 4382 hospitalized patients receiving PD-1/PD-L1 inhibitor therapy between 2020 and 2024. Demographic characteristics, oncological history, immune checkpoint inhibitor regimens, laboratory parameters (including glycemic control, C-peptide and islet autoantibodies) and clinical outcomes were systematically collected. Causality was evaluated using the Naranjo algorithm. RESULTS:Among 4382 patients who received PD-1/PD-L1 inhibitors, seven (0.16%) were diagnosed with CIADM during the study period. Seven patients were predominantly male, with a median age of 52 years (range: 44-62), and hepatocellular carcinoma was the most common primary malignancy (3/7). All patients developed CIADM after a median of 8 cycles (range: 5-23) of PD-1/PD-L1 inhibitors (sintilimab, camrelizumab, envafolimab or atezolizumab). Notably, 86% (6/7) of patients presented with diabetic ketoacidosis (DKA) at onset. Severe pancreatic β-cell dysfunction was universal, with undetectable fasting and postprandial C-peptide levels. Islet autoantibodies were positive in only one patient. The Naranjo score indicated a 'probable' to 'highly probable' causal relationship in all cases. All patients required lifelong insulin therapy. Following glycemic stabilization, immunotherapy was successfully reinitiated in six patients without exacerbating hyperglycemia. CONCLUSION:CIADM is a severe immune-related adverse event (irAE) characterized by abrupt onset, a high rate of DKA, and profound insulin deficiency, often in the absence of conventional islet autoantibodies. A definitive causal link exists between PD-1/PD-L1 inhibitors and CIADM. Our findings underscore the necessity for proactive glycemic monitoring in patients undergoing ICI therapy, especially in populations such as middle-aged males with cancers known to have specific demographic profiles (e.g., hepatocellular carcinoma). Importantly, the resumption of immunotherapy is feasible with careful management, highlighting the critical role of a multidisciplinary approach to optimize oncological and metabolic outcomes.

Previous studies suggest a potential link between interstitial lung diseases (ILD) and EGFR-TKI use, with proton pump inhibitors (PPIs) possibly affecting EGFR-TKI-associated ILD differently. Our objective is to use the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to explore the potential link between ILD and the combination of PPIs and EGFR-TKI. A retrospective examination of adverse event reports in the FAERS database spanning from the initial quarter of 2016 and the fourth quarter of 2023 was conducted. Disproportionality analysis, generalized linear models, and adjusted multivariable logistic regression were employed to assess the occurrence of EGFR-TKI-associated ILD in non-small cell lung cancer (NSCLC) patients receiving PPIs compared to those not receiving PPIs. The reporting odds ratio (ROR) for PPIs combined with EGFR-TKIs demonstrated statistical significance (ROR 1.84, 95

There is a lack of comprehensive research investigating the relationship between proton pump inhibitors (PPIs) and osimertinib combination therapy concerning cardiotoxicity. We conducted a retrospective analysis of adverse event reports from the US Food and Drug Administration Adverse Event Reporting System (FAERS). In this analysis, we used patients with non-small cell lung cancer (NSCLC) who did not receive osimertinib or PPIs as a control group to assess the association between cardiotoxicity occurrence in patients receiving osimertinib with PPIs and those without PPIs. We employed disproportionality analysis along with both additive and multiplicative models. The reporting odds ratios (ROR) for cardiac events, including torsade de pointes/QT prolongation, cardiomyopathy, cardiac arrhythmias, cardiac failure, ischaemic heart disease, and embolic and thrombotic events, were significantly higher in patients using PPIs with osimertinib (14.11, 9.04-22.04; 4.67, 2.67-8.16; 4.43, 3.17-6.20; 3.67, 2.53-5.34; 2.24, 1.31-3.84; 1.92, 1.43-2.56, respectively) compared to osimertinib alone (4.87, 3.91-6.07; 2.50, 2.02-3.09; 1.59, 1.37-1.84; 2.00, 1.74-2.29; 0.65, 0.50-0.84; 1.01, 0.91-1.11). Our investigation unveiled an elevated risk of cardiotoxicity in NSCLC patients when osimertinib was combined with PPIs, compared to osimertinib monotherapy. Therefore, vigilant monitoring for cardiotoxicity is paramount in NSCLC patients undergoing these combined treatments.

