1.A Real-World Pharmacovigilance Study of Adverse Drug Reactions to CD19- and BCMA-Targeted CAR-T Cell Therapies
Lu LU ; Pengjiao AN ; Zhiqing XU ; Bin ZHAO
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1384-1391
To evaluate the clinical safety of four CD19-targeted and two BCMA-targeted chimeric antigen receptor T-cell (CAR-T) therapies. Adverse drug reaction (ADR) reports for six CAR-T products (Breyanzi, Kymriah, Tecartus, Yescarta, Abecma, Carvykti) from the US FDA Adverse Event Reporting System (FAERS) database between January 2004 and March 2025 were retrieved. The basic characteristics of the reports were analyzed. ADRs were categorized by System Organ Class (SOC) and coded into corresponding preferred term(PT) using MedDRA (Version 27.1). The reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were used to detect association signals between the six drugs and the PT. A total of 54 833 ADR reports were included in this study: Breyanzi (1511, 2.76%), Kymriah (18 087, 32.99%), Tecartus (4408, 8.04%), Yescarta (23 937, 43.65%), Abecma (2762, 5.04%), and Carvykti (4128, 7.53%). These reports corresponded to 15 210 unique patients, comprising 7136 males (46.92%), 4483 females (29.47%), and 3591 (23.61%) with missing gender information. Regarding age distribution, all patients in the Abecma and Carvykti groups were ≥18 years old, while 22.52% of patients in the Kymriah group were < 18 years old. The proportion of male patients was higher than that of females across all six drug groups. The top seven ADRs by report count were, in order: various nervous system disorders; immune system disorders; general disorders and administration site conditions; various investigations; infections and infestations; various neoplasms; and blood and lymphatic system disorders. The top ten PTs by report count included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), pyrexia, neurotoxicity, death, hypotension, disease progression, fatigue, platelet count decreased, and malignant neoplasm progression. Among the six CAR-T therapies, the BCMA-targeted Abecma showed the strongest association with CRS [ROR 2412.12(95% CI: 2093.06-2779.83), PRR 891.75( Clinicians should implement rigorous safety monitoring for patients receiving CAR-T therapy, paying particular attention to the early symptoms of CRS and neurotoxicity, and enhance surveillance for malignant neoplasm progression.
2.Comprehensive Clinical Evaluation of Nusinersen Based on Multi-criteria Decision Analysis Method
Jinghan QU ; Xin LIU ; Xin TIAN ; Pengjiao AN ; Tingting XU ; Bo ZHANG
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1083-1090
To provide a theoretical basis for different drug decision-making scenarios by conducting a comprehensive clinical evaluation of nusinersen. Based on the method of multi-criteria decision analysis, a comprehensive clinical evaluation index system of nusinersen was established. This system, including core criterion model and contextualized criterion model, covered multiple evaluation dimensions such as safety, effectiveness, economy, and social attributes. The evidence of nusinersen in various criteria was summarized and integrated through systematic reviews. Then, different stakeholders were assigned weights and scores in various criteria of the core criterion model. Finally, a holistic value of nusinersen was estimatedthrough standardizing and combining the results in contextualized criterion model. The criteria, type of therapeutic benefit disease severity (0.08±0.02), unmet needs (0.08±0.01), quality of evidence (0.08±0.01), effectiveness (0.08±0.01) and safety (0.08±0.02) received the greatest weights after standardization. The higher mean scores for nusinersen versus placebo for the treatment of spinal muscular atrophy were disease severity (4.8±0.4), innovation of the drug (4.7±0.6), expert consensus or clinical practice guidelines (4.5±0.6), effectiveness (4.0±1.0) and quality of evidence (4.0±0.8).The holistic value of nusinersen was 0.41. The overall impact of the contextualized model on the evaluation of the drug was 0.26, indicating that it may overestimate the comprehensive value of nusinersen. The method of multi-criteria decision analysis proves the positive role that nusinersen plays in spinal muscular atrophy treatment.