Objective Methicillin-resistant Staphylococcus aureus (MRSA) infections among children are escalating annually. Vancomycin stands as the frontline therapeutic agent against MRSA infections. However, determining the therapeutic window for vancomycin in pediatric patients remains a challenge. Methods This retrospective study collected data from hospitalized children aged 1 month to 18 years, who underwent routine therapeutic drug monitoring for vancomycin. We analyzed the distribution patterns of vancomycin concentrations in these patients. Factors influencing clinical outcomes and adverse reaction (nephrotoxicity) were investigated. ROC analysis was used to establish the therapeutic window for vancomycin in pediatric patients. Results A comprehensive dataset encompassing 183 pediatric patients with 330 samples was analyzed. The mean trough concentration ( C min ) of vancomycin was 7.6 ± 5.5 mg/L. 74.3% of patients exhibited concentrations below the conventionally recommended therapeutic window of 10-20 mg/L. Patients responding positively to treatment exhibited significantly higher C min values (8.4 ± 5.7 mg/L) compared to those with treatment failure (5.9 ± 4.4 mg/L, P = 0.006). Similarly, patients who developed nephrotoxicity had significantly elevated C min levels (17.8 ± 5.3 mg/L) compared to those without nephrotoxicity (6.4 ± 3.9 mg/L, P < 0.001). Both univariate and multivariate logistic regressions revealed that the C min of vancomycin was the predictor of both clinical outcomes and adverse reaction. Furthermore, receiver operating characteristic curve analysis pinpointed that C min of vancomycin with 5.9 mg/L and 14.8 mg/L associated with clinical effectiveness and safety, respectively. Referring to the therapeutic window of adults, vancomycin underexposure in pediatrics is serious extremely. Conclusion Based on our findings, we propose a revised therapeutic window of 5.9-14.8 mg/L for vancomycin in pediatric patients, which could aid in optimizing treatment outcomes and minimizing adverse effects.

Methicillin-resistant Staphylococcus aureus (MRSA) infections among children are escalating annually. Vancomycin serves as the frontline therapeutic agent against MRSA infections. However, determining the therapeutic window that maximizes efficacy while minimizing the risk of toxicity for vancomycin in pediatric patients remains a challenge. This study aimed to explore a therapeutic window for vancomycin in pediatric patients. This retrospective study collected data from hospitalized children aged 1 month to 18 years, who underwent routine therapeutic drug monitoring for vancomycin. We analyzed the distribution patterns of vancomycin concentrations in these patients. Factors influencing clinical outcomes and adverse reaction (nephrotoxicity) were investigated. ROC analysis was used to establish the therapeutic window for vancomycin in pediatric patients. A comprehensive dataset encompassing 183 pediatric patients with 330 samples was analyzed. The mean trough concentration (Cmin) of vancomycin was 7.6 ± 5.5 mg/L. 74.3

Background Methicillin-resistant Staphylococcus aureus (MRSA) infections among children are escalating annually. Vancomycin stands as the frontline therapeutic agent against MRSA infections. However, determining the therapeutic window for vancomycin in pediatric patients remains a challenge. Methods This retrospective study collected data from hospitalized children aged 1 month to 18 years, who underwent routine therapeutic drug monitoring for vancomycin. We analyzed the distribution patterns of vancomycin concentrations in these patients. Factors influencing clinical outcomes and adverse reaction (nephrotoxicity) were investigated. ROC analysis was used to establish the therapeutic window for vancomycin in pediatric patients. Results A comprehensive dataset encompassing 183 pediatric patients with 330 samples was analyzed. The mean trough concentration ( C min ) of vancomycin was 7.6 ± 5.5 mg/L. 74.3% of patients exhibited concentrations below the conventionally recommended therapeutic window of 10–20 mg/L. Patients responding positively to treatment exhibited significantly higher C min values (8.4 ± 5.7 mg/L) compared to those with treatment failure (5.9 ± 4.4 mg/L, P = 0.006). Similarly, patients who developed nephrotoxicity had significantly elevated C min levels (17.8 ± 5.3 mg/L) compared to those without nephrotoxicity (6.4 ± 3.9 mg/L, P < 0.001). Both univariate and multivariate logistic regressions revealed that the C min of vancomycin was the predictor of both clinical outcomes and adverse reaction. Furthermore, receiver operating characteristic curve analysis pinpointed that C min of vancomycin with 5.9 mg/L and 14.8 mg/L associated with clinical effectiveness and safety, respectively. Conclusion Referring to the therapeutic window of adults, vancomycin underexposure in pediatrics is serious extremely. Based on our findings, we propose a revised therapeutic window of 5.9–14.8 mg/L for vancomycin in pediatric patients, which could aid in optimizing treatment outcomes and minimizing adverse effects.

目的 描述抗菌药物潜在的药物相互作用(pDAAIs)在重症监护室(ICU)的流行情况,分析临床药师的药学干预对提高ICU患者抗菌药物使用安全性和有效性的作用.方法 前瞻性选取西安交通大学第二附属医院 2021 年 1-12 月有临床药师审核医嘱的ICU患者作为干预组,同时回顾性选取 2019 年 1-12 月未进行药学干预的该院ICU感染患者病历资料作为对照组,对比有无临床药师干预的感染患者的ICU住院天数、抗菌药物相关肝肾损伤发生率.干预组采用Micromedex数据库鉴别确定pDAAIs,并对其严重程度及临床意义进行分析.结果 共纳入 778 例患者,其中干预组 406 例,临床药师审核了 3619 条药物医嘱,发现 30 种药物相互作用组合,286 对pDAAIs,其中 10种组合占所观察到pDAAIs的 60.5%.干预组中已发生和未发生pDDIs的患者,在抗菌药物类别、平均使用药物品种数之间差异有统计学意义(P＜0.01).临床药师药学干预pDAAIs 537 条,医师接受 503 条,总接受率为 93.7%.与对照组相比,干预组患者ICU住院时间明显缩短,抗菌药物相关肝、肾损伤发生率明显下降(P＜0.05).结论 ICU感染患者pDAAIs发生率较高,药物治疗易受药物相互作用影响.临床药师的药学干预可预防或处置pDAAIs,提高ICU患者抗菌药物使用的安全性和有效性.

Aims: Tyrosine kinase inhibitors (TKIs) improve patient outcomes, but the prevalence of clinically significant TKI-associated drug–drug interaction (DDI) is unknown. We aim to assess the risk prevalence between TKIs and other drugs in cancer patients. Methods: This was a retrospective cross-sectional study conducted in three tertiary care hospitals. All medical data were collected in the computer-based medication prescription system from January 2020 to December 2020. The hazardous DDIs identification has been performed using US Food and Drug Administration-approved labels. Descriptive statistics and univariate and multivariate logistic regression analyses were applied to identify risk factors associated with potential hazardous interactions. Results: A total of 2754 patients were included in our study. 413 hazardous DDIs were identified and 387 (14.1%) patients experienced at least one DDI. Proton pump inhibitor, dexamethasone and fluoroquinolones were most frequently implicated in clinically relevant DDIs with TKIs. In a multivariate analysis, younger age, the number of drugs and lung cancer had a higher risk for the occurrence of hazardous DDIs. Conclusions: The prevalence of hazardous DDIs is relatively high in the cancer patient population receiving TKIs treatment. The awareness of potential clinically relevant DDIs can help patients reduce the probability of adverse event of drugs.

目的:探索药师参与医保特殊药品审核的必要性和可行性.方法:以合理用药为基础,结合国家医保政策,建立以药师为审核主体的医保药品三方联审工作模式(医师-药师-医保),对特殊药品进行事前审核.结果:2019年11月—2021年5月,共审核特殊药品4652人次,通过率82％.其中申报材料不全623人次,超医保限定条件211人次,涉及违规金额1200余万元.结论:药师参与特殊药品医保审核,既减少了医保基金的不合理支出,又提高了特殊药品的合理使用率,同时也为其他医疗机构医保精细化管理提供参考.

Background: Oral administration increases the risk of interactions, because most oral antineoplastic agents (OAAs) are taken on a daily basis. Interactions can increase exposure to antitumoral agents or cause treatment failure. Potential drug-drug interactions (DDIs) are commonly observed in patients with cancer, while the extent to which OAAs related hazardous DDIs remains unclear.Methods: We studied the contraindication patterns between oral antineoplastic agents and other medications among cancer patients in two tertiary care teaching hospitals in China. A total of 20 clinically significant hazardous DDI pairs that involved 30 OAAs were identified based on the predetermined criteria. Patient medications were checked for DDIs by using the US Food and Drug Administration approved labeling. Descriptive statistics and uni- and multivariate logistic regression analyses were carried out.Results: In this study, 13,917 patients were included and a total of 297 DDIs were identified. The results revealed that proton pump inhibitors (PPIs), dexamethasone and fluoroquinolones were the most often involved hazardous DDIs with OAAs. The most prevalent contraindication is the simultaneous use of certain molecular targeted agents and PPIs. In the result of the multivariate analysis, younger age (0-20 group), increasing number of drugs and patient treated with targeted therapy had a higher risk for DDIs.Conclusion: The prevalence of OAAs related hazardous DDIs appears to be low in the cancer patients. However, physicians and clinical pharmacologists should be aware of the potential hazardous DDIs when prescribing OAAs, especially certain pH-dependent molecular targeted agents and potential QTc prolonging drugs.