3.Propranolol combined with memory retrieval reconsolidation procedure for the intervention of alcohol craving in patients with alcohol dependence
Pengjiao XU ; Shuai YU ; Han WANG ; Chuansheng WANG ; Ruiling ZHANG ; Yahui XU
Chinese Journal of Psychiatry 2023;56(2):106-113
Objective:This study aims to explore the effect of propranolol combined with memory retrieval reconsolidation procedure on alcohol craving.Methods:A total of 54 patients with alcohol dependence who met the diagnostic criteria for alcohol dependence in DSM-Ⅳ were enrolled. The patients were randomly located into the alcohol retrieval-propranolol group (study group, n=28) and the alcohol retrieval-placebo group (control group, n=26) using the random number table. The study group used propranolol combined with a memory retrieval reconsolidation procedure, while the control group used a placebo combined with a memory retrieval reconsolidation procedure. The Visual Analog Scale (VAS) was used to evaluate the degree of alcohol craving induced by images such as wine bottle, pouring wine, and drinking (alcohol-related cue images, previous cue images) and neutral images (new cue) at stages of baseline measures, relevance learning, and memory test. The systolic blood pressure, diastolic blood pressure, and heart rate were applied to evaluate cue responsiveness. Repeated measures analysis of variance was used to compare the craving degree, systolic blood pressure, diastolic blood pressure, and heart rate between the two groups. The correlation between cue responsiveness and craving degree was analyzed. Results:Relevance learning stage: Compared with before learning, the levels of systolic blood pressure, diastolic blood pressure, and heart rate of the two groups increased in varying degrees after learning conditional stimulation-relevance learning+(CS+, namely neutral images paired learning with alcohol) ( F=52.79, 42.44, 49.53, P<0.05). Compared with the baseline measures, the VAS of neutral images in relevancy learning increased ( F=99.88, 68.69, both P<0.01). Memory test stage: (1) Compared with the control group, the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images were lower in the study group ( F=7.38, 13.27, 11.34, 4.62, P<0.05). Compared with the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images in the relevance learning stage, the VAS scores of the study group in the memory test stage were significantly lower ( F=43.89, 23.53, 15.93, 31.01, P<0.05). For the control group, VAS scores induced by pouring wine and drinking images were significantly increased ( F=13.40, 63.65, P<0.05). (2) After the memory test stage, compared with the control group, the levels of diastolic blood pressure and heart rate in the study group decreased ( F=20.99, 15.42, P<0.05). Compared with before the test, the levels of diastolic blood pressure and heart rate in the study group decreased after the test ( F=4.11, 8.05, P<0.05), while those in the control group increased ( F=81.86, 41.13, P<0.05). (3) The difference in diastolic blood pressure before and after the memory test stage was positively correlated with the difference in neutral VAS score between the memory test and association learning ( r=0.394, P=0.038). Heart rate difference before and after the memory test stage positively correlated with the VAS score difference between the memory test and associated learning drinking images ( r=0.389, P=0.041). Conclusion:Propranolol combined with memory retrieval reconsolidation procedure can reduce alcohol cravings induced by previous and new cues in patients with alcohol dependence.
4.Propranolol combined with memory retrieval reconsolidation procedure for the intervention of alcohol craving in patients with alcohol dependence
Pengjiao XU ; Shuai YU ; Han WANG ; Chuansheng WANG ; Ruiling ZHANG ; Yahui XU
Chinese Journal of Psychiatry 2023;56(2):106-113
Objective:This study aims to explore the effect of propranolol combined with memory retrieval reconsolidation procedure on alcohol craving.Methods:A total of 54 patients with alcohol dependence who met the diagnostic criteria for alcohol dependence in DSM-Ⅳ were enrolled. The patients were randomly located into the alcohol retrieval-propranolol group (study group, n=28) and the alcohol retrieval-placebo group (control group, n=26) using the random number table. The study group used propranolol combined with a memory retrieval reconsolidation procedure, while the control group used a placebo combined with a memory retrieval reconsolidation procedure. The Visual Analog Scale (VAS) was used to evaluate the degree of alcohol craving induced by images such as wine bottle, pouring wine, and drinking (alcohol-related cue images, previous cue images) and neutral images (new cue) at stages of baseline measures, relevance learning, and memory test. The systolic blood pressure, diastolic blood pressure, and heart rate were applied to evaluate cue responsiveness. Repeated measures analysis of variance was used to compare the craving degree, systolic blood pressure, diastolic blood pressure, and heart rate between the two groups. The correlation between cue responsiveness and craving degree was analyzed. Results:Relevance learning stage: Compared with before learning, the levels of systolic blood pressure, diastolic blood pressure, and heart rate of the two groups increased in varying degrees after learning conditional stimulation-relevance learning+(CS+, namely neutral images paired learning with alcohol) ( F=52.79, 42.44, 49.53, P<0.05). Compared with the baseline measures, the VAS of neutral images in relevancy learning increased ( F=99.88, 68.69, both P<0.01). Memory test stage: (1) Compared with the control group, the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images were lower in the study group ( F=7.38, 13.27, 11.34, 4.62, P<0.05). Compared with the VAS scores of cravings induced by wine bottles, pouring wine, drinking images, and neutral images in the relevance learning stage, the VAS scores of the study group in the memory test stage were significantly lower ( F=43.89, 23.53, 15.93, 31.01, P<0.05). For the control group, VAS scores induced by pouring wine and drinking images were significantly increased ( F=13.40, 63.65, P<0.05). (2) After the memory test stage, compared with the control group, the levels of diastolic blood pressure and heart rate in the study group decreased ( F=20.99, 15.42, P<0.05). Compared with before the test, the levels of diastolic blood pressure and heart rate in the study group decreased after the test ( F=4.11, 8.05, P<0.05), while those in the control group increased ( F=81.86, 41.13, P<0.05). (3) The difference in diastolic blood pressure before and after the memory test stage was positively correlated with the difference in neutral VAS score between the memory test and association learning ( r=0.394, P=0.038). Heart rate difference before and after the memory test stage positively correlated with the VAS score difference between the memory test and associated learning drinking images ( r=0.389, P=0.041). Conclusion:Propranolol combined with memory retrieval reconsolidation procedure can reduce alcohol cravings induced by previous and new cues in patients with alcohol dependence.
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