Purpose:To determine whether combinations of antifungal drugs are effective and safe for patients in intensive-care units.Methods:This study compared the efficacy and safety of caspofungin (CAS), voriconazole (VOR), amphotericin B liposome (L-AmB), CAS+VOR, and CAS+L-AmB as empirical, preemptive, and targeted therapies for invasive fungal infection (IFI).Results:Comparing the CAS, VOR, and CAS+VOR groups revealed that there were no differences in response rates between all therapy types, IFI-associated death within 90 days was less common in the CAS+VOR group (1.8%) than the VOR group (14.3%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For empirical or preemptive therapy, the CAS group had a better response rate (80.0%) than the CAS+VOR group (47.1%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For targeted therapy, no differences were found for efficacy and safety. There were no differences among the CAS, L-AmB, and CAS+L-AmB groups in efficacy and safety.Conclusion:Patients who received CAS monotherapy as an empirical or preemptive therapy could achieve good outcomes. Patients who received CAS+VOR or CAS+L-AmB achieved almost the same outcomes when compared with those who received CAS, VOR, and L-AmB monotherapy as targeted therapies, but those who received CAS+VOR had a lower IFI mortality rate than did those who received VOR monotherapy.

Objectives: Increased resistance of Candida species, especially Candida. glabrata is problematic. Combination antifungal therapies were studied to solve the problem. Methods: In this study, combinations of caspofungin with fluconazole and voriconazole were evaluated in 28 Candida species (including 15 C. glabrata and 12 with FKS mutation) at 24 and 48 hours using two Etest methods (direct cover method and MIC/MIC method). Results: For Candida isolates, direct cover method showed synergy of caspofungin-fluconazole and caspofungin-voriconazole against 12/28 (43%) isolates at 24 hours, and against 16/28 (57%) isolates at 48 hours. The MIC/MIC method showed synergy of caspofungin-fluconazole and caspofungin-voriconazole against 11/28 (39%) and 12/28 (43%) isolates at 24 hours, and against 16/28 (57%) and 17/28 (61%) isolates at 48 hours, respectively. For C. glabrata, direct cover method showed synergy of caspofungin-fluconazole and caspofungin-voriconazole against 11/15 (73%) and 10/15 (67%) isolates at 24 hours, and 11/15 (73%) and 13/15 (87%) isolates at 48 hours, respectively. The MIC/MIC method showed synergy of caspofungin-fluconazole and caspofungin-voriconazole against both 11/15 (73%) isolates at 24 hours, and 10/15 (67%) and 14/15 (93%) isolates at 48 hours, respectively. Conclusion: A combination of caspofungin and fluconazole or voriconazole might be effective against infections caused by Candida species, especially C. glabrata with FKS mutation.

Background: To develop a population pharmacokinetic (PPK) model for caspofungin, identify parameters influencing caspofungin pharmacokinetics, and assess the required probability of target attainment (PTA) and cumulative fraction of response (CFR) for various dosing regimens of caspofungin in all patients and intensive care unit (ICU)-subgroup patients. Method: The general PPK model was developed based on data sets from all patients (299 patients). A ICU-subgroup PPK model based on data sets from 136 patients was then analyzed. The effects of demographics, clinical data, laboratory data, and concomitant medications were tested. Monte-Carlo simulations (MCS) were used to evaluate the effectiveness of different caspofungin dosage regimens. Results: One-compartment model best described the data of all patients and ICU patients. Clearances (CL) were 0.32 L/h and 0.40 L/h and volumes of distribution (V) were 13.31 L and 10.20 L for the general and ICU-subgroup PPK models, respectively. In the general model, CL and V were significantly associated with albumin (ALB) concentration and body weight (WT). In the ICU-subgroup model, CL was associated with WT. The simulated exposure in ICU patients was lower than that in all patients (p < 0.05). MCS indicated that higher caspofungin maintenance doses of 70–150 mg may achieve target CFR of >90% for patients with higher WT (>70 kg) or with C. albicans or C. parapsilosis infections, and especially for ICU patients with hypoalbuminaemia. Conclusion: The PPK model and MCS presented in the study demonstrated that the recommended dosage regimen for caspofungin in patients with higher body weight or hypoalbuminaemia will result in low exposure.

Differences in pharmacokinetics/pharmacodynamics (PK/PD) target attainment are rarely considered when antifungals are switched in critically ill patients. This study intends to explore whether the antifungal de-escalation treatment strategy and the new intermittent dosing strategy of echinocandins in critically ill patients are able to achieve the corresponding PK/PD targets. The published population PK models of antifungals in critically ill patients and a public data set from the MIMIC-III database (n = 662) were employed to evaluate PK/PD target attainment of different dosing regimens of antifungals. Cumulative fraction of response (CFR) was calculated for each dosing regimen. Most guideline-recommended dosing regimens of fluconazole and voriconazole could achieve target exposure as de-escalation treatment in critically ill patients. For initial echinocandin treatment, achievement of the target exposure decreased as body weight increased, and the intermittent dosing strategy had a slightly higher CFR value in most simulations compared to conventional dosing strategy. For Candida albicans and Candida glabrata infection, caspofungin at the lowest dose achieved a CFR of >90%, while micafungin or anidulafungin required almost the highest doses simulated in this study to achieve the same effect. None of the echinocandins other than 150 mg every 24 h (q24h) or 200 mg q48h of caspofungin achieved the target CFR for Candida parapsilosis infection. These findings support the guideline-recommended dose of triazoles for antifungal de-escalation treatment and confirm the insufficient dosage of echinocandins in critically ill patients, indicating that a dosing regimen based on body weight or intermittent dosing of echinocandins may be required.

RATIONALEIn order to characterize the intracellular pharmacokinetic properties of tigecycline, we developed and fully validated a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for quantification of tigecycline in human lung epithelial cells (BEAS-2B) and polymorphonuclear neutrophils (PMNs).METHODSTetracycline was used as internal standard, and chromatographic separation was achieved on a C18 Hypersil Gold aQ column using two mobile phases, a mixture solution of water (containing 0.1% formic acid) and acetonitrile. The flow rate was 0.4 mL/min for 5.0 min. Tigecycline drug uptake was evaluated by incubating the BEAS-2B and PMNs up to 3 h at tigecycline concentrations of 1 mg/L.RESULTSThe assay was linear over the tested concentration range of 0.01-2 mg/L for tigecycline in BEAS-2B and PMNs (r2 >0.99). The inter- and inter-day precisions (RSD, %) were <10.02% and the accuracies (%) were within the range of 85-115%. The uptake study showed that after incubation with tigecycline (1 mg/L) for 3h at 37 °C, the intracellular peak concentration of BEAS-2B was 14.44 ± 7.12 mg/L at 1h, and 41.43 ± 25.66 mg/L in PMNs at 20 min. The mean intracellular concentrations fluctuated in the range of 0.8-14.44 mg/L in BEAS-2B and 10.14-41.43 mg/L in PMNs for 1 mg/L tigecycline exposure.CONCLUSIONSValidated LC-MS/MS is a simple, rapid, and sensitive method for determining the intracellular concentration of tigecycline, and tigecycline has good penetrations both in human BEAS-2B and PMNs. The method described in this paper can be efficiently used for future studies of the intracellular pharmacokinetics of tigecycline.

Rationale In order to characterize the intracellular pharmacokinetic properties of tigecycline, we developed and fully validated a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for quantification of tigecycline in human lung epithelial (BEAS-2B) cells and polymorphonuclear neutrophils (PMNs). Methods Tetracycline was used as an internal standard and chromatographic separation was achieved on a C18 Hypersil Gold aQ column using two mobile phases, a solution of water (containing 0.1% formic acid) and acetonitrile. The flow rate was 0.4 mL/min for 5.0 min. Tigecycline drug uptake was evaluated by incubating the BEAS-2B cells and the PMNs for up to 3 h at tigecycline concentrations of 1 mg/L. Results The assay was linear over the tested concentration range of 0.01-2 mg/L for tigecycline in BEAS-2B cells and PMNs (r(2) >0.99). The inter- and inter-day precisions (RSD, %) were <10.02% and the accuracies (%) were within the range of 85-115%. The uptake study showed that after incubation with tigecycline (1 mg/L) for 3 h at 37 degrees C, the intracellular peak concentration of BEAS-2B cells was 14.44 +/- 7.12 mg/L at 1 h, and 41.43 +/- 25.66 mg/L in PMNs at 20 min. The mean intracellular concentrations fluctuated in the range of 0.8-14.44 mg/L in BEAS-2B cells and 10.14-41.43 mg/L in PMNs for 1 mg/L tigecycline exposure. Conclusions Validated LC/MS/MS is a simple, rapid, and sensitive method for determining the intracellular concentration of tigecycline, and tigecycline has good penetrations both in human BEAS-2B cells and PMNs. The method can be efficiently used for future studies of the intracellular pharmacokinetics of tigecycline.

We sought to determine the proportion of cryptococcal antigen (CrAg) positivity and compare a CrAg lateral flow assay (LFA) versus latex agglutination test in Atlanta, GA. CrAg positivity was moderately high, and there were important discrepancies between diagnostic tests. Background Cryptococcus neoformans is a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected persons worldwide, and there are scarce recent data on cryptococcal antigen (CrAg) positivity in the United States We sought to determine the frequency of cryptococcal disease and compare the performance of a CrAg lateral flow assay (LFA) versus latex agglutination (LA) test. Methods All patients from Grady Health System in Atlanta who had a serum or cerebrospinal fluid (CSF) sample sent for CrAg testing as part of clinical care from November 2017 to July 2018 were included. Percentage positivity and test agreement were calculated. Results Among 467 patients, 557 diagnostic tests were performed; 413 on serum and 144 on CSF. The mean age was 44 years, and most were male (69%) and had HIV (79%). Twenty-four (6.4%, 95% confidence interval [CI] = 4.1-9.4) patients were serum CrAg positive, and 8 (5.8%, 95% CI = 2.6-11.2) individuals tested positive for CSF CrAg. Although overall agreement between the LA and LFA was substantial to high for CSF (kappa = 0.71, 95% CI = 0.51-0.91) and serum (kappa = 0.93, 95% CI = 0.86-1.00), respectively, there were important discrepancies. Five patients had false-positive CSF LA tests that affected clinical care, and 4 patients had discordant serum tests. Conclusions We found a moderately high proportion of cryptococcal disease and important discrepancies between the LA test and LFA. Clinical implications of these findings include accurate detection of serum CrAg and averting unnecessary treatment of meningitis with costly medications associated with high rates of adverse events.

Patients with residual invasive HER2-positive early breast cancer after completion of neoadjuvant therapy have a high risk of recurrence or death despite of receiving standard treatment of Trastuzumab. Trastuzumab emtansine (T-DM1), which act as a breakthrough therapy, has been proved to reduce 50% incidence of recurrence or death compared with Trastuzumab alone. This study was aimed to estimate cost-effectiveness of T-DM1 vs. trastuzumab as the adjuvant treatment in China. A validated 6-state Markov model with monthly cycle was constructed to estimate the lifetime incremental cost-effectiveness ratio (ICER). Main clinical input was the time spent in invasive disease-free survival state, estimated by parametric extrapolations to survival data observed in the clinical trial Katherine. Utilities were calculated from EQ-5D of patients in Katherine and the published literatures. The costs obtained both from real world data and local published resources including drugs, administration, adverse events management, follow-up and therapeutic costs. Furthermore, indirect costs were included when analyzed from the society perspective. Costs and outcomes were both discounted at 5%. Sensitivity analysis were conducted to verify the robustness of the results. T-DM1 provided 1.49 more QALYs with additional costs than trastuzumab. From healthcare system perspective, the ICER was CNY 112,004/QALY. Further 39% lower indirect costs in T-DM1 group resulting an ICER of CNY 98,757/QALY from the society perspective. Both ICERs were between 1∼2 times GDP per capita, far below the local threshold of 3 times GDP per capita in 2019 (CNY 212,676). Acquisition cost of T-DM1 is partially offset by the prevention of disease recurrences over the time. Cost for managing recurrences in T-DM1 group was 44% lower than that in trastuzumab group. Probabilistic sensitivity analysis showed that T-DM1 was more cost-effective in more than 95% simulations at local threshold regardless of the perspective. Compared to trastuzumab, T-DM1 is more cost-effective as the adjuvant treatment for patients with residual invasive HER2-positive early breast cancer in China